Glenn M. Chertow

All Publications

• Baseline Diastolic BP and BP-Lowering Effects on Cardiovascular Outcomes and All-Cause Mortality: A Meta Analysis. Journal of the American Society of Nephrology : JASN Sarwal, A., Boucher, R. E., Hartsell, S. E., Wei, G., Shen, J., Chertow, G. M., Whelton, P. K., Cheung, A. K., McEvoy, J. W., Greene, T., Beddhu, S. 2024

  Abstract

  Lowering blood pressure (BP) in persons with low diastolic BP could be harmful. Hence, we examined whether baseline diastolic BP modifies the effects of BP lowering on clinical outcomes in a meta-analysis of five large BP lowering trials.In a study-level meta-analysis based on individual participant data of the Systolic Blood Pressure Intervention Trial (N = 9361), the Action to Control Cardiovascular Risk in Diabetes Blood Pressure (N = 2362), the Secondary Prevention of Small Subcortical Strokes (N = 3020), the African American Study of Kidney Disease and Hypertension (N = 1094) and the Modification of Diet in Renal Disease (N = 840) studies, we used DerSimonian-Laird random-effects models to examine the dependence of the effect of the BP lowering intervention on baseline diastolic BP for cardiovascular, all-cause mortality and kidney outcomes.Mean baseline age was 65 ± 10 years old. Mean baseline systolic and diastolic BP were 141 ± 17 and 79 ± 12 mm Hg, respectively. More intensive BP control resulted in lower risk of composite cardiovascular outcome (HR 0.79, 95% CI 0.72, 0.87) and all-cause mortality (HR 0.86, 95% CI 0.75, 0.99) without evidence that the BP intervention effects differed by level of baseline diastolic BP (interaction p = 0.76 for cardiovascular composite and 0.85 for all-cause mortality). The mean baseline diastolic BP in the lowest and the upper three quartiles of baseline diastolic BP were 65 ± 6 mm Hg and 84 ± 9 mm Hg, respectively but the effects of the BP interventions on the outcomes were similar in both groups. Furthermore, there was no evidence of interaction of the BP intervention and baseline diastolic BP for kidney outcomes.Within the included diastolic BP range, there was no evidence that baseline diastolic BP modified the beneficial effects of intensive BP lowering.

  View details for DOI 10.1681/ASN.0000000539

  View details for PubMedID 39514294

• Pesticides and prostate cancer incidence and mortality: An environment-wide association study. Cancer Soerensen, S. J., Lim, D. S., Montez-Rath, M. E., Chertow, G. M., Chung, B. I., Rehkopf, D. H., Leppert, J. T. 2024

  Abstract

  Prostate cancer is the most common cancer among men in the United States, yet modifiable risk factors remain elusive. In this study, the authors investigated the potential role of agricultural pesticide exposure in prostate cancer incidence and mortality.For this environment-wide association study (EWAS), linear regression was used to analyze county-level associations between the annual use of 295 distinct pesticides (measured in kg per county) and prostate cancer incidence and mortality rates in the contiguous United States. Data were analyzed in two cohorts: 1997-2001 pesticide use with 2011-2015 outcomes (discovery) and 2002-2006 use with 2016-2020 outcomes (replication). The reported effect sizes highlight how a 1-standard-deviation increase in log-transformed pesticide use (kg per county) corresponds to changes in incidence. Analyses were adjusted for county-level demographics, agricultural data, and multiple testing.Twenty-two pesticides showed consistent, direct associations with prostate cancer incidence across both cohorts. Of these, four pesticides were also associated with prostate cancer mortality. In the replication cohort, each 1-standard-deviation increase in log-transformed pesticide use corresponded to incidence increases per 100,000 individuals (trifluralin, 6.56 [95% confidence interval (CI), 5.04-8.07]; cloransulam-methyl, 6.18 [95% CI, 4.06-8.31]; diflufenzopyr, 3.20 [95% CI, 1.09-5.31]; and thiamethoxam, 2.82 [95% CI, 1.14-4.50]). Limitations included ecological study design, potential unmeasured confounding, and lack of individual-level exposure data.The results of this study suggest a potential link between certain pesticides and increased prostate cancer incidence and mortality. These findings warrant further investigation of these specific pesticides to confirm their role in prostate cancer risk and to develop potential public health interventions.

  View details for DOI 10.1002/cncr.35572

  View details for PubMedID 39492609

• Contemporary epidemiology of hospitalised heart failure with reduced versus preserved ejection fraction in England: a retrospective, cohort study of whole-population electronic health records LANCET PUBLIC HEALTH Fletcher, R. A., Rockenschaub, P., Neuen, B. L., Walter, I., Conrad, N., Mizani, M. A., Bolton, T., Lawson, C. A., Tomlinson, C., Logothetis, S., Petitjean, C., Brizzi, L., Kaptoge, S., Raffetti, E., Calvert, P. A., Di Angelantonio, E., Banerjee, A., Mamas, M. A., Squire, I., Denaxas, S., McDonagh, T. A., Sudlow, C., Petersen, S. E., Chertow, G. M., Khunti, K., Sundstrom, J., Arnott, C., Cleland, J. F., Danesh, J., McMurray, J. J., Vaduganathan, M., Wood, A. M., CVD-COVID-UK COVID-IMPACT Consortium 2024; 9 (11)

  View details for Web of Science ID 001350551100001

• Contemporary epidemiology of hospitalised heart failure with reduced versus preserved ejection fraction in England: a retrospective, cohort study of whole-population electronic health records. The Lancet. Public health Fletcher, R. A., Rockenschaub, P., Neuen, B. L., Walter, I. J., Conrad, N., Mizani, M. A., Bolton, T., Lawson, C. A., Tomlinson, C., Logothetis, S. B., Petitjean, C., Brizzi, L. F., Kaptoge, S., Raffetti, E., Calvert, P. A., Di Angelantonio, E., Banerjee, A., Mamas, M. A., Squire, I., Denaxas, S., McDonagh, T. A., Sudlow, C., Petersen, S. E., Chertow, G. M., Khunti, K., Sundström, J., Arnott, C., Cleland, J. G., Danesh, J., McMurray, J. J., Vaduganathan, M., Wood, A. M. 2024; 9 (11): e871-e885

  Abstract

  Heart failure is common, complex, and often associated with coexisting chronic medical conditions and a high mortality. We aimed to assess the epidemiology of people admitted to hospital with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), including the period covering the COVID-19 pandemic, which was previously not well characterised.In this retrospective, cohort study, we used whole-population electronic health records with 57 million individuals in England to identify patients hospitalised with heart failure as the primary diagnosis in any consultant episode of an in-patient admission to a National Health Service (NHS) hospital. We excluded individuals with less than 1 year of medical history records in primary or secondary care; admissions to NHS hospitals for which less than 10% of heart failure cases were linkable to the National Heart Failure Audit (NHFA); individuals younger than 18 years at the time of the heart failure hospitalisation; and patients who died in hospital during the index heart failure admission. For patients with new onset heart failure, we assessed incidence rates of 30-day and 1-year all-cause and cause-specific (cardiovascular, non-cardiovascular, and heart failure-related) emergency rehospitalisation and mortality after discharge, and dispensed guideline-recommended medical therapy (GRMT). Follow-up occurred from the index admission to the earliest occurrence of the event of interest, death, or end of data coverage. We estimated adjusted hazard ratios (HRs) to compare HFrEF with HFpEF. We computed population-attributable fractions to quantify the percentage of outcomes attributable to coexisting chronic medical conditions.Among 233 320 patients identified who survived the index heart failure admission across 335 NHS hospitals between Jan 1, 2019, and Dec 31, 2022, 101 320 (43·4%) had HFrEF, 71 910 (30·8%) had HFpEF, and 60 090 (25·8%) had an unknown classification. In patients with new onset heart failure, there were reductions in all-cause 30-day (-5·2% [95% CI -7·7 to -2·6] in 2019-22) and 1-year rehospitalisation rates (-3·9% [-6·6 to -1·2]). Declining 30-day rehospitalisation rates affected patients with HFpEF (-4·8% [-9·2 to -0·2]) and HFrEF (-6·2% [-10·5 to -1·6]), although 1-year rates were not statistically significant for patients with HFpEF (-2·2% [-6·6 to 2·3] vs -5·7% [-10·6 to -0·5] for HFrEF). There were no temporal trends in incidence rates of 30-day or 1-year mortality after discharge. The rates of all-cause (HR 1·20 [1·18-1·22]) and cause-specific rehospitalisation were uniformly higher in those with HFpEF than those with HFrEF. Patients with HFpEF also had higher rates of 1-year all-cause mortality after discharge (HR 1·07 [1·05-1·09]), driven by excess risk of non-cardiovascular death (HR 1·25 [1·21-1·29]). Rates of rehospitalisation and mortality were highest in patients with coexisting chronic kidney disease, chronic obstructive pulmonary disease, dementia, and liver disease. Chronic kidney disease contributed to 6·5% (5·6-7·4) of rehospitalisations within 1 year for HFrEF and 5·0% (4·1-5·9) of rehospitalisations for HFpEF, double that of any other coexisting condition. There was swift implementation of newer GRMT, but markedly lower dispensing of these medications in patients with coexisting chronic kidney disease.Rates of rehospitalisation in patients with heart failure in England have decreased during 2019-22. Further population health improvements could be reached through enhanced implementation of GRMT, particularly in patients with coexisting chronic kidney disease, who, despite being at high risk, remain undertreated.Wellcome Trust, Health Data Research UK, British Heart Foundation Data Science Centre.

  View details for DOI 10.1016/S2468-2667(24)00215-9

  View details for PubMedID 39486903

• Chronic kidney disease in older adults: challenges and opportunities for the primary care provider. BMC primary care Brady, B. M., Suffoletto, J. A., Sankary, R., Chertow, G. M. 2024; 25 (1): 388

  Abstract

  Kidney disease and its comorbidities disproportionately affect older persons. Kidney disease modifying therapy is underutilized in older adults, as guidelines lack consensus on approaching diagnosis and treatment in older adults. This review aims to highlight the challenges presented by, and opportunities for, identifying and treating CKD in older adults.

  View details for DOI 10.1186/s12875-024-02638-4

  View details for PubMedID 39487419

  View details for PubMedCentralID PMC11529074

• Populationwide Screening for Chronic Kidney Disease: A Cost-Effectiveness Analysis. JAMA health forum Cusick, M. M., Tisdale, R. L., Chertow, G. M., Owens, D. K., Goldhaber-Fiebert, J. D., Salomon, J. A. 2024; 5 (11): e243892

  Abstract

  Sodium-glucose cotransporter-2 (SGLT2) inhibitors have changed clinical management of chronic kidney disease (CKD) and made populationwide screening for CKD a viable strategy. Optimal age of screening initiation has yet to be evaluated.To compare the clinical benefits, costs, and cost-effectiveness of population-wide CKD screening at different initiation ages and screening frequencies.This cost-effectiveness study used a previously published decision-analytic Markov cohort model that simulated progression of CKD among US adults from age 35 years and older and was calibrated to population-level data from the National Health and Nutrition Examination Survey (NHANES). Effectiveness of SGLT2 inhibitors was derived from the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial. Mortality, quality-of-life weights, and cost estimates were obtained from published cohort studies, randomized clinical trials, and US Centers for Medicare & Medicaid Services data. Analyses were performed from June 2023 through September 2024.One-time or periodic (every 10 or 5 years) screening for albuminuria, initiated at ages between 35 and 75 years, with and without addition of SGLT2 inhibitors to conventional CKD therapy (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers).Cumulative incidence of kidney failure requiring kidney replacement therapy (KRT); life years, quality-adjusted life years (QALYs), lifetime health care costs (2024 US currency), and incremental cost-effectiveness ratios discounted at 3% annually.For those aged 35 years, starting screening at age 55 years, and continuing every 5 years through age 75 years, combined with SGLT2 inhibitors, decreased the cumulative incidence of kidney failure requiring KRT from 2.4% to 1.9%, increased life expectancy by 0.13 years, and cost $128 400 per QALY gained. Although initiation of screening every 5 years at age 35 or 45 years yielded greater gains in population-wide health benefits, these strategies cost more than $200 000 per additional QALY gained. The comparative values of starting screening at different ages were sensitive to the cost and effectiveness of SGLT2 inhibitors; if SGLT2 inhibitor prices drop due to patent expirations, screening at age 55 years continued to be cost-effective even if SGLT2 inhibitor effectiveness were 30% lower than in the base case.This study found that, based on conventional benchmarks for cost-effectiveness in medicine, initiating population-wide CKD screening with SGLT2 inhibitors at age 55 years would be cost-effective.

  View details for DOI 10.1001/jamahealthforum.2024.3892

  View details for PubMedID 39514193

• Effects of dialysate potassium concentration of 3.0mEq/l with sodium zirconium cyclosilicate on dialysis-free days versus dialysate potassium concentration of 2.0mEq/l alone on rates of cardiac arrhythmias in hemodialysis patients with hyperkalemia. Kidney international Charytan, D. M., Winkelmayer, W. C., Granger, C. B., Middleton, J. P., Herzog, C. A., Chertow, G. M., Eudicone, J. M., Whitson, J. D., Tumlin, J. A. 2024

  Abstract

  The optimal approach towards managing serum potassium and hemodialysate potassium concentrations is uncertain. To study this, adults receiving hemodialysis for three months or more with hyperkalemia (pre-dialysis serum potassium (sK+) 5.1-6.5 mEq/l) had cardiac monitors implanted and were randomized to either eight weeks of 2.0 potassium/2.5 calcium mEq/l dialysate without sodium zirconium cyclosilicate (SZC) (2.0 potassium/noSZC) or 3.0 potassium/2.5 calcium mEq/l dialysate combined with SZC (3.0 potassium/SZC) on non-dialysis days to maintain pre-dialysis sK+ 4.0-5.5 mEq/l, followed by treatment crossover for another eight weeks. The primary outcome was the rate of adjudicated atrial fibrillation (AF) episodes of 2 minutes or more duration. Secondary outcomes included clinically significant arrhythmias (bradycardia, ventricular tachycardia, and/or asystole) and the proportion of sK+ measurements within an optimal window of 4.0- 5.5 mEq/l. Among 88 participants (mean age: 57.1 years; 51% male; mean pre-dialysis sK+: 5.5 mmol/l) with 25.5 person-years of follow-up, 296 AF episodes were detected in nine patients. The unadjusted AF rate was lower with 3.0 potassium/SZC versus 2.0 potassium/noSZC; 9.7 vs. 13.4/person-year (modeled rate ratio 0.52; 95% confidence interval: 0.41; 0.65). Clinically significant arrhythmias were reduced with 3.0 potassium/SZC vs. 2.0 potassium/noSZC 6.8 vs. 10.2/person-year modeled rate ratio 0.47: 0.38;0.58). Fewer sK+ measurements outside the optimal window occurred with 3.0 potassium/SZC (modeled odds ratio: 0.27:0.12, 0.35). Hypokalemia was less frequent (33 vs. 58 patients) with 3.0 potassium/SZC compared with 2.0 potassium/noSZC. Thus, in patients with hyperkalemia on maintenance hemodialysis, a combination of potassium 3.0 mEq/l and SZC on non-hemodialysis days reduced the rates of AF, other clinically significant arrhythmias, and post-dialysis hypokalemia compared with potassium 2.0/noSZC.

  View details for DOI 10.1016/j.kint.2024.10.010

  View details for PubMedID 39490411

• Baseline, Early Changes, and Residual Albuminuria: Post-hoc Analysis of a Clinical Trial of Dapagliflozin in Chronic Kidney Disease. Clinical journal of the American Society of Nephrology : CJASN van Mil, D., Vart, P., Chertow, G. M., Gansevoort, R. T., Rossing, P., Toto, R. D., Correa-Rotter, R., Langkilde, A. M., Sjöström, C. D., Wheeler, D. C., Heerspink, H. J. 2024

  Abstract

  Albuminuria is a strong indicator of kidney and cardiovascular risk in patients with chronic kidney disease (CKD). We assessed risk associations between albuminuria at baseline and four months after randomization in a placebo-controlled trial of dapagliflozin and kidney endpoints in patients with CKD and albuminuria, with and without type 2 diabetes.In this post-hoc analysis of the DAPA-CKD trial, 4304 adult patients with CKD were randomized to dapagliflozin 10mg or placebo as adjunct to maximally tolerated renin-angiotensin-system (RAAS) inhibitors. The primary endpoint was a composite of sustained ≥50% decline in estimated glomerular filtration rate, kidney failure, or death from kidney or cardiovascular cause. The kidney composite endpoint was similar but excluded cardiovascular death. We assessed associations among baseline albuminuria, early change in albuminuria, (baseline to Month 4), and residual albuminuria (Month 4) with the primary composite and kidney composite endpoints using Cox proportional hazards regression analyses.Compared to placebo, dapagliflozin reduced urinary albumin-to-creatinine ratio (UACR; baseline to Month 4) by 36% (95% CI: 30.2%, 42.5%) and 21% (95% CI: 12, 30%) in participants with and without type 2 diabetes, respectively (p-interaction: 0.02). A reduction in UACR from baseline to Month 4 was associated with a lower risk for the primary and kidney composite endpoints with a similar risk gradient for participants with and without type 2 diabetes (p-interaction: 0.10 and 0.19, respectively). Residual albuminuria was associated with a similar risk for the primary and kidney composite endpoints in each treatment arm (p-interaction: 0.19 and 0.18, respectively).Dapagliflozin reduced albuminuria, and the magnitude of albuminuria reduction showed similar proportional reductions in risks for the primary and kidney composite endpoints in participants with and without type 2 diabetes. Patients with residual albuminuria at Month 4 - whether randomized to dapagliflozin or placebo - experienced relatively high rates of CKD progression kidney endpoints, suggesting that therapies added to RAAS inhibitors and dapagliflozin may be required to sustain kidney and cardiovascular health.A Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients with Chronic Kidney Disease (DAPA-CKD), NCT03036150.

  View details for DOI 10.2215/CJN.0000000000000550

  View details for PubMedID 39475817

• Variation in Urology Care after Urinary Stone Surgery among Veterans at High-risk for Recurrence. Urology Ganesan, C., Shahzad, S. R., Thomas, I. C., Montez-Rath, M. E., Soerensen, S. J., Chertow, G. M., Pao, A. C., Leppert, J. T. 2024

  Abstract

  To determine rates of urology follow-up and implementation of stone prevention measures after stone surgery and to assess variation in care delivery within a large, integrated healthcare system.We used nationwide data from the United States Veterans Health Administration to identify patients who had stone surgery between 2016 and 2018 and who were at higher risk for recurrence. Our cohort included 13,444 Veterans across 90 facilities. We examined the proportion of patients who had a post-operative urology visit or who received a prevention measure (24-hour urine test, serum parathyroid hormone measurement, or prescription of a stone-related medication) within 6 months of stone surgery. We calculated the median odds ratio to quantify facility-level variation in urology care after stone surgery, adjusting for patient- and facility-level characteristics.Within 6 months of stone surgery, 94.2% Veterans had a urology visit, yet only 8.8% completed 24-hour urine testing, 8.4% had a parathyroid hormone measurement, and 31.0% were prescribed a stone-related medication. Implementation of prevention measures varied widely across facilities with the median odds ratio ranging between 1.18 for medication prescriptions and 1.77 for 24-hour urine testing.While most patients have a urology visit after stone surgery, stone prevention measures were implemented infrequently and inconsistently for patients at higher risk for recurrence, indicating an opportunity for quality improvement.

  View details for DOI 10.1016/j.urology.2024.10.012

  View details for PubMedID 39419204

• Prevalence of Mendelian Kidney Disease Among Patients With High-Risk APOL1 Genotypes Undergoing Commercial Genetic Testing in the United States KIDNEY INTERNATIONAL REPORTS Francisco, R., Punj, S., Vincent, L., Sanapareddy, N., Bhalla, V., Chertow, G. M., Keen-Kim, D., Charu, V. 2024; 9 (9): 2667-2676

  View details for DOI 10.1016/j.ekir.2024.06.028

  View details for Web of Science ID 001307959400001

• Acceptance of SARS-CoV-2 Surveillance Testing Among Patients Receiving Dialysis: A Cluster Randomized Trial. JAMA network open Montez-Rath, M., Varkila, M., Yu, X., Brillhart, S., Morgan, C., Leppink, A., Block, M. S., Mehta, S., Hunsader, P., Fountaine, A., Subramanian, N., Dittrich, M., Owens, D. K., Chertow, G. M., Parsonnet, J., Anand, S., Block, G. A. 2024; 7 (9): e2434159

  Abstract

  Integrating routine SARS-CoV-2 testing in dialysis facilities may benefit patients receiving dialysis by mitigating risks of serious illness and reducing transmission. Patient acceptance of nonmandatory testing is unknown.To evaluate the acceptance of 2 SARS-CoV-2 testing strategies among patients in hemodialysis facilities nationwide.This nationwide cluster (dialysis facility-level) randomized trial investigated the acceptance of SARS-CoV-2 testing among patients receiving maintenance hemodialysis at facilities located in 22 states.Anterior nares real-time reverse transcriptase-polymerase chain reaction tests offered once every 2 weeks (static testing facilities) vs offered once a week, once every 2 weeks, or once a month depending on county COVID-19 infection prevalence (dynamic testing facilities). Facilities were randomized by county, and tests were offered for 3 months between February 4 and July 24, 2023.The primary outcome was test acceptance. Secondary outcomes included the proportion of patients who accepted at least 1 test.In total, 62 hemodialysis facilities were randomized and 57 participated. Among 2389 participating patients, the median age was 64 (IQR, 54-74) years, 1341 (56%) were male, 138 (6%) were categorized as American Indian, 60 (3%) Asian, 885 (37%) Black, 75 (3%) Native Hawaiian or Pacific Islander, 338 (14%) Hispanic, and 876 (37%) White; and 1603 (67%) had diabetes. A median of 6 (IQR, 6-6) tests were offered per patient in the static arm and 4 (3-6) tests in the dynamic arm. Test acceptance was low: 8% of offered tests were accepted in each of the test arms. Among 503 patients who accepted at least 1 test, the median percentage of offered tests that were accepted was 16% (IQR, 17%-42%) using the static testing strategy and 50% (IQR, 33%-75%) using the dynamic testing strategy (P < .001). Older patients (odds ratio [OR], 1.08 [95% CI, 1.01-1.16] per 5-year age increment), patients with (vs without) diabetes (OR, 1.59 [95% CI, 1.18-2.16]), and women compared with men (OR, 1.30 [95% CI, 0.98-1.73]) were more likely to accept multiple tests. Patients designated in the electronic health record as Hispanic were more likely than patients designated as White (OR, 1.78 [95% CI, 1.15-2.76]) to accept at least 1 test, whereas patients living in zip codes electing Republican representatives to Congress were less likely than patients living in zip codes electing Democratic representatives (OR, 0.34 [95% CI, 0.17-0.69]) to accept multiple tests.In this cluster randomized trial evaluating 2 SARS-CoV-2 testing strategies in dialysis facilities, test acceptance was low, and a dynamic testing strategy anchored to COVID-19 infection prevalence did not outperform a static testing strategy of every 2 weeks.ClinicalTrials.gov Identifier: NCT05225298.

  View details for DOI 10.1001/jamanetworkopen.2024.34159

  View details for PubMedID 39298171

  View details for PubMedCentralID PMC11413714

• Hexasodium fytate for the treatment of calciphylaxis: a randomised, double-blind, phase 3, placebo-controlled trial with an open-label extension ECLINICALMEDICINE Sinha, S., Nigwekar, S. U., Brandenburg, V., Gould, L. J., Serena, T. E., Moe, S. M., Aronoff, G. R., Chatoth, D. K., Hymes, J. L., Carroll, K. J., Alperovich, G., Keller, L. H., Perello, J., Gold, A., Chertow, G. M. 2024; 75

  View details for DOI 10.1016/j.eclinm.2024.102784

  View details for Web of Science ID 001300972300001

• Prevalence of Mendelian Kidney Disease Among Patients With High-Risk APOL1 Genotypes Undergoing Commercial Genetic Testing in the United States. Kidney international reports da Silva Francisco, R., Punj, S., Vincent, L., Sanapareddy, N., Bhalla, V., Chertow, G. M., Keen-Kim, D., Charu, V. 2024; 9 (9): 2667-2676

  Abstract

  Among individuals with high-risk APOL1 genotypes, the lifetime risk of developing kidney failure is ∼15%, indicating that other genetic variants or nongenetic modifiers likely contribute substantially to an individual patient's risk of progressive kidney disease. Here, we estimate the prevalence and distribution of Mendelian kidney diseases among patients with high-risk APOL1 genotypes undergoing commercial genetic testing in the United States.We analyzed clinical exome sequencing data from 15,181 individuals undergoing commercial genetic testing for Mendelian kidney disease in the United States from 2020 to 2021. We identified patients with high-risk APOL1 genotypes by the presence of G1/G1, G1/G2, or G2/G2 alleles. Patients carrying single risk APOL1 alleles were identified as G1/G0, G2/G0; the remainder of patients were G0/G0. We estimated the prevalence and distribution of Mendelian kidney disease stratified by APOL1 genotype and genetically predicted ancestry.Of 15,181 patients, 3119 had genetic testing results consistent with a molecular diagnosis of Mendelian kidney disease (20.5%). Of 15,181 patients, 1035 (6.8%) had high-risk APOL1 genotypes. Among patients with recent genomic African ancestry, the prevalence of Mendelian kidney diseases was lower in those with high-risk APOL1 genotypes (9.6%; n = 91/944) compared with single risk APOL1 allele carriers (13.6%; n = 198/1453) and those with G0/G0 APOL1 genotypes (16.6%; n = 213/1281). Among patients with Mendelian kidney disease and recent genomic African ancestry, we observed differences in the prevalence of pathogenic/likely pathogenic variants in PKD1 (19.8% in high-risk vs. 30.2% in low-risk genotypes), and COL4A4 (24.2% in high-risk vs. 10.5% in low-risk genotypes).In this selected population of patients undergoing clinical genetic testing, we found evidence of Mendelian kidney disease in ∼10% patients with high-risk APOL1 genotypes.

  View details for DOI 10.1016/j.ekir.2024.06.028

  View details for PubMedID 39291188

  View details for PubMedCentralID PMC11403072

• Hexasodium fytate for the treatment of calciphylaxis: a randomised, double-blind, phase 3, placebo-controlled trial with an open-label extension. EClinicalMedicine Sinha, S., Nigwekar, S. U., Brandenburg, V., Gould, L. J., Serena, T. E., Moe, S. M., Aronoff, G. R., Chatoth, D. K., Hymes, J. L., Carroll, K. J., Alperovich, G., Keller, L. H., Perelló, J., Gold, A., Chertow, G. M. 2024; 75: 102784

  Abstract

  In the CALCIPHYX trial, we investigated hexasodium fytate, an inhibitor of vascular calcification, for the treatment of calcific uraemic arteriolopathy (calciphylaxis), a rare condition characterised by painful, non-healing skin lesions.In this international, phase 3, randomised, double-blind, placebo-controlled trial, adults with an ulcerated calciphylaxis lesion and pain visual analogue scale (VAS) score ≥50/100 were randomised 1:1 to hexasodium fytate 7 mg/kg or placebo intravenously during maintenance haemodialysis. Primary efficacy outcomes were an 8-item modification of the Bates-Jensen Wound Assessment Tool (BWAT-CUA) and Pain VAS in the intention-to-treat population. ClinicalTrials.gov number: NCT04195906.Overall, 34/37 patients randomised to hexasodium fytate and 26/34 patients randomised to placebo completed the 12-week randomised treatment period. At Week 12, both groups (hexasodium fytate versus placebo) showed similar improvements in BWAT-CUA (mean [standard deviation (SD)], -5.3 [5.2] versus -6.0 [6.2]; least squares mean difference, 0.3 [96% confidence interval (CI): -2.5, 3.0]; p = 0.88) and Pain VAS (mean [SD], -19.5 [26.9] versus -32.2 [38.5]; least squares mean difference, 11.5 [96% CI: -4.8, 27.8]; p = 0.15). One patient randomised to placebo briefly received hexasodium fytate in error. Serious adverse events through Week 12 included: calciphylaxis-related events leading to hospitalisation (2/38 [5%] versus 11/33 [33%]) and death (1/38 [3%] versus 5/33 [15%]). During the subsequent 12 weeks of open-label hexasodium fytate and 4 weeks of follow-up, there were no additional calciphylaxis-related events leading to hospitalisation. Over the course of the entire trial, deaths were 2/38 [5%] for the hexasodium fytate group and 7/33 [21%] for the placebo group.In patients with calciphylaxis, BWAT-CUA and Pain VAS improved similarly in hexasodium fytate- and placebo-treated patients; over the course of the entire trial, there were fewer deaths and calciphylaxis-related events leading to hospitalisation in the hexasodium fytate group.Funded by Sanifit, a CSL Vifor company.

  View details for DOI 10.1016/j.eclinm.2024.102784

  View details for PubMedID 39252867

  View details for PubMedCentralID PMC11381625

• Where Are Patients' Voices in Chronic Kidney Disease? Clinical journal of the American Society of Nephrology : CJASN Rüssmann, D., Roy-Chaudhury, P., Chertow, G. M., Gee, P., Chauhan, C., Macari, S., Murphy, M., Rossignol, P. 2024

  View details for DOI 10.2215/CJN.0000000581

  View details for PubMedID 39213129

• Practical Considerations and Implementation of Sodium-Glucose Co-Transporter-2 Inhibitors in Chronic Kidney Disease: Who, When, and How? A Position Statement by Nephrologists. Journal of primary care & community health Rastogi, A., Collins, A., Kelepouris, E., Kotzker, W., Middleton, J. P., Rajpal, M., Roy-Chaudhury, P., Chertow, G. M. 2024; 15: 21501319241259905

  Abstract

  There remains an unmet need to reduce kidney and cardiovascular risk in patients with chronic kidney disease (CKD). This report is therefore intended to provide real-world clinical guidance to primary care providers on sodium-glucose co-transporter-2 (SGLT2) inhibitor use in patients with CKD, focusing on practical considerations. Initially developed as glucose-lowering drugs, SGLT2 inhibitors preserve kidney function and reduce risks of cardiovascular events and mortality. Clinical benefits of SGLT2 inhibitors in CKD have been demonstrated in multiple clinical trials, yet utilization in practice remains relatively low, likely due to the complexity of labeled indications (past and present) and misconceptions about SGLT2 inhibitors as a class.A panel of 8 US-based nephrologists convened in August 2022 to develop consensus guidance for the primary care community surrounding risk assessment as well as initiation and implementation of SGLT2 inhibitors in patients with CKD. Here, we provide an adapted version of the Kidney Disease: Improving Global Outcomes (KDIGO) heatmap and a treatment-decision algorithm.We advocate SGLT2 inhibitors as co-first-line therapy with renin-angiotensin-aldosterone system (RAAS) inhibitors, where RAAS inhibitor dose titration need not be completed before initiation of an SGLT2 inhibitor. In fact, SGLT2 inhibitor therapy may facilitate up-titration or maintenance of optimal RAAS inhibitor dosing. We describe potential strategies to aid implementation of an SGLT2 inhibitor in clinical practice, including improving education and awareness among care providers and patients and dispelling misconceptions about the safety of SGLT2 inhibitors. In summary, we support the use of SGLT2 inhibitors with RAAS inhibitors as co-first-line therapy in most patients with CKD.

  View details for DOI 10.1177/21501319241259905

  View details for PubMedID 39143759

• In memoriam: George L. Bakris, MD, 1952-2024. Kidney international Chapman, A. B., Rafey, M. A., Chertow, G. M., Weir, M. 2024

  View details for DOI 10.1016/j.kint.2024.08.003

  View details for PubMedID 39178909

• Hyperkalemia and risk of chronic kidney disease progression: A propensity score matched analysis. Kidney360 Agiro, A., Cook, E., Mu, F., Greatsinger, A., Chen, J., Zhao, A., Louden, E., Colman, E., Desai, P., Chertow, G. M. 2024

  Abstract

  Hyperkalemia is a known complication of chronic kidney disease (CKD); however, it is not known whether hyperkalemia directly contributes to CKD progression and the risk of death. Clarifying the extent to which hyperkalemia is associated with CKD progression and mortality can inform clinical practice and guide future research. The objective of this study was to quantify the risks of CKD progression and mortality associated with hyperkalemia in patients with stages 3b/4 CKD.This was a real-world, exact and propensity score-matched, observational cohort study using data (January 2016-December 2021) from Optum's deidentified Market Clarity Data, a large US integrated insurance claims/electronic medical record database. The study included matched adult patients with stages 3b/4 CKD with and without hyperkalemia, not regularly treated with an intestinal potassium (K+) binder. Measured outcomes were CKD progression and all-cause mortality. CKD progression was defined as diagnosis of CKD stage 4 (if stage 3b at index), CKD stage 5 or kidney failure, or receipt of dialysis or kidney transplantation.After matching, there were 6,619 patients in each of the hyperkalemia and non-hyperkalemia cohorts, with a mean (standard deviation) follow-up time of 2.12 (1.42) years. Use of any renin-angiotensin-aldosterone system inhibitors (RAASi) during baseline was common (75.9%) and most patients had CKD stage 3b (71.2%). Patients with hyperkalemia had a 1.60-fold (95% confidence interval [CI] 1.50, 1.71) higher risk of CKD progression and a 1.09-fold (1.02, 1.16) higher risk of all-cause mortality relative to patients without hyperkalemia. Relative risks of CKD progression associated with hyperkalemia were similar within the subset of patients receiving RAASi and across CKD stages, and when alternative definitions of CKD progression were used.Patients with CKD stages 3b/4 and hyperkalemia experienced significantly higher risks of CKD progression and all-cause mortality than propensity score-matched patients without hyperkalemia.

  View details for DOI 10.34067/KID.0000000000000541

  View details for PubMedID 39120948

• SGLT2 Inhibitor Use in Chronic Kidney Disease: Supporting Cardiovascular, Kidney, and Metabolic Health KIDNEY MEDICINE Madero, M., Chertow, G. M., Mark, P. B. 2024; 6 (8)

  View details for DOI 10.1016/j.xkme.2024.100851

  View details for Web of Science ID 001270728700001

• Prospective Study on Kidney Dysfunction Markers and Risk for Mortality among South Asians. Kidney international reports Jagannathan, R., Anand, S., Kondal, D., Han, J., Montez-Rath, M., Ali, M. K., Patel, S. A., Singh, K., Shivashankar, R., Anjana, R. M., Gupta, R., Mohan, S., Chertow, G. M., Mohan, V., Tandon, N., Venkat Narayan, K. M., Prabhakaran, D. 2024; 9 (8): 2537-2545

  Abstract

  Associations between markers of impaired kidney function and adverse outcomes among South Asians is understudied and could differ from existing data derived mostly from North American or European cohorts.We conducted a prospective analysis of 9797 participants from the ongoing cardiometabolic risk reduction study in South Asia, India. We examined the associations between baseline spot urine albumin-to-creatinine (UACR) ratio and creatinine-based estimated glomerular filtration rate (eGFR) estimating equations with all-cause mortality using Cox proportional hazards regression, adjusting for baseline age, sex, diabetes, systolic blood pressure, tobacco, history of cardiovascular disease, and cholesterol. Additionally, we calculated population attributable fraction (PAF) for both markers.Over a median 7-year follow-up, with 66,909 person-years, 791 deaths occurred. At baseline, the weighted prevalence of UACR ≥ 30 mg/g and eGFRCKD-EPI 2009 <60 ml/min per 1.73 m2 was 6.6% and 1.6%, respectively. The risk for mortality was increased with higher UACR (10-30 hazard ratio [HR]: 1.6 [1.2-2.1]), 30-300 HR: 2.4 [1.8-3.1]), and ≥300 (HR: 6.0 [3.8-9.4] relative to UACR <10 mg/g). Risk for mortality was also higher with lower eGFRCKD-EPI 2009 (44-30; HR: 4.5 [2.5-8.3] and <30 HR: 7.0 [3.7-13.0], relative to 90-104 ml/min per 1.73 m2). PAF for mortality because of UACR ≥30 mg/g and eGFRCKD-EPI 2009 <45 ml/min per 1.73 m2 were 24.4% and 13.4%, respectively.Single-time point assessment of UACR ≥30 mg/g or eGFRCKD-EPI 2009 <45 ml/min per 1.73 m2 portends higher mortality risk among urban South Asians. Because albuminuria is common and associated with accelerated decline in GFR, screening and targeted efforts to reduce albuminuria are warranted.

  View details for DOI 10.1016/j.ekir.2024.05.025

  View details for PubMedID 39156172

  View details for PubMedCentralID PMC11328749

• Prospective Study on Kidney Dysfunction Markers and Risk for Mortality among South Asians KIDNEY INTERNATIONAL REPORTS Jagannathan, R., Anand, S., Kondal, D., Han, J., Montez-Rath, M., Ali, M. K., Patel, S. A., Singh, K., Shivashankar, R., Anjana, R., Gupta, R., Mohan, S., Chertow, G. M., Mohan, V., Tandon, N., Narayan, K., Prabhakaran, D. 2024; 9 (8): 2537-2545

  View details for DOI 10.1016/j.ekir.2024.05.025

  View details for Web of Science ID 001289221400001

• The Legacy Effect of Intensive versus Standard Blood Pressure Control on the Incidence of Dialysis or Kidney Transplantation. Journal of the American Society of Nephrology : JASN Pajewski, N. M., Beddhu, S., Bress, A. P., Chang, T. I., Chertow, G. M., Cheung, A. K., Cushman, W. C., Freedman, B. I., Greene, T., Johnson, K. C., Jaeger, B. C., Tamura, M. K., Lewis, C. E., Rahman, M., Reboussin, D. M., Rocco, M. V., Williamson, J. D., Whelton, P. K., Wright, J. T., Drawz, P. E., Ix, J. H. 2024

  Abstract

  The Systolic Blood Pressure Intervention Trial (SPRINT) showed that intensive lowering of systolic blood pressure (BP) increased the risk of incident chronic kidney disease and episodes of acute kidney injury. Whether intensive treatment changes the risk of kidney failure is unknown. The goal of this study was to estimate the legacy effect of intensive versus standard systolic BP lowering on the longer-term incidence of kidney failure.Secondary analysis of a randomized, open-label clinical trial with observational follow-up. Between 2010 and 2013, patients 50 years and older with hypertension and higher cardiovascular risk excluding those with diabetes mellitus, history of stroke, proteinuria >1g / day or polycystic kidney disease were recruited from 102 clinic sites in the United States and Puerto Rico. Participants were randomized to a systolic BP goal of <120 mm Hg (intensive treatment) or <140 mm Hg (standard treatment group). We linked participants with the US Renal Data System to ascertain kidney failure (initiation of dialysis therapy or transplantation) and the US National Death Index to ascertain all-cause mortality through 2020.Based on analysis of 9279 (99.1%) of 9361 randomized participants, 101 cases of kidney failure occurred over a median follow-up of 8.6 years (interquartile range 8.0 to 9.1 years), with the majority occurring in 74 (73.3%) participants with an eGFR<45 ml/min/1.73 m2 at baseline. Intensive treatment did not significantly increase the risk of kidney failure either overall (cause-specific Hazard Ratio (HR) = 1.20, 95% CI: 0.81 - 1.78) or in the subgroup of participants with baseline eGFR<45 ml/min/1.73 m2 (HR = 1.43, 95% CI: 0.89 - 2.30).Overall, and in patients with eGFR <45 ml/min/1.73 m2, there were higher rates of dialysis or transplantation among SPRINT participants randomized to intensive treatment, but the modest differences observed were not statistically significant.

  View details for DOI 10.1681/ASN.0000000000000459

  View details for PubMedID 39078712

• Sodium-Glucose Cotransporter 2 Inhibitors in Older Patients with CKD. Journal of the American Society of Nephrology : JASN Bakker, W. M., Gansevoort, R. T., Yang, C., Chertow, G. M., Heerspink, H. J., Vart, P. 2024

  View details for DOI 10.1681/ASN.0000000000000466

  View details for PubMedID 39133046

• Tenapanor improves long-term control of high phosphate concentrations in the blood in patients receiving maintenance dialysis: a plain language summary of the NORMALIZE study. Current medical research and opinion Silva, A., Edelstein, S., Yang, Y., Rosenbaum, D., Battelli, L., Chertow, G. M. 2024: 1-12

  View details for DOI 10.1080/03007995.2024.2364824

  View details for PubMedID 39041778

• Selonsertib in Patients with Diabetic Kidney Disease: A Phase 2b Randomized Active Run-In Clinical Trial. Journal of the American Society of Nephrology : JASN Heerspink, H. J., Perkovic, V., Tuttle, K. R., Pergola, P. E., Mahaffey, K. W., Patel, U. D., Ishida, J. H., Kuo, A., Chen, F., Kustra, R., Petrovic, V., Rossing, P., Kashihara, N., Chertow, G. M. 2024

  Abstract

  Selonsertib is an apoptosis signal-regulating kinase 1 inhibitor that reduces inflammation, fibrosis, and apoptosis. The MOSAIC study evaluated whether selonsertib attenuated kidney function decline in patients with diabetic kidney disease.We conducted a phase 2b study in adults with type 2 diabetes and eGFR 20 to <60 ml/min/1.73 m2 with UACR 150 to 5000 mg/g on maximum tolerated dose of ACE inhibitor or ARB. To account for an acute selonsertib-related decrease in eGFRcr, patients entered a 4-week selonsertib run-in period to establish treatment-specific baseline eGFRcr. Patients were randomized 1:1 to selonsertib 18 mg or matching placebo once daily. We followed all participants up until the last randomized participant completed 48 weeks follow-up. The primary efficacy outcome was the difference in eGFRcr slopes from treatment-specific baselines to week 84, evaluated at a prespecified two-sided P = 0.30. We also evaluated kidney clinical events (eGFRcr ≥40% decline from pre-run-in baseline, kidney failure, or death due to kidney disease) and adverse events.In total, 310 patients were randomized (selonsertib n=154, placebo n=156; 68% male, mean age 65 years, mean baseline eGFRcr 35 ml/min/1.73 m2). Mean difference between selonsertib and placebo eGFRcr slopes at week 84 was 1.20 ml/min/1.73 m2/year (95% CI, -0.41 to 2.81; P = 0.14). Kidney clinical events occurred in 17% (26/154) of patients randomized to selonsertib and 12% (19/156) of those randomized to placebo (difference 4.7%; 95% CI, -6.3% to 15.9%). The most common investigator-reported adverse event was acute kidney injury (selonsertib 11.0/100 and placebo 5.9/100 patient-years).Selonsertib attenuated the decline in eGFRcr over up to 84 weeks; however, it resulted in a numerically higher number of patients reaching a kidney clinical event and a numerically higher rate of investigator-reported acute kidney injury.

  View details for DOI 10.1681/ASN.0000000000000444

  View details for PubMedID 39018154

• Plasmapheresis in ANCA-Associated Vasculitis with Active Kidney Involvement in the United States (2016-2020): A Cross-Sectional Study. Kidney360 Tao, J., Yasui, O. W., Kamdar, N. S., Zheng, S., Popat, R. A., Rehkopf, D. H., Chertow, G. M. 2024

  Abstract

  Plasmapheresis is currently recommended when antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) presents with severe kidney and/or lung involvement. This cross-sectional study aimed at describing characteristics of hospitalized patients diagnosed with AAV with severe kidney involvement undergoing plasmapheresis in the US.We defined the study population as adults hospitalized for active kidney involvement with a new diagnosis of AAV (by subtype or unspecified). We established the cohort from the 2016-2020 National Inpatient Sample by ICD-10-CM codes. In this cross-sectional study, we described demographic and clinical characteristics, associated inpatient procedures, lengths of stay, hospital costs, and disposition at discharge comparing patients treated and not treated with plasmapheresis.We identified a total of 975 cases of hospitalized AAV with acute kidney involvement in the US treated by plasmapheresis over the 5-year period. Demographic characteristics of patients who received plasmapheresis were similar to those in patients who did not (n=5670). There were no regional differences in the proportion of patients who received plasmapheresis; however, plasmapheresis was deployed more frequently among patients admitted to urban teaching hospitals relative to rural and non-teaching hospitals. Cases treated with plasmapheresis were more likely to have had acute kidney injury (AKI) (96% vs. 90%, p=0.0007), AKI requiring dialysis (52% vs 16%, p<0.001), hypoxia (40% vs. 16%, p<0.0001), and respiratory failure requiring mechanical ventilation (13% vs. 3%, p=0.0003).During 2016-2020, plasmapheresis was deployed in approximately 20% of patients being admitted for AAV and acute kidney involvement in the US. As standards of care and practice evolve, the role of plasmapheresis in the management of AAV with acute kidney involvement will require further study.

  View details for DOI 10.34067/KID.0000000000000496

  View details for PubMedID 39008365

• Tenapanor: A Phosphate Absorption Inhibitor for the Management of Hyperphosphatemia in Patients with Kidney Failure. Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation Hill Gallant, K. M., Sprague, S. M., Rosenbaum, D. P., Spiegel, D. M., Kozuka, K., Edelstein, S., Chertow, G. M. 2024

  Abstract

  Because of increased risks of cardiovascular disease and death, patients with hyperphosphatemia receiving maintenance dialysis are advised to limit phosphorus consumption and are prescribed phosphate binders in an effort to better control serum phosphate concentrations. Because of large pill size, pill burden, and tolerability issues, phosphate binder adherence is relatively poor. On ingestion, phosphate is absorbed from the intestine via transcellular or paracellular transport. Data show that inhibiting sodium-hydrogen exchanger 3 modulates paracellular phosphate absorption (the predominant pathway in humans). Tenapanor is a first-in-class, minimally absorbed, phosphate absorption inhibitor that selectively inhibits sodium-hydrogen exchanger 3, with a mechanism distinct from, and complementary to, that of phosphate binders. In phase 3 and postregistrational studies, tenapanor conferred statistically significant and clinically meaningful reductions in serum phosphate in patients receiving maintenance dialysis with hyperphosphatemia. Here, we review the available preclinical and clinical data on the effects of tenapanor on controlling intestinal phosphate absorption.

  View details for DOI 10.1053/j.jrn.2024.07.003

  View details for PubMedID 38992521

• Author Correction: IL-6 inhibition with clazakizumab in patients receiving maintenance dialysis: a randomized phase 2b trial. Nature medicine Chertow, G. M., Chang, A. M., Felker, G. M., Heise, M., Velkoska, E., Fellström, B., Charytan, D. M., Clementi, R., Gibson, C. M., Goodman, S. G., Jardine, M., Levin, A., Lokhnygina, Y., Mears, J., Mehran, R., Stenvinkel, P., Wang, A. Y., Wheeler, D. C., Zoccali, C., Ridker, P. M., Mahaffey, K. W., Tricoci, P., Wolf, M. 2024

  View details for DOI 10.1038/s41591-024-03156-7

  View details for PubMedID 38961226

• Patient Perspectives on Using Telemedicine During In-Center Hemodialysis: A Qualitative Study. Kidney medicine Haltom, T. M., Lew, S. Q., Winkelmayer, W. C., Chertow, G. M., Jaure, A., Erickson, K. F. 2024; 6 (7): 100848

  Abstract

  In the wake of the coronavirus disease 2019 (COVID-19) pandemic, the United States federal government expanded originating telemedicine sites to include outpatient dialysis units. For the first time, nephrology practitioners across the United States could replace face-to-face visits with telemedicine for patients receiving in-center hemodialysis. This study describes patients' perspectives on the use of telemedicine during in-center hemodialysis.A qualitative study.Thirty-two patients from underserved populations (older, less educated, unemployed, persons of color) receiving in-center hemodialysis who used telemedicine with their nephrologist during the COVID-19 pandemic.Telephone semistructured interviews were conducted in English or Spanish. Transcripts were thematically analyzed.We identified 6 themes with subthemes: adapting to telemedicine (gaining familiarity and confidence, overcoming and resolving technical difficulties, and relying on staff for communication); ensuring availability of the physician (enabling an immediate response to urgent medical needs, providing peace of mind, addressing patient needs adequately, and enhanced attention and contact from physicians); safeguarding against infection (limiting COVID-19 exposures and decreasing use); straining communication and physical interactions (loss of personalized touch, limited physical examination, and unable to reapproach physicians about forgotten issues); maintaining privacy (enhancing privacy and projecting voice enables others to hear); and supporting confidence in telemedicine (requiring established rapport with physicians, clinical stabilty of health, and ability to have in-person visits when necessary).Interviews were conducted later in the pandemic when some nephrology care providers were using telemedicine infrequently.Patients receiving in-center hemodialysis adapted to telemedicine visits by their nephrologists in the context of the COVID-19 pandemic and observed its benefits. However, further considerations regarding communication, privacy, and physical assessments are necessary. Integrating telemedicine into future in-center hemodialysis care using a hybrid approach could potentially build trust, optimize communication, and augment care.

  View details for DOI 10.1016/j.xkme.2024.100848

  View details for PubMedID 38938646

  View details for PubMedCentralID PMC11209005

• Effects of Dapagliflozin in Patients with Membranous Nephropathy. Glomerular diseases Chertow, G. M., Heerspink, H. L., Mark, P. B., Dwyer, J. P., Nowicki, M., Wheeler, D. C., Correa-Rotter, R., Rossing, P., Toto, R. D., Langkilde, A. M., Jongs, N. 2024; 4 (1): 137-145

  Abstract

  Despite the provision of renin-angiotensin-aldosterone-system inhibitors and immunosuppressive therapies, membranous nephropathy often progresses to end-stage kidney disease (ESKD). The objective of this prespecified analysis was to assess the safety and efficacy of dapagliflozin in patients with membranous nephropathy enrolled in the DAPA-CKD trial.Patients with an estimated glomerular filtration rate (eGFR) of 25-75 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio (UACR) 200-5,000 mg/g were randomized to dapagliflozin 10 mg once daily or placebo, along with standard-of-care and followed for median 2.4 years. The primary endpoint was a composite of ≥50% sustained decline in eGFR, ESKD, or kidney or cardiovascular death. Exploratory efficacy endpoints included eGFR slope and UACR.Among DAPA-CKD participants with membranous nephropathy, 19 were randomized to dapagliflozin and 24 to placebo. The mean (SD) age was 59.9 ± 12.1 years, the mean eGFR was 45.7 ± 12.1 mL/min/1.73 m2, and the median UACR was 1,694.5 (25%, 75% range 891-2,582.5) mg/g. Two of 19 (11%) patients randomized to dapagliflozin and five of 24 (21%) randomized to placebo experienced the primary composite endpoint. Total and chronic mean eGFR slopes for dapagliflozin and placebo were -3.87 and -4.29 and -2.66 and -4.22 mL/min/1.73 m2/year, respectively; corresponding between-group mean differences were 0.42 and 1.57 mL/min/1.73 m2/year. Dapagliflozin reduced geometric mean (SEM) UACR relative to placebo (-29.3% ± 1.2% vs. -3.6% ± 1.1%; between-group mean difference [95% CI] -26.7 [-50.4, 8.3]). Four (21%) patients randomized to dapagliflozin and seven (29%) randomized to placebo experienced a serious adverse event.In membranous nephropathy, the effects of dapagliflozin on kidney disease progression and albuminuria were generally favorable; there was insufficient power to justify formal inference testing.

  View details for DOI 10.1159/000539770

  View details for PubMedID 39144475

  View details for PubMedCentralID PMC11324228

• The Medical Costs of Determining Eligibility and Waiting for a Kidney Transplantation. Medical care Xu, K., Dor, A., Mohanty, S., Han, J., Parvathinathan, G., Braggs-Gresham, J. L., Held, P. J., Roberts, J. P., Vaughan, W., Tan, J. C., Scandling, J. D., Chertow, G. M., Busque, S., Cheng, X. S. 2024

  Abstract

  Recent efforts to increase access to kidney transplant (KTx) in the United States include increasing referrals to transplant programs, leading to more pretransplant services. Transplant programs reconcile the costs of these services through the Organ Acquisition Cost Center (OACC).The aim of this study was to determine the costs associated with pretransplant services by applying microeconomic methods to OACC costs reported by transplant hospitals.For all US adult kidney transplant hospitals from 2013 through 2018 (n=193), we crosslinked the total OACC costs (at the hospital-fiscal year level) to proxy measures of volumes of pretransplant services. We used a multiple-output cost function, regressing total OACC costs against proxy measures for volumes of pretransplant services and adjusting for patient characteristics, to calculate the marginal cost of each pretransplant service.Over 1015 adult hospital-years, median OACC costs attributable to the pretransplant services were $5 million. Marginal costs for the pretransplant services were: initial transplant evaluation, $9k per waitlist addition; waitlist management, $2k per patient-year on the waitlist; deceased donor offer management, $1k per offer; living donor evaluation, procurement and follow-up: $26k per living donor. Longer time on dialysis among patients added to the waitlist was associated with higher OACC costs at the transplant hospital.To achieve the policy goals of more access to KTx, sufficient funding is needed to support the increase in volume of pretransplant services. Future studies should assess the relative value of each service and explore ways to enhance efficiency.

  View details for DOI 10.1097/MLR.0000000000002028

  View details for PubMedID 38889200

• Revisiting a "Paradigm" in Cardiovascular and Kidney Disease. Journal of the American College of Cardiology Chertow, G. M. 2024; 83 (22): 2160-2162

  View details for DOI 10.1016/j.jacc.2024.04.018

  View details for PubMedID 38811093

• The Use of KDIGO AKI Definitions in AKI Research: PRO. Kidney360 McCoy, I. E., Chertow, G. M. 2024

  View details for DOI 10.34067/KID.0000000000000486

  View details for PubMedID 38833308

• Projecting the clinical burden of chronic kidney disease at the patient level (Inside CKD): a microsimulation modelling study. EClinicalMedicine Chertow, G. M., Correa-Rotter, R., Eckardt, K. U., Kanda, E., Karasik, A., Li, G., Christiansen, C. F., Stafylas, P., Holt, S. G., Hagen, E. C., Garcia Sanchez, J. J., Barone, S., Cabrera, C., Nolan, S., Coker, T., Webber, L., Retat, L. 2024; 72: 102614

  Abstract

  Chronic kidney disease (CKD) is a global concern that presents significant challenges for disease management. Several factors drive CKD prevalence, including primary risk factors, such as type 2 diabetes and hypertension, and an ageing population. Inside CKD is an international initiative that aims to raise awareness of the substantial burden incurred by CKD.Using a peer-reviewed microsimulation method, the clinical burden of CKD was estimated from 2022 to 2027. Demographic data from the Americas, Europe, and Asia-Pacific/Middle East were used to generate virtual populations and to project the prevalence of CKD, kidney replacement therapy, associated cardiovascular complications, comorbid conditions, and all-cause mortality in the CKD population over the modelled time frame.Across the 31 participating countries/regions, the total prevalence of CKD was projected to rise to 436.6 million cases by 2027 (an increase of 5.8% from 2022), with most cases (∼80%) undiagnosed. Inside CKD projected a mean of 8859 cases of heart failure, 10,244 of myocardial infarction, and 7797 of stroke per 100,000 patients with CKD by 2027.The clinical impact of CKD is substantial and likely to increase; the high prevalence of undiagnosed cases and associated complications may benefit from the implementation of health policy interventions that promote screening, earlier diagnosis, and interventions to improve outcomes.AstraZeneca.

  View details for DOI 10.1016/j.eclinm.2024.102614

  View details for PubMedID 39010981

  View details for PubMedCentralID PMC11247147

• CALCIMIMETIC PRESCRIPTIONS FOLLOWING THE TRANSITIONAL DRUG ADD-ON PAYMENT ADJUSTMENT IN FEE-FOR-SERVICE MEDICARE PATIENTS ON DIALYSIS Caldwell, J., Cheng, X. S., Bendavid, E., Chertow, G. M., Lin, E. ELSEVIER SCIENCE INC. 2024: S213

  View details for Web of Science ID 001277006602073

• IL-6 inhibition with clazakizumab in patients receiving maintenance dialysis: a randomized phase 2b trial. Nature medicine Chertow, G. M., Chang, A. M., Felker, G. M., Heise, M., Velkoska, E., Fellström, B., Charytan, D. M., Clementi, R., Gibson, C. M., Goodman, S. G., Jardine, M., Levin, A., Lokhnygina, Y., Mears, J., Mehran, R., Stenvinkel, P., Wang, A., Wheeler, D. C., Zoccali, C., Ridker, P. M., Mahaffey, K. W., Tricoci, P., Wolf, M. 2024

  Abstract

  Inflammation mediated by interleukin-6 (IL-6) is strongly associated with cardiovascular risk. Here we evaluated clazakizumab, a monoclonal antibody targeting the IL-6 ligand, in a phase 2b dose-finding study. Adults with cardiovascular disease and/or diabetes receiving maintenance dialysis with high-sensitivity C-reactive protein (hs-CRP) ≥ 2 mg l-1 at baseline were randomized to receive clazakizumab (2.5 mg, 5 mg or 10 mg, n = 32 per dose group) or placebo (n = 31) every 4 weeks. The primary endpoint was the change from baseline in hs-CRP to week 12, expressed as the geometric mean ratio. Clazakizumab treatment signficantly reduced serum hs-CRP concentrations at week 12 by 86%, 90% and 92% relative to placebo in patients randomized to 2.5 mg, 5 mg or 10 mg clazakizumab, respectively (all P < 0.0001), meeting the primary outcome. With regard to secondary endpoints, clazakizumab treatment reduced serum fibrinogen, amyloid A, secretory phospholipase A2, and lipoprotein(a) concentrations, as well as increased mean serum albumin concentrations at 12 weeks, relative to placebo. The proportion of patients who achieved hs-CRP < 2.0 mg l-1 was 79%, 82% and 79% in the 2.5 mg, 5 mg and 10 mg clazakizumab groups, respectively, compared with 0% of placebo-treated patients. With regard to safety, no cases of sustained grade 3 or 4 thrombocytopenia or neutropenia were observed. Serious infections were seen with similar frequency in the placebo, clazakizumab 2.5 mg and clazakizumab 5 mg groups, but were numerically more frequent in the clazakizumab 10 mg group. The results of this trial indicate that in patients receiving maintenance dialysis, clazakizumab reduced inflammatory biomarkers associated with cardiovascular events. ClinicalTrials.gov registration: NCT05485961 .

  View details for DOI 10.1038/s41591-024-03043-1

  View details for PubMedID 38796655

  View details for PubMedCentralID 3145073

• Association of Diabetes with Changes in Blood Pressure during Hemodialysis: A Secondary Analysis of the Frequent Hemodialysis Network Daily Trial. American journal of nephrology Moloney, B. M., Chertow, G. M., Mc Causland, F. R. 2024: 1-8

  Abstract

  Diabetes mellitus is a common cause of kidney failure and is often complicated by autonomic neuropathy, which may have implications for blood pressure (BP) homeostasis during hemodialysis (HD).In this post hoc analysis of the Frequent Hemodialysis Network (FHN) Daily Trial, we used random effects Poisson and linear regression models to estimate the association of diabetes (vs. not) with intra-dialytic hypotension (IDH) and peri-dialytic BP parameters, respectively. We tested for differential associations according to the randomized treatment (6/week vs. 3/week HD) and pre-HD systolic BP.Of the 244 patients with intra-dialytic BP data, 100 (41%) had diabetes at baseline. The mean age was 51 ± 14 years; overall, 39% were female. In adjusted models, diabetes (vs. not) was associated with a 93% higher risk of developing IDH (IRR: 1.93; 95% CI: 1.26, 2.95). There was no evidence that the randomized treatment assignment modified the association between diabetes and IDH (pinteraction = 0.32), but more potent associations were noted among those with higher pre-HD systolic BP (pinteraction < 0.001). Diabetes (vs. not) was associated with a lower adjusted nadir intra-HD BP (-4.2; 95% CI: -8.3, -0.2 mm Hg) but not with the pre- or post-HD systolic BP.Among participants of the FHN Daily Trial, patients with diabetes had a higher risk of IDH and lower nadir intra-HD systolic BP than patients without diabetes, even when undergoing HD up to 6 times per week.

  View details for DOI 10.1159/000539451

  View details for PubMedID 38781949

• My Plate Awareness and Engagement and Perceived and Objective Diet Quality in US Adults with Chronic Kidney Disease. Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation Thule, J., Yu, X., Montez-Rath, M. E., Chertow, G. M. 2024

  Abstract

  OBJECTIVE: Awareness of federal dietary guidelines has been associated with better perceived and objective diet quality. Little is known about the awareness of federal dietary recommendations among persons with chronic kidney disease (CKD) and the associations between recognition of guidelines, perception of diet quality, and objective quality of the diet in this population.DESIGN: We compared awareness of, and engagement with, MyPlate (a representation of five food groups from the US Department of Agriculture) along with perceived and objective diet quality, the latter assessed via Dietary Approaches to Stop Hypertension (DASH) index scores, among US adults with and without CKD during 2017-2020.RESULTS: Among non-institutionalized adults in the US, 8.3% had albuminuria with normal or near normal kidney function, 4.0% had estimated glomerular filtration rate (eGFR) 45-59 mL/min/1.73m2 (CKD stage G3a) and 1.6% had eGFR <45 mL/min/1.73m2 (CKD stages G3b/G4/G5). MyPlate awareness was lower among persons with CKD compared with those without CKD (19.6% versus 26.4%, p<0.001) and was lower among persons with more advanced CKD stages: 20.8%, 18.2%, and 16.3% in persons with CKD stages G1/G2, G3a, and G3b/G4/G5, respectively (trend p<0.001). Among persons aware of MyPlate, a numerically higher proportion with CKD attempted to follow My Plate recommendations (43.9% versus 32.3%, p=0.10); the proportion was highest among persons with moderate-to-advanced CKD (41.9%, 42.9%, and 56.9% among persons with CKD stages G1/G2, G3a, and G3b/G4/G5, respectively (trend p<0.001). Perceived and objective dietary quality (the latter based on concordance with the Dietary Approaches to Stop Hypertension diet) were slightly higher among persons with CKD relative to those without CKD.CONCLUSIONS: Adults with CKD have lower MyPlate awareness than adults without CKD. Enhancing diet education to persons with CKD could improve diet quality and potentially ameliorate CKD-associated complications.

  View details for DOI 10.1053/j.jrn.2024.04.007

  View details for PubMedID 38740314

• PESTICIDES AND PROSTATE CANCER INCIDENCE AND MORTALITY: AN ENVIRONMENTAL WIDE ASSOCIATION STUDY Soerensen, S., Lim, D. S., Montez-Rath, M. E., Chertow, G. M., Chung, B. I., Rehkopf, D. H., Leppert, J. T. LIPPINCOTT WILLIAMS & WILKINS. 2024: E620

  View details for Web of Science ID 001263885302097

• Safety and efficacy of vadadustat vs darbepoetin alfa in patients on maintenance dialysis by prespecified subgroups of baseline ESA dose Chertow, G., Jardine, A. G., Burke, S., Luo, W., Minga, T., Koury, M. J., Eckardt, K. OXFORD UNIV PRESS. 2024: I1421-I1422

  View details for Web of Science ID 001267529301377

• Association of Changes in Vector Length with Changes in Left Ventricular Mass Among Patients on Maintenance Hemodialysis: A Secondary Analysis of the Frequent Hemodialysis Network Daily Trial. Kidney360 Elsayed, E., Farag, Y. M., Ravi, K. S., Chertow, G. M., Mc Causland, F. R. 2024

  Abstract

  Hypervolemia is thought to be a major contributor to higher left ventricular mass (LVM), a potent predictor for cardiovascular mortality among patients on maintenance hemodialysis. We hypothesized that a decrease in vector length (a bioimpedance proxy of hypervolemia) would be associated with an increase in LVM.Using data from the Frequent Hemodialysis Network Daily Trial (n=160) we used linear regression to assess the association of changes in vector length from baseline to month 12 with changes in magnetic resonance imaging (MRI) measures of LVM and other cardiac parameters. We adjusted models for the randomized group, baseline vector length, age, sex, race, body mass index, vascular access, dialysis vintage, history of hypertension, heart failure, and diabetes, residual kidney function, pre-dialysis systolic blood pressure (BP), ultrafiltration rate, serum-dialysate sodium gradient, hemoglobin, phosphate, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use, erythropoietin dose, and equilibrated Kt/V.The mean age was 50 ±13 years; 35% were female. In the fully adjusted models, a decline in vector length (per 50 Ω/m; i.e., increase in volume) was associated with a 6.8 g (95%CI -0.1, 13.7) and 2.6 g/m2 (95%CI -1.2, 6.3) increase in LVM and LVM index, respectively; and an increase of 15.0 mL (95%CI 7.5, 22.4), 7.3 mL (95%CI 3.0, 12.7), 7.8 mL (95%CI 3.0, 12.7), and -0.9 % (95%CI -3.1, 1.3) in left ventricular (LV) end-diastolic volume (LVEDV), end-systolic volume (LVESV), stroke volume (LVSV), and ejection fraction (LVEF), respectively. The lowest tertile of change in vector length (i.e., greater increase in volume) was associated with greater increases in LVEDV and LVSV, versus the highest tertile. There was no evidence of heterogeneity by randomized group.Change in vector length, a bioimpedance-derived proxy of volume status, was inversely associated with indices of left ventricular mass and volume measured by cardiac MRI in patients randomized to conventional or frequent hemodialysis over 12 months.

  View details for DOI 10.34067/KID.0000000000000443

  View details for PubMedID 38656312

• Effects of SGLT2 inhibitors on cause-specific cardiovascular death in patients with chronic kidney disease: a meta-analysis of CKD progression trials. Clinical journal of the American Society of Nephrology : CJASN Fletcher, R. A., Herrington, W. G., Agarwal, R., Mayne, K. J., Arnott, C., Jardine, M. J., Mahaffey, K. W., Perkovic, V., Staplin, N., Wheeler, D. C., Chertow, G. M., Heerspink, H. J., Neuen, B. L. 2024

  View details for DOI 10.2215/CJN.0000000000000470

  View details for PubMedID 38622766

• Ambient heat exposure and kidney function in patients with chronic kidney disease: a post-hoc analysis of the DAPA-CKD trial. The Lancet. Planetary health Zhang, Z., Heerspink, H. J., Chertow, G. M., Correa-Rotter, R., Gasparrini, A., Jongs, N., Langkilde, A. M., McMurray, J. J., Mistry, M. N., Rossing, P., Toto, R. D., Vart, P., Nitsch, D., Wheeler, D. C., Caplin, B. 2024; 8 (4): e225-e233

  Abstract

  Higher temperatures are associated with higher rates of hospital admissions for nephrolithiasis and acute kidney injury. Occupational heat stress is also a risk factor for kidney dysfunction in resource-poor settings. It is unclear whether ambient heat exposure is associated with loss of kidney function in patients with established chronic kidney disease. We assessed the association between heat index and change in estimated glomerular filtration rate (eGFR) in participants from the DAPA-CKD trial in a post-hoc analysis.DAPA-CKD was a randomised controlled trial of oral dapagliflozin 10 mg once daily or placebo that enrolled participants aged 18 years or older, with or without type 2 diabetes, with a urinary albumin-to-creatinine ratio of 200-5000 mg/g, and an eGFR of 25-75 mL/min per 1·73 m2. In this post-hoc analysis, we explored the association between time-varying daily centre-level heat index (ERA5 dataset) and individual-level change in eGFR in trial participants using linear mixed effect models and case-time series. The DAPA-CKD trial is registered with ClinicalTrials.gov, NCT03036150.Climate and eGFR data were available for 4017 (93·3%) of 4304 participants in 21 countries (mean age: 61·9 years; mean eGFR: 43·3 mL per 1·73 m2; median 28 months follow-up). Across centres, a heat index of more than 30°C occurred on a median of 0·6% of days. In adjusted linear mixed effect models, within each 120-day window, each 30 days' heat index of more than 30°C was associated with a -0·6% (95% CI -0·9% to -0·3%) change in eGFR. Similar estimates were obtained using case-time series. Additional analyses over longer time-windows showed associations consistent with haemodynamic or seasonal variability, or both, but overall estimates corresponded to an additional 3·7 mL per 1·73 m2 (95% CI 0·1 to 7·0) loss of eGFR per year in a patient with an eGFR of 45 mL per 1·73 m2 located in a very hot versus a temperate environment.Higher ambient heat exposure is associated with more rapid eGFR decline in those with established chronic kidney disease. Efforts to mitigate heat exposure should be tested as part of strategies to attenuate chronic kidney disease progression.None.

  View details for DOI 10.1016/S2542-5196(24)00026-3

  View details for PubMedID 38580424

• SERUM BICARBONATE CONCENTRATIONS AND CKD PROGRESSION IN PATIENTS WITH METABOLIC ACIDOSIS: EVIDENCE FROM VALOR-CKD Singh, B., Tangri, N., Bushinsky, D., Chertow, G., Pergola, P., Kendrick, I., Li, E., Turner, S., Wesson, D. W B SAUNDERS CO-ELSEVIER INC. 2024: S107

  View details for Web of Science ID 001282605100349

• The Use of Telemedicine by US Nephrologists for In-Center Hemodialysis Care During the Pandemic: AnAnalysis of National Medicare Claims. Kidney medicine Niu, J., Rosales, O., Oluyomi, A., Lew, S. Q., Winkelmayer, W. C., Chertow, G. M., Erickson, K. F. 2024; 6 (4): 100798

  Abstract

  Rationale & Objective: Because of coronavirus disease 2019 (COVID-19), the US government issued emergency waivers in March 2020 that removed regulatory barriers around the use of telemedicine. For the first time, nephrologists were reimbursed for telemedicine care delivered during in-center hemodialysis. We examined the use of telemedicine for in-center hemodialysis during the first 16 months of the pandemic.Study Design: We ascertained telemedicine modifiers on nephrologist claims. We used multivariable regression to examine time trends and patient, dialysis facility, and geographic correlates of telemedicine use. We also examined whether the estimated effects of predictors of telemedicine use changed over time.Setting & Participants: US Medicare beneficiaries receiving in-center hemodialysis between March 1, 2020, and June 30, 2021.Exposures: Patient, geographic, and dialysis facility characteristics.Outcomes: The use of telehealth for in-center hemodialysis care.Analytic Approach: Retrospective cohort analysis.Results: Among 267,434 Medicare beneficiaries identified, the reported use of telemedicine peaked at 9% of patient-months in April 2020 and declined to 2% of patient-months by June 2021. Telemedicine use varied geographically and was more common in areas that were remote and socioeconomically disadvantaged. Patients were more likely to receive care by telemedicine in areas with higher incidence of COVID-19, although the predictive value of COVID-19 diminished later in the pandemic. Patients were more likely to receive care using telemedicine if they were at facilities with more staff, and the use of telemedicine varied by facility ownership type.Limitations: Limited reporting of telemedicine on claims could lead to underestimation of its use. Reported telemedicine use was higher in an analysis designed to address this limitation by focusing on patients whose physicians used telemedicine at least once during the pandemic.Conclusions: Some US nephrologists continued to use telemedicine for in-center hemodialysis throughout the pandemic, even as the association between COVID-19 incidence and telemedicine use diminished over time. These findings highlight unique challenges and opportunities to the future use of telemedicine in dialysis care.

  View details for DOI 10.1016/j.xkme.2024.100798

  View details for PubMedID 38645734

• A Prospective Clinical Study to EvaluAte the AbiliTy of the CloudCath System to Detect Peritonitis During In-Home Peritoneal Dialysis (CATCH). Kidney international reports Mehrotra, R., Williamson, D. E., Betts, C. R., Greco, B. A., Yu, E., El-Badry, A., Fisher, B., Mehoudar, P. D., Briggs, B., Chertow, G. M. 2024; 9 (4): 929-940

  Abstract

  Peritonitis is the leading complication of peritoneal dialysis (PD). Patients are instructed to seek care promptly for signs (cloudy effluent) or symptoms (abdominal pain), and earlier treatment improves outcomes. The CloudCath Peritoneal Dialysis Drain Set Monitoring (CloudCath) system monitors turbidity in dialysis effluent and sends notifications of changes signaling possible peritonitis.We conducted this single-arm, open-label, multicenter study of CloudCath system use during PD. We deactivated system notifications to participants and investigators, who followed standard-of-care for peritonitis signs and symptoms. Effectiveness endpoints measured time between CloudCath system notifications and peritonitis events using International Society of Peritoneal Dialysis (ISPD) criteria.Two hundred forty-three participants used the CloudCath system for 178.8 patient-years. Of 71 potential peritonitis events, 51 events (0.29 per patient-year) met ISPD white blood cell (WBC) count criteria. The system triggered notifications for 41 of 51 events (80.4%), with a median lead time of 2.6 days (10%-90% range, -1.0 to 15.7; P < 0.0001). Excluding 6 peritonitis events that occurred when the system was not in use, the system triggered notifications for 41 of 45 events (91.1%), with a median lead time of 3.0 days (10%-90% range, -0.5 to 18.8; P < 0.0001). Of the 0.78 notifications per patient-year, the majority were peritonitis events or nonperitonitis events such as exit site and tunnel infections or catheter/cycler issues.The CloudCath system detected peritonitis events during PD several days earlier than the current standard-of-care and has the capacity to send notifications that could expedite peritonitis diagnosis and treatment.

  View details for DOI 10.1016/j.ekir.2024.01.033

  View details for PubMedID 38765568

  View details for PubMedCentralID PMC11101817

• A Prospective Clinical Study to EvaluAte the AbiliTy of the CloudCath System to Detect Peritonitis During In-Home Peritoneal Dialysis (CATCH) KIDNEY INTERNATIONAL REPORTS Mehrotra, R., Williamson, D. E., Betts, C., Greco, B. A., Yu, E., El-Badry, A., Fisher, B., Mehoudar, P. D., Briggs, B., Chertow, G. M. 2024; 9 (4): 929-940

  View details for DOI 10.1016/j.ekir.2024.01.033

  View details for Web of Science ID 001218441100001

• Bias and Accuracy of Glomerular Filtration Rate Estimating Equations in the US: A Systematic Review and Meta-Analysis. JAMA network open Yan, A. F., Williams, M. Y., Shi, Z., Oyekan, R., Yoon, C., Bowen, R., Chertow, G. M. 2024; 7 (3): e241127

  Abstract

  There is increasing concern that continued use of a glomerular filtration rate (GFR) estimating equation adjusted for a single racial group could exacerbate chronic kidney disease-related disparities and inequalities.To assess the performance of GFR estimating equations across varied patient populations.PubMed, Embase, Web of Science, ClinicalTrials.gov, and Scopus databases were systematically searched from January 2012 to February 2023.Inclusion criteria were studies that compared measured GFR with estimated GFR in adults using established reference standards and methods. A total of 6663 studies were initially identified for screening and review.Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 2 authors independently extracted data on studies that examined the bias and accuracy of GFR estimating equations. For each outcome, a random-effects model was used to calculate pooled estimates. Data analysis was conducted from March to December 2023.The primary outcomes were bias and accuracy of estimated GFRs in Black vs non-Black patients, as well as in individuals with chronic conditions. Bias was defined as the median difference between the measured GFR and the estimated GFR. Accuracy was assessed with P30 (the proportion of persons in a data set whose estimated GFR values were within 30% of measured GFR values) and measures of heterogeneity.A total of 12 studies with a combined 44 721 patients were included. Significant heterogeneity was found in the bias of various GFR estimation equations. Race-corrected equations and creatinine-based equations tended to overestimate GFR in Black populations and showed mixed results in non-Black populations. For creatinine-based equations, the mean bias in subgroup analysis was 2.1 mL/min/1.73 m2 (95% CI, -0.2 mL/min/1.73 m2 to 4.4 mL/min/1.73 m2) in Black persons and 1.3 mL/min/1.73 m2 (95% CI, 0.0 mL/min/1.73 m2 to 2.5 mL/min/1.73 m2) in non-Black persons. Equations using only cystatin C had small biases. Regarding accuracy, heterogeneity was high in both groups. The overall P30 was 84.5% in Black persons and 87.8% in non-Black persons. Creatinine-based equations were more accurate in non-Black persons than in Black persons. For creatinine-cystatin C equations, the P30 was higher in non-Black persons. There was no significant P30 difference in cystatin C-only equations between the 2 groups. In patients with chronic conditions, P30 values were generally less than 85%, and the biases varied widely.This systematic review and meta-analysis of GFR estimating equations suggests that there is bias in race-based GFR estimating equations, which exacerbates kidney disease disparities. Development of a GFR equation independent of race is a crucial starting point, but not the sole solution. Addressing the disproportionate burden of kidney failure on Black individuals in the US requires an enduring, multifaceted approach that should include improving diagnostics, tackling social determinants of health, confronting systemic racism, and using effective disease prevention and management strategies.

  View details for DOI 10.1001/jamanetworkopen.2024.1127

  View details for PubMedID 38441895

• Dapagliflozin and Blood Pressure in Patients with Chronic Kidney Disease and Albuminuria. American heart journal Heerspink, H. J., Provenzano, M., Vart, P., Jongs, N., Correa-Rotter, R., Rossing, P., Mark, P. B., Pecoits-Filho, R., McMurray, J. J., Langkilde, A. M., Wheeler, D. C., Toto, R. B., Chertow, G. M. 2024

  Abstract

  BACKGROUND AND AIMS: Sodium-glucose cotransporter 2 inhibitors decrease blood pressure in patients with type 2 diabetes, but the consistency and magnitude of blood pressure lowering with dapagliflozin in patients with chronic kidney disease (CKD) is unknown. A pre-specified analysis of the DAPA-CKD trial to investigate the effect of dapagliflozin on systolic blood pressure (SBP) in patients with CKD, with and without type 2 diabetes was conducted.METHODS: A total of 4304 adults with baseline estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73m2 and urinary albumin-to-creatinine ratio (UACR) 200-5000 mg/g were randomized to either dapagliflozin 10 mg or placebo once daily; median follow-up was 2.4 years. The primary endpoint was a composite of sustained ≥50% eGFR decline, end-stage kidney disease, or death from a kidney or cardiovascular cause. Change in SBP was a pre-specified outcome.RESULTS: Baseline mean (SD) SBP was 137.1 mmHg (17.4). By Week 2, dapagliflozin compared to placebo reduced SBP by 3.6 mmHg (95% CI 2.8-4.4 mmHg), an effect maintained over the duration of the trial (2.9 mmHg, 2.3-3.6 mmHg). Time-averaged reductions in SBP were 3.2 mmHg (2.5-4.0 mmHg) in patients with diabetes and 2.3 mmHg (1.2-3.4 mmHg) in patients without diabetes. The time-averaged effect of dapagliflozin on diastolic blood pressure (DBP) was 1.0 mmHg (0.6-1.4 mmHg); 0.8 mmHg (0.4-1.3 mmHg) in patients with diabetes and 1.4 mmHg (0.7-2.1 mmHg) in patients without diabetes. Benefits of dapagliflozin on the primary composite and secondary endpoints were evident across the spectrum of baseline SBP and DBP.CONCLUSION: In patients with CKD and albuminuria, randomization to dapagliflozin was associated with modest reductions in systolic and diastolic BP.

  View details for DOI 10.1016/j.ahj.2024.02.006

  View details for PubMedID 38367893

• Dapagliflozin in chronic kidney disease: cost-effectiveness beyond the DAPA-CKD trial. Clinical kidney journal McEwan, P., Davis, J. A., Gabb, P. D., Wheeler, D. C., Rossing, P., Chertow, G. M., Correa-Rotter, R., Tamura, K., Barone, S., Garcia Sanchez, J. J. 2024; 17 (2): sfae025

  Abstract

  Background: The Dapagliflozin and Prevention of Adverse Outcomes in CKD (DAPA-CKD) trial enrolled patients with estimated glomerular filtration rate 25-75mL/min/1.73 m2 and urine albumin-to-creatinine ratio >200mg/g. The Dapagliflozin Effect on CardiovascuLAR Events-Thrombolysis in Myocardial Infarction 58 (DECLARE-TIMI 58) trial enrolled patients with type 2 diabetes, a higher range of kidney function and no albuminuria criterion. The study objective was to estimate the cost-effectiveness of dapagliflozin in a broad chronic kidney disease population based on these two trials in the UK, Spain, Italy and Japan.Methods: We adapted a published Markov model based on the DAPA-CKD trial but to a broader population, irrespective of urine albumin-to-creatinine ratio, using patient-level data from the DAPA-CKD and DECLARE-TIMI 58 trials. We sourced cost and utility inputs from literature and the DAPA-CKD trial. The analysis considered healthcare system perspectives over a lifetime horizon.Results: Treatment with dapagliflozin was predicted to attenuate disease progression and extend projected life expectancy by 0.64 years (12.5 versus 11.9 years, undiscounted) in the UK, with similar estimates in other settings. Clinical benefits translated to mean quality-adjusted life year (QALY; discounted) gains between 0.45 and 0.68 years across countries. Incremental cost-effectiveness ratios in the UK, Spain, Italy and Japan ($10676/QALY, $14479/QALY, $7771/QALY and $13723/QALY, respectively) were cost-effective at country-specific willingness-to-pay thresholds. Subgroup analyses suggest dapagliflozin is cost-effective irrespective of urinary albumin-to-creatine ratio and type 2 diabetes status.Conclusion: Treatment with dapagliflozin may be cost-effective for patients across a wider spectrum of estimated glomerular filtration rates and albuminuria than previously demonstrated, with or without type 2 diabetes, in the UK, Spanish, Italian and Japanese healthcare systems.

  View details for DOI 10.1093/ckj/sfae025

  View details for PubMedID 38389710

• Effects of RBT-1 on preconditioning response biomarkers in patients undergoing coronary artery bypass graft or heart valve surgery: a multicentre, double-blind, randomised, placebo-controlled phase 2 trial. EClinicalMedicine Lamy, A., Chertow, G. M., Jessen, M., Collar, A., Brown, C. D., Mack, C. A., Marzouk, M., Scavo, V., Washburn, T. B., Savage, D., Smith, J., Bennetts, J., Assi, R., Shults, C., Arghami, A., Butler, J., Devereaux, P. J., Zager, R., Wang, C., Snapinn, S., Browne, A., Rodriguez, J., Ruiz, S., Singh, B. 2024; 68: 102364

  Abstract

  RBT-1 is a combination drug of stannic protoporfin (SnPP) and iron sucrose (FeS) that elicits a preconditioning response through activation of antioxidant, anti-inflammatory, and iron-scavenging pathways, as measured by heme oxygenase-1 (HO-1), interleukin-10 (IL-10), and ferritin, respectively. Our primary aim was to determine whether RBT-1 administered before surgery would safely and effectively elicit a preconditioning response in patients undergoing cardiac surgery.This phase 2, double-blind, randomised, placebo-controlled, parallel-group, adaptive trial, conducted in 19 centres across the USA, Canada, and Australia, enrolled patients scheduled to undergo non-emergent coronary artery bypass graft (CABG) and/or heart valve surgery with cardiopulmonary bypass. Patients were randomised (1:1:1) to receive either a single intravenous infusion of high-dose RBT-1 (90 mg SnPP/240 mg FeS), low-dose RBT-1 (45 mg SnPP/240 mg FeS), or placebo within 24-48 h before surgery. The primary outcome was a preoperative preconditioning response, measured by a composite of plasma HO-1, IL-10, and ferritin. Safety was assessed by adverse events and laboratory parameters. Prespecified adaptive criteria permitted early stopping and enrichment. This trial is registered with ClinicalTrials.gov, NCT04564833.Between Aug 4, 2021, and Nov 9, 2022, of 135 patients who were enrolled and randomly allocated to a study group (46 high-dose, 45 low-dose, 44 placebo), 132 (98%) were included in the primary analysis (46 high-dose, 42 low-dose, 44 placebo). At interim, the trial proceeded to full enrollment without enrichment. RBT-1 led to a greater preconditioning response than did placebo at high-dose (geometric least squares mean [GLSM] ratio, 3.58; 95% CI, 2.91-4.41; p < 0.0001) and low-dose (GLSM ratio, 2.62; 95% CI, 2.11-3.24; p < 0.0001). RBT-1 was generally well tolerated by patients. The primary drug-related adverse event was dose-dependent photosensitivity, observed in 12 (26%) of 46 patients treated with high-dose RBT-1 and in six (13%) of 45 patients treated with low-dose RBT-1 (safety population).RBT-1 demonstrated a statistically significant cytoprotective preconditioning response and a manageable safety profile. Further research is needed. A phase 3 trial is planned.Renibus Therapeutics, Inc.

  View details for DOI 10.1016/j.eclinm.2023.102364

  View details for PubMedID 38586479

  View details for PubMedCentralID PMC10994969

• Role of Diuretics in Cardiovascular Events and Mortality in Systolic Blood Pressure Intervention Trial: A Post Hoc Analysis. Clinical journal of the American Society of Nephrology : CJASN Bansal, S., Boucher, R., Shen, J., Wei, G., Chertow, G. M., Whelton, P. K., Cushman, W. C., Cheung, A. K., Beddhu, S. 2024

  Abstract

  In a post hoc analysis, we examined whether postrandomization diuretics use can explain and/or mediate the beneficial effects of intensive systolic BP lowering on cardiovascular disease and all-cause mortality in the Systolic Blood Pressure Intervention Trial (SPRINT).SPRINT was a randomized, controlled trial of 9361 participants comparing the effects of intensive (systolic BP target <120 mm Hg) versus standard (systolic BP target <140 mm Hg) BP control on a primary composite cardiovascular end point in participants aged 50 years or older with systolic BP of 130-180 mm Hg. In time-varying multivariable Cox analyses, we assessed hazard ratios (HRs) of cardiovascular end points and all-cause mortality in participants on thiazide type, loop and/or potassium (K) sparing, or no diuretics. We also conducted mediation analysis to formally assess the role of diuretics in the effects of intensive systolic BP lowering.At baseline, diuretics were prescribed in 46% and 48% of participants in standard and intensive systolic BP-lowering groups, respectively, and in 46% and 74% in the corresponding groups during the trial. The lower risk of cardiovascular end points in the intensive group (HR, 0.75; 95% confidence interval [CI], 0.64 to 0.89) persisted after adjustment for postrandomization time-varying diuretics use (HR, 0.74; 95% CI, 0.62 to 0.89). Across the entire study population, time-varying diuretics use was not associated with cardiovascular end points (compared with no diuretics, HR for thiazide type, 0.89; 95% CI, 0.73 to 1.10, and loop/K sparing, 1.29; 95% CI, 0.97 to 1.73). However, thiazide-type diuretics were associated with lower risk of cardiovascular end points in the intensive (HR, 0.62; 95% CI, 0.46 to 0.85) but not in the standard (HR, 1.07; 95% CI, 0.82 to 1.39) group. In mediation analysis, HRs for total effect, direct effect (not mediated through diuretics use), and indirect effect (mediated through diuretics) of the intervention on cardiovascular end points were 0.66 (95% CI, 0.54 to 0.79), 0.67 (95% CI, 0.54 to 0.81), and 0.98 (95% CI, 0.88 to 1.10), respectively. The results were largely similar for all-cause mortality.The favorable effects of intensive systolic BP lowering on cardiovascular end points and all-cause mortality in SPRINT were independent of and not mediated by time-varying diuretics use. However, thiazide-type diuretics use associated with benefit if intensive systolic BP lowering was targeted.

  View details for DOI 10.2215/CJN.0000000000000406

  View details for PubMedID 38262377

• Antineutrophil Cytoplasmic Antibody-Associated Vasculitis with Active Kidney Involvement in the United States: 2016-2020. Glomerular diseases Tao, J., Liu, S., Montez-Rath, M., Charu, V., Chertow, G. M. 2024; 4 (1): 33-42

  Abstract

  Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and its subtypes, granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic GPA (EGPA), frequently present with acute kidney injury and can often lead to kidney failure, even with successful induction therapy. Few contemporary, nationally representative studies have described hospital complications of AAV.Using data from the 2016-2020 National Inpatient Sample, a nationally representative database, we identified hospitalizations from adults with a new diagnosis of AAV (subtype or unspecified) and an inpatient kidney biopsy during the index hospitalization. We described baseline characteristics, associated inpatient procedures and complications, and compared lengths of stay and costs by geographic region, hospital characteristics, and AAV subtype.We identified an average of 1,329 cases of hospitalized AAV with a concurrent kidney biopsy per year over the 5-year period. More than 50% were not designated as having a specific subtype, likely owing to delays in documentation of histopathology. Kidney involvement was severe as the majority of patients developed acute kidney injury, and the proportion of patients who required inpatient dialysis was approximately 24%. Approximately 20% of patients developed hypoxia. Inpatient plasmapheresis was delivered to 20.4% and 20.6% of patients with GPA and MPA, respectively. There were no clinically meaningful or statistically significant differences in adjusted length of stay or inpatient costs among AAV subtypes. Admission in the Midwest region was associated with shorter hospital stays and lower costs than that in the Northeast, South, or West regions of the USA (adjusted p = 0.007 and <0.001, respectively).AAV with acute kidney involvement remains a challenging, high-risk condition. Maintaining a high index of suspicion and a low threshold for kidney biopsy should help ameliorate short- and long-term complications.

  View details for DOI 10.1159/000536168

  View details for PubMedID 38328771

  View details for PubMedCentralID PMC10849749

• Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors versus glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes and mild/moderate chronic kidney disease. Diabetes, obesity & metabolism Rhee, J. J., Han, J., Montez-Rath, M. E., Chertow, G. M. 2024

  Abstract

  To determine the comparative effectiveness regarding major cardiovascular events of glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD).We assembled a cohort of commercially insured adult patients with T2DM in the United States (derived from Optum Clinformatics DataMart 2003-2021) who were new users of GLP-1 receptor agonists or SGLT-2 inhibitors. We compared risks of non-fatal myocardial infarction or stroke in patients with and without CKD, and further categorized by CKD stage: stages G1 or G2 [estimated glomerular filtration rate (eGFR) ≥60 ml/min] and A2 (urine albumin to creatinine ratio 30 to <300 mg/g) or A3 (urine albumin to creatinine ratio ≥300 mg/g), stage G3a (eGFR 45 to <60 ml/min/1.73 m2 ) and stage G3b (eGFR 30 to <45 ml/min/1.73 m2 ). We used proportional hazards regression after inverse probability of treatment weighting to compute hazard ratios and 95% confidence intervals.After accounting for the probability of treatment, patients with T2DM and CKD treated with SGLT-2 inhibitors experienced a 14% lower risk of non-fatal myocardial infarction or stroke (hazard ratio 0.86, 95% confidence interval 0.78-0.94) relative to those treated with GLP-1 receptor agonists.Recognizing the potential for residual confounding, selection bias and immortal time bias, commercially insured patients in the United States with T2DM and CKD treated with SGLT-2 inhibitors experienced significantly lower risks of non-fatal myocardial infarction or stroke relative to those treated with GLP-1 receptor agonists.

  View details for DOI 10.1111/dom.15427

  View details for PubMedID 38186297

• Population-Wide Screening for Chronic Kidney Disease. Annals of internal medicine Cusick, M. M., Tisdale, R. L., Chertow, G. M., Owens, D. K., Goldhaber-Fiebert, J. D. 2024; 177 (1): eL230370

  View details for DOI 10.7326/L23-0370

  View details for PubMedID 38224602

• Safety and Tolerability of the APOL1 Inhibitor, Inaxaplin, following Single- and Multiple-Ascending Doses in Healthy Adults. Glomerular diseases Egbuna, O., Audard, V., Manos, G., Tian, S., Hagos, F., Chertow, G. M. 2024; 4 (1): 64-73

  Abstract

  Introduction: Toxic gain-of-function Apolipoprotein L1 (APOL1) variants contribute to the development of proteinuric nephropathies collectively referred to as APOL1-mediated kidney disease (AMKD). Despite standard-of-care treatments, patients with AMKD experience accelerated progression to end-stage kidney disease. The identification of two APOL1 variants as the genetic cause of AMKD inspired development of inaxaplin, an inhibitor of APOL1 channel activity that reduces proteinuria in patients with AMKD.Methods: We conducted two phase 1 studies evaluating the safety, tolerability, and pharmacokinetics of single-ascending doses (SAD) and multiple-ascending doses (MAD) of inaxaplin in healthy participants. In the SAD cohorts, participants were randomized to receive inaxaplin as a single dose (range, 7.5 mg to 165 mg) or placebo. In the MAD cohorts, participants were randomized to receive multiple doses of inaxaplin (range, 15 to 120 mg daily) or placebo for 14 days. We assessed safety and tolerability based on adverse events (AEs), clinical laboratory values, electrocardiograms (ECGs), and vital signs.Results: A total of 178 participants were randomized in the SAD/MAD cohorts of both studies (mean age: 36.7 years; 94.9% male). The proportion of participants with any AEs was similar in the inaxaplin (24.6%) and placebo (22.7%) groups. All AEs were mild or moderate in severity; there were no serious AEs. Headache was the most common AE: 10.4% and 2.3% in the inaxaplin and placebo groups, respectively. There were no drug-related treatment discontinuations and no clinically relevant trends in laboratory values, ECGs, or vital signs.Discussion/Conclusion: Inaxaplin is safe and well tolerated at single doses up to 165 mg and multiple doses up to 120 mg daily for 14 days. These results are consistent with the favorable safety profile of inaxaplin in a completed phase 2a proof-of-concept study. Together, these findings support continued evaluation of inaxaplin in an ongoing phase 2/3 pivotal trial as a potential precision medicine for patients with AMKD.

  View details for DOI 10.1159/000538255

  View details for PubMedID 38600955

• Hexasodium fytate exposure-response correlations in a randomized, placebo-controlled study of patients on dialysis with cardiovascular calcification. Frontiers in pharmacology Perello, J., Alberti, J., Torres, J. V., Ferrer, M. D., Perez, M. M., Bassissi, F., Gold, A., Raggi, P., Chertow, G. M., Salcedo, C. 2024; 15: 1325186

  Abstract

  Background: Patients receiving dialysis have high cardiovascular risk in part due to extensive vascular calcification. In the CaLIPSO study, infusion of hexasodium fytate (SNF472), the hexasodium salt of inositol hexaphosphate, for 52weeks thrice weekly during hemodialysis significantly reduced progression of coronary artery calcification (CAC). This report examines pharmacokinetic/pharmacodynamic (PK/PD) and exposure-efficacy in CaLIPSO. Methods: We measured hexasodium fytate plasma concentrations (PK) by validated liquid chromatography-mass spectroscopy, and hydroxyapatite crystallization in plasma (PD) by validated spectrophotometry. Analyses included patients evaluable for PK, PD, and CAC change (per-protocol analysis). We developed a simple Emax model for maximum concentration (Cmax) and PD effect, and linear and non-linear Emax models for exposure-efficacy among individual average Cmax and absolute and percent changes in CAC score from baseline to week 52. Results: Among evaluable patients receiving placebo (n = 15), 300mg (n = 20), or 600mg (n = 20), average Cmax across visits was not quantifiable (<0.76muM), 15muM, and 46muM, respectively. These results suggest a more-than-proportional increase, without accumulation, with a Cmax ratio of approximately 3 for the doses administered. Average inhibition of hydroxyapatite crystallization was 15%, 61%, and 75%, respectively, and similar across visits. Simple Emax models described 80% maximal effect at exposures >21.9M and a plateau in exposure-efficacy above the third quartile of Cmax (≥32M). Conclusion: Hexasodium fytate has exposure-dependent effects on hydroxyapatite crystallization and progression of cardiovascular calcification. Simple Emax models show robust relations among exposure, inhibition of hydroxyapatite crystallization, and change in CAC volume. Clinical Trial Registration: https://www.clinicaltrials.gov; identifier NCT02966028.

  View details for DOI 10.3389/fphar.2024.1325186

  View details for PubMedID 38384289

• Effects of Dapagliflozin in Chronic Kidney Disease Across the Spectrum of Age and by Sex. Journal of general internal medicine Yu, M. K., Vart, P., Jongs, N., Correa-Rotter, R., Rossing, P., McMurray, J. J., Hou, F., Douthat, W., Khullar, D., Langkilde, A. M., Wheeler, D. C., Heerspink, H. J., Chertow, G. M. 2023

  Abstract

  BACKGROUND: The sodium-glucose cotransporter type 2 inhibitor dapagliflozin reduces the risk of progressive kidney disease and cardiovascular events in patients with chronic kidney disease, with and without type 2 diabetes. Whether its effects are uniform across the spectrum of age and among men and women is unknown.OBJECTIVE: We performed a pre-specified analysis in DAPA-CKD to evaluate efficacy and safety of dapagliflozin according to baseline age and sex.DESIGN: Prospective randomized placebo-controlled trial.PARTICIPANTS: A total of 4304 adults with chronic kidney disease (estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73 m2; urinary albumin-to-creatinine ratio 200-5000 mg/g) with and without type 2 diabetes.INTERVENTION: Dapagliflozin 10 mg versus placebo once daily.MAIN MEASURES: Primary endpoint was a composite of ≥ 50% sustained eGFR decline, end-stage kidney disease, and kidney or cardiovascular death. Secondary endpoints included kidney composite endpoint (same as primary composite endpoint but without cardiovascular death), cardiovascular composite endpoint (hospitalized heart failure or cardiovascular death), and all-cause mortality.KEY RESULTS: Median follow-up was 2.4 years. Absolute risks of cardiovascular composite endpoint and all-cause mortality were higher in older patients. Absolute risk of kidney composite endpoint was highest in patients < 50 years (10.7 and 6.2 per 100 patient-years in the placebo and dapagliflozin groups, respectively) and lowest in patients ≥ 80 years (3.0 and 1.2 per 100 patient-years in the placebo and dapagliflozin groups, respectively). There was no evidence of heterogeneity of the effects of dapagliflozin on the primary or secondary endpoints based on age or sex. Neither age nor sex modified the effects of dapagliflozin on total or chronic eGFR slope.CONCLUSIONS: Dapagliflozin reduced the risks of mortality, cardiovascular events, and CKD progression in older patients, including in septuagenarians and octogenarians who comprised 25% of participants. Ageism and/or therapeutic nihilism should not discourage the use of dapagliflozin in older women and men who are likely to experience considerable benefit.TRIAL REGISTRY: clinicaltrials.gov NIH TRIAL REGISTRY NUMBER: NCT03036150.

  View details for DOI 10.1007/s11606-023-08397-9

  View details for PubMedID 38097862

• Heterogeneous Treatment Effects of Intensive Glycemic Control on Kidney Microvascular Outcomes and Mortality in ACCORD. Journal of the American Society of Nephrology : JASN Charu, V., Liang, J. W., Chertow, G. M., Li, J., Montez-Rath, M. E., Geldsetzer, P., de Boer, I. H., Tian, L., Tamura, M. K. 2023

  Abstract

  Clear criteria to individualize glycemic targets in patients with type II diabetes are lacking. In this post-hoc analysis of the Action to Control Cardiovascular Risk in Diabetes trial (ACCORD), we evaluate whether the kidney failure risk equation (KFRE) can identify patients for whom intensive glycemic control confers more benefit in preventing kidney microvascular outcomes.We divided the ACCORD trial population into quartiles based on 5-year kidney failure risk using the KFRE. We estimated conditional treatment effects within each quartile and compared them to the average treatment effect in the trial. The treatment effects of interest were the 7-year restricted-mean-survival-time (RMST) differences between intensive and standard glycemic control arms on (1) time-to-first development of severely elevated albuminuria or kidney failure and (2) all-cause mortality.We found evidence that the effect of intensive glycemic control on kidney microvascular outcomes and all-cause mortality varies with baseline risk of kidney failure. Patients with elevated baseline risk of kidney failure derived the most from intensive glycemic control in reducing kidney microvascular outcomes (7-year RMST difference of 114.8 (95% CI 58.1, 176.4)v. 48.4 (25.3, 69.6) days in the entire trial population) However, this same patient group also experienced a shorter time to death (7-year RMST difference of -56.7 (-100.2, -17.5) v. -23.6 (-42.2, -6.6)days).We found evidence of heterogenous treatment effects of intensive glycemic control on kidney microvascular outcomes in ACCORD as a function of predicted baseline risk of kidney failure. Patients with higher kidney failure risk experienced the most pronounced reduction in kidney microvascular outcomes but also experienced the highest risk of all-cause mortality.

  View details for DOI 10.1681/ASN.0000000000000272

  View details for PubMedID 38073026

• Association of Bioimpedance Parameters with Increases in Blood Pressure during Hemodialysis. Clinical journal of the American Society of Nephrology : CJASN Elsayed, E., Farag, Y. M., Ravi, K. S., Chertow, G. M., McCausland, F. R. 2023

  Abstract

  Intra-dialytic hypertension, defined as an increase in blood pressure (BP) from pre- to post-hemodialysis (HD), affects 5-15% of patients receiving maintenance HD and is associated with cardiovascular and all-cause mortality. Hypervolemia is thought to be a major etiological factor, yet the association of more objective biomarkers of volume status with intra-dialytic hypertension is not well described.In a post hoc analysis of the Frequent Hemodialysis Network Daily Trial (n=234), using data from baseline, 1, 4, and 12-month visits (n=800), we used random effects regression to assess the association of bioimpedance estimates of volume (vector length) with post-HD systolic BP (continuous) and any increase in systolic BP (categorical) from pre- to post-HD. We adjusted models for randomized group, age, sex, self-reported race, Quételet (body mass) index, vascular access, HD vintage, hypertension, a history of heart failure, diabetes, residual kidney function (urea clearance), pre-HD systolic BP, ultrafiltration rate, serum-dialysate sodium gradient, and baseline values of hemoglobin, phosphate, and equilibrated Kt/V urea.The mean age of participants was 50 ±14 years, 39% were female, and 43% were Black. In adjusted models, shorter vector length (per 50 Ω/m) was associated with higher post-HD systolic BP (2.9 mmHg; 95%CI 1.6, 4.3) and higher odds of intra-dialytic hypertension (OR 1.66; 95%CI 1.07, 2.55). Similar patterns of association were noted with a more stringent definition of intra-dialytic hypertension (>10 mmHg increase from pre-to post-HD systolic BP), where shorter vector length (per 50 Ω/m) was associated with a higher odds of intra-dialytic hypertension (OR 2.17; 95%CI 0.88, 5.36).Shorter vector length, a bioimpedance-derived proxy of hypervolemia, was independently associated with higher post-HD systolic BP and risk of intra-dialytic hypertension.

  View details for DOI 10.2215/CJN.0000000000000356

  View details for PubMedID 37971865

• Report From a Multidisciplinary Symposium on the Future of Living Kidney Donor Transplantation. Progress in transplantation (Aliso Viejo, Calif.) Peters, T. G., Fung, J. J., Radcliffe-Richards, J., Satel, S., Roth, A. E., McCormick, F., Gershun, M., Matas, A. J., Roberts, J. P., Morrison, J., Chertow, G. M., Lee, L. D., Held, P. J., Ojo, A. 2023: 15269248231212911

  Abstract

  Virtually all clinicians agree that living donor renal transplantation is the optimal treatment for permanent loss of kidney function. Yet, living donor kidney transplantation has not grown in the United States for more than 2 decades. A virtual symposium gathered experts to examine this shortcoming and to stimulate and clarify issues salient to improving living donation. The ethical principles of rewarding kidney donors and the limits of altruism as the exclusive compelling stimulus for donation were emphasized. Concepts that donor incentives could save up to 40 000 lives annually and considerable taxpayer dollars were examined, and survey data confirmed voter support for donor compensation. Objections to rewarding donors were also presented. Living donor kidney exchanges and limited numbers of deceased donor kidneys were reviewed. Discussants found consensus that attempts to increase living donation should include removing artificial barriers in donor evaluation, expansion of living donor chains, affirming the safety of live kidney donation, and assurance that donors incur no expense. If the current legal and practice standards persist, living kidney donation will fail to achieve its true potential to save lives.

  View details for DOI 10.1177/15269248231212911

  View details for PubMedID 37968881

• Effect of SGLT2 Inhibitors on Discontinuation of Renin-angiotensin System Blockade: A Joint Analysis of the CREDENCE and DAPA-CKD Trials. Journal of the American Society of Nephrology : JASN Fletcher, R. A., Jongs, N., Chertow, G. M., McMurray, J. J., Arnott, C., Jardine, M. J., Mahaffey, K. W., Perkovic, V., Rockenschaub, P., Rossing, P., Correa-Rotter, R., Toto, R. D., Vaduganathan, M., Wheeler, D. C., Heerspink, H. J., Neuen, B. L. 2023

  Abstract

  Strategies to enable persistent use of renin-angiotensin system (RAS) blockade to improve outcomes in CKD have long been sought. The effect of SGLT2 inhibitors on discontinuation of RAS blockade has yet to be evaluated.We conducted a joint analysis of canagliflozin and renal events in diabetes with established nephropathy clinical evaluation (CREDENCE) and dapagliflozin and prevention of adverse outcomes in CKD (DAPA-CKD), two randomized, double-blind, placebo-controlled, event-driven trials of SGLT2 inhibitors in patients with albuminuric CKD. The main outcome was time to incident temporary or permanent discontinuation of RAS blockade, defined as interruption of an ACE inhibitor or ARB for at least 4 weeks or complete cessation during the double-blind on-treatment period. Cox regression analyses were used to estimate the treatment effects from each trial. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were pooled with fixed effects meta-analysis to obtain summary treatment effects, overall and across key subgroups.During median follow-up of 2.2 years across both trials, 740 of 8483 (8.7%) patients discontinued RAS blockade. The relative risk for discontinuation of RAS blockade was 15% lower in patients randomized to receiving SGLT2 inhibitors (HR, 0.85; 95% CI, 0.74 to 0.99), with consistent effects across trials (P-heterogeneity = 0.92). The relative effect on RAS blockade discontinuation was more pronounced among patients with baseline urinary albumin:creatinine ratio ≥1000 mg/g (pooled HR, 0.77; 95% CI, 0.63 to 0.94; P-heterogeneity = 0.009).In patients with albuminuric CKD with and without type 2 diabetes, SGLT2 inhibitors facilitate the use of RAS blockade.ClinicalTrials.gov, NCT02065791 and NCT03036150.

  View details for DOI 10.1681/ASN.0000000000000248

  View details for PubMedID 37876229

• Tenapanor Improves Long-term Control of Hyperphosphatemia in Patients Receiving Maintenance Dialysis: the NORMALIZE Study. Kidney360 Silva, A. L., Chertow, G. M., Hernandez, G. T., Lynn, R. I., Tietjen, D. P., Rosenbaum, D. P., Yang, Y., Edelstein, S. 2023

  Abstract

  Most patients with end-stage kidney disease and hyperphosphatemia have difficulty controlling serum phosphate concentrations (sP) despite maintenance dialysis, dietary restriction, and phosphate binder treatment. NORMALIZE evaluated the efficacy and safety of tenapanor 30 mg twice daily alone or in combination with phosphate binders to achieve sP within the adult population reference range (2.5-4.5 mg/dL).Patients who completed the phase 3 PHREEDOM study could enroll in NORMALIZE. Patients enrolled in NORMALIZE who had received tenapanor during the PHREEDOM study (n=111) added sevelamer carbonate if sP was >4.5 mg/dL. Patients who had received sevelamer carbonate during the PHREEDOM study (n=61) added tenapanor and decreased sevelamer carbonate if sP was ≤4.5 mg/dL, per protocol titration schedule. Patients were followed in NORMALIZE for up to 18 months. We assessed efficacy in the full analysis set (FAS), defined as patients who received ≥1 dose of study drug and had ≥1 posttreatment sP measurement (n=171). We assessed safety in all patients who received ≥1 dose of study drug (n=172).At the endpoint visit, 57 of 171 patients (33%) in the FAS achieved sP between 2.5 and 4.5 mg/dL. Eight of 23 patients (35%) who were on tenapanor alone at the endpoint visit achieved sP between 2.5 and 4.5 mg/dL. The mean reduction from PHREEDOM baseline to end of NORMALIZE in sP was 2.0 mg/dL. Serum iFGF23 was significantly reduced; serum iPTH was significantly reduced among patients with iPTH ≥300 pg/mL at PHREEDOM baseline. The most commonly reported treatment-emergent adverse event was diarrhea in 38 of 172 patients (22%), which led to tenapanor discontinuation in 4 patients (2%).Tenapanor alone or in combination with phosphate binders helped adult patients on maintenance dialysis achieve normal sP concentrations. Safety was consistent with previous studies of tenapanor.A Long-Term Study to Evaluate the Ability of Tenapanor Alone or in Combination With Sevelamer to Treat to Goal Serum Phosphorus in Patients With End-Stage Kidney Disease on Dialysis (NORMALIZE), NCT03988920.

  View details for DOI 10.34067/KID.0000000000000280

  View details for PubMedID 37853560

• Muscle Mass and Serum Creatinine Concentration by Race and Ethnicity Among Hemodialysis Patients. Journal of the American Society of Nephrology : JASN Delgado, C., Powe, N. R., Chertow, G. M., Grimes, B., Johansen, K. L. 2023

  Abstract

  Differences in serum creatinine concentration among groups defined by race and ethnicity have been ascribed to differences in muscle mass. We examined differences in serum creatinine by race and ethnicity in a cohort of patients receiving hemodialysis in whom creatinine elimination by the kidney should have little or no effect on serum creatinine concentration and considered whether these differences persisted after adjustment for proxies of muscle mass.We analyzed data from 501 participants in the ACTIVE/ADIPOSE study who had been receiving hemodialysis for >1 year. We examined the independent associations among race/ethnicity (Black, Asian, non-Hispanic White, and Hispanic), serum creatinine, and intracellular water [ICW, L/m2], a proxy for muscle mass, derived by whole-body multi-frequency bioimpedance spectroscopy, using multivariable linear regression with adjustment for several demographic, clinical, and laboratory characteristics. We examined the association of race/ethnicity with serum creatinine concentration with and without adjustment for ICW.Black, Asian, and Hispanic patients had higher serum creatinine concentrations (+1.68 mg/dl [95%CI 1.09, 2.27], +1.61 mg/dl [95%CI 0.90, 2.32], and +0.83 [95% CI 0.08, 1.57], respectively) than non-Hispanic White patients. Overall, ICW was associated with serum creatinine concentration (0.26 mg/dl per L/m2 ICW, 95% CI 0.006, 0.51) but was not statistically significantly different by race/ethnicity. Black, Asian, and Hispanic race/ethnicity remained significantly associated with serum creatinine concentration after adjustment for ICW.Among patients receiving dialysis, serum creatinine was higher in Black, Asian, and Hispanic patients than in non-Hispanic Whites. Differences in ICW did not explain the differences in serum creatinine concentration across race groups.

  View details for DOI 10.1681/ASN.0000000000000240

  View details for PubMedID 37822022

• Implications of a Race Term in GFR Estimates Used to Predict AKI After Coronary Intervention. JACC. Cardiovascular interventions Uzendu, A., Kennedy, K., Chertow, G., Amin, A. P., Giri, J. S., Rymer, J. A., Bangalore, S., Lavin, K., Anderson, C., Spertus, J. A. 2023; 16 (18): 2309-2320

  Abstract

  The prediction of mortality, bleeding, and acute kidney injury (AKI) after percutaneous coronary intervention (PCI) traditionally relied on race-based estimates of the glomerular filtration rate (GFR). Recently, race agnostic equations were developed to advance equity.The authors aimed to compare the accuracy and implications of various GFR equations when used to predict AKI after PCI.Using the National Cardiovascular Data Registry (NCDR) CathPCI data set, we identified patients undergoing PCI in 2020 and calculated their AKI risk using the 2014 NCDR AKI risk model. We created 4 AKI models per patient for each estimate of baseline renal function: the traditional GFR equation with a race term, 2 GFR equations without a race term, and serum creatinine alone. We then compared each model's performance predicting AKI.Among 455,806 PCI encounters, the median age was 67 years, 32.2% were women, and 8.5% were Black. In Black patients, risk models without a race term were better calibrated than models incorporating an equation with a race term (intercept: -0.01 vs 0.15). Race-agnostic models reclassified 6% of Black patients into higher-risk categories, potentially prompting appropriate mitigation efforts. However, even with a race-agnostic model, AKI occurred in Black patients 18% more often than expected, which was not explained by captured patient or procedural characteristics.Incorporating a GFR estimate without a Black race term into the NCDR AKI risk prediction model yielded more accurate prediction of AKI risk for Black patients, which has important implications for reducing disparities and benchmarking.

  View details for DOI 10.1016/j.jcin.2023.07.031

  View details for PubMedID 37758386

• Contemporary Methods for Predicting Acute Kidney Injury After Coronary Intervention. JACC. Cardiovascular interventions Uzendu, A., Kennedy, K., Chertow, G., Amin, A. P., Giri, J. S., Rymer, J. A., Bangalore, S., Lavin, K., Anderson, C., Wang, T. Y., Curtis, J. P., Spertus, J. A. 2023; 16 (18): 2294-2305

  Abstract

  Acute kidney injury (AKI) is the most common complication after percutaneous coronary intervention (PCI). Accurately estimating patients' risks not only creates a means of benchmarking performance but can also be used prospectively to inform practice.The authors sought to update the 2014 National Cardiovascular Data Registry (NCDR) AKI risk model to provide contemporary estimates of AKI risk after PCI to further improve care.Using the NCDR CathPCI Registry, we identified all 2020 PCIs, excluding those on dialysis or lacking postprocedural creatinine. The cohort was randomly split into a 70% derivation cohort and a 30% validation cohort, and logistic regression models were built to predict AKI (an absolute increase of 0.3 mg/dL in creatinine or a 50% increase from preprocedure baseline) and AKI requiring dialysis. Bedside risk scores were created to facilitate prospective use in clinical care, along with threshold contrast doses to reduce AKI. We tested model calibration and discrimination in the validation cohort.Among 455,806 PCI procedures, the median age was 67 years (IQR: 58.0-75.0 years), 68.8% were men, and 86.8% were White. The incidence of AKI and new dialysis was 7.2% and 0.7%, respectively. Baseline renal function and variables associated with clinical instability were the strongest predictors of AKI. The final AKI model included 13 variables, with a C-statistic of 0.798 and excellent calibration (intercept = -0.03 and slope = 0.97) in the validation cohort.The updated NCDR AKI risk model further refines AKI prediction after PCI, facilitating enhanced clinical care, benchmarking, and quality improvement.

  View details for DOI 10.1016/j.jcin.2023.07.041

  View details for PubMedID 37758384

• The Association of Class I and II Human Leukocyte Antigen Serotypes With End-Stage Kidney Disease Due to Membranoproliferative Glomerulonephritis and Dense Deposit Disease. American journal of kidney diseases : the official journal of the National Kidney Foundation Afolabi, H., Zhang, B. M., O'Shaughnessy, M., Chertow, G. M., Lafayette, R., Charu, V. 2023

  Abstract

  RATIONALE & OBJECTIVE: Membranoproliferative glomerulonephritis (MPGN), encompassing several distinct diseases, is a rare but significant cause of kidney failure in the US. Potential etiologies of MPGN are unclear, but prior studies have suggested dysregulation of the alternative complement pathway, and recently, autoimmunity as potential mechanisms driving MPGN pathogenesis. In this study, we examined HLA associations with end-stage kidney disease (ESKD) due to MPGN and Dense Deposit Disease (DDD) in a large racially and ethnically diverse US-based cohort.STUDY DESIGN: Case-control study.SETTING &PARTICIPANTS: Using USRDS and UNOS data, we identified 3424 patients with kidney failure due to MPGN and 263 due to DDD. We matched patients to kidney donor controls on designated race and ethnicity in a 1:15 ratio.EXPOSURES: 58 class I and II HLA serotypes.OUTCOMES: Case-control status.ANALYTICAL APPROACH: For each disease cohort, univariable and multivariable logistic regression analyses were used to investigate associations between the disease and 58 HLA serotypes. In subgroup analyses, we investigated HLA associations in White and Black patients. We also studied anti-GBM nephritis as a positive-control outcome. We applied a Bonferroni correction to account for multiple comparisons.RESULTS: Eighteen serotypes were significantly associated with the odds of having MPGN in univariable analyses, with DR17 having the strongest association ([OR]: 1.55, 95% CI: 1.44-1.68; p-value 4.33e-28). No significant associations were found between any HLA serotype and DDD. Designated race-specific analyses showed comparable findings. We recapitulated known HLA associations in anti-GBM nephritis.LIMITATIONS: Reliance on HLA serotypes (rather than genotype), lack of biopsy-confirmed diagnoses.CONCLUSIONS: HLA-DR17 is associated with ESKD due to MPGN in a racially and ethnically diverse cohort. The strength of association was similar in White and Black patients, suggesting a role in the pathogenesis of MPGN. No HLA associations were observed in patients with DDD.

  View details for DOI 10.1053/j.ajkd.2023.06.005

  View details for PubMedID 37739026

• Performance characteristics of a prototype dialysate turbidity monitoring system to detect peritonitis in patients receiving peritoneal dialysis. Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis Briggs, B., Garcia-Garcia, G., Ibarra-Hernandez, M., Alcantar-Vallin, L., Walker, G., Yu, E., ElBadry, A., Fisher, B., Williamson, D., Chertow, G. M. 2023: 8968608231195532

  Abstract

  BACKGROUND: The risk of peritonitis has limited wider adoption of peritoneal dialysis (PD) in the United States. We developed a prototype bedside dialysate turbidity monitoring system, aiming to improve diagnostic accuracy relative to conventional approaches which depend on visual inspection and reporting of insensitive and non-specific symptoms.METHODS: The prototype system was tested in a single-centre, proof-of-principle clinical study in patients receiving intermittent PD. We obtained multiple effluent dialysate samples from each consenting participant. We compared turbidity measurements with diagnostic criteria endorsed by the International Society of Peritoneal Dialysis (ISPD).RESULTS: Overall, we analysed 983 specimens from 65 patients, including 105 samples from patients with peritonitis and 878 samples from patients without peritonitis. An operating point derived from a previous in vitro study yielded an unadjusted sensitivity and specificity of 95.2% and 91.5%, respectively. The majority of samples that did not meet ISPD diagnostic criteria were either cases detected before criteria were met or were related to active peritonitis treatment and resolution.CONCLUSION: This proof-of-principle study demonstrates the feasibility and diagnostic accuracy of a prototype dialysate turbidity monitoring system for peritonitis surveillance.

  View details for DOI 10.1177/08968608231195532

  View details for PubMedID 37723968

• Market Competition and Anemia Management in the United States following Dialysis Payment Reform. Medical care Bhatnagar, A., Parvathareddy, V., Winkelmayer, W. C., Chertow, G. M., Erickson, K. F. 2023

  Abstract

  BACKGROUND: Whether market competition influences health care provider responses to national reimbursement reforms is unknown.OBJECTIVES: We examined whether changes in anemia management after the expansion of Medicare's dialysis payment bundle varied with market competition.RESEARCH DESIGN: With data from the US dialysis registry, we used a difference-in-differences (DID) design to estimate the independent associations of market competition with changes in anemia management after dialysis reimbursement reform.SUBJECTS: A total of 326,150 patients underwent in-center hemodialysis in 2009 and 2012, representing periods before and after reimbursement reform.MEASURES: Outcomes were erythropoiesis-stimulating agent (ESA) and intravenous iron dosage, the probability of hemoglobin <9g/dL, hospitalizations, and mortality. We also examined serum ferritin concentration, an indicator of body iron stores. We used a dichotomous market competition index, with less competitive areas defined as effectively having <2 competing dialysis providers.RESULTS: Compared with areas with more competition, patients in less competitive areas had slightly more pronounced declines in ESA dose (60% vs. 57%) following reimbursement reform (DID estimate: -3%; 95% CI, -5% to -1%) and less pronounced declines in intravenous iron dose (-14% vs. -19%; DID estimate: 5%; 95% CI, 1%-9%). The likelihoods of hemoglobin <9g/dL, hospitalization, and mortality did not vary with market competition. Serum ferritin concentrations in 2012 were 4% (95% CI, 3%-6%) higher in less competitive areas.CONCLUSIONS: After the expansion of Medicare's dialysis payment bundle, ESA use declined by more, and intravenous iron use declined by less in concentrated markets. More aggressive cost-reduction strategies may be implemented in less competitive markets.

  View details for DOI 10.1097/MLR.0000000000001924

  View details for PubMedID 37721983

• Using Relative Survival to Estimate the Burden of Kidney Failure. American journal of kidney diseases : the official journal of the National Kidney Foundation Stedman, M. R., Tamura, M. K., Chertow, G. M. 2023

  Abstract

  Estimates of mortality from kidney failure are misleading because the mortality from kidney failure is inseparable from the mortality attributed to comorbid conditions. We sought to develop an alternative method to reduce the bias in estimating mortality due to kidney failure using life table methods.Longitudinal cohort study.Using data from the United States Renal Data System and the Medicare 5% sample, we identified an incident cohort of patients, age 66+, who first had kidney failure in 2009 and a similar general population cohort without kidney failure.Kidney failure.Death.We created comorbidity, age, sex, race, and year-specific life tables to estimate relative survival of patients with incident kidney failure and to attain an estimate of excess kidney failure-related deaths. Estimates were compared with those based on standard life tables (not adjusted for comorbidity).The analysis included 31,944 adults with kidney failure with a mean age of 77 +/- 7 years. 5-year relative survival was 31% using standard life tables (adjusted for age, sex, race, and year) versus 36% using life tables also adjusted for comorbidities. Compared with other chronic diseases, patients with kidney failure have among the lowest relative survival. Patients with incident kidney failure ages 66-70 and 76-80 have a survival comparable to adults without kidney failure roughly 86-90 and 91-95 years old, respectively.Relative survival estimates can be improved by narrowing the specificity of the covariates collected, (e.g. disease severity and ethnicity).Estimates of survival relative to a matched general population partition the mortality due to kidney failure from other causes of death. Results highlight the immense burden of kidney failure on mortality and the importance of disease prevention efforts among older adults.

  View details for DOI 10.1053/j.ajkd.2023.05.015

  View details for PubMedID 37678740

• Hypocitraturia and Risk of Bone Disease in Patients With Kidney Stone Disease. JBMR plus Ganesan, C., Thomas, I. C., Montez-Rath, M. E., Chertow, G. M., Leppert, J. T., Pao, A. C. 2023; 7 (9): e10786

  Abstract

  Patients with kidney stone disease are at higher risk for bone disease. Hypocitraturia is common in patients with kidney stone disease and a key risk factor for stone recurrence. In this retrospective cohort study, we sought to determine whether hypocitraturia is also a risk factor for incident bone disease in patients with kidney stone disease. We used nationwide data from the Veterans Health Administration and identified 9025 patients with kidney stone disease who had a 24-hour urine citrate measurement between 2007 and 2015. We examined clinical characteristics of patients by level of 24-hour urine citrate excretion (<200, 200-400, and >400 mg/d) and the time to osteoporosis or fracture according to 24-hour urine citrate excretion level. Almost one in five veterans with kidney stone disease and a 24-hour urine citrate measurement had severe hypocitraturia, defined as <200 mg/d. Patients with severe hypocitraturia were at risk for osteoporosis or fracture (hazard ratio [HR] = 1.23; confidence interval [CI] 1.03-1.48), but after adjustment for demographic factors, comorbid conditions, and laboratory abnormalities associated with hypocitraturia, the association was no longer statistically significant (HR = 1.18; CI 0.98-1.43). Our results in a predominantly male cohort suggest a modest association between hypocitraturia and osteoporosis or fracture; there are likely to be other explanations for the potent association between kidney stone disease and diminished bone health. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

  View details for DOI 10.1002/jbm4.10786

  View details for PubMedID 37701146

  View details for PubMedCentralID PMC10494504

• Efficacy and Safety of Dapagliflozin in Patients with Chronic Kidney Disease across the Spectrum of Frailty. The journals of gerontology. Series A, Biological sciences and medical sciences Vart, P., Butt, J. H., Jongs, N., Schechter, M., Chertow, G. M., Wheeler, D. C., Pecoits-Filho, R., Langkilde, A. M., Correa-Rotter, R., Rossing, P., McMurray, J. J., Heerspink, H. J. 2023

  Abstract

  BACKGROUND: A sizeable proportion of patients with chronic kidney disease (CKD) are reported to be frail. Here we examined the safety and efficacy of dapagliflozin in patients with CKD by frailty level.METHODS: Adults with CKD, with/without type 2 diabetes, with estimated glomerular filtration rate (eGFR) 25-75mL/min/1.73m 2 and urinary albumin-to-creatinine ratio 200-5000mg/g were randomized to dapagliflozin (10mg/day) or placebo. The primary endpoint was composite of sustained ≥50% eGFR decline, end-stage kidney disease (ESKD) or death from kidney or cardiovascular (CV) causes.RESULTS: Frailty index (FI), assessed by Rockwood cumulative deficit approach, was calculable in 4303/4304 (99.9%) patients: 1162 (27.0%) in not-to-mildly frail(FI≤0.210), 1642 (38.2%) in moderately frail(FI 0.211-0.310), and 1499 (34.8%) in severely frail categories (FI>0.311). Dapagliflozin reduced the risk of the primary composite endpoint across all FI categories (hazard ratios [95% CI]: 0.50 [0.33-0.76], 0.62 [0.45-0.85], and 0.64 [0.49-0.83], respectively (P-interaction =0.67). Results were similar for secondary outcomes including kidney composite outcome (sustained ≥50% eGFR decline, ESKD or death from kidney cause; P-interaction=0.44), CV endpoint (heart failure hospitalization or CV death; P-interaction=0.63), and all-cause mortality (P-interaction p=0.42). Results were consistent when using FI as a continuous variable. Occurrence of serious adverse events was numerically lower in patients receiving dapagliflozin vs. placebo in all FI categories (16.9% vs. 20.1%, 26.3% vs. 30.7%, and 42.9% vs 47.8%, in not-to-mildly, moderately and severely frail categories, respectively).CONCLUSIONS: The relative benefit of dapagliflozin for all outcomes was consistent across all frailty categories, with no difference in associated safety.

  View details for DOI 10.1093/gerona/glad181

  View details for PubMedID 37527836

• Disparities in the Timing of Preoperative Hemodialysis Among Patients With End-Stage Kidney Disease. JAMA network open Fielding-Singh, V., Vanneman, M. W., Morris, A. M., Chertow, G. M., Lin, E. 2023; 6 (7): e2326326

  View details for DOI 10.1001/jamanetworkopen.2023.26326

  View details for PubMedID 37505500

• Use of Wastewater Metrics to Track COVID-19 in the US. JAMA network open Varkila, M. R., Montez-Rath, M. E., Salomon, J. A., Yu, X., Block, G. A., Owens, D. K., Chertow, G. M., Parsonnet, J., Anand, S. 2023; 6 (7): e2325591

  Abstract

  Importance: Widespread use of at-home COVID-19 tests hampers determination of community COVID-19 incidence.Objective: To examine the association of county-level wastewater metrics with high case and hospitalization rates nationwide both before and after widespread use of at-home tests.Design, Setting, and Participants: This observational cohort study with a time series analysis was conducted from January to September 2022 in 268 US counties in 22 states participating in the US Centers for Disease Control and Prevention's National Wastewater Surveillance System. Participants included the populations of those US counties.Exposures: County level of circulating SARS-CoV-2 as determined by metrics based on viral wastewater concentration relative to the county maximum (ie, wastewater percentile) and 15-day percentage change in SARS-CoV-2 (ie, percentage change).Main Outcomes and Measures: High county incidence of COVID-19 as evidenced by dichotomized reported cases (current cases ≥200 per 100 000 population) and hospitalization (≥10 per 100 000 population lagged by 2 weeks) rates, stratified by calendar quarter.Results: In the first quarter of 2022, use of the wastewater percentile detected high reported case (area under the curve [AUC], 0.95; 95% CI, 0.94-0.96) and hospitalization (AUC, 0.86; 95% CI, 0.84-0.88) rates. The percentage change metric performed poorly, with AUCs ranging from 0.51 (95% CI, 0.50-0.53) to 0.57 (95% CI, 0.55-0.59) for reported new cases, and from 0.50 (95% CI, 0.48-0.52) to 0.55 (95% CI, 0.53-0.57) for hospitalizations across the first 3 quarters of 2022. The Youden index for detecting high case rates was wastewater percentile of 51% (sensitivity, 0.82; 95% CI, 0.80-0.84; specificity, 0.93; 95% CI, 0.92-0.95). A model inclusive of both metrics performed no better than using wastewater percentile alone. The performance of wastewater percentile declined over time for cases in the second quarter (AUC, 0.84; 95% CI, 0.82-0.86) and third quarter (AUC, 0.72; 95% CI, 0.70-0.75) of 2022.Conclusions and Relevance: In this study, nationwide, county wastewater levels relative to the county maximum were associated with high COVID-19 case and hospitalization rates in the first quarter of 2022, but there was increasing dissociation between wastewater and clinical metrics in subsequent quarters, which may reflect increasing underreporting of cases, reduced testing, and possibly lower virulence of infection due to vaccines and treatments. This study offers a strategy to operationalize county wastewater percentile to improve the accurate assessment of community SARS-CoV-2 infection prevalence when reliability of conventional surveillance data is declining.

  View details for DOI 10.1001/jamanetworkopen.2023.25591

  View details for PubMedID 37494040

• Effects of Dapagliflozin on Hospitalizations in Patients With Chronic Kidney Disease. Annals of internal medicine Schechter, M., Chertow, G. M., Heerspink, H. J. 2023; 176 (7): eL230070

  View details for DOI 10.7326/L23-0070

  View details for PubMedID 37459628

• Safety Endpoints With Vadadustat Versus Darbepoetin Alfa in Patients With Non-Dialysis-Dependent CKD: A Post Hoc Regional Analysis of the PRO2TECT Randomized Clinical Trial of ESA-Naive Patients. Kidney medicine Winkelmayer, W. C., Arnold, S., Burke, S. K., Chertow, G. M., Eckardt, K., Jardine, A. G., Lewis, E. F., Luo, W., Matsushita, K., McCullough, P. A., Minga, T., Parfrey, P. S. 2023; 5 (7): 100666

  Abstract

  Rationale & Objective: Prespecified analyses of the PRO2TECT trials comparing the safety of the oral hypoxia-inducible factor prolyl hydroxylase inhibitor vadadustat with darbepoetin alfa in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) found no difference in major adverse cardiovascular events (MACE; death from any cause or nonfatal myocardial infarction or stroke) among US patients and a higher risk among patients treated with vadadustat outside the United States. We investigated regional differences in MACE in the PRO2TECT trial that enrolled 1,751 patients previously untreated with erythropoiesis-stimulating agents.Study Design: Phase 3, global, open-label, randomized, active-controlled clinical trial.Setting and Participants: Erythropoiesis-stimulating agent-untreated patients with anemia and NDD-CKD.Intervention: Eligible patients were randomized 1:1 to receive vadadustat or darbepoetin alfa.Outcomes: The primary safety end point was time to first MACE. Secondary safety end points included time to first expanded MACE (MACEplus hospitalization for heart failure or thromboembolic event, excluding vascular access thrombosis).Results: In the non-US/non-Europe region, there was a higher proportion of patients with baseline estimated glomerular filtration rate (eGFR) level of≤10mL/min/1.73m2 in the vadadustat group [96 (34.7%)] than in the darbepoetin alfa group [66 (24.0%)]. In this region, there were 21 excess MACEs reported in the vadadustat group [78 events (n=276)] versus the darbepoetin alfa [57 events (n=275)], including 13 excess noncardiovascular deaths, largely from kidney failure. Noncardiovascular deaths were concentrated in Brazil and South Africa, which enrolled higher proportions of patients with an eGFR of≤10mL/min/1.73m2 and who may not have had access to dialysis.Limitations: Different regional treatment patterns of patients with NDD-CKD.Conclusions: The higher MACE rate in the non-US/non-Europe vadadustat group may have been partly because of imbalances in the baseline eGFR level in countries where dialysis was not uniformly available resulting in many kidney-related deaths.

  View details for DOI 10.1016/j.xkme.2023.100666

  View details for PubMedID 37427293

• Safety Endpoints With Vadadustat Versus Darbepoetin Alfa in Patients With Non-Dialysis-Dependent CKD: A Post Hoc Regional Analysis of the PRO2TECT Randomized Clinical Trial of ESA-Treated Patients. Kidney medicine Parfrey, P. S., Burke, S. K., Chertow, G. M., Eckardt, K., Jardine, A. G., Lewis, E. F., Luo, W., Matsushita, K., McCullough, P. A., Minga, T., Winkelmayer, W. C. 2023; 5 (7): 100667

  Abstract

  Rationale & Objective: In the PRO2TECT trials, vadadustat was found to be noninferior to darbepoetin alfa in hematologic efficacy but not for major adverse cardiovascular events (MACE; all-cause death or nonfatal myocardial infarction or stroke) in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD). We investigated the regional differences in MACE in the PRO2TECT trials.Study Design: Phase 3, global, open-label, randomized, active-controlled clinical trial.Setting & Participants: A total of 1,725 erythropoiesis-stimulating agent (ESA)-treated patients with anemia and NDD-CKD.Intervention: 1:1 randomization to receive vadadustat or darbepoetin alfa.Outcomes: The primary safety end point was the time to first MACE.Results: At baseline, patients in Europe (n=444) were primarily treated with darbepoetin alfa, showed higher proportions on low ESA doses (<90U/kg/wk epoetin alfa equivalents) with a hemoglobin concentration of≥10g/dL compared with patients in the US (n=665) and non-US/non-Europe (n=614) regions. The MACE rates per 100 person-years in the 3 vadadustat groups across regions were 14.5 in the US, 11.6 in Europe, and 10.0 in the non-US/non-Europe groups, whereas event rates in the darbepoetin alfa group were considerably lower in Europe than in the US and non-US/non-Europe groups (6.7 vs 13.3 and 10.5, respectively). The overall hazard ratio for MACE for vadadustat vs darbepoetin alpha was 1.16; 95% CI, 0.93-1.45, but varied by geographical region, with a greater hazard ratio seen in Europe (US, 1.07; 95% CI, 0.78-1.46; Europe, 2.05; 95% CI, 1.24-3.39; non-US/non-Europe, 0.91; 95% CI, 0.60-1.37); interaction between study treatment and geographical region, P=0.07). In Europe, ESA rescue was associated with a higher risk of MACE in both groups.Limitations: Several analyses are exploratory.Conclusions: In this trial, there was a low risk of MACE in the darbepoetin alfa group in Europe. Patients in Europe were generally on low doses of ESA, with hemoglobin already within target range. The low risk of MACE may have been related to a limited need to switch and titrate darbepoetin alfa compared with the non-US/non-Europe group.Funding: Akebia Therapeutics, Inc.Trial Registration: ClinicalTrials.gov identifier: NCT02680574.

  View details for DOI 10.1016/j.xkme.2023.100667

  View details for PubMedID 37427292

• Inaxaplin for Proteinuric Kidney Disease in Persons with Two APOL1 Variants. Reply. The New England journal of medicine Egbuna, O., Chertow, G. M. 2023; 388 (26): 2491

  View details for DOI 10.1056/NEJMc2304780

  View details for PubMedID 37379148

• Inaxaplin for Proteinuric Kidney Disease in Persons with Two <i>APOL1</i> Variants NEW ENGLAND JOURNAL OF MEDICINE Egbuna, O., Chertow, G. M. 2023; 388 (26): 2491

  View details for Web of Science ID 001058999200021

  View details for PubMedID 37379148

• Hypocitraturia and Risk of Bone Disease in Patients With Kidney Stone Disease JBMR PLUS Ganesan, C., Thomas, I., Montez-Rath, M. E., Chertow, G. M., Leppert, J. T., Pao, A. C. 2023

  View details for DOI 10.1002/jbm4.10786

  View details for Web of Science ID 001018463200001

• Heterogeneous treatment effects of intensive glycemic control on kidney microvascular outcomes in ACCORD. medRxiv : the preprint server for health sciences Charu, V., Liang, J. W., Chertow, G. M., Li, Z. J., Montez-Rath, M. E., Geldsetzer, P., de Boer, I. H., Tian, L., Tamura, M. K. 2023

  Abstract

  Objective: Clear criteria to individualize glycemic targets are lacking. In this post-hoc analysis of the Action to Control Cardiovascular Risk in Diabetes trial (ACCORD), we evaluate whether the kidney failure risk equation (KFRE) can identify patients who disproportionately benefit from intensive glycemic control on kidney microvascular outcomes.Research design and methods: We divided the ACCORD trial population in quartiles based on 5-year kidney failure risk using the KFRE. We estimated conditional treatment effects within each quartile and compared them to the average treatment effect in the trial. The treatment effects of interest were the 7-year restricted-mean-survival-time (RMST) differences between intensive and standard glycemic control arms on (1) time-to-first development of severely elevated albuminuria or kidney failure and (2) all-cause mortality.Results: We found evidence that the effect of intensive glycemic control on kidney microvascular outcomes and all-cause mortality varies with baseline risk of kidney failure. Patients with elevated baseline risk of kidney failure benefitted the most from intensive glycemic control on kidney microvascular outcomes (7-year RMST difference of 115 v. 48 days in the entire trial population) However, this same patient group also experienced shorter times to death (7-year RMST difference of -57 v. -24 days).Conclusions: We found evidence of heterogenous treatment effects of intensive glycemic control on kidney microvascular outcomes in ACCORD as a function of predicted baseline risk of kidney failure. Patients with higher kidney failure risk experienced the most pronounced benefits of treatment on kidney microvascular outcomes but also experienced the highest risk of all-cause mortality.

  View details for DOI 10.1101/2023.06.14.23291396

  View details for PubMedID 37398349

• Groundwater constituents and the incidence of kidney cancer. Cancer Soerensen, S. J., Montez-Rath, M. E., Cheng, I., Gomez, S. L., Oh, D. L., Jackson, C., Li, J., Rehkopf, D., Chertow, G. M., Langston, M. E., Ganesan, C., Pao, A. C., Chung, B. I., Leppert, J. T. 2023

  Abstract

  Kidney cancer incidence demonstrates significant geographic variation suggesting a role for environmental risk factors. This study sought to evaluate associations between groundwater exposures and kidney cancer incidence.The authors identified constituents from 18,506 public groundwater wells in all 58 California counties measured in 1996-2010, and obtained county-level kidney cancer incidence data from the California Cancer Registry for 2003-2017. The authors developed a water-wide association study (WWAS) platform using XWAS methodology. Three cohorts were created with 5 years of groundwater measurements and 5-year kidney cancer incidence data. The authors fit Poisson regression models in each cohort to estimate the association between county-level average constituent concentrations and kidney cancer, adjusting for known risk factors: sex, obesity, smoking prevalence, and socioeconomic status at the county level.Thirteen groundwater constituents met stringent WWAS criteria (a false discovery rate <0.10 in the first cohort, followed by p values <.05 in subsequent cohorts) and were associated with kidney cancer incidence. The seven constituents directly related to kidney cancer incidence (and corresponding standardized incidence ratios) were chlordane (1.06; 95% confidence interval [CI], 1.02-1.10), dieldrin (1.04; 95% CI, 1.01-1.07), 1,2-dichloropropane (1.04; 95% CI, 1.02-1.05), 2,4,5-TP (1.03; 95% CI, 1.01-1.05), glyphosate (1.02; 95% CI, 1.01-1.04), endothall (1.02; 95% CI, 1.01-1.03), and carbaryl (1.02; 95% CI, 1.01-1.03). Among the six constituents inversely related to kidney cancer incidence, the standardized incidence ratio furthest from the null was for bromide (0.97; 95% CI, 0.94-0.99).This study identified several groundwater constituents associated with kidney cancer. Public health efforts to reduce the burden of kidney cancer should consider groundwater constituents as environmental exposures that may be associated with the incidence of kidney cancer.

  View details for DOI 10.1002/cncr.34898

  View details for PubMedID 37287332

• Estimating Life Years from Transplant in Older Candidates Stedman, M., Ahearn, P., Liu, C. K., Chertow, G. M., Tan, J. C. ELSEVIER SCIENCE INC. 2023: S681

  View details for Web of Science ID 001087126902166

• Dapagliflozin and Anemia in Patients with Chronic Kidney Disease. NEJM evidence Koshino, A., Schechter, M., Chertow, G. M., Vart, P., Jongs, N., Toto, R. D., Rossing, P., Correa-Rotter, R., McMurray, J. J., Gorriz, J. L., Isidto, R., Kashihara, N., Langkilde, A. M., Wheeler, D. C., Heerspink, H. J. 2023; 2 (6): EVIDoa2300049

  Abstract

  DAPA and Anemia in Patients with CKDThis post hoc analysis of the DAPA-CKD (Dapagliflozin in Patients with Chronic Kidney Disease) trial assessed the impact of dapagliflozin treatment on the correction and prevention of anemia. Results over a 2.4-year median follow-up show that dapagliflozin is associated with increase in hematocrit, correction of anemia, and reduced risk of incident anemia in patients with CKD with or without type 2 diabetes.

  View details for DOI 10.1056/EVIDoa2300049

  View details for PubMedID 38320128

• APOL1 GENOTYPING AND PROTEINURIC KIDNEY DISEASE IN EUROPE Knebelmann, B., Bramham, K., Mccafferty, K., Zaidan, M., Torres, P., Audard, V., Boffa, J., Powell, T., Shahid, N., Echeverri, D., Provenzano, C., Bauman, J., Zamauskaite, A., Delestre-Levai, I., Yang, Y., Krause, S., Ferreira, A., Egbuna, O., Chertow, G. OXFORD UNIV PRESS. 2023: I144-I145

  View details for Web of Science ID 001022961100136

• REASONS FOR DIALYSIS INITIATION AND SAFETY OF DAPAGLIFLOZIN AMONG DIALYSIS PARTICIPANTS: NEW INSIGHTS FROMDAPA-CKD Heerspink, H., Wheeler, D. C., Jong, N., Correa-Rotter, R., Rossing, P., Gansevoort, R., Mcmurray, J., Langkilde, A., Toto, R., Chertow, G. OXFORD UNIV PRESS. 2023: I52-I53

  View details for Web of Science ID 001022961100049

• EFFECT OF DAPAGLIFLOZIN IN PATIENTS WITH CKD ACROSS THE SPECTRUM OF AGE AND BY SEX Yu, M., Vart, P., Heerspink, H., Jong, N., Correa-Rotter, R., Mcmurray, J., Rossing, P., Langkilde, A., Toto, R., Wheeler, D. C., Chertow, G. OXFORD UNIV PRESS. 2023: I638-I639

  View details for Web of Science ID 001022961102124

• AMBIENT HEAT EXPOSURE AND ESTIMATED GLOMERULAR FILTRATION RATE TRAJECTORY: A POST-HOC ANALYSIS OF THE DAPA-CKD TRIAL Zhang, Z., Ileerspink, H., Chertow, G., Correa-Rotter, R., Gasparrini, A., Jong, N., Langkilde, A., Mistry, M., Mcmurray, J., Rossing, P., Toto, R., Vart, P., Misch, D., Wheeler, D. C., Ben Caplin OXFORD UNIV PRESS. 2023: I472

  View details for Web of Science ID 001022961101270

• Population-Wide Screening for Chronic Kidney Disease : A Cost-Effectiveness Analysis. Annals of internal medicine Cusick, M. M., Tisdale, R. L., Chertow, G. M., Owens, D. K., Goldhaber-Fiebert, J. D. 2023

  Abstract

  BACKGROUND: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have the potential to alter the natural history of chronic kidney disease (CKD), and they should be included in cost-effectiveness analyses of screening for CKD.OBJECTIVE: To determine the cost-effectiveness of adding population-wide screening for CKD.DESIGN: Markov cohort model.DATA SOURCES: NHANES (National Health and Nutrition Examination Survey), U.S. Centers for Medicare & Medicaid Services data, cohort studies, and randomized clinical trials, including the DAPA-CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease) trial.TARGET POPULATION: Adults.TIME HORIZON: Lifetime.PERSPECTIVE: Health care sector.INTERVENTION: Screening for albuminuria with and without adding SGLT2 inhibitors to the current standard of care for CKD.OUTCOME MEASURES: Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs), all discounted at 3% annually.RESULTS OF BASE-CASE ANALYSIS: One-time CKD screening at age 55 years had an ICER of $86300 per QALY gained by increasing costs from $249800 to $259000 and increasing QALYs from 12.61 to 12.72; this was accompanied by a decrease in the incidence of kidney failure requiring dialysis or kidney transplant of 0.29 percentage points and an increase in life expectancy from 17.29 to 17.45 years. Other options were also cost-effective. During ages 35 to 75 years, screening once prevented dialysis or transplant in 398000 people and screening every 10 years until age 75 years cost less than $100000 per QALY gained.RESULTS OF SENSITIVITY ANALYSIS: When SGLT2 inhibitors were 30% less effective, screening every 10 years during ages 35 to 75 years cost between $145400 and $182600 per QALY gained, and price reductions would be required for screening to be cost-effective.LIMITATION: The efficacy of SGLT2 inhibitors was derived from a single randomized controlled trial.CONCLUSION: Screening adults for albuminuria to identify CKD could be cost-effective in the United States.PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality, Veterans Affairs Office of Academic Affiliations, and National Institute of Diabetes and Digestive and Kidney Diseases.

  View details for DOI 10.7326/M22-3228

  View details for PubMedID 37216661

• Deceased Donor Kidney Transplantation for Older Transplant Candidates: A New Microsimulation Model for Determining Risks and Benefits. Medical decision making : an international journal of the Society for Medical Decision Making Kaufmann, M. B., Tan, J. C., Chertow, G. M., Goldhaber-Fiebert, J. D. 2023: 272989X231172169

  Abstract

  Under the current US kidney allocation system, older candidates receive a disproportionately small share of deceased donor kidneys despite a reserve of potentially usable kidneys that could shorten their wait times. To consider potential health gains from increasing access to kidneys for these candidates, we developed and calibrated a microsimulation model of the transplantation process and long-term outcomes for older deceased donor kidney transplant candidates.We estimated risk equations for transplant outcomes using the Scientific Registry of Transplant Recipients (SRTR), which contains data on all US transplants (2010-2019). A microsimulation model combined these equations to account for competing events. We calibrated the model to key transplant outcomes and used acceptance sampling, retaining the best-fitting 100 parameter sets. We then examined life expectancy gains from allocating kidneys even of lower quality across patient subgroups defined by age and designated race/ethnicity.The best-fitting 100 parameter sets (among 4,000,000 sampled) enabled our model to closely match key transplant outcomes. The model demonstrated clear survival benefits for those who receive a deceased donor kidney, even a lower quality one, compared with remaining on the waitlist where there is a risk of removal. The expected gain in survival from receiving a lower quality donor kidney was consistent gains across age and race/ethnic subgroups.Limited available data on socioeconomic factors.Our microsimulation model accurately replicates a range of key kidney transplant outcomes among older candidates and demonstrates that older candidates may derive substantial benefits from transplantation with lower quality kidneys. This model can be used to evaluate policies that have been proposed to address concerns that the current system disincentivizes deceased donor transplants for older patients.The microsimulation model was consistent with the data after calibration and accurately simulated the transplantation process for older deceased donor kidney transplant candidates.There are clear survival benefits for older transplant candidates who receive deceased donor kidneys, even lower quality ones, compared with remaining on the waitlist.This model can be used to evaluate policies aimed at increasing transplantation among older candidates.

  View details for DOI 10.1177/0272989X231172169

  View details for PubMedID 37170943

• Effects of Dapagliflozin in Chronic Kidney Disease, With and Without Other Cardiovascular Medications: DAPA-CKD Trial. Journal of the American Heart Association Chertow, G. M., Correa-Rotter, R., Vart, P., Jongs, N., McMurray, J. J., Rossing, P., Langkilde, A. M., Sjöström, C. D., Toto, R. D., Wheeler, D. C., Heerspink, H. J. 2023: e028739

  Abstract

  Background The DAPA-CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease) trial (NCT03036150) demonstrated that dapagliflozin reduced the risk of kidney and cardiovascular events in patients with chronic kidney disease and albuminuria with and without type 2 diabetes. We aimed to determine whether baseline cardiovascular medication use modified the dapagliflozin treatment effect. Methods and Results We randomized 4304 adults with baseline estimated glomerular filtration rate 25 to 75 mL/min per 1.73 m2 and urinary albumin:creatinine ratio 200 to 5000 mg/g to dapagliflozin 10 mg or placebo once daily. The primary end point was a composite of ≥50% estimated glomerular filtration rate decline, end-stage kidney disease, and kidney or cardiovascular death. Secondary end points included a kidney composite end point (primary composite end point without cardiovascular death), a cardiovascular composite end point (hospitalized heart failure or cardiovascular death), and all-cause mortality. We categorized patients according to baseline cardiovascular medication use/nonuse. Patients were required by protocol to receive a stable (and maximally tolerated) dose of a renin-angiotensin-aldosterone system inhibitor. We observed consistent benefits of dapagliflozin relative to placebo, irrespective of baseline use/nonuse of renin-angiotensin-aldosterone system inhibitors (98.1%), calcium channel blockers (50.7%), β-adrenergic antagonists (39.0%), diuretics (43.7%), and antithrombotic (47.4%), and lipid-lowering (15.0%) agents. Use of these drugs in combination with dapagliflozin did not increase the number of serious adverse events. Conclusions The safety profile and efficacy of dapagliflozin on kidney and cardiovascular end points in patients with chronic kidney disease were consistent among patients treated and not treated at baseline with a range of cardiovascular medications. Registration Information clinicaltrials.gov. Identifier: NCT03036150.

  View details for DOI 10.1161/JAHA.122.028739

  View details for PubMedID 37119064

• Effects of newer kidney protective agents on kidney endpoints provide implications for future clinical trials. Kidney international Heerspink, H. L., Jongs, N., Neuen, B., Schloemer, P., Vaduganathan, M., Inker, L., Fletcher, R. A., Wheeler, D. C., Bakris, G., Greene, T., Chertow, G. M., Perkovic, V. 2023

  Abstract

  Doubling of serum creatinine (equivalent to a 57% decline in the estimated glomerular filtration rate (eGFR)) is an accepted component of a composite kidney endpoint in clinical trials. Smaller declines in eGFR (40%, 50%) have been applied in several recently conducted clinical trials. Here, we assessed the effects of newer kidney protective agents on endpoints including smaller proportional declines in eGFR to compare relative event rates and the magnitude of observed treatment effects. We performed a post hoc analysis of 4401 patients in the CREDENCE, 4304 in the DAPA-CKD, 5734 in the FIDELIO-DKD, and 3668 in the SONAR trials, which assessed the effects of canagliflozin, dapagliflozin, finerenone and atrasentan in patients with chronic kidney disease. Effects of active therapies versus placebo on alternative composite kidney endpoints incorporating different eGFR decline thresholds (40%, 50%, or 57% eGFR reductions from baseline) with kidney failure or death due to kidney failure were compared Cox-proportional hazards regression models were used to assess and compare treatment effects. During follow-up, event rates were higher for endpoints incorporating smaller versus larger eGFR decline thresholds. Compared to the treatment effects on kidney failure or death due to kidney failure, the magnitude of relative treatment effects was generally similar when considering composite endpoints incorporating smaller declines in eGFR. Hazard ratios for the four interventions ranged from 0.63 to 0.82 for the endpoint incorporating 40% eGFR decline and 0.59 to 0.76 for the endpoint incorporating 57% eGFR decline. Clinical trials incorporating a 40% eGFR decline in a composite endpoint would require approximately half the number of participants compared to 57% eGFR decline with equivalent statistical power. Thus, in populations at high risk of CKD progression, the relative effects of newer kidney protective therapies appear generally similar across endpoints based on varying eGFR decline thresholds.

  View details for DOI 10.1016/j.kint.2023.03.037

  View details for PubMedID 37119876

• Vadadustat for treatment of anemia in patients with dialysis-dependent chronic kidney disease receiving peritoneal dialysis. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association Sarnak, M. J., Agarwal, R., Boudville, N., Chowdhury, P. C., Eckardt, K. U., Gonzalez, C. R., Kooienga, L. A., Koury, M. J., Ntoso, K. A., Luo, W., Parfrey, P. S., Vargo, D. L., Winkelmayer, W. C., Zhang, Z., Chertow, G. M. 2023

  Abstract

  Hypoxia-inducible factor prolyl hydroxylase inhibitors such as vadadustat may provide an oral alternative to injectable erythropoiesis-stimulating agents for treating anemia in patients receiving peritoneal dialysis. In two randomized (1:1), global, phase 3, open-label, sponsor-blind, parallel-group, active-controlled noninferiority trials in patients with dialysis-dependent chronic kidney disease (INNO2VATE), vadadustat was noninferior to darbepoetin alfa with respect to cardiovascular safety and hematological efficacy. Vadadustat's effects in patients receiving only peritoneal dialysis is unclear.We conducted a post hoc analysis of patients in the INNO2VATE trials receiving peritoneal dialysis at baseline. The prespecified primary safety endpoint was time to first major cardiovascular event (MACE; defined as all-cause mortality or nonfatal myocardial infarction or stroke). The primary efficacy endpoint was mean change in hemoglobin from baseline to the primary efficacy period (weeks 24-36).Of the 3923 patients randomized in the two INNO2VATE trials, 309 were receiving peritoneal dialysis (vadadustat, n = 152; darbepoetin alfa, n = 157) at baseline. Time to first MACE was similar in the vadadustat and darbepoetin alfa groups (hazard ratio 1.10; 95% CI 0.62, 1.93). In patients receiving peritoneal dialysis, the difference in mean change in hemoglobin concentrations was -0.10 g/dL (95% CI -0.33, 0.12) in the primary efficacy period. The incidence of treatment-emergent adverse events (TEAEs) was 88.2% versus 95.5%, and serious TEAEs was 52.6% versus 73.2% in the vadadustat and darbepoetin alfa groups, respectively.In the subgroup of patients receiving peritoneal dialysis in the phase 3 INNO2VATE trials, safety and efficacy of vadadustat were similar to darbepoetin alfa.

  View details for DOI 10.1093/ndt/gfad074

  View details for PubMedID 37096396

• Kidney Stone Events after Kidney Transplant in the United States. Clinical journal of the American Society of Nephrology : CJASN Ganesan, C., Holmes, M., Liu, S., Montez-Rath, M., Conti, S., Chang, T. C., Lenihan, C. R., Cheng, X. S., Chertow, G. M., Leppert, J. T., Pao, A. C. 2023

  Abstract

  BACKGROUND: Kidney stone disease is common and can lead to complications such as acute kidney injury, urinary tract obstruction, and urosepsis. In kidney transplant recipients, complications from kidney stone events can also lead to rejection and allograft failure. There is limited information on the incidence of kidney stone events in transplant recipients.METHODS: We identified 83,535 patients from the United States Renal Data System who received their first kidney transplant between January 1st, 2007 and December 31st, 2018. We examined the incidence of kidney stone events and identified risk factors associated with a kidney stone event in the first 3 years after transplantation.RESULTS: We found 1,436 (1.7%) patients who were diagnosed with a kidney stone in the 3 years following kidney transplant. The unadjusted incidence rate for a kidney stone event was 7.8 per 1000 person-years. The median time from transplant to a kidney stone diagnosis was 0.61 (25%,75% range 0.19-1.46) years. Patients with a prior history of kidney stones were at greatest risk for a kidney stone event after transplant (HR 4.65; 95% CI, 3.82-5.65). Other notable risk factors included a diagnosis of gout (HR 1.53; 95% CI, 1.31-1.80), hypertension (HR 1.29; 95% CI, 1.00-1.66), and a dialysis of vintage of > 9 years (HR 1.48; 95% CI, 1.18-1.86; ref vintage < 2.5 years).CONCLUSIONS: Approximately 2% of kidney transplant recipients were diagnosed with a kidney stone in the 3 years following kidney transplant. Risk factors for a kidney stone event include a prior history of kidney stones and longer dialysis vintage.

  View details for DOI 10.2215/CJN.0000000000000176

  View details for PubMedID 37071657

• Estimated Effect of Parathyroidectomy on Long-Term Kidney Function in Adults With Primary Hyperparathyroidism. Annals of internal medicine Seib, C. D., Ganesan, C., Furst, A., Pao, A. C., Chertow, G. M., Leppert, J. T., Suh, I., Montez-Rath, M. E., Harris, A. H., Trickey, A. W., Kebebew, E., Tamura, M. K. 2023

  Abstract

  BACKGROUND: Multidisciplinary guidelines recommend parathyroidectomy to slow the progression of chronic kidney disease in patients with primary hyperparathyroidism (PHPT) and an estimated glomerular filtration rate (eGFR) less than 60mL/min/1.73 m2. Limited data address the effect of parathyroidectomy on long-term kidney function.OBJECTIVE: To compare the incidence of a sustained decline in eGFR of at least 50% among patients with PHPT treated with parathyroidectomy versus nonoperative management.DESIGN: Target trial emulation was done using observational data from adults with PHPT, using an extended Cox model with time-varying inverse probability weighting.SETTING: Veterans Health Administration.PATIENTS: Patients with a new biochemical diagnosis of PHPT in 2000 to 2019.MEASUREMENTS: Sustained decline of at least 50% from pretreatment eGFR.RESULTS: Among 43697 patients with PHPT (mean age, 66.8years), 2928 (6.7%) had a decline of at least 50% in eGFR over a median follow-up of 4.9years. The weighted cumulative incidence of eGFR decline was 5.1% at 5years and 10.8% at 10 years in patients managed with parathyroidectomy, compared with 5.1% and 12.0%, respectively, in those managed nonoperatively. The adjusted hazard of eGFR decline did not differ between parathyroidectomy and nonoperative management (hazard ratio [HR], 0.98 [95% CI, 0.82 to 1.16]). Subgroup analyses found no heterogeneity of treatment effect based on pretreatment kidney function. Parathyroidectomy was associated with a reduced hazard of the primary outcome among patients younger than 60years (HR, 0.75 [CI, 0.59 to 0.93]) that was not evident among those aged 60years or older (HR, 1.08 [CI, 0.87 to 1.34]).LIMITATION: Analyses were done in a predominantly male cohort using observational data.CONCLUSION: Parathyroidectomy had no effect on long-term kidney function in older adults with PHPT. Potential benefits related to kidney function should not be the primary consideration for PHPT treatment decisions.PRIMARY FUNDING SOURCE: National Institute on Aging.

  View details for DOI 10.7326/M22-2222

  View details for PubMedID 37037034

• Effectiveness and Safety of Dapagliflozin for Black vs White Patients With Chronic Kidney Disease in North and South America: A Secondary Analysis of a Randomized Clinical Trial. JAMA network open Vart, P., Jongs, N., Wheeler, D. C., Heerspink, H. J., Langkilde, A. M., Chertow, G. M. 2023; 6 (4): e2310877

  Abstract

  This secondary analysis of a randomized clinical trial investigates the relative effectiveness and safety of the sodium-glucose cotransporter-2 inhibitor dapagliflozin for Black vs White patients with chronic kidney disease (CKD) in North and South America.

  View details for DOI 10.1001/jamanetworkopen.2023.10877

  View details for PubMedID 37103935

• Clinically Indicated, Equitable Care for Ischemic Heart Disease in CKD: A Call to Action. Journal of the American Society of Nephrology : JASN Fielding-Singh, V., Chertow, G. M. 2023; 34 (4): 525-526

  View details for DOI 10.1681/ASN.0000000000000100

  View details for PubMedID 37000953

• Feasibility and Acceptability of SARS-CoV-2 Screening among Patients Receiving Hemodialysis: A Pilot Study. Clinical journal of the American Society of Nephrology : CJASN Anand, S., Montez-Rath, M., Varkila, M., Yu, X., Block, M., Brillhart, S., Leppink, A., Hunsader, P., Owens, D. K., Chertow, G. M., Parsonnet, J., Block, G. 2023

  View details for DOI 10.2215/CJN.0000000000000137

  View details for PubMedID 36976655

• Inaxaplin for Proteinuric Kidney Disease in Persons with Two APOL1 Variants. The New England journal of medicine Egbuna, O., Zimmerman, B., Manos, G., Fortier, A., Chirieac, M. C., Dakin, L. A., Friedman, D. J., Bramham, K., Campbell, K., Knebelmann, B., Barisoni, L., Falk, R. J., Gipson, D. S., Lipkowitz, M. S., Ojo, A., Bunnage, M. E., Pollak, M. R., Altshuler, D., Chertow, G. M., VX19-147-101 Study Group, Aqeel, A., Audard, V., Boffa, J., Bramham, K., Campbell, K., Cheung, C. K., Cortes-Maisonet, G., Derebail, V., Gillespie, A., Greenbaum, L., Khan, N., Luscy, C. P., Mandayam, S., Meyer, J., Raj, D., Rizk, D., Ryu, J., Tumlin, J., Velar, A., Velez, J. C., Waikar, S., Wooldridge, T. 2023; 388 (11): 969-979

  Abstract

  BACKGROUND: Persons with toxic gain-of-function variants in the gene encoding apolipoprotein L1 (APOL1) are at greater risk for the development of rapidly progressive, proteinuric nephropathy. Despite the known genetic cause, therapies targeting proteinuric kidney disease in persons with two APOL1 variants (G1 or G2) are lacking.METHODS: We used tetracycline-inducible APOL1 human embryonic kidney (HEK293) cells to assess the ability of a small-molecule compound, inaxaplin, to inhibit APOL1 channel function. An APOL1 G2-homologous transgenic mouse model of proteinuric kidney disease was used to assess inaxaplin treatment for proteinuria. We then conducted a single-group, open-label, phase 2a clinical study in which inaxaplin was administered to participants who had two APOL1 variants, biopsy-proven focal segmental glomerulosclerosis, and proteinuria (urinary protein-to-creatinine ratio of ≥0.7 to <10 [with protein and creatinine both measured in grams] and an estimated glomerular filtration rate of ≥27 ml per minute per 1.73 m2 of body-surface area). Participants received inaxaplin daily for 13 weeks (15 mg for 2 weeks and 45 mg for 11 weeks) along with standard care. The primary outcome was the percent change from the baseline urinary protein-to-creatinine ratio at week 13 in participants who had at least 80% adherence to inaxaplin therapy. Safety was also assessed.RESULTS: In preclinical studies, inaxaplin selectively inhibited APOL1 channel function in vitro and reduced proteinuria in the mouse model. Sixteen participants were enrolled in the phase 2a study. Among the 13 participants who were treated with inaxaplin and met the adherence threshold, the mean change from the baseline urinary protein-to-creatinine ratio at week 13 was -47.6% (95% confidence interval, -60.0 to -31.3). In an analysis that included all the participants regardless of adherence to inaxaplin therapy, reductions similar to those in the primary analysis were observed in all but 1 participant. Adverse events were mild or moderate in severity; none led to study discontinuation.CONCLUSIONS: Targeted inhibition of APOL1 channel function with inaxaplin reduced proteinuria in participants with two APOL1 variants and focal segmental glomerulosclerosis. (Funded by Vertex Pharmaceuticals; VX19-147-101 ClinicalTrials.gov number, NCT04340362.).

  View details for DOI 10.1056/NEJMoa2202396

  View details for PubMedID 36920755

• Kidney and Cardiovascular Effects of Canagliflozin According to Age and Sex: A Post Hoc Analysis of the CREDENCE Randomized Clinical Trial. American journal of kidney diseases : the official journal of the National Kidney Foundation Yi, T. W., Smyth, B., Di Tanna, G. L., Arnott, C., Cardoza, K., Kang, A., Pollock, C., Agarwal, R., Bakris, G., Charytan, D. M., de Zeeuw, D., Heerspink, H. J., Neal, B., Wheeler, D. C., Cannon, C. P., Zhang, H., Zinman, B., Perkovic, V., Levin, A., Mahaffey, K. W., Jardine, M. 2023

  Abstract

  It is unclear whether the effect of canagliflozin on adverse kidney and cardiovascular events in those with diabetic kidney disease varies by age and sex. We assessed the effects of canagliflozin among age group categories and between sexes in the CREDENCE study.Secondary analysis of a randomized controlled trial.Participants in the CREDENCE trial.Participants were randomly assigned to canagliflozin 100 mg daily or placebo.Primary composite outcome of kidney failure, doubling of serum creatinine, or death due to kidney or cardiovascular disease. Pre-specified secondary and safety outcomes were also analyzed. Outcomes were evaluated by age at baseline (<60, 60-69, and ≥70 years) and sex in the intention-to-treat population using Cox regression models.The mean age of the cohort was 63.0±9.2 years and 34% were female. Older age and female sex were independently associated with a lower risk of the composite of adverse kidney outcomes. There was no evidence that the effect of canagliflozin on the primary outcome (a composite of kidney failure, a doubling of the serum creatinine, or death from kidney or cardiovascular causes) differed between age groups (HR 0.67, 95% CI 0.52 to 0.87; HR 0.63, 95% CI 0.48 to 0.82; and HR 0.89, 95% CI 0.61 to 1.29; for the <60, 60-69, and ≥70 year groups, respectively; Pinteraction=0.3); or among females and males (HR 0.71, 95% CI 0.54 to 0.95; and HR 0.69, 95% CI 0.56 to 0.84, respectively; Pinteraction=0.8). No differences in safety outcomes by age group or sex were observed.This was a post hoc analysis with multiple comparisons.Canagliflozin consistently reduced the relative risk of kidney events in people with diabetic kidney disease in both sexes and across age subgroups. Owing to higher background risk, the absolute reduction in adverse kidney outcomes was greater in younger participants.

  View details for DOI 10.1053/j.ajkd.2022.12.015

  View details for PubMedID 36889425

• Class I and II Human Leukocyte Antigen Serotypes Associated with End-Stage Kidney Disease due to Membranoproliferative Glomerulonephritis and Dense Deposit Disease Afolabi, H., Zhang, B., O'Shaughnessy, M., Chertow, G., Lafayette, R., Charu, V. ELSEVIER SCIENCE INC. 2023: S1422-S1423

  View details for Web of Science ID 000990969803123

• The potential roles of galectin-3 in AKI and CKD. Frontiers in physiology Wang, F., Zhou, L., Eliaz, A., Hu, C., Qiang, X., Ke, L., Chertow, G., Eliaz, I., Peng, Z. 2023; 14: 1090724

  Abstract

  Acute kidney injury (AKI) is a common condition with high morbidity and mortality, and is associated with the development and progression of chronic kidney disease (CKD). The beta-galactoside binding protein galectin-3 (Gal3), with its proinflammatory and profibrotic properties, has been implicated in the development of both AKI and CKD. Serum Gal3 levels are elevated in patients with AKI and CKD, and elevated Gal3 is associated with progression of CKD. In addition, Gal3 is associated with the incidence of AKI among critically ill patients, and blocking Gal3 in murine models of sepsis and ischemia-reperfusion injury results in significantly lower AKI incidence and mortality. Here we review the role of Gal3 in the pathophysiology of AKI and CKD, as well as the therapeutic potential of targeting Gal3.

  View details for DOI 10.3389/fphys.2023.1090724

  View details for PubMedID 36909244

  View details for PubMedCentralID PMC9995706

• Use of wastewater metrics to track COVID-19 in the U.S.: a national time-series analysis over the first three quarters of 2022. medRxiv : the preprint server for health sciences Varkila, M., Montez-Rath, M., Salomon, J., Yu, X., Block, G., Owens, D. K., Chertow, G. M., Parsonnet, J., Anand, S. 2023

  Abstract

  Widespread use of at-home COVID-19 tests hampers determination of community COVID-19 incidence. Using nationwide data available through the US National Wastewater Surveillance System, we examined the performance of two wastewater metrics in predicting high case and hospitalizations rates both before and after widespread use of at-home tests.We performed area under the receiver operating characteristic (ROC) curve analysis (AUC) for two wastewater metrics-viral concentration relative to the peak of January 2022 ("wastewater percentile") and 15-day percent change in SARS-CoV-2 ("percent change"). Dichotomized reported cases (≥ 200 or <200 cases per 100,000) and new hospitalizations (≥ 10 or <10 per 100,000) were our dependent variables, stratified by calendar quarter. Using logistic regression, we assessed the performance of combining wastewater metrics.Among 268 counties across 22 states, wastewater percentile detected high reported case and hospitalizations rates in the first quarter of 2022 (AUC 0.95 and 0.86 respectively) whereas the percent change did not (AUC 0.54 and 0.49 respectively). A wastewater percentile of 51% maximized sensitivity (0.93) and specificity (0.82) for detecting high case rates. A model inclusive of both metrics performed no better than using wastewater percentile alone. The predictive capability of wastewater percentile declined over time (AUC 0.84 and 0.72 for cases for second and third quarters of 2022).Nationwide, county wastewater levels above 51% relative to the historic peak predicted high COVID rates and hospitalization in the first quarter of 2022, but performed less well in subsequent quarters. Decline over time in predictive performance of this metric likely reflects underreporting of cases, reduced testing, and possibly lower virulence of infection due to vaccines and treatments.

  View details for DOI 10.1101/2023.02.06.23285542

  View details for PubMedID 36798337

  View details for PubMedCentralID PMC9934789

• Cardiovascular Drug Use After Acute Kidney Injury Among Hospitalized Patients With a History of Myocardial Infarction. Kidney international reports Meraz-Muñoz, A. Y., Jeyakumar, N., Luo, B., Beaubien-Souligny, W., Chanchlani, R., Clark, E. G., Harel, Z., Kitchlu, A., Neyra, J. A., Zappitelli, M., Chertow, G. M., Garg, A. X., Wald, R., Silver, S. A. 2023; 8 (2): 294-304

  Abstract

  Patients who survive acute kidney injury (AKI) may receive fewer cardioprotective drugs. Our objective was to measure the difference in time to dispensing of evidence-based cardiovascular drugs in patients with a history of myocardial infarction (MI) with and without AKI.This was a population-based cohort study of patients 66 years of age and older with a history of MI who survived a hospitalization complicated with AKI, propensity-score matched to patients without AKI. The primary outcome was time to outpatient dispensing of an angiotensin-converting enzyme inhibitor (ACEi)/angiotensin II receptor blocker (ARB), statin, or β-blocker within 1 year of hospital discharge.We identified 28,871 patients with AKI, of whom 21,452 were matched 1:1 to patients without AKI. In the matched cohort, mean age was 80 years, 40% were female, and 34% had an MI during the index hospitalization. AKI was associated with less frequent dispensing of all 3 cardiovascular drug classes within 1 year of hospital discharge (subdistribution hazard ratio [sHR], 0.93; 95% confidence interval [CI], 0.91-0.95). This association was most pronounced in patients with stage 2 (sHR, 0.81; 95% CI, 0.75-0.88) and stage 3 (sHR, 0.71; 95% CI, 0.64-0.79) AKI. We observed less frequent dispensing of statins in patients with stage 2 (sHR, 0.87; 95% CI, 0.81-0.92) and stage 3 (sHR, 0.85; 95% CI, 0.78-0.93) AKI and less frequent dispensing of β-blockers in patients with stage 3 AKI (sHR, 0.86; 95% CI, 0.79-0.94).In patients with a history of MI, survivors of AKI were less likely to receive prescriptions for ACEi/ARB, statins, or β-blockers within 1 year of hospital discharge. This association was most pronounced in patients with stages 2 and 3 AKI.

  View details for DOI 10.1016/j.ekir.2022.10.027

  View details for PubMedID 36815105

  View details for PubMedCentralID PMC9939314

• Efficacy of Dapagliflozin by Baseline Diabetes Medications: A Prespecified Analysis From the DAPA-CKD Study. Diabetes care Beernink, J. M., Persson, F., Jongs, N., Laverman, G. D., Chertow, G. M., McMurray, J. J., Langkilde, A. M., Correa-Rotter, R., Rossing, P., Sjostrom, C. D., Toto, R. D., Wheeler, D. C., Heerspink, H. J. 2023

  Abstract

  OBJECTIVE: To determine whether the benefits of dapagliflozin in patients with type 2 diabetes and chronic kidney disease (CKD) in the Dapagliflozin And Prevention of Adverse Outcomes in CKD trial (DAPA-CKD) varied by background glucose-lowering therapy (GLT).RESEARCH DESIGN AND METHODS: We randomized 4,304 adults (including 2,906 with type 2 diabetes) with a baseline estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio of 200-5,000 mg/g to dapagliflozin 10 mg or placebo once daily (NCT03036150). The primary end point was a composite of ≥50% eGFR decline, end-stage kidney disease, and kidney or cardiovascular cause of death. Secondary end points included a kidney composite end point (primary composite end point without cardiovascular death), a cardiovascular composite end point (hospitalized heart failure or cardiovascular death), and all-cause mortality. In this prespecified analysis, we investigated the effects of dapagliflozin on these and other outcomes according to baseline GLT class or number of GLTs.RESULTS: The effects of dapagliflozin on the primary composite outcome were consistent across GLT classes and according to the number of GLTs (all interaction P > 0.08). Similarly, we found consistent benefit of dapagliflozin compared with placebo on the secondary end points regardless of background GLT class or number of GLTs. The same applied to the rate of decline in the eGFR rate and safety end points. Dapagliflozin reduced the initiation of insulin therapy during follow-up compared with placebo (hazard ratio 0.72; 95% CI 0.54-0.96; P = 0.025).CONCLUSIONS: Dapagliflozin reduced kidney and cardiovascular events in patients with type 2 diabetes and CKD across baseline GLT class or classes in combination.

  View details for DOI 10.2337/dc22-1514

  View details for PubMedID 36662635

• Association of Pretransplant Coronary Heart Disease Testing With Early Kidney Transplant Outcomes. JAMA internal medicine Cheng, X. S., Liu, S., Han, J., Stedman, M. R., Baiocchi, M., Tan, J. C., Chertow, G. M., Fearon, W. F. 2023

  Abstract

  Importance: Testing for coronary heart disease (CHD) in asymptomatic kidney transplant candidates before transplant is widespread and endorsed by various professional societies, but its association with perioperative outcomes is unclear.Objective: To estimate the association of pretransplant CHD testing with rates of death and myocardial infarction (MI).Design, Setting, and Participants: This retrospective cohort study included all adult, first-time kidney transplant recipients from January 2000 through December 2014 in the US Renal Data System with at least 1 year of Medicare enrollment before and after transplant. An instrumental variable (IV) analysis was used, with the program-level CHD testing rate in the year of the transplant as the IV. Analyses were stratified by study period, as the rate of CHD testing varied over time. A combination of US Renal Data System variables and Medicare claims was used to ascertain exposure, IV, covariates, and outcomes.Exposures: Receipt of nonurgent invasive or noninvasive CHD testing during the 12 months preceding kidney transplant.Main Outcomes and Measures: The primary outcome was a composite of death or acute MI within 30 days of after kidney transplant.Results: The cohort comprised 79 334 adult, first-time kidney transplant recipients (30 147 women [38%]; 25 387 [21%] Black and 48 394 [61%] White individuals; mean [SD] age of 56 [14] years during 2012 to 2014). The primary outcome occurred in 4604 patients (244 [5.3%]; 120 [2.6%] death, 134 [2.9%] acute MI). During the most recent study period (2012-2014), the CHD testing rate was 56% in patients in the most test-intensive transplant programs (fifth IV quintile) and 24% in patients at the least test-intensive transplant program (first IV quintile, P<.001); this pattern was similar across other study periods. In the main IV analysis, compared with no testing, CHD testing was not associated with a change in the rate of primary outcome (rate difference, 1.9%; 95% CI, 0%-3.5%). The results were similar across study periods, except for 2000 to 2003, during which CHD testing was associated with a higher event rate (rate difference, 6.8%; 95% CI, 1.8%-12.0%).Conclusions and Relevance: The results of this cohort study suggest that pretransplant CHD testing was not associated with a reduction in early posttransplant death or acute MI. The study findings potentially challenge the ubiquity of CHD testing before kidney transplant and should be confirmed in interventional studies.

  View details for DOI 10.1001/jamainternmed.2022.6069

  View details for PubMedID 36595271

• Potassium reduction with sodium zirconium cyclosilicate in patients with heart failure. ESC heart failure Tardif, J., Rouleau, J., Chertow, G. M., Al-Shurbaji, A., Lisovskaja, V., Gustavson, S., Zhao, Y., Bouabdallaoui, N., Desai, A. S., Chernyavskiy, A., Evsina, M., Merkely, B., McMurray, J. J., Pfeffer, M. A. 2022

  Abstract

  AIMS: Several patients with heart failure and reduced ejection fraction (HFrEF) do not receive renin-angiotensin-aldosterone system (RAAS) inhibitors at the recommended dose or at all, frequently due to actual or feared hyperkalaemia. Sodium zirconium cyclosilicate (SZC) is an orally administered non-absorbed intestinal potassium binder proven to lower serum potassium concentrations.METHODS AND RESULTS: PRIORITIZE-HF was an international, multicentre, parallel-group, randomized, double-blind, placebo-controlled study to evaluate the benefits and risks of using SZC to intensify RAAS inhibitor therapy. Patients with symptomatic HFrEF were eligible and randomly assigned to receive SZC 5g or placebo once daily for 12weeks. Doses of study medication and RAAS inhibitors were titrated during the treatment period. The primary endpoint was the proportion of patients at 12weeks in the following categories: (i) any RAAS inhibitor at less than target dose, and no MRA; (ii) any RAAS inhibitor at target dose and no MRA; (ii) MRA at less than target dose; and (iv) MRA at target dose. Due to challenges in participant management related to the COVID-19 pandemic, the study was prematurely terminated with 182 randomized patients. There was no statistically significant difference in the distribution of patients by RAAS inhibitor treatment categories at 3months (P=0.43). The proportion of patients at target MRA dose was numerically higher in the SZC group (56.4%) compared with the placebo group (47.0%). Overall, SZC was well tolerated.CONCLUSIONS: PRIORITIZE-HF was terminated prematurely due to COVID-19 and did not demonstrate a statistically significant increase in the intensity of RAAS inhibitor therapies with the potassium-reducing agent SZC compared with placebo.

  View details for DOI 10.1002/ehf2.14268

  View details for PubMedID 36564955

• Effects of Dapagliflozin on Hospitalizations in Patients With Chronic Kidney Disease : A Post Hoc Analysis of DAPA-CKD. Annals of internal medicine Schechter, M., Jongs, N., Chertow, G. M., Mosenzon, O., McMurray, J. J., Correa-Rotter, R., Rossing, P., Langkilde, A. M., Sjöström, C. D., Toto, R. D., Wheeler, D. C., Heerspink, H. J. 2022

  Abstract

  Acute hospitalizations are common in patients with chronic kidney disease (CKD) and often lead to decreases in health-related quality of life and increased care costs.To determine the effects of dapagliflozin on first hospitalizations and all (first and subsequent) hospitalizations and to explore effects on cause-specific hospitalizations.Post hoc analysis of a randomized, double-blind, placebo-controlled clinical trial. (ClinicalTrials.gov: NCT03036150).386 ambulatory practice sites in 21 countries from 2 February 2017 through 12 June 2020.Adults with an estimated glomerular filtration rate of 25 to 75 mL/min/1.73 m2 and a urinary albumin-creatinine ratio of 200 to 5000 mg/g, with and without type 2 diabetes.Dapagliflozin, 10 mg once daily, or matching placebo (1:1 ratio).The effects of dapagliflozin on first hospitalizations for any cause, all hospitalizations, and cause-specific (first and recurrent) hospitalizations were determined. The reported system organ class was used to evaluate reasons for admission. Hospitalizations were analyzed using Cox proportional hazards regression models (first hospitalization), the Lin-Wei-Yang-Ying method (all hospitalizations or death), and negative binomial models (cause-specific hospitalizations).The study included 4304 patients (mean age, 61.8 years; 33.1% women). During a median follow-up of 2.4 years, 2072 hospitalizations were reported among 1224 (28.4%) participants. Compared with placebo, dapagliflozin reduced risk for a first hospitalization (hazard ratio, 0.84 [95% CI, 0.75 to 0.94]) and all hospitalizations or death (rate ratio, 0.79 [CI, 0.70 to 0.89]). There was no evidence that the effects of dapagliflozin on first and all hospitalizations varied by baseline presence of type 2 diabetes (P for interaction = 0.60 for each). Compared with placebo, dapagliflozin reduced the rate of admissions due to cardiac disorders, renal and urinary disorders, metabolism and nutrition disorders, and neoplasms.This was a post hoc analysis and should be viewed as hypothesis-generating. Hospitalizations and causes were reported by site investigators and were not centrally adjudicated.Dapagliflozin reduced the risk for hospitalization for any cause in patients with CKD with and without type 2 diabetes.AstraZeneca.

  View details for DOI 10.7326/M22-2115

  View details for PubMedID 36469914

• Association between cause of kidney failure and fracture incidence in a national US dialysis population cohort study. Clinical kidney journal Ziolkowski, S., Liu, S., Montez-Rath, M. E., Denburg, M., Winkelmayer, W. C., Chertow, G. M., O'Shaughnessy, M. M. 2022; 15 (12): 2245-2257

  Abstract

  Whether fracture rates, overall and by fracture site, vary by cause of kidney failure in patients receiving dialysis is unknown.Using the US Renal Data System, we compared fracture rates across seven causes of kidney failure in patients who started dialysis between 1997 and 2014. We computed unadjusted and multivariable adjusted proportional sub-distribution hazard models, with fracture events (overall, and by site) as the outcome and immunoglobulin A nephropathy as the reference group. Kidney transplantation and death were competing events.Among 491 496 individuals, with a median follow-up of 2.0 (25%, 75% range 0.9-3.9) years, 62 954 (12.8%) experienced at least one fracture. Patients with diabetic nephropathy, vasculitis or autosomal polycystic kidney disease (ADPKD) had the highest (50, 46 and 40 per 1000 person-years, respectively), and patient with lupus nephritis had the lowest (20 per 1000 person-years) fracture rates. After multivariable adjustment, diabetic nephropathy [hazard ratio (HR) 1.43, 95% confidence interval 1.33-1.53], ADPKD (HR 1.37, 1.26-1.48), vasculitis (HR 1.22, 1.09-1.34), membranous nephropathy (HR 1.16, 1.02-1.30) and focal segmental glomerulosclerosis (FSGS) (HR 1.13, 1.02-1.24) were associated with a significantly higher, and lupus nephritis with a significantly lower (HR 0.85, 0.71-0.98) fracture hazard. The hazards for upper extremity and lower leg fractures were significantly higher in diabetic nephropathy, ADPKD, FSGS and membranous nephropathy, while the hazard for vertebral fracture was significantly higher in vasculitis. Our findings were limited by the lack of data on medication use and whether fractures were traumatic or non-traumatic, among other factors.Fracture risk, overall and by fracture site, varies by cause of end-stage kidney disease. Future work to determine underlying pathogenic mechanisms contributing to differential risks might inform more tailored treatment strategies. Our study was limited by lack of data regarding numerous potential confounders or mediators including medications and measures or bone biomarkers.

  View details for DOI 10.1093/ckj/sfac193

  View details for PubMedID 36381373

  View details for PubMedCentralID PMC9664571

• Overall Adverse Event Profile of Vadadustat for the Treatment of Anemia Associated With Chronic Kidney Disease in Phase 3 Trials AMERICAN JOURNAL OF NEPHROLOGY Agarwal, R., Anand, S., Eckardt, K., Luo, W., Parfrey, P. S., Sarnak, M. J., Solinsky, C. M., Vargo, D. L., Winkelmayer, W. C., Chertow, G. M. 2022

  Abstract

  Anemia frequently occurs in chronic kidney disease (CKD), is associated with poor quality of life and cardiovascular outcomes, and its treatment represents a considerable economic burden to the healthcare system. Although effective, the current standard of care for the treatment of anemia in chronic kidney disease patients with erythropoiesis-stimulating agents requires chronic/ongoing injections, making the treatment less accessible or desirable to patients not treated by in-center maintenance hemodialysis. Furthermore, safety concerns, including an increased risk of cardiovascular events and mortality, have emerged from their use in studies targeting hemoglobin concentrations in the normal or near-normal range. The orally active hypoxia-inducible factor prolyl hydroxylase inhibitor vadadustat may offer advantages over erythropoiesis-stimulating agents by correcting anemia via pathways activating endogenous erythropoietin production, with fewer excursions of hemoglobin concentrations above the target range.To comprehensively analyze the safety profile of vadadustat in patients with CKD-related anemia, we pooled the safety populations from each of the four trials in the phase 3 clinical program (n=7373) and compared the risk of treatment-emergent adverse events (TEAEs) for each treatment arm.In patients randomized to vadadustat vs darbepoetin alfa, rates of TEAEs (88.9% vs 89.3%), treatment-emergent serious adverse events (58.0% vs. 59.3%), and TEAEs leading to death (16.1% vs 16.2%) were similar, as were rates of adverse events of special interest, including cardiovascular-, hepatic-, and neoplasm-related adverse events.Among patients with CKD-related anemia treated with vadadustat, we observed similar rates of adverse events relative to those treated with darbepoetin alfa.

  View details for DOI 10.1159/000528443

  View details for Web of Science ID 000892801700001

  View details for PubMedID 36450264

• Estimated Lifetime Benefit of Combined RAAS and SGLT2 Inhibitor Therapy in Patients with Albuminuric CKD without Diabetes. Clinical journal of the American Society of Nephrology : CJASN Vart, P., Vaduganathan, M., Jongs, N., Remuzzi, G., Wheeler, D. C., Hou, F. F., McCausland, F., Chertow, G. M., Heerspink, H. J. 2022

  Abstract

  BACKGROUND AND OBJECTIVES: Despite high rates of complications in patients with CKD without diabetes, the implementation of proven therapies in this group remains low. Expressing the clinical benefit of a therapy in terms of extra years free from the disease or death may facilitate implementation. We estimated lifetime survival free of kidney failure for patients with albuminuric CKD without diabetes treated with the combination therapy of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and sodium-glucose cotransporter-2 (SGLT2) inhibitors relative to patients not treated.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used trial-level estimates of the effect of treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ramipril/benazepril; n=690) and SGLT2 inhibitors (dapagliflozin; n=1398) compared with placebo to derive the effect of combination therapy versus no treatment. Using this effect, we estimated treatment effect of combination therapy to the active treatment group of patients with albuminuric CKD without diabetes participating in the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial (n=697) and projected eventfree and overall survival for those treated and not treated with combination therapy. We also performed our calculations anticipating lower adherence and less pronounced benefits than were observed in the clinical trials. The primary outcome was a composite of doubling of serum creatinine, kidney failure, or death.RESULTS: The aggregate estimated hazard ratio comparing combination therapy with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and SGLT2 inhibitor versus no treatment for the primary end point was 0.35 (95% confidence interval, 0.30 to 0.41). For a 50-year-old patient until the age of 75 years, the estimated survival free from the primary composite end point was 17.0 (95% confidence interval, 12.4 to 19.6) years with the combination therapy and 9.6 years (95% confidence interval, 8.4 to 10.7) with no treatment with any of these agents, corresponding to a gain in eventfree survival of 7.4 (95% confidence interval, 6.4 to 8.7) years. When assuming lower adherence and less pronounced efficacy of combination therapy, the gain in eventfree survival ranged from 5.3 years (95% confidence interval, 4.4 to 6.1) to 5.8 years (95% confidence interval, 4.8 to 6.8).CONCLUSIONS: Treatment with the combination of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and SGLT2 inhibitor in patients with albuminuric CKD without diabetes is expected to substantially increase kidney failure-free survival.CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Benazepril for Advanced Chronic Renal Insufficiency, NCT00270426, and a Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients with Chronic Kidney Disease (Dapa-CKD), NCT03036150.

  View details for DOI 10.2215/CJN.08900722

  View details for PubMedID 36414316

• Effects of Bardoxolone Methyl in Alport Syndrome. Clinical journal of the American Society of Nephrology : CJASN Warady, B. A., Pergola, P. E., Agarwal, R., Andreoli, S., Appel, G. B., Bangalore, S., Block, G. A., Chapman, A. B., Chin, M. P., Gibson, K. L., Goldsberry, A., Iijima, K., Inker, L. A., Kashtan, C. E., Knebelmann, B., Mariani, L. H., Meyer, C. J., Nozu, K., O'Grady, M., Rheault, M. N., Silva, A. L., Stenvinkel, P., Torra, R., Chertow, G. M. 2022

  Abstract

  BACKGROUND AND OBJECTIVES: Alport syndrome is an inherited disease characterized by progressive loss of kidney function. We aimed to evaluate the safety and efficacy of bardoxolone methyl in patients with Alport syndrome.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We randomly assigned patients with Alport syndrome, ages 12-70 years and eGFR 30-90 ml/min per 1.73 m2, to bardoxolone methyl (n=77) or placebo (n=80). Primary efficacy end points were change from baseline in eGFR at weeks 48 and 100. Key secondary efficacy end points were change from baseline in eGFR at weeks 52 and 104, after an intended 4 weeks off treatment. Safety was assessed by monitoring for adverse events and change from baseline in vital signs, 12-lead electrocardiograms, laboratory measurements (including, but not limited to, aminotransferases, urinary albumin-creatinine ratio, magnesium, and B-type natriuretic peptide), and body weight.RESULTS: Patients randomized to bardoxolone methyl experienced preservation in eGFR relative to placebo at 48 and 100 weeks (between-group differences: 9.2 [97.5% confidence interval, 5.1 to 13.4; P<0.001] and 7.4 [95% confidence interval, 3.1 to 11.7; P=0.0008] ml/min per 1.73 m2, respectively). After a 4-week off-treatment period, corresponding mean differences in eGFR were 5.4 (97.5% confidence interval, 1.8 to 9.1; P<0.001) and 4.4 (95% confidence interval, 0.7 to 8.1; P=0.02) ml/min per 1.73 m2 at 52 and 104 weeks, respectively. In a post hoc analysis with no imputation of missing eGFR data, the difference at week 104 was not statistically significant (1.5 [95% confidence interval, -1.9 to 4.9] ml/min per 1.73 m2). Discontinuations from treatment were more frequent among patients randomized to bardoxolone methyl; most discontinuations were due to protocol-specified criteria being met for increases in serum transaminases. Serious adverse events were more frequent among patients randomized to placebo. Three patients in each group developed kidney failure.CONCLUSIONS: In adolescent and adult patients with Alport syndrome receiving standard of care, treatment with bardoxolone methyl resulted in preservation in eGFR relative to placebo after a 2-year study period; off-treatment results using all available data were not significantly different.CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: A Phase 2/3 Trial of the Efficacy and Safety of Bardoxolone Methyl in Patients with Alport Syndrome - CARDINAL (CARDINAL), NCT03019185.

  View details for DOI 10.2215/CJN.02400222

  View details for PubMedID 36411058

• Apixaban for Patients with Atrial Fibrillation on Hemodialysis: A Multicenter Randomized Controlled Trial. Circulation Pokorney, S. D., Chertow, G. M., Al-Khalidi, H. R., Gallup, D., Dignaco, P., Mussina, K., Bansal, N., Gadegbeku, C. A., Garcia, D. A., Garonzik, S., Lopes, R. D., Mahaffey, K. W., Matsuda, K., Middleton, J. P., Rymer, J. A., Sands, G. H., Thadhani, R., Thomas, K. L., Washam, J. B., Winkelmayer, W. C., Granger, C. B. 2022

  Abstract

  BACKGROUND: There is no randomized data evaluating the safety or efficacy of apixaban for stroke prevention in patients with end-stage kidney disease (ESKD) on hemodialysis and with atrial fibrillation (AF).METHODS: The RENAL-AF trial was a prospective, randomized, open-label, blinded-outcome evaluation (PROBE) of apixaban versus warfarin in patients receiving hemodialysis with AF and CHA2DS2-VASc score ≥2. Patients were randomized 1:1 to apixaban 5mg twice daily (2.5mg twice daily with age ≥80 years and/or weight ≤60kg) or dose-adjusted warfarin. The primary outcome was time to major or clinically relevant non-major bleeding. Secondary outcomes included stroke, mortality, and apixaban pharmacokinetics. Pharmacokinetic sampling was day 1, day 3, and month 1.RESULTS: From January 2017 through January 2019, 154 patients were randomized to apixaban (n=82) or warfarin (n=72). The trial stopped prematurely due to enrollment challenges. Time in therapeutic range (INR 2.0-3.0) for warfarin-treated patients was 44% (interquartile range; 23-59%). The 1-year rates for major or clinically relevant non-major bleeding were 32% and 26% in apixaban and warfarin groups, respectively (HR 1.20, 95% CI 0.63-2.30), while 1-year rates for stroke or systemic embolism were 3.0% and 3.3% in apixaban and warfarin groups, respectively. Death was the most common major event in the apixaban (21 patients [26%]) and warfarin (13 patients [18%]) arms. The pharmacokinetic substudy enrolled the target 50 patients. Median steady state 12-hour area under the curve (AUC0-12) was 2,475 ng-h/mL (10th-90th percentiles 1,342-3,285) for 5mg apixaban twice daily and 1,269 ng-h/mL (10th-90th percentiles 615-1,946) for 2.5mg apixaban twice daily. There was substantial overlap between minimum apixaban blood concentration, 12-hour AUC0-12, and maximum apixaban blood concentration for patients with and without a major or clinically relevant non-major bleeding events.CONCLUSIONS: There was inadequate power to draw any conclusion regarding rates of major or clinically relevant non-major bleeding comparing apixaban and warfarin in patients with AF and ESKD on hemodialysis. Clinically relevant bleeding events were approximately 10-fold more frequent than stroke or systemic embolism among this population on anticoagulation, highlighting the need for future randomized studies evaluating the risks versus benefits of anticoagulation among patients with AF and ESKD on hemodialysis.

  View details for DOI 10.1161/CIRCULATIONAHA.121.054990

  View details for PubMedID 36335914

• Risks for Anaphylaxis With Intravenous Iron Formulations. Annals of internal medicine Dave, C. V., Brittenham, G. M., Carson, J. L., Setoguchi, S. 2022; 175 (11): W143-W144

  View details for DOI 10.7326/L22-0283

  View details for PubMedID 36375166

• A Phase 2b Randomized Controlled Trial of Selonsertib in Moderate to Severe Diabetic Kidney Disease (MOSAIC) Perkovic, V., Tuttle, K. R., Pergola, P. E., Mahaffey, K. W., Patel, U. D., Ishida, J. H., Chen, F., Crans, G., Kustra, R., Trivedi, M., Heerspink, H. L., Rossing, P., Kashihara, N., Chertow, G. AMER SOC NEPHROLOGY. 2022: 28

  View details for Web of Science ID 001261054400095

• Association Between Cause of Kidney Failure and Fracture Incidence in a National US Dialysis Population Cohort Study Ziolkowski, S., Liu, S., Montez-Rath, M. E., Denburg, M., Winkelmayer, W. C., Chertow, G., O'Shaughnessy, M. M. AMER SOC NEPHROLOGY. 2022: 652

  View details for Web of Science ID 001261054404215

• Effects of Dapagliflozin in People without Diabetes and with Microalbuminuria. Clinical journal of the American Society of Nephrology : CJASN Heerspink, H. J., Chertow, G. M., Jongs, N., Correa-Rotter, R., Rossing, P., Sjöström, C. D., Langkilde, A. M., Wheeler, D. C. 2022; 17 (11): 1665-1668

  View details for DOI 10.2215/CJN.07290622

  View details for PubMedID 36344217

• Risks for Anaphylaxis With Intravenous Iron Formulations. Annals of internal medicine Al-Samkari, H., Glaspy, J. A., Means, R. T., Chertow, G. M., Auerbach, M. 2022; 175 (11): W143

  View details for DOI 10.7326/L22-0282

  View details for PubMedID 36375165

• National Imaging Trends for Suspected Urinary Stone Disease in the Emergency Department. JAMA internal medicine Ganesan, C., Stedman, M. R., Liu, S., Conti, S. L., Chertow, G. M., Leppert, J. T., Pao, A. C. 2022

  View details for DOI 10.1001/jamainternmed.2022.4939

  View details for PubMedID 36315134

• APOL1 G3 Variant Is Associated with Cardiovascular Mortality and Sudden Cardiac Death in Patients Receiving Maintenance Hemodialysis of European Ancestry. Cardiorenal medicine Schwantes-An, T., Robinson-Cohen, C., Liu, S., Zheng, N., Stedman, M., Wetherill, L., Edenberg, H. J., Vatta, M., Foroud, T. M., Chertow, G. M., Moe, S. M. 2022: 1-7

  Abstract

  INTRODUCTION: The G1 and G2 variants in the APOL1 gene convey high risk for the progression of chronic kidney disease in African Americans. The G3 variant in APOL1 is more common in patients of European ancestry (EA); outcomes associated with this variant have not been explored previously in EA patients receiving dialysis.METHODS: DNA was collected from approximately half of the patients enrolled in the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) trial and genotyped for the G3 variants. We utilized an additive genetic model to test associations of G3 with the EVOLVE adjudicated endpoints of all-cause mortality, cardiovascular mortality, sudden cardiac death (SCD), and heart failure. EA and African ancestry samples were analyzed separately. Validation was done in the Vanderbilt BioVU using ICD codes for cardiovascular events that parallel the adjudicated endpoints in EVOLVE.RESULTS: In EVOLVE, G3 in EA patients was associated with the adjudicated endpoints of cardiovascular mortality and SCD. In a validation cohort from the Vanderbilt BioVU, cardiovascular events and cardiovascular mortality defined by ICD codes showed similar associations in EA participants who had been on dialysis for 2 to <5 years.DISCUSSION/CONCLUSIONS: G3 in APOL1 variant was associated with cardiovascular events and cardiovascular mortality in the EA patients receiving dialysis. This suggests that variations in the APOL1 gene that differ in populations of different ancestry may contribute to cardiovascular disease.

  View details for DOI 10.1159/000525448

  View details for PubMedID 36310009

• Extrapolated longer-term effects of the DAPA-CKD trial: a modelling analysis. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association McEwan, P., Boyce, R., Sanchez, J. J., Sjostrom, C. D., Stefansson, B., Nolan, S., Correa-Rotter, R., Rossing, P., Chertow, G. M., McMurray, J. J., Wheeler, D. C., Heerspink, H. J. 2022

  Abstract

  BACKGROUND: The Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial assessed dapagliflozin versus placebo, in addition to standard therapy, in patients with chronic kidney disease (CKD) and albuminuria, and was terminated prematurely due to overwhelming efficacy. The study objective was to model the long-term clinical outcomes of DAPA-CKD beyond the trial follow-up.METHODS: A Markov model extrapolated event incidence per 1000 patients and CKD progression rates for patients receiving dapagliflozin or placebo over a 10-year time horizon. We derived treatment-specific CKD stage transition matrices using DAPA-CKD trial data. We extrapolated relevant efficacy endpoints using parametric survival equations for all-cause mortality and generalized estimating equations for recurrent events.RESULTS: When extrapolated over a 10-year period, patients randomized to dapagliflozin spent more time in CKD stages 1-3 and less in stages 4-5 than placebo [0.65 (95% CrI 0.41, 0.90) and -0.23 (95% CrI -0.45, 0.00) years per patient, respectively]. Dapagliflozin prevented an estimated 83 deaths and 51 patients initiating kidney replacement therapy per 1000 patients over 10 years. Predicted rates of hospitalized heart failure and abrupt declines in kidney function were reduced (19 and 39 estimated events per 1000 patients, respectively).CONCLUSIONS: Adding dapagliflozin to standard therapeutic management of CKD is expected to have long-term cardiorenal benefit beyond what has been demonstrated in the DAPA-CKD trial, with patients predicted to live longer with fewer complications.

  View details for DOI 10.1093/ndt/gfac280

  View details for PubMedID 36301617

• Effects of Dapagliflozin in People without Diabetes and with Microalbuminuria CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Heerspink, H. L., Chertow, G. M., Jongs, N., Correa-Rotter, R., Rossing, P., Sjostrom, C., Langkilde, A., Wheeler, D. C., DAPA CKD Trial Comm 2022

  View details for DOI 10.2215/CJN.07290622

  View details for Web of Science ID 000863520500001

• EFFECTS OF DAPAGLIFLOZIN IN PATIENTS WITH CHRONIC KIDNEY DISEASE AND ALBUMINURIA, WITH AND WITHOUT DIABETES, BY USE AND NON-USE OF CARDIOVASCULAR MEDICATIONS: DAPA-CKD TRIAL Correa-Rotter, R., Chertow, G., Mark, P., Nowicki, M., Vart, P., Niels, J., Langkilde, A., Mcmurray, J., Rossing, P., Sjostrom, C., Stefansson, B., Toto, R., Wheeler, D., Heerspink, H. WILEY. 2022: 31

  View details for Web of Science ID 000864433100054

• Effects of dapagliflozin on cardiovascular and kidney events by baseline eGFR and UACR in patients with type 2 diabetes mellitus: a patient-level pooled analysis of DECLARE-TIMI 58 and DAPA-CKD trials Moura, F., Wiviott, S., Chertow, G., Dwyer, J., Gause-Nilsson, Johansson, P., Langkilde, A., McMurray, J., Mosenzon, O., Raz, Rossing, P., Wheeler, D., Sabatine, M., Heerspink, H. OXFORD UNIV PRESS. 2022: 2407

  View details for Web of Science ID 000894947901652

• Testosterone concentrations andoutcomes in hemodialysis patients of the EVOLVE trial. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association Nilsson, E., Stenvinkel, P., Liu, S., Stedman, M. R., Chertow, G. M., Floege, J. 2022

  Abstract

  Hypogonadism is common in end-stage kidney disease and may contribute to morbidity and mortality.Using data from the randomized controlled EVOLVE trial of cinacalcet, we analyzed the associations of total testosterone, free testosterone, and sex-hormone binding globulin (SHBG) serum concentrations with mortality and major cardiovascular events in 1692 men and 1059 women receiving hemodialysis. We also describe the effect of cinacalcet treatment on serum concentrations of testosterone.Among men, lower serum free testosterone (OR 0.18 95%, CI 0.04-0.82, p = 0.026) and higher SHBG (OR 1.05 per 10 nmol/L, 95% CI 1.01-1.10, p = 0.012), but not total testosterone, were associated with higher risk of death or cardiovascular event. Only SHBG was associated with all-cause mortality (OR 1.07 per 10 nmol/L, 95% CI 1.02-1.12, p = 0.0073). Among women, neither total- or free testosterone, nor SHBG were associated with outcomes. We found no statistically significant effect of cinacalcet treatment on SHBG, free- or total testosterone.Lower free testosterone and higher SHBG in serum are associated with higher risk of death or cardiovascular event in men undergoing chronic hemodialysis.

  View details for DOI 10.1093/ndt/gfac278

  View details for PubMedID 36175142

• Parathyroidectomy and Cinacalcet Use in Medicare-Insured Kidney Transplant Recipients. American journal of kidney diseases : the official journal of the National Kidney Foundation Wang, A. X., Liu, S., Montez-Rath, M. E., Chertow, G. M., Lenihan, C. R. 2022

  Abstract

  RATIONALE & OBJECTIVE: Post-transplant hyperparathyroidism is common and treatment practices are poorly characterized. The goal of this study was to examine the incidence, associations, and outcomes of post-transplant parathyroidectomy and calcimimetic use in a cohort of Medicare-insured US kidney transplant recipients.STUDY DESIGN: Retrospective observational cohort study.SETTING & PARTICIPANTS: We used the US Renal Data System to extract demographic, clinical, and prescription data from Medicare Parts A, B and D-insured patients who received their first kidney transplant between 2007 and 2013. We excluded patients with pre-transplant parathyroidectomy.PREDICTORS: Calendar year of transplantation and pre-transplant patient characteristics.OUTCOMES: 1) Incidence of and secular trends in parathyroidectomy and cinacalcet use in the 3 years following transplant, 2) 90-day outcomes following post-transplant parathyroidectomy and cinacalcet initiation.ANALYTICAL APPROACH: Temporal trends and pre-transplant correlates of parathyroidectomy and cinacalcet use were assessed using proportional hazards models and multivariable Poisson regression, respectively.RESULTS: 30,127 patients met the inclusion criteria. 10,707 used cinacalcet pre-transplant. 551 patients underwent post-transplant parathyroidectomy and 5413 patients filled ≥ 1 prescription for cinacalcet. The rate of post-transplant parathyroidectomy was stable over time. In contrast, cinacalcet use increased during the period studied. Long dialysis vintage and pre-transplant cinacalcet use were strongly associated with post-transplant parathyroidectomy and cinacalcet use. Roughly one in four patients were hospitalized within 90 days of post-transplant parathyroidectomy, with hypocalcemia-related diagnoses being the most common complication. Parathyroidectomy (versus cinacalcet initiation) was not associated with an increase in acute kidney injury.LIMITATIONS: We lacked access to laboratory data to help assess severity of secondary/tertiary hyperparathyroidism. The cohort was limited to Medicare beneficiaries.CONCLUSIONS: Almost one fifth of our study cohort was treated with parathyroidectomy and/or cinacalcet. Further studies are needed to establish the optimal treatment for post-transplant hyperparathyroidism.

  View details for DOI 10.1053/j.ajkd.2022.07.015

  View details for PubMedID 36162617

• Cardiovascular Effects of Home Dialysis Therapies: A Scientific Statement From the American Heart Association CIRCULATION Sarnak, M. J., Auguste, B. L., Brown, E., Chang, A. R., Chertow, G. M., Hannan, M., Herzog, C. A., Nadeau-Fredette, A., Tang, W., Wang, A., Weiner, D. E., Chan, C. T., Amer Heart Assoc Council Kidney Ca, Council Arteriosclerosis Thrombosi, Council Cardiovasc Radiology Inter, Council Clinical Cardiology, Council Hypertension, Council Lifestyle Cardiometab Hlth 2022; 146 (11): E146-E164

  Abstract

  Cardiovascular disease is the leading cause of morbidity and mortality in patients with end-stage kidney disease. Currently, thrice-weekly in-center hemodialysis for 3 to 5 hours per session is the most common therapy worldwide for patients with treated kidney failure. Outcomes with thrice-weekly in-center hemodialysis are poor. Emerging evidence supports the overarching hypothesis that a more physiological approach to administering dialysis therapy, including in the home through home hemodialysis or peritoneal dialysis, may lead to improvement in several cardiovascular risk factors and cardiovascular outcomes compared with thrice-weekly in-center hemodialysis. The Advancing American Kidney Health Initiative, which has a goal of increasing the use of home dialysis, is aligned with the American Heart Association's 2024 mission to champion a full and healthy life and health equity. We conclude that incorporation of interdisciplinary care models to increase the use of home dialysis therapies in an equitable manner will contribute to the ultimate goal of improving outcomes for patients with kidney failure and cardiovascular disease.

  View details for DOI 10.1161/CIR.0000000000001088

  View details for Web of Science ID 000853194300003

  View details for PubMedID 35968722

• Association between cause of kidney failure and fracture incidence in a national US dialysis population cohort study CLINICAL KIDNEY JOURNAL Ziolkowski, S., Liu, S., Montez-Rath, M. E., Denburg, M., Winkelmayer, W. C., Chertow, G. M., O'Shaughnessy, M. M. 2022

  View details for DOI 10.1093/ckj/sfac193

  View details for Web of Science ID 000855410400001

• Management of Patients With Kidney Disease in Need of Cardiovascular Catheterization: A Scientific Workshop Cosponsored by the National Kidney Foundation and the Society for Cardiovascular Angiography and Interventions. Journal of the Society for Cardiovascular Angiography & Interventions Prasad, A., Palevsky, P. M., Bansal, S., Chertow, G. M., Kaufman, J., Kashani, K., Kim, E. S., Sridharan, L., Amin, A. P., Bangalore, S., Briguori, C., Charytan, D. M., Eng, M., Jneid, H., Brown, J. R., Mehran, R., Sarnak, M. J., Solomon, R., Thakar, C. V., Fowler, K., Weisbord, S. 2022; 1 (6): 100445

  Abstract

  Patients with chronic kidney disease (CKD) are at an increased risk of developing cardiovascular disease (CVD), whereas those with established CVD are at risk of incident or progressive CKD. Compared with individuals with normal or near normal kidney function, there are fewer data to guide the management of patients with CVD and CKD. As a joint effort between the National Kidney Foundation and the Society for Cardiovascular Angiography and Interventions, a workshop and subsequent review of the published literature was held. The present document summarizes the best practice recommendations of the working group and highlights areas for further investigation.

  View details for DOI 10.1016/j.jscai.2022.100445

  View details for PubMedID 39132354

  View details for PubMedCentralID PMC11307971

• Correlates and Consequences of an Acute Change in eGFR in Response to the SGLT2 Inhibitor Dapagliflozin in Patients with Chronic Kidney Disease. Journal of the American Society of Nephrology : JASN Jongs, N., Chertow, G., Greene, T., McMurray, J., Langkilde, A. M., Correa-Rotter, R., Kashihara, N., Rossing, P., Sjostrom, C. D., Stefansson, B., Toto, R., Wheeler, D., Heerspink, H. 2022

  Abstract

  Background Dapagliflozin reduces kidney failure risk in patients with chronic kidney disease (CKD) but can result in a reversible acute reduction in estimated glomerular filtration rate (eGFR) upon treatment initiation. Determinants of this eGFR reduction and its associations with efficacy and safety outcomes are unknown. Methods The DAPA-CKD trial randomized 4304 adults with CKD and albuminuria to oncedaily dapagliflozin 10 mg or placebo. We prespecified an analysis comparing the effects of dapagliflozin among patients who experienced relative reductions in eGFR (>10% or >0 to 10%) or an increase in eGFR from baseline to 2 weeks, and assessed long-term efficacy and safety. Results A total of 4157 (96.6%) patients had eGFR data available at baseline and at 2 weeks. In the dapagliflozin and placebo groups, 1026 (49.4%) and 494 (23.7%), respectively, experienced an acute reduction in eGFR >10%. Among patients receiving dapagliflozin, those with an acute reduction in eGFR >10% experienced a long-term eGFR decline of -1.58 mL/min per 1.73m2 per year compared with -2.44 and -2.48 mL/min per 1.73m2 per year among those experiencing a less pronounced reduction or increase in eGFR, respectively (P-interaction, 0.05). In the placebo group, long-term eGFR decline was -3.27, -3.84, and -3.77 mL/min per 1.73m2 per year for acute eGFR reduction subgroups of >10%, >0 to 10%, or increase in eGFR (P-interaction, 0.48). Rates of serious adverse events and adverse events of special interest in patients randomized to dapagliflozin were unrelated to the acute eGFR change. Conclusions Among patients with CKD and albuminuria treated with dapagliflozin, an acute reduction in eGFR (from baseline to 2 weeks) is not associated with higher rates of CKD progression.

  View details for DOI 10.1681/ASN.2022030306

  View details for PubMedID 35977807

• SARS-CoV-2 Infection during the Omicron Surge among Patients Receiving Dialysis: The Role of Circulating Receptor-Binding Domain Antibodies and Vaccine Doses. Journal of the American Society of Nephrology : JASN Montez-Rath, M. E., Garcia, P., Han, J., Cadden, L., Hunsader, P., Morgan, C., Kerschmann, R., Beyer, P., Dittrich, M., Block, G. A., Parsonnet, J., Chertow, G. M., Anand, S. 2022

  Abstract

  It is unclear whether circulating antibody levels conferred protection against SARS-CoV-2 infection among patients receiving dialysis during the Omicron-dominant period.We followed monthly semiquantitative SARS-CoV-2 RBD IgG index values in a randomly selected nationwide cohort of patients receiving dialysis and ascertained SARS-CoV-2 infection during the Omicron-dominant period of December 25, 2021 to January 31, 2022 using electronic health records. We estimated the relative risk for documented SARS-CoV-2 infection by vaccination status and by circulating RBD IgG using a log-binomial model accounting for age, sex, and prior COVID-19.Among 3576 patients receiving dialysis, 901 (25%) received a third mRNA vaccine dose as of December 24, 2021. Early antibody responses to third doses were robust (median peak index IgG value at assay limit of 150). During the Omicron-dominant period, SARS-CoV-2 infection was documented in 340 (7%) patients. Risk for infection was higher among patients without vaccination and with one to two doses (RR, 2.1; 95% CI, 1.6 to 2.8, and RR, 1.3; 95% CI, 1.0 to 1.8 versus three doses, respectively). Irrespective of the number of vaccine doses, risk for infection was higher among patients with circulating RBD IgG <23 (506 BAU/ml) (RR range, 2.1 to 3.2, 95% CI, 1.3 to 3.4 and 95% CI, 2.2 to 4.5, respectively) compared with RBD IgG ≥23.Among patients receiving dialysis, a third mRNA vaccine dose enhanced protection against SARS-CoV-2 infection during the Omicron-dominant period, but a low circulating RBD antibody response was associated with risk for infection independent of the number of vaccine doses. Measuring circulating antibody levels in this high-risk group could inform optimal timing of vaccination and other measures to reduce risk of SARS-CoV-2 infection.

  View details for DOI 10.1681/ASN.2022040504

  View details for PubMedID 35973733

• Clinical and Quality-of-Life Outcomes Following Invasive vs Conservative Treatment of Patients With Chronic Coronary Disease Across the Spectrum of Kidney Function. JAMA cardiology Bangalore, S., Hochman, J. S., Stevens, S. R., Jones, P. G., Spertus, J. A., O'Brien, S. M., Reynolds, H. R., Boden, W. E., Fleg, J. L., Williams, D. O., Stone, G. W., Sidhu, M. S., Mathew, R. O., Chertow, G. M., Maron, D. J. 2022

  Abstract

  Prior trials of invasive vs conservative management of chronic coronary disease (CCD) have not enrolled patients with severe chronic kidney disease (CKD). As such, outcomes across kidney function are not well characterized.To evaluate clinical and quality-of-life (QoL) outcomes across the spectrum of CKD following conservative and invasive treatment strategies.Participants from the International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) and ISCHEMIA-Chronic Kidney Disease (CKD) trials were categorized by CKD stage: stage 1 (estimated glomerular filtration rate [eGFR] 90 mL/min/1.73m2 or greater), stage 2 (eGFR 60-89 mL/min/1.73m2), stage 3 (eGFR 30-59 mL/min/1.73m2), stage 4 (eGFR 15-29 mL/min/1.73m2), or stage 5 (eGFR less than 15 mL/min/1.73m2 or receiving dialysis). Enrollment took place from July 26, 2012, through January 31, 2018, with a median follow-up of 3.1 years. Data were analyzed from January 2020 to May 2021.Initial invasive management of coronary angiography and revascularization with guideline-directed medical therapy (GDMT) vs initial conservative management of GDMT alone.The primary clinical outcome was a composite of death or nonfatal myocardial infarction (MI). The primary QoL outcome was the Seattle Angina Questionnaire (SAQ) summary score.Among the 5956 participants included in this analysis (mean [SD] age, 64 [10] years; 1410 [24%] female and 4546 [76%] male), 1889 (32%), 2551 (43%), 738 (12%), 311 (5%), and 467 (8%) were in CKD stages 1, 2, 3, 4, and 5, respectively. By self-report, 18 participants (<1%) were American Indian or Alaska Native; 1676 (29%), Asian; 267 (5%), Black; 861 (16%), Hispanic or Latino; 18 (<1%), Native Hawaiian or Other Pacific Islander; 3884 (66%), White; and 13 (<1%), multiple races or ethnicities. There was a monotonic increase in risk of the primary composite end point (3-year rates, 9.52%, 10.72%, 18.42%, 34.21%, and 38.01% respectively), death, cardiovascular death, MI, and stroke in individuals with higher CKD stages. Invasive management was associated with an increase in stroke (3-year event rate difference, 1%; 95% CI, 0.3 to 1.7) and procedural MI (1.6%; 95% CI, 0.9 to 2.3) and a decrease in spontaneous MI (-2.5%; 95% CI, -3.9 to -1.1) with no difference in other outcomes; the effect was similar across CKD stages. There was heterogeneity of treatment effect for QoL outcomes such that invasive management was associated with an improvement in angina-related QoL in individuals with CKD stages 1 to 3 and not in those with CKD stages 4 to 5.Among participants with CCD, event rates were inversely proportional to kidney function. Invasive management was associated with an increase in stroke and procedural MI and a reduced risk in spontaneous MI, and the effect was similar across CKD stages with no difference in other outcomes, including death. The benefit for QoL with invasive management was not observed in individuals with poorer kidney function.

  View details for DOI 10.1001/jamacardio.2022.1763

  View details for PubMedID 35767253

• Erythropoietic effects of vadadustat in patients with anemia associated with chronic kidney disease. American journal of hematology Koury, M. J., Agarwal, R., Chertow, G. M., Eckardt, K., Fishbane, S., Ganz, T., Haase, V. H., Hanudel, M. R., Parfrey, P. S., Pergola, P. E., Roy-Chaudhury, P., Tumlin, J. A., Anders, R., Farag, Y. M., Luo, W., Minga, T., Solinsky, C., Vargo, D. L., Winkelmayer, W. C. 2022

  Abstract

  Patients with chronic kidney disease develop anemia largely because of inappropriately low erythropoietin production and insufficient iron available to erythroid precursors. In four phase 3, randomized, open-label, clinical trials in dialysis-dependent and non-dialysis-dependent patients with chronic kidney disease and anemia, the hypoxia-inducible factor prolyl hydroxylase inhibitor, vadadustat, was non-inferior to the erythropoiesis-stimulating agent, darbepoetin alfa, in increasing and maintaining target hemoglobin concentrations. In these trials, vadadustat increased the concentrations of serum erythropoietin, the numbers of circulating erythrocytes, and the numbers of circulating reticulocytes. Achieved hemoglobin concentrations were similar in patients treated with either vadadustat or darbepoetin alfa, but compared with patients receiving darbepoetin alfa, those receiving vadadustat had erythrocytes with increased mean corpuscular volume and mean corpuscular hemoglobin, while the red cell distribution width was decreased. Increased serum transferrin concentrations, as measured by total iron-binding capacity, combined with stable serum iron concentrations, resulted in decreased transferrin saturation in patients randomized to vadadustat compared with patients randomized to darbepoetin alfa. The decreases in transferrin saturation were associated with relatively greater declines in serum hepcidin and ferritin in patients receiving vadadustat compared with those receiving darbepoetin alfa. These results for serum transferrin saturation, hepcidin, ferritin, and erythrocyte indices were consistent with improved iron availability in the patients receiving vadadustat. Thus, overall, vadadustat had beneficial effects on three aspects of erythropoiesis in patients with anemia associated with chronic kidney disease: increased endogenous erythropoietin production, improved iron availability to erythroid cells, and increased reticulocytes in the circulation. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/ajh.26644

  View details for PubMedID 35751858

• Projecting the Economic Impact of Compensating Living Kidney Donors in the United States: Cost-Benefit Analysis Demonstrates Substantial Patient and Societal Gains. Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research McCormick, F., Held, P. J., Chertow, G. M., Peters, T. G., Roberts, J. P. 2022

  Abstract

  The aim of this study was to show how the US government could save approximately 47 000 patients with chronic kidney failure each year from suffering on dialysis and premature death by compensating living kidney donors enough to completely end the kidney shortage.Supply and demand analysis was used to estimate the number of donated kidneys needed to end the kidney shortage and the level of compensation required to encourage this number of donations. These results were then input into a detailed cost-benefit analysis to estimate the economic value of kidney transplantation to (1) the average kidney recipient and their caregiver, (2) taxpayers, and (3) society in general.We estimate half of patients diagnosed with kidney failure each year-approximately 62 000 patients-could be saved from suffering on dialysis and premature death if they could receive an average of 1½ kidney transplants. However, currently there are only enough donated kidneys to save approximately 15 000 patients. To encourage sufficient donations to save the other 47 000 patients, the government would have to compensate living kidney donors approximately $77 000 (±50%) per donor. The value of transplantation to an average kidney recipient (and caregiver) would be approximately $1.5 million, and the savings from the recipient not needing expensive dialysis treatments would be approximately $1.2 million.This analysis reveals the huge benefit that compensating living kidney donors would provide to patients with kidney failure and their caregivers and, conversely, the huge cost that is being imposed on these patients and their families by the current legal prohibition against such compensation.

  View details for DOI 10.1016/j.jval.2022.04.1732

  View details for PubMedID 35690519

• APOL1 INHIBITION BY VX-147 AS A TARGETED THERAPY FOR APOL1-MEDIATED KIDNEY DISEASE Pollak, M., Friedman, D., Barisoni, L., Falk, R., Gipson, D., Lipkowitz, M., Ojo, A., Chirieac, M., Xu, C., Fortier, A., Egbuna, O., Bunnage, M., Chertow, G., VX 147 Study Grp W B SAUNDERS CO-ELSEVIER INC. 2022: 769

  View details for Web of Science ID 000797690900026

• CARDIOVASCULAR EVENTS IN PATIENTS WITH NON-DIALYSIS-DEPENDENT CHRONIC KIDNEY DISEASE AND ANEMIA: REGIONAL ANALYSIS OF PATIENTS PREVIOUSLY TREATED WITH ERYTHROPOIESIS-STIMULATING AGENTS IN THE PRO2TECT TRIAL Parfrey, P., Chertow, G., Eckardt, K., Burke, S., Luo, W., Minga, T., Winkelmayer, W. OXFORD UNIV PRESS. 2022: I386-I387

  View details for Web of Science ID 000813350702002

• CARDIOVASCULAR EVENTS IN PATIENTS WITH ANEMIA ASSOCIATED WITH NON-DIALYSIS-DEPENDENT CHRONIC KIDNEY DISEASE: REGIONAL ANALYSIS OF PATIENTS NOT PREVIOUSLY TREATED WITH ERYTHROPOIESIS-STIMULATING AGENTS IN THE PRO2TECT TRIAL Winkelmayer, W., Arnold, S., Burke, S., Chertow, G., Eckardt, K., Luo, W., Minga, T., Parfrey, P. OXFORD UNIV PRESS. 2022: I392-I393

  View details for Web of Science ID 000813350702006

• EFFECTS OF DAPAGLIFLOZIN IN PATIENTS WITH CHRONIC KIDNEY DISEASE ACCORDING TO BACKGROUND ANGIOTENSIN-CONVERTING ENZYME INHIBITOR AND ANGIOTENSIN RECEPTOR BLOCKER DOSE Heerspink, H., Jong, N., Stefansson, B., Chertow, G., Langkilde, A., Mcmurray, J., Correa-Rotter, R., Rossing, P., Toto, R., Wheeler, D. OXFORD UNIV PRESS. 2022: I847-I848

  View details for Web of Science ID 000813350704141

• Effect of dapagliflozin on kidney and cardiovascular outcomes by baseline KDIGO risk categories: a post hoc analysis of the DAPA-CKD trial. Diabetologia Waijer, S. W., Vart, P., Cherney, D. Z., Chertow, G. M., Jongs, N., Langkilde, A. M., Mann, J. F., Mosenzon, O., McMurray, J. J., Rossing, P., Correa-Rotter, R., Stefansson, B. V., Toto, R. D., Wheeler, D. C., Heerspink, H. J. 2022

  Abstract

  AIMS/HYPOTHESIS: In the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial, dapagliflozin reduced the risks of progressive kidney disease, hospitalised heart failure or cardiovascular death, and death from all causes in patients with chronic kidney disease (CKD) with or without type 2 diabetes. Patients with more severe CKD are at higher risk of kidney failure, cardiovascular events and all-cause mortality. In this post hoc analysis, we assessed the efficacy and safety of dapagliflozin according to baseline Kidney Disease Improving Global Outcomes (KDIGO) risk categories.METHODS: DAPA-CKD was a double-blind, placebo-controlled trial that randomised patients with an eGFR of 25-75mlmin-1 [1.73m]-2 and urinary albumin/creatinine ratio (UACR) of ≥22.6 and <565.0mg/mmol (200-5000mg/g) to dapagliflozin 10mg/day or placebo. The primary endpoint was a composite of ≥50% reduction in eGFR, end-stage kidney disease (ESKD), and death from a kidney or cardiovascular cause. Secondary endpoints included a kidney composite (≥50% reduction in eGFR, ESKD and death from a kidney cause), a cardiovascular composite (heart failure hospitalisation or cardiovascular death), and death from all causes. We used Cox proportional hazards regression analyses to assess relative and absolute effects of dapagliflozin across KDIGO risk categories.RESULTS: Of the 4304 participants in the DAPA-CKD study, 619 (14.4%) were moderately high risk, 1349 (31.3%) were high risk and 2336 (54.3%) were very high risk when categorised by KDIGO risk categories at baseline. Dapagliflozin reduced the hazard of the primary composite (HR 0.61; 95% CI 0.51, 0.72) and secondary endpoints consistently across KDIGO risk categories (all p for interaction >0.09). Absolute risk reductions for the primary outcome were also consistent irrespective of KDIGO risk category (p for interaction 0.26). Analysing patients with and without type 2 diabetes separately, the relative risk reduction with dapagliflozin in terms of the primary outcome was consistent across subgroups of KDIGO risk categories. The relative frequencies of adverse events and serious adverse events were also similar across KDIGO risk categories.CONCLUSION/INTERPRETATIONS: The consistent benefits of dapagliflozin on kidney and cardiovascular outcomes across KDIGO risk categories indicate that dapagliflozin is efficacious and safe across a wide spectrum of kidney disease severity.TRIAL REGISTRATION: ClinicalTrials.gov NCT03036150.FUNDING: The study was funded by AstraZeneca.

  View details for DOI 10.1007/s00125-022-05694-6

  View details for PubMedID 35445820

• SARS-CoV-2 Booster Vaccine Response among Patients Receiving Dialysis. Clinical journal of the American Society of Nephrology : CJASN Garcia, P., Han, J., Montez-Rath, M., Sun, S., Shang, T., Parsonnet, J., Chertow, G., Anand, S., Schiller, B., Abra, G. 2022

  Abstract

  N/A.

  View details for DOI 10.2215/CJN.00890122

  View details for PubMedID 35383042

• <p>Emerging Role of Clinical Genetics in CKD & nbsp;</p> KIDNEY MEDICINE Devarajan, P., Chertow, G. M., Susztak, K., Levin, A., Agarwal, R., Stenvinkel, P., Chapman, A. B., Warady, B. A. 2022; 4 (4)

  View details for DOI 10.1016/ j.xkme.2022.100435

  View details for Web of Science ID 000793559900004

• TABLO HEMODIALYSIS SYSTEMS COULD INCREASE RECOMMENDATIONS OF HOME HEMODIALYSIS FOR PATIENTS Saffer, T., Aragon, M., Chertow, G. W B SAUNDERS CO-ELSEVIER INC. 2022: S105

  View details for Web of Science ID 000772365300347

• THE TABLO HEMODIALYSIS SYSTEM INCREASES PATIENT LIKELIHOOD FOR HHD ADOPTION Saffer, T., Aragon, M., Chertow, G. W B SAUNDERS CO-ELSEVIER INC. 2022: S108

  View details for Web of Science ID 000772365300357

• Efficacy and Safety of Dapagliflozin in Patients With CKD Across Major Geographic Regions. Kidney international reports Vart, P., Correa-Rotter, R., Hou, F. F., Jongs, N., Chertow, G. M., Langkilde, A. M., McMurray, J. J., Rossing, P., Sjöström, C. D., Stefansson, B. V., Toto, R. D., Douthat, W., Escudero, E., Isidto, R., Khullar, D., Bajaj, H. S., Wheeler, D. C., Heerspink, H. J. 2022; 7 (4): 699-707

  Abstract

  This study aimed to examine the efficacy and safety of dapagliflozin in the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial (NCT03036150) by geographic region.Adults with chronic kidney disease (CKD) with or without type 2 diabetes, with estimated glomerular filtration rate (eGFR) 25 to 75 ml/min per 1.73 m2 and urinary albumin-to-creatinine ratio (UACR) 200 to 5000 mg/g were randomized to dapagliflozin (10 mg once daily) or placebo. The primary end point was a composite of a sustained decline in eGFR of ≥50%, end-stage kidney disease or death from kidney or cardiovascular causes. We categorized recruiting countries into 4 broad global regions: Asia, Europe, Latin America, and North America. Of 4304 randomized patients, 1346 (31.3%) were from Asia, 1233 (28.6%) from Europe, 912 (21.2%) from Latin America, and 813 (18.9%) from North America.The relative risk of the primary composite end point was lower in patients randomized to dapagliflozin (relative to placebo) in all regions, with hazard ratios (95% CI) of 0.70 (0.48-1.00), 0.60 (0.43-0.85), 0.61 (0.43-0.86), and 0.51 (0.34-0.76) among patients from Asia, Europe, Latin America, and North America, respectively. There was no effect modification by region (interaction P = 0.77). Occurrence of serious adverse events (SAEs) was lower among patients randomized to dapagliflozin versus placebo (21.9% vs. 26.8%, 34.1% vs. 38.6%, 29.8% vs. 31.5%, and 34.9% vs. 41.0% in Asia, Europe, Latin America, and North America, respectively).Dapagliflozin reduced kidney and cardiovascular events and prolonged survival in patients with CKD, with and without type 2 diabetes, with no apparent effect modification by geographic region.

  View details for DOI 10.1016/j.ekir.2022.01.1060

  View details for PubMedID 35497805

  View details for PubMedCentralID PMC9039473

• Emerging Role of Clinical Genetics in CKD. Kidney medicine Devarajan, P., Chertow, G. M., Susztak, K., Levin, A., Agarwal, R., Stenvinkel, P., Chapman, A. B., Warady, B. A. 2022; 4 (4): 100435

  Abstract

  Chronic kidney disease (CKD) afflicts 15% of adults in the United States, of whom 25% have a family history. Genetic testing is supportive in identifying and possibly confirming diagnoses of CKD, thereby guiding care. Advances in the clinical genetic evaluation include next-generation sequencing with targeted gene panels, whole exome sequencing, and whole genome sequencing. These platforms provide DNA sequence reads with excellent coverage throughout the genome and have identified novel genetic causes of CKD. New pathologic genetic variants identified in previously unrecognized biological pathways have elucidated disease mechanisms underlying CKD etiologies, potentially establishing prognosis and guiding treatment selection. Molecular diagnoses using genetic sequencing can detect rare, potentially treatable mutations, avoid misdiagnoses, guide selection of optimal therapy, and decrease the risk of unnecessary and potentially harmful interventions. Genetic testing has been widely adopted in pediatric nephrology; however, it is less frequently used to date in adult nephrology. Extension of clinical genetic approaches to adult patients may achieve similar benefits in diagnostic refinement and treatment selection. This review aimed to identify clinical CKD phenotypes that may benefit the most from genetic testing, outline the commonly available platforms, and provide examples of successful deployment of these approaches in CKD.

  View details for DOI 10.1016/j.xkme.2022.100435

  View details for PubMedID 35372818

• Trends in Coronary Artery Disease Screening before Kidney Transplantation. Kidney360 Cheng, X. S., Liu, S., Han, J., Stedman, M. R., Chertow, G. M., Tan, J. C., Fearon, W. F. 2022; 3 (3): 516-523

  Abstract

  Background: Coronary artery disease (CAD) screening in asymptomatic kidney transplant candidates is widespread but not well supported by contemporary cardiology literature. In this study we describe temporal trends in CAD screening before kidney transplant in the United States.Methods: Using the United States Renal Data System, we examined Medicare-insured adults who received a first kidney transplant from 2000 through 2015. We stratified analysis on the basis of whether the patient's comorbidity burden met guideline definitions of high risk for CAD. We examined temporal trends in nonurgent CAD tests within the year before transplant and the composite of death and nonfatal myocardial infarction in the 30 days after transplant.Results: Of 94,832 kidney transplant recipients, 37,139 (39%) underwent at least one nonurgent CAD test in the 1 year before transplant. From 2000 to 2015, the transplant program waitlist volume had increased as transplant volume stayed constant, whereas patients in the later eras had a slightly higher comorbidity burden (older, longer dialysis vintage, and a higher prevalence of diabetes mellitus and CAD). The likelihood of CAD test in the year before transplant increased from 2000 through 2003 and remained relatively stable thereafter. When stratified by CAD risk status, test rates decreased modestly in patients who were high risk but remained constant in patients who were low risk after 2008. Death or nonfatal myocardial infarction within 30 days after transplant decreased from 3% in 2000 to 2% in 2015. Nuclear perfusion scan was the most frequent modality of testing throughout the examined time periods.Conclusions: CAD testing rates before kidney transplantation have remained constant from 2000 through 2015, despite widespread changes in cardiology guidelines and practice.

  View details for DOI 10.34067/KID.0005282021

  View details for PubMedID 35582172

• SARS-CoV-2 infection during the Omicron surge among patients receiving dialysis: the role of circulating receptor-binding domain antibodies and vaccine doses. medRxiv : the preprint server for health sciences Montez-Rath, M. E., Garcia, P., Han, J., Cadden, L., Hunsader, P., Morgan, C., Kerschmann, R., Beyer, P., Dittrich, M., Block, G. A., Anand, S., Parsonnet, J., Chertow, G. M. 2022

  Abstract

  Background: It is unclear whether a third dose of mRNA platform vaccines, or antibody response to prior infection or vaccination confer protection from the Omicron variant among patients receiving dialysis.Methods: Monthly since February 2021, we tested plasma from 4,697 patients receiving dialysis for antibodies to the receptor-binding domain (RBD) of SARS-CoV-2. We assessed semiquantitative median IgG index values over time among patients vaccinated with at least one dose of the two mRNA vaccines. We ascertained documented COVID-19 diagnoses after December 25, 2021 and up to January 31, 2022. We estimated the relative risk for documented SARS-CoV-2 infection by vaccination status using a log-binomial model accounting for age, sex, and prior clinical COVID-19. Among patients with RBD IgG index value available during December 1-December 24, 2021, we also evaluated the association between the circulating RBD IgG titer and risk for Omicron variant SARS-CoV-2 infection.Results: Of the 4,697 patients we followed with monthly RBD assays, 3576 are included in the main analysis cohort; among these, 852 (24%) were unvaccinated. Antibody response to third doses was robust (median peak index IgG value at assay limit of 150, equivalent to 3270 binding antibody units/mL). Between December 25-January 31, 2022, SARS-CoV-2 infection was documented 340 patients (7%), 115 (36%) of whom were hospitalized. The final doses of vaccines were given a median of 272 (25 th , 75 th percentile, 245-303) days and 58 (25 th , 75 th percentile, 51-95) days prior to infection for the 1-2 dose and 3 dose vaccine groups respectively. Relative risks for infection were higher among patients without vaccination (RR 2.1 [95%CI 1.6, 2.8]), and patients with 1-2 doses (RR 1.3 [95%CI 1.0, 1.8]), compared with patients with three doses of the mRNA vaccines. Relative risks for infection were higher among patients with RBD index values < 23 (506 BAU/mL), compared with RBD index value a 23 (RR 2.4 [95%CI 1.9, 3.0]). The higher risk for infection among patients with RBD index values < 23 was present among patients who received three doses (RR 2.1 [95%CI 1.3, 3.4]).Conclusions: Among patients receiving hemodialysis, patients unvaccinated, without a third mRNA vaccine dose, or those lacking robust circulating antibody response are at higher risk for Omicron variant infection. Low circulating antibodies could identify the subgroup needing intensified surveillance, prophylaxis or treatment in this patient population.

  View details for DOI 10.1101/2022.03.15.22272426

  View details for PubMedID 35313586

• Dialysis Initiation in Patients With Chronic Coronary Disease and Advanced Chronic Kidney Disease in ISCHEMIA-CKD. Journal of the American Heart Association Briguori, C., Mathew, R. O., Huang, Z., Mavromatis, K., Hickson, L. J., Lau, W. L., Mathew, A., Mahajan, S., Wheeler, D. C., Claes, K. J., Chen, G., Nolasco, F. E., Stone, G. W., Fleg, J. L., Sidhu, M. S., Rockhold, F. W., Chertow, G. M., Hochman, J. S., Maron, D. J., Bangalore, S. 2022: e022003

  Abstract

  Background In participants with concomitant chronic coronary disease and advanced chronic kidney disease (CKD), the effect of treatment strategies on the timing of dialysis initiation is not well characterized. Methods and Results In ISCHEMIA-CKD (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Chronic Kidney Disease), 777 participants with advanced CKD and moderate or severe ischemia were randomized to either an initial invasive or conservative management strategy. Herein, we compare the proportion of randomized participants with non-dialysis-requiring CKD at baseline (n=362) who initiated dialysis and compare the time to dialysis initiation between invasive versus conservative management arms. Using multivariable Cox regression analysis, we also sought to identify the effect of invasive versus conservative chronic coronary disease management strategies on dialysis initiation. At a median follow-up of 23months (25th-75th interquartile range, 14-32 months), dialysis was initiated in 18.9% of participants (36/190) in the invasive strategy and 16.9% of participants (29/172) in the conservative strategy (P=0.22). The median time to dialysis initiation was 6.0months (interquartile range, 3.0-16.0 months) in the invasive group and 18.2months (interquartile range, 12.2-25.0 months) in the conservative group (P=0.004), with no difference in procedural acute kidney injury rates between the groups (7.8% versus 5.4%; P=0.26). Baseline clinical factors associated with earlier dialysis initiation were lower baseline estimated glomerular filtration rate (hazard ratio [HR] associated with 5-unit decrease, 2.08 [95% CI, 1.72-2.56]; P<0.001), diabetes (HR, 2.30 [95% CI, 1.28-4.13]; P=0.005), hypertension (HR, 7.97 [95% CI, 1.09-58.21]; P=0.041), and Hispanic ethnicity (HR, 2.34 [95% CI, 1.22-4.47]; P=0.010). Conclusions In participants with non-dialysis-requiring CKD in ISCHEMIA-CKD, randomization to an invasive chronic coronary disease management strategy (relative to a conservative chronic coronary disease management strategy) is associated with an accelerated time to initiation of maintenance dialysis for kidney failure. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01985360.

  View details for DOI 10.1161/JAHA.121.022003

  View details for PubMedID 35261290

• Long-Term Clinical Impact of Contrast-Associated Acute Kidney Injury Following PCI: AnADAPT-DES Substudy. JACC. Cardiovascular interventions Mohebi, R., Karimi Galougahi, K., Garcia, J. J., Horst, J., Ben-Yehuda, O., Radhakrishnan, J., Chertow, G. M., Jeremias, A., Cohen, D. J., Cohen, D. J., Maehara, A., Mintz, G. S., Chen, S., Redfors, B., Leon, M. B., Stuckey, T. D., Rinaldi, M. J., Weisz, G., Witzenbichler, B., Kirtane, A. J., Mehran, R., Dangas, G. D., Stone, G. W., Ali, Z. A. 2022

  Abstract

  OBJECTIVES: This study sought to determine correlates and consequences of contrast-associated acute kidney injury (CA-AKI) on clinical outcomes in patients with or without pre-existing chronic kidney disease (CKD).BACKGROUND: The incidence and impact of CA-AKI on clinical outcomes during contemporary percutaneous coronary intervention (PCI) are not fully defined.METHODS: The ADAPT-DES (Assessment of Dual AntiPlatelet Therapy With Drug Eluting Stents) study was a prospective, multicenter registry of 8,582 patients treated with≥1 drug-eluting stent(s). CA-AKI was defined as a post-PCI increase in serum creatinine of >0.5mg/dL or a relative increase of≥25% compared with pre-PCI. CKD was defined as estimated glomerular filtration rate<60mL/min/1.73m2. The primary endpoint was the 2-year rate of net adverse clinical events (NACE): All-cause mortality, myocardial infarction (MI), definite or probable stent thrombosis, or major bleeding.RESULTS: Of 7287 (85%) patients with evaluable data, 476 (6.5%) developed CA-AKI. In a multivariable model, older age, female sex, Caucasian race, congestive heart failure, diabetes, hypertension, CKD, presentation with ST-segment elevation MI, Killip class II to IV, radial access, intra-aortic balloon pump use, hypotension, and number of stents were independent predictors of CA-AKI. The 2-year NACE rate was higher in patients with CA-AKI (adjusted hazard ratio [HR]: 1.88; 95% CI: 1.42-2.49), as was each component of NACE (all-cause mortality, HR: 1.77; 95%CI: 1.22-2.55; MI, HR: 1.67; 95%CI: 1.18-2.36; definite/probable stent thrombosis, HR: 1.71; 95%CI: 1.10-2.65; and major bleeding, HR: 1.38; 95%CI: 1.06-1.80). Compared with the CA-AKI-/CKD- group, the CA-AKI+/CKD- (HR: 1.83; 95%CI: 1.33-2.52), CA-AKI-/CKD+ (HR: 1.56; 95%CI: 1.15-2.13), CA-AKI+/CKD+ (HR: 3.29; 95%CI: 1.92-5.67), and maintenance dialysis (HR: 2.67; 95%CI: 1.65-4.31) groups were at higher risk of NACE.CONCLUSIONS: CA-AKI was relatively common after contemporary PCI and was associated with increased 2-year rates of NACE. Patients with pre-existing CKD were at particularly high risk for NACE after CA-AKI.

  View details for DOI 10.1016/j.jcin.2021.11.026

  View details for PubMedID 35305904

• Changing the Trajectory of Heart Failure and Kidney Disease. Clinical journal of the American Society of Nephrology : CJASN Rangaswami, J., Bhalla, V., Chertow, G., Harrington, R., Staruschenko, A., Tuttle, K., Braunwald, E. 2022

  View details for DOI 10.2215/CJN.00470122

  View details for PubMedID 35232819

• Trends in Cost Attributable to Kidney Transplantation Evaluation and Waiting List Management in the United States, 2012-2017. JAMA network open Cheng, X. S., Han, J., Braggs-Gresham, J. L., Held, P. J., Busque, S., Roberts, J. P., Tan, J. C., Scandling, J. D., Chertow, G. M., Dor, A. 2022; 5 (3): e221847

  Abstract

  Importance: While recent policy reforms aim to improve access to kidney transplantation for patients with end-stage kidney disease, the cost implications of kidney waiting list expansion are not well understood. The Organ Acquisition Cost Center (OACC) is the mechanism by which Medicare reimburses kidney transplantation programs, at cost, for costs attributable to kidney transplantation evaluation and waiting list management, but these costs have not been well described to date.Objectives: To describe temporal trends in mean OACC costs per kidney transplantation and to identify factors most associated with cost.Design, Setting, and Participants: This economic evaluation included all kidney transplantation waiting list candidates and recipients in the United States from 2012 to 2017. A population-based study of cost center reports was conducted using data from all Center of Medicare & Medicaid-certified transplantation hospitals. Data analysis was conducted from June to August 2021.Exposures: Year, local price index, transplantation and waiting list volume of transplantation program, and comorbidity burden.Main Outcomes and Measures: Mean OACC costs per kidney transplantation.Results: In 1335 hospital-years from 2012 through 2017, Medicare's share of OACC costs increased from $0.95 billion in 2012 to $1.32 billion in 2017 (3.7% of total Medicare End-Stage Renal Disease program expenditure). Median (IQR) OACC costs per transplantation increased from $81 000 ($66 000 to $103 000) in 2012 to $100 000 ($82 000 to $125 000) in 2017. Kidney organ procurement costs contributed to 36% of mean OACC costs per transplantation throughout the study period. During the study period, transplantation hospitals experienced increases in kidney waiting list volume, kidney waiting list active volume, kidney transplantation volume, and comorbidity burden. For a median-sized transplantation program, mean OACC costs per transplantation decreased with more transplants (-$3500 [95% CI, -$4300 to -$2700] per 10 transplants; P<.001) and increased with year ($4400 [95% CI, $3500 to $5300] per year; P<.001), local price index ($1900 [95% CI, $200 to $3700] per 10-point increase; P=.03), patients listed active on the waiting list ($3100 [95% CI, $1700 to $4600] per 100 patients; P<.001), and patients on the waiting list with high comorbidities ($1500 [9% CI, $600 to $2500] per 1% increase in proportion of waitlisted patients with the highest comorbidity score; P=.002).Conclusions and Relevance: In this study, OACC costs increased at 4% per year from 2012 to 2017 and were not solely attributable to the cost of organ procurement. Expanding the waiting list will likely contribute to further increases in the mean OACC costs per transplantation and substantially increase Medicare liability.

  View details for DOI 10.1001/jamanetworkopen.2022.1847

  View details for PubMedID 35267033

• The Kidney Protective Effects of the Sodium-Glucose Cotransporter-2 Inhibitor, Dapagliflozin, Are Present in Patients With CKD Treated With Mineralocorticoid Receptor Antagonists. Kidney international reports Provenzano, M., Jongs, N., Vart, P., Stefansson, B. V., Chertow, G. M., Langkilde, A. M., McMurray, J. J., Correa-Rotter, R., Rossing, P., Sjostrom, C. D., Toto, R. D., Wheeler, D. C., Heerspink, H. J., DAPA-CKD Trial Committees and Investigators 2022; 7 (3): 436-443

  Abstract

  Introduction: Mineralocorticoid receptor antagonists (MRAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors reduce the risk of kidney failure in chronic kidney disease (CKD). We performed an analysis of the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial by baseline conventional MRA (spironolactone and eplerenone) prescription.Methods: Participants with CKD (estimated glomerular filtration rate [eGFR] 25-75 ml/min per 1.73 m2; urinary albumin-to-creatinine ratio 200-500 mg/g), with or without type 2 diabetes, were randomized 1:1 to dapagliflozin 10 mg or placebo, once daily. The primary outcome was a composite of sustained≥50% eGFR decline, end-stage kidney disease, or kidney or cardiovascular (CV) death. A prespecified kidney-specific secondary outcome was as the primary outcome but without CV death. Hyperkalemia (serum potassium≥6.0 mmol/l) was an exploratory end point. Time-to-event analyses (proportional hazards [Cox] regression) assessed dapagliflozin versus placebo in patient subgroups defined by baseline conventional MRA use.Results: A total of 229 of 4304 DAPA-CKD participants (5.3%) were receiving conventional MRAs at baseline (dapagliflozin n= 109, placebo n= 120). The effect of dapagliflozin on the primary outcome was consistent in participants prescribed (hazard ratio [HR] 0.76, 95% CI 0.40-1.47) and not prescribed (HR 0.60, 95% CI 0.50-0.72, P-interaction= 0.59) MRAs. This consistency was maintained for the kidney-specific outcome. The effect of dapagliflozin on hyperkalemia (HR 0.87, 95% CI 0.70-1.09) was consistent among those prescribed (HR 0.94, 95% CI 0.41-2.20) and not prescribed (HR 0.87, 95% CI 0.69-1.10, P-interaction= 0.96) MRAs. Adverse events (AEs) leading to discontinuation and serious AEs were similar between treatment groups, regardless of baseline MRA prescription.Conclusion: Dapagliflozin was similarly safe and efficacious in reducing major adverse kidney outcomes in participants with CKD who were or were not prescribed MRAs at baseline.

  View details for DOI 10.1016/j.ekir.2021.12.013

  View details for PubMedID 35257056

• Cost-Effectiveness of Dapagliflozin for Non-diabetic Chronic Kidney Disease. Journal of general internal medicine Tisdale, R. L., Cusick, M. M., Aluri, K. Z., Handley, T. J., Joyner, A. K., Salomon, J. A., Chertow, G. M., Goldhaber-Fiebert, J. D., Owens, D. K. 2022

  Abstract

  BACKGROUND: In the USA, chronic kidney disease (CKD) affects 1 in 7 adults and costs $100 billion annually. The DAPA-CKD trial found dapagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, to be effective in reducing CKD progression and mortality in patients with diabetic and non-diabetic CKD. Currently, SGLT2 inhibitors are not considered standard of care for patients with non-diabetic CKD.OBJECTIVE: Determine the cost-effectiveness of adding dapagliflozin to standard management of patients with non-diabetic CKD.DESIGN: Markov model with lifetime time horizon and US healthcare sector perspective.PATIENTS: Patients with non-diabetic CKD INTERVENTION: Dapagliflozin plus standard care versus standard care only.MAIN MEASURES: Quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs), all discounted at 3% annually; total incidence of kidney failure on kidney replacement therapy; average years on kidney replacement therapy.KEY RESULTS: Adding dapagliflozin to standard care improved life expectancy by 2 years, increased discounted QALYS (from 6.75 to 8.06), and reduced the total incidence of kidney failure on kidney replacement therapy (KRT) (from 17.4 to 11.0%) and average years on KRT (from 0.77 to 0.43) over the lifetime of the cohort. Dapagliflozin plus standard care was more effective than standard care alone while increasing lifetime costs (from $245,900 to $324,8900, or $60,000 per QALY gained). Results were robust to variations in assumptions about dapagliflozin's efficacy over time and by CKD stage, added costs of kidney replacement therapy, and expected population annual CKD progression rates and sensitive to the cost of dapagliflozin. The net 1-year budgetary implication of treating all US patients with non-diabetic CKD could be up to $21 billion.CONCLUSIONS: Dapagliflozin improved life expectancy and reduced progression of CKD, the proportion of patients requiring kidney replacement therapy, and time on kidney replacement therapy in patients with non-diabetic CKD. Use of dapagliflozin meets conventional criteria for cost-effectiveness.

  View details for DOI 10.1007/s11606-021-07311-5

  View details for PubMedID 35137296

• Cardiovascular outcomes associated with prescription of SGLT-2 inhibitors versus DPP-4 inhibitors in patients with diabetes mellitus and chronic kidney disease. Diabetes, obesity & metabolism Rhee, J. J., Han, J., Montez-Rath, M. E., Kim, S. H., Cullen, M. R., Stafford, R. S., Winkelmayer, W. C., Chertow, G. M. 1800

  Abstract

  AIMS: To determine the association with cardiovascular (CV) outcomes of sodium glucose cotransporter-2 (SGLT-2) inhibitors compared with dipeptidyl peptidase-4 (DPP-4) inhibitors in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD).MATERIALS AND METHODS: We conducted a population-based cohort study of new users of SGLT-2 inhibitors and DPP-4 inhibitors with T2DM and CKD using data from Optum Clinformatics DataMart. We assembled three cohorts: T2DM/no CKD, T2DM/CKD 1-2, and T2DM/ CKD 3a. Study outcomes were 1) time to first heart failure (HF) hospitalization; and 2) time to a composite CV endpoint comprised of non-fatal myocardial infarction (MI) or stroke. After inverse probability of treatment weighting, we used proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (CI).RESULTS: New users of SGLT-2 inhibitors versus of DPP-4 inhibitors had lower risks of HF hospitalization in the T2DM/no CKD (HR, 0.76; 95% CI, 0.70, 0.82) and T2DM/CKD 1-2 (HR, 0.63; 95% CI, 0.48, 0.84), but no significant association was present in the T2DM/CKD 3a cohort. Compared with prescription of DPP-4 inhibitors, SGLT-2 inhibitors were associated with lower risks of non-fatal MI or stroke of 23% (HR, 0.77; 95% CI, 0.70, 0.85) in the T2DM/no CKD cohort, but no significant associations were present in the T2DM/CKD 1-2 and T2DM/CKD 3a cohorts.CONCLUSIONS: Incident prescription of SGLT-2 inhibitors was associated with lower risks of HF hospitalization but not with non-fatal MI or stroke despite suggesting benefit, relative to prescription of DPP-4 inhibitor across different stages of CKD. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/dom.14657

  View details for PubMedID 35118793

• SARS-CoV-2 Neutralizing Monoclonal Antibodies for the Treatment of COVID-19 in Kidney Transplant Recipients. Kidney360 Wang, A. X., Busque, S., Kuo, J., Singh, U., Roeltgen, K., Pinsky, B. A., Chertow, G. M., Scandling, J. D., Lenihan, C. R. 2022; 3 (1): 133-143

  Abstract

  Background: Morbidity and mortality associated with coronavirus disease 2019 (COVID-19) infection in kidney transplant recipients are high and early outpatient interventions to prevent progression to severe disease are needed. SARS-CoV-2 neutralizing mAbs, including bamlanivimab and casirivimab-imdevimab, received emergency use authorization in the United States in November 2020 for treatment of mild to moderate COVID-19 disease.Methods: We performed a retrospective analysis of 27 kidney transplant recipients diagnosed with COVID-19 between July 2020 and February 2021 who were treated with bamlanivimab or casirivimab-imdevimab and immunosuppression reduction. We additionally identified 13 kidney transplant recipients with COVID-19 who had mild to moderate disease at presentation, who did not receive mAbs, and had SARS-CoV-2 serology testing available.Results: There were no deaths or graft failures in either group. Both infusions were well tolerated. Four of the 27 patients treated with mAbs required hospitalization due to COVID-19. Four of 13 patients who did not receive mAbs required hospitalization due to COVID-19. Patients who received mAbs demonstrated measurable anti-SARS-CoV-2 IgG with angiotensin-converting enzyme 2 (ACE2) receptor blocking activity at the highest level detectable at 90 days postinfusion, whereas ACE2 blocking activity acquired from natural immunity in the mAb-untreated group was weak.Conclusions: Bamlanivimab and casirivimab-imdevimab combined with immunosuppression reduction were well tolerated and associated with favorable clinical outcomes in kidney transplant recipients diagnosed with mild to moderate COVID-19.

  View details for DOI 10.34067/KID.0005732021

  View details for PubMedID 35368573

• Quetelet (Body Mass) Index and Effects of Dapagliflozin in CKD. Diabetes, obesity & metabolism Chertow, G. M., Vart, P., Jongs, N., Langkilde, A. M., McMurray, J. J., Correa-Rotter, R., Rossing, P., Sjostrom, C. D., Stefansson, B. V., Toto, R. D., Wheeler, D. C., Heerspink, H. J. 1800

  Abstract

  AIMS: This post-hoc analysis of DAPA-CKD (NCT03036150) assessed the effects of dapagliflozin in patients with chronic kidney disease (CKD) and albuminuria, with and without type 2 diabetes, stratified by the Quetelet (body mass) index (BMI).METHODS: We randomized 4304 adult patients with estimated glomerular filtration rate (eGFR) of 25-75mL/min/1.73m2 and urinary albumin-to-creatinine ratio of 200-5000mg/g to dapagliflozin 10mg/day or placebo. The primary outcome was a composite of sustained decline in eGFR of ≥50%, kidney failure, or death from kidney or cardiovascular causes. Secondary outcomes included kidney composite endpoint (primary composite endpoint without cardiovascular death), cardiovascular composite endpoint (hospitalized heart failure/ cardiovascular death), and all-cause mortality. We categorized participants according to World Health Organization BMI criteria: lean/ideal (<25kg/m2 ), overweight (25-<30kg/m2 ), grade 1 obesity (30-<35kg/m2 ) and grade 2/3 obesity (≥35kg/m2 ).RESULTS: Of 4296 (99.8%) randomized participants, 888 (20.7%), 1491 (34.7%), 1136 (26.4%), and 781 (18.2%) were categorized as lean/ideal, overweight, grade 1 obesity, and grade 2/3 obesity, respectively. Median follow-up was 2.4years. Benefits of dapagliflozin were observed independent of baseline BMI for primary and secondary endpoints. Hazard ratios (95% CI) for dapagliflozin versus placebo for the primary composite endpoint were 0.60 (0.43, 0.85), 0.55 (0.40, 0.75), 0.71 (0.49, 1.04), and 0.57 (0.37, 0.87), among participants in the lean/ideal, overweight, grade 1 obesity, and grade 2/3 obesity groups (interaction p=0.72).CONCLUSION: Among participants with CKD and albuminuria, with or without type 2 diabetes, kidney and cardiovascular benefits of dapagliflozin were evident and consistent across the BMI spectrum. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/dom.14641

  View details for PubMedID 34984791

• Twenty-four-hour Urine Testing and Urinary Stone Disease Recurrence in Veterans UROLOGY Song, S., Thomas, I., Ganesan, C., Velaer, K. N., Chertow, G. M., Pao, A. C., Leppert, J. T. 2022; 159: 33-40

  View details for DOI 10.1016/j.urology.2021.10.005

  View details for Web of Science ID 000743888900008

• Renal Morbidity Following Radical Cystectomy in Patients with Bladder Cancer. European urology open science Schmidt, B., Velaer, K. N., Thomas, I., Ganesan, C., Song, S., Pao, A. C., Thong, A. E., Liao, J. C., Chertow, G. M., Skinner, E. C., Leppert, J. T. 1800; 35: 29-36

  Abstract

  Background: Patients with chronic kidney disease (CKD) are poor candidates for standard treatments for muscle-invasive bladder cancer (MIBC) and may be more likely to experience adverse outcomes when diagnosed with MIBC.Objective: To investigate factors associated with the development of advanced CKD following radical cystectomy.Design setting and participants: Using national Veterans Health Administration utilization files, we identified 3360 patients who underwent radical cystectomy for MIBC between 2004 and 2018.Outcome measurements and statistical analysis: We examined factors associated with the development of advanced CKD (estimated glomerular filtration rate [eGFR] of <30 ml/min/1.73 m2) after radical cystectomy using multivariable logistic and proportional hazard regression, with and without consideration of competing risks. We examined survival using Kaplan-Meier product limit estimates and proportional hazard regression.Results and limitations: The median age at surgery was 67 yr and the mean preoperative eGFR was 69.1 ± 20.3 ml/min/1.73 m2. Approximately three out of ten patients (n = 962, 29%) progressed to advanced CKD within 12 mo. Older age (hazard ratio [HR] per 5-yr increase 1.15, 95% confidence interval [CI] 1.10-1.20), preoperative hydronephrosis (HR 1.50, 95% CI 1.29-1.76), adjuvant chemotherapy (HR 1.19, 95% CI 1.00-1.41), higher comorbidity index (HR 1.13, 95% CI 1.11-1.16 per point), and lower baseline kidney function (HR 0.75, 95% CI 0.73-0.78) were associated with the development of advanced CKD. Baseline kidney function at the time of surgery was associated with survival. Generalizability is limited due to the predominantly male cohort.Conclusions: Impaired kidney function at baseline is associated with progression to advanced CKD and mortality after radical cystectomy. Preoperative kidney function should be incorporated into risk stratification algorithms for patients undergoing radical cystectomy.Patient summary: Impaired kidney function at baseline is associated with progression to advanced chronic kidney disease and mortality after radical cystectomy.

  View details for DOI 10.1016/j.euros.2021.11.001

  View details for PubMedID 35024629

• The CALCIPHYX study: a randomized, double-blind, placebo-controlled, Phase 3 clinical trial of SNF472 for the treatment of calciphylaxis. Clinical kidney journal Sinha, S., Gould, L. J., Nigwekar, S. U., Serena, T. E., Brandenburg, V., Moe, S. M., Aronoff, G., Chatoth, D. K., Hymes, J. L., Miller, S., Padgett, C., Carroll, K. J., Perello, J., Gold, A., Chertow, G. M. 1800; 15 (1): 136-144

  Abstract

  Background: Calcific uraemic arteriolopathy (CUA; calciphylaxis) is a rare disease seen predominantly in patients receiving dialysis. Calciphylaxis is characterized by poorly healing or non-healing wounds, and is associated with mortality, substantial morbidity related to infection and typically severe pain. In an open-label Phase 2 clinical trial, SNF472, a selective inhibitor of vascular calcification, was well-tolerated and associated with improvement in wound healing, reduction of wound-related pain and improvement in wound-related quality of life (QoL). Those results informed the design of the CALCIPHYX trial, an ongoing, randomized, placebo-controlled, Phase 3 trial of SNF472 for treatment of calciphylaxis.Methods: In CALCIPHYX, 66 patients receiving haemodialysis who have an ulcerated calciphylaxis lesion will be randomized 1:1 to double-blind SNF472 (7 mg/kg intravenously) or placebo three times weekly for 12 weeks (Part 1), then receive open-label SNF472 for 12 weeks (Part 2). All patients will receive stable background care, which may include pain medications and sodium thiosulphate, in accordance with the clinical practices of each site. A statistically significant difference between the SNF472 and placebo groups for improvement of either primary endpoint at Week 12 will demonstrate efficacy of SNF472: change in Bates-Jensen Wound Assessment Tool-CUA (a quantitative wound assessment tool for evaluating calciphylaxis lesions) or change in pain visual analogue scale score. Additional endpoints will address wound-related QoL, qualitative changes in wounds, wound size, analgesic use and safety.Conclusions: This randomized, placebo-controlled Phase 3 clinical trial will examine the efficacy and safety of SNF472 in patients who have ulcerated calciphylaxis lesions. Patient recruitment is ongoing.

  View details for DOI 10.1093/ckj/sfab117

  View details for PubMedID 35035944

• Breaking the Barriers to Innovation in Kidney Care. Clinical journal of the American Society of Nephrology : CJASN Nissenson, A., Chertow, G., Conway, P. 2022

  View details for DOI 10.2215/CJN.15721221

  View details for PubMedID 35168993

• INSIDE CKD: PROJECTING THE ECONOMIC BURDEN OF CHRONIC KIDNEY DISEASE USING PATIENT-LEVEL MICROSIMULATION Mennini, F. S., Cabrera, C. S., Card-Gowers, J., Chertow, G. M., De Nicola, L., Halimi, J. M., Nolan, S., Power, A., Retat, L., Vesga, J. F., Webber, L., Wish, J. B., Xu, M., Sanchez, G. J. ELSEVIER SCIENCE INC. 2022: S73

  View details for Web of Science ID 000746490200321

• SARS-CoV-2 Vaccine Antibody Response and Breakthrough Infection in Patients Receiving Dialysis. Annals of internal medicine Anand, S., Montez-Rath, M. E., Han, J., Garcia, P., Cadden, L., Hunsader, P., Morgan, C., Kerschmann, R., Beyer, P., Dittrich, M., Block, G. A., Chertow, G. M., Parsonnet, J. 1800

  Abstract

  BACKGROUND: Whether breakthrough SARS-CoV-2 infections after vaccination are related to the level of postvaccine circulating antibody is unclear.OBJECTIVE: To determine longitudinal antibody-based response and risk for breakthrough infection after SARS-CoV-2 vaccination.DESIGN: Prospective study.SETTING: Nationwide sample from dialysis facilities.PATIENTS: 4791 patients receiving dialysis.MEASUREMENTS: Remainder plasma from a laboratory processing routine monthly tests was used to measure qualitative and semiquantitative antibodies to the receptor-binding domain (RBD) of SARS-CoV-2. To evaluate whether peak or prebreakthrough RBD values were associated with breakthrough infection, a nested case-control analysis matched each breakthrough case patient to 5 control patients by age, sex, and vaccination month and adjusted for diabetes status and region of residence.RESULTS: Of the 4791 patients followed with monthly RBD assays, 2563 were vaccinated as of 14 September 2021. Among the vaccinated patients, the estimated proportion with an undetectable RBD response increased from 6.6% (95% CI, 5.5% to 7.8%) 14 to 30 days after vaccination to 20.2% (CI, 17.0% to 23.3%) 5 to 6 months after vaccination. Estimated median index values decreased from 91.9 (CI, 78.6 to 105.2) 14 to 30 days after vaccination to 8.4 (CI, 7.6 to 9.3) 5 to 6 months after vaccination. Breakthrough infections occurred in 56 patients, with samples collected a median of 21 days before breakthrough infection. Compared with prebreakthrough index RBD values of 23 or higher (equivalent to ≥506 binding antibody units per milliliter), prebreakthrough RBD values less than 10 and values from 10 to less than 23 were associated with higher odds for breakthrough infection (rate ratios, 11.6 [CI, 3.4 to 39.5] and 6.0 [CI, 1.5 to 23.6], respectively).LIMITATIONS: Single measure of vaccine response; ascertainment of COVID-19 diagnosis from electronic health records.CONCLUSION: The antibody response to SARS-CoV-2 vaccination wanes rapidly in persons receiving dialysis. In this population, the circulating antibody response is associated with risk for breakthrough infection.PRIMARY FUNDING SOURCE: Ascend Clinical Laboratory.

  View details for DOI 10.7326/M21-4176

  View details for PubMedID 34904856

• Dapagliflozin and new-onset type 2 diabetes in patients with chronic kidney disease or heart failure: pooled analysis of the DAPA-CKD and DAPA-HF trials. The lancet. Diabetes & endocrinology Rossing, P., Inzucchi, S. E., Vart, P., Jongs, N., Docherty, K. F., Jhund, P. S., Kober, L., Kosiborod, M. N., Martinez, F. A., Ponikowski, P., Sabatine, M. S., Solomon, S. D., DeMets, D. L., Bengtsson, O., Lindberg, M., Langkilde, A. M., Sjostrand, M., Stefansson, B. V., Karlsson, C., Chertow, G. M., Hou, F. F., Correa-Rotter, R., Toto, R. D., Wheeler, D. C., McMurray, J. J., Heerspink, H. J., DAPA-CKD and DAPA-HF Trial Committees and Investigators 2021

  Abstract

  BACKGROUND: Chronic kidney disease and heart failure are insulin resistant states associated with a high incidence of diabetes. We assessed the effect of dapagliflozin on new-onset type 2 diabetes in a pooled analysis of patient-level data from the DAPA-CKD and DAPA-HF trials.METHODS: This study is a pooled analysis of individual participant data from two phase 3, randomised, double-blind, placebo-controlled, multicentre, clinical trials. Participants with no history of diabetes and HbA1c less than 6·5% (48 mmol/mol) at baseline were included in this pooled analysis. New-onset type 2 diabetes was a prespecified exploratory endpoint in both DAPA-CKD and DAPA-HF trials and is the focus of this analysis. New-onset type 2 diabetes was identified by serial trial measurements of HbA1c (two consecutive values ≥6·5% [≥48 mmol/mol]) or following a clinical diagnosis of diabetes between trial visits. Time to new-onset type 2 diabetes was analysed in a Cox proportional Hazards model from random assignment to end of treatment.FINDINGS: 4003 participants (1398 [34·9%] from the DADA-CKD trial and 2605 [65·1%] from the DAPA-HF trial) were included in our analysis: 1995 (49·8%) had received dapagliflozin and 2008 (50·2%) had received placebo. Over a median follow-up of 21·2 months (IQR 16·0 to 25·4), 126 (6·3%) of 2008 patients in the placebo group (event rate 3·9 per 100 patient-years) and 85 (4·3%) of 1995 patients in the dapagliflozin group (event rate 2·6 per 100 patient-years) developed type 2 diabetes (hazard ratio 0·67 [95% CI 0·51 to 0·88]; p=0·0040). There was no heterogeneity between studies (p interaction 0·77) and there was no clear evidence that the effect of dapagliflozin varied in prespecified subgroups including sex, age, glycaemic status, BMI, glomerular filtration rate, systolic blood pressure, and baseline cardiovascular medication use. More than 90% of the participants who developed type 2 diabetes had prediabetes at baseline (HbA1c 5·7% to 6·4% [39 to 46 mmol/mol]). Mean HbA1c remained unchanged (placebo-adjusted change in the dapagliflozin group of -0·01% [95% CI -0·03 to 0·01], -0·1 mmol/mol [95% CI -0·3 to 0·1] at 12 months).INTERPRETATION: Treatment with dapagliflozin reduced the incidence of new-onset type 2 diabetes in participants with chronic kidney disease and HF without a reduction in HbA1c.FUNDING: AstraZeneca.

  View details for DOI 10.1016/S2213-8587(21)00295-3

  View details for PubMedID 34856173

• Safety and efficacy of dapagliflozin in patients with focal segmental glomerulosclerosis: A prespecified analysis of the DAPA-CKD trial. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association Wheeler, D. C., Jongs, N., Stefansson, B. V., Chertow, G. M., Greene, T., Hou, F. F., Langkilde, A. M., McMurray, J. J., Rossing, P., Nowicki, M., Wittmann, I., Correa-Rotter, R., Sjostrom, C. D., Toto, R. D., Heerspink, H. J., DAPA-CKD Trial Committees and Investigators 2021

  Abstract

  BACKGROUND: Despite renin-angiotensin-aldosterone-system blockade and immunosuppressive treatment, focal segmental glomerulosclerosis (FSGS) often progresses to kidney failure. The objective of this pre-specified analysis of DAPA-CKD was to assess efficacy and safety of dapagliflozin in a small subgroup participants with FSGS confirmed by kidney biopsy.METHODS: In DAPA-CKD, patients with estimated glomerular filtration rate (eGFR) 25-75mL/min/1.73m2 and urinary albumin-to-creatinine ratio (UACR) 200-5000mg/g (22.6-565mg/mol) were randomised to dapagliflozin 10mgonce-daily or placebo as an adjunct to standard care, and followed for median 2.4 years. The primary composite endpoint was sustained eGFR decline≥50%, end-stage kidney disease (ESKD), or kidney or cardiovascular death. The endpoint of interest for this analysis was eGFR slope (acute effects from baseline to Week 2 and chronic effects from Week 2 to end of treatment).RESULTS: Of 104 participants with biopsy-confirmed FSGS, 45 were randomised to dapagliflozin and 59 to placebo. Mean (SD) age was 54.0 (14.3) years, mean eGFR 41.9 (11.5) mL/min/1.73m2 and median (IQR) UACR 1248 (749-2211) mg/g. The primary outcome occurred in 4 (8.9%) and 7 (11.9%) participants randomised to dapagliflozin and placebo, respectively (HR 0.62, 95%CI 0.17-2.17). Dapagliflozin led to a larger acute reduction (SE) in eGFR compared to placebo (-4.5 [95% CI-5.9--3.1] vs-0.9 [-2.1-0.4] mL/min/1.73m2 per 2 wks). Thereafter, mean rates of chronic eGFR decline with dapagliflozin and placebo were-1.9 (-3.0--0.9) and-4.0 (-4.9--3.0) mL/min/1.73m2/year, respectively (difference 2.0 [95%CI 0.6-3.5] mL/min/1.73m2/year). Adverse events leading to study drug discontinuation were similar in both groups; there were fewer serious adverse events with dapagliflozin.CONCLUSION: Among DAPA-CKD participants with FSGS, dapagliflozin reduced the rate of chronic decline of eGFR compared to placebo, although this difference was not statistically significant.

  View details for DOI 10.1093/ndt/gfab335

  View details for PubMedID 34850160

• Timing of Antihypertensive Medications on Key Outcomes in Hemodialysis: A Cluster Randomized Trial. Kidney360 Chang, T. I., Tatoian, E. T., Montez-Rath, M. E., Chertow, G. M. 2021; 2 (11): 1752-1760

  Abstract

  Background: We conducted this study to examine the effect of taking versus holding BP medications before hemodialysis on intradialytic hypotension (IDH).Methods: In this cluster randomized trial, each dialysis unit was randomly designated as TAKE or HOLD units. Participants within a TAKE unit were instructed to take all BP medications as prescribed, whereas participants within a HOLD unit were instructed to hold medications dosed more than once daily before hemodialysis. The intervention lasted for 4 weeks. We hypothesized that TAKE would be noninferior to HOLD on the primary outcome of asymptomatic IDH, defined as ≥30% of sessions with nadir systolic BP <90 mm Hg and on the following secondary outcomes: uncontrolled hypertension (predialysis systolic BP >160 mm Hg), failure to achieve dry weight, and shortened dialysis sessions.Results: We randomized 10 dialysis units in a 1:1 ratio to TAKE or HOLD, which included 65 participants in TAKE and 66 participants in HOLD. We did not show that TAKE was noninferior to HOLD for the primary IDH outcome (mean unadjusted difference of 8%; 95% CI, -3% to 19%). TAKE was superior to HOLD for the outcome of uncontrolled hypertension (mean unadjusted difference of -15%, 95% CI, -28% to -1%). TAKE was noninferior to HOLD for the outcomes of failure to achieve dry weight and shortened dialysis sessions.Conclusions: In this cluster randomized trial that randomized patients to either taking or holding BP medications before hemodialysis, a strategy of taking BP medications dosed more than once daily was not noninferior to holding BP medications for the primary outcome of IDH, but did reduce the occurrence of uncontrolled hypertension. Whether any potential benefit of holding BP medications on reducing IDH is offset by any potential harm related to higher predialysis BP remains to be seen.

  View details for DOI 10.34067/KID.0001922021

  View details for PubMedID 35373003

• Dysgeusia and Dysosmia in Chronic Kidney Disease: NHANES 2011-2014. Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation Vengalasetti, Y. V., Chertow, G. M., Popat, R. 2021

  Abstract

  OBJECTIVE: Dysgeusia and dysosmia are known to be associated with end-stage renal disease. Whether dysgeusia and dysosmia are associated with nondialysis-requiring chronic kidney disease (CKD) is unknown.METHODS: We utilized data from the National Health and Nutrition Examination Survey during years 2011-14. We classified CKD by stage using standard criteria for the estimated glomerular filtration rate and the urine albumin-to-creatinine ratio. We used multivariable logistic regression analysis to determine the independent associations among CKD, CKD stage, and dysgeusia and dysosmia using a ChemoSensory Questionnaire.RESULTS: After adjusting for the residual effects of age, sex, self-reported race, and diabetes, nondialysis-requiring CKD was significantly associated with dysgeusia ([odds ratio, 95% confidence interval] 1.34 [1.05, 1.70]); the association with dysosmia was of borderline significance, odds ratio 1.27 (0.97, 1.68). Odds of dysgeusia were higher at more severe CKD stages.CONCLUSION: Nondialysis-requiring CKD is significantly associated with self-reported dysgeusia.

  View details for DOI 10.1053/j.jrn.2021.11.003

  View details for PubMedID 35339348

• Challenging Assumptions of Outcomes and Costs Comparing Peritoneal and Hemodialysis. Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research Lin, E., Lung, K. I., Chertow, G. M., Bhattacharya, J., Lakdawalla, D. 2021; 24 (11): 1592-1602

  Abstract

  OBJECTIVES: Policy makers have suggested increasing peritoneal dialysis (PD) would improve end-stage kidney disease (ESKD) outcomes and reduce Medicare spending compared with hemodialysis (HD). We compared mortality, hospitalizations, and Medicare spending between PD and HD among uninsured adults with incident ESKD.METHODS: Using an instrumental variable design, we exploited a natural experiment encouraging PD among the uninsured. Uninsured patients usually receive Medicare at dialysis month 4. For those initiating PD, Medicare covers the first 3 dialysis months, including predialysis services in the calendar month when dialysis started. Starting dialysis later in a calendar month increases predialysis coverage that is essential for PD catheter placements. The policy encourages PD incrementally when ESKD develops later in the month. Dialysis start day appears to be unrelated to patient characteristics and effectively "randomizes patients" to dialysis modality, mitigating selection bias.RESULTS: Starting dialysis later in the month was associated with an increased PD uptake: every week later in the month wasassociated with an absolute increase of 0.8% (95% confidence interval [CI] 0.6%-0.9%) at dialysis day 1 and 0.5% (95% CI0.3%-0.7%) at dialysis month 12. We observed no significant absolute difference between PD and HD for 12-month mortality (-0.9%, 95% CI-3.3% to 0.8%), hospitalizations during months 7 to 12 (-0.05, 95% CI-0.20 to 0.07), and Medicare spending during months 7 to 12 (-$702, 95% CI-$4004 to $2909).CONCLUSIONS: In an instrumental variable analysis, PD did not result in improved outcomes or lower costs than HD.

  View details for DOI 10.1016/j.jval.2021.05.017

  View details for PubMedID 34711359

• Obesity and Incident Kidney Disease: Busting the Myth of Metabolically Healthy Obesity. American journal of kidney diseases : the official journal of the National Kidney Foundation Anand, S., Chertow, G. M., Beddhu, S. 2021

  View details for DOI 10.1053/j.ajkd.2021.08.008

  View details for PubMedID 34728104

• Safety and Efficacy of Tenapanor for Long-term Serum Phosphate Control in Maintenance Dialysis: A 52-Week Randomized Phase 3 Trial (PHREEDOM) KIDNEY360 Block, G. A., Bleyer, A. J., Silva, A. L., Weiner, D. E., Lynn, R., Yang, Y., Rosenbaum, D. P., Chertow, G. M., PHREEDOM Study Investigators 2021; 2 (10): 1600-1610

  Abstract

  Treating hyperphosphatemia is a tenet of dialysis care. This trial assessed the safety and efficacy of tenapanor for the management of hyperphosphatemia.In this 52-week phase 3 study (NCT03427125), participants receiving maintenance dialysis with both hyperphosphatemia (serum phosphate 6.0-10.0 mg/dl) and a 1.5 mg/dl increase after phosphate binder washout were randomized (3:1) to tenapanor 30 mg twice daily for 26 weeks (randomized treatment period) or sevelamer carbonate (52-week safety control). Participants completing 26 weeks of treatment with tenapanor were rerandomized (1:1) to tenapanor or placebo for 12 weeks (randomized withdrawal period), and were eligible to enter the 14-week safety extension period. With input from the US Food and Drug Administration, the primary efficacy end point was the difference in the change in serum phosphate from the end of the randomized treatment period to the end of the randomized withdrawal period, among participants who achieved ≥1.2 mg/dl decrease in serum phosphate during the randomized treatment period (efficacy analysis set). Efficacy was also evaluated in the intention-to-treat (ITT) analysis set.Of 564 eligible participants randomized to receive tenapanor (n=423) or sevelamer carbonate (n=141) during the randomized treatment period, 255 (60%) in the tenapanor group subsequently were rerandomized to tenapanor (n=128) or placebo (n=127) during the randomized withdrawal period. In the efficacy analysis set (n=131), the difference in estimated mean change in serum phosphate level between tenapanor and placebo from the beginning to the end of the randomized withdrawal period was -1.4 mg/dl (P<0.0001); in the ITT analysis set (n=243), the estimated mean difference was -0.7 mg/dl (P=0.002). Loosened stools were the most frequently reported adverse event (53% during the randomized treatment period). Serious adverse events were reported more frequently for participants treated with sevelamer carbonate (16%-23% across the three study periods) compared with tenapanor (11%-17%).Tenapanor reduced serum phosphate concentrations and maintained control of serum phosphate in participants receiving maintenance dialysis, with an acceptable safety and tolerability profile.

  View details for DOI 10.34067/KID.0002002021

  View details for Web of Science ID 000859986400009

  View details for PubMedID 35372979

  View details for PubMedCentralID PMC8785778

• Vadadustat for Anemia in Patients with Dialysis-Dependent or Non-Dialysis-Dependent Chronic Kidney Disease NEW ENGLAND JOURNAL OF MEDICINE Chertow, G. M., Eckardt, K. 2021; 385 (16)

  View details for Web of Science ID 000706806300028

• COVID19 Vaccine Type and Humoral Immune Response in Patients Receiving Dialysis. Journal of the American Society of Nephrology : JASN Garcia, P., Anand, S., Han, J., Montez-Rath, M., Sun, S., Shang, T., Parsonnet, J., Chertow, G., Schiller, B., Abra, G. 2021

  View details for DOI 10.1681/ASN.2021070936

  View details for PubMedID 34645698

• The Predialysis Serum Sodium Level Modifies the Effect of Hemodialysis Frequency on Left-Ventricular Mass: The Frequent Hemodialysis Network Trials. Kidney & blood pressure research Raimann, J. G., Chan, C. T., Daugirdas, J. T., Depner, T., Greene, T., Kaysen, G. A., Kliger, A. S., Kotanko, P., Larive, B., Beck, G., Lindsay, R. M., Rocco, M. V., Chertow, G. M., Levin, N. W., Frequent Hemodialysis Network (FHN) Trial Group 2021: 1-9

  Abstract

  INTRODUCTION: The Frequent Hemodialysis Network (FHN) Daily and Nocturnal trials aimed to compare the effects of hemodialysis (HD) given 6 versus 3 times per week. More frequent in-center HD significantly reduced left-ventricular mass (LVM), with more pronounced effects in patients with low urine volumes. In this study, we aimed to explore another potential effect modifier: the predialysis serum sodium (SNa) and related proxies of plasma tonicity.METHODS: Using data from the FHN Daily and Nocturnal Trials, we compared the effects of frequent HD on LVM among patients stratified by SNa, dialysate-to-predialysis serum-sodium gradient (GNa), systolic and diastolic blood pressure, time-integrated sodium-adjusted fluid load (TIFL), and extracellular fluid volume estimated by bioelectrical impedance analysis.RESULTS: In 197 enrolled subjects in the FHN Daily Trial, the treatment effect of frequent HD on ∆LVM was modified by SNa. When the FHN Daily Trial participants are divided into lower and higher predialysis SNa groups (less and greater than 138 mEq/L), the LVM reduction in the lower group was substantially higher (-28.0 [95% CI -40.5 to -15.4] g) than in the higher predialysis SNa group (-2.0 [95% CI -15.5 to 11.5] g). Accounting for GNa, TIFL also showed more pronounced effects among patients with higher GNa or higher TIFL. Results in the Nocturnal Trial were similar in direction and magnitude but did not reach statistical significance.DISCUSSION/CONCLUSION: In the FHN Daily Trial, the favorable effects of frequent HD on left-ventricular hypertrophy were more pronounced among patients with lower predialysis SNa and higher GNa and TIFL. Whether these metrics can be used to identify patients most likely to benefit from frequent HD or other dialytic or nondialytic interventions remains to be determined. Prospective, adequately powered studies studying the effect of GNa reduction on mortality and hospitalization are needed.

  View details for DOI 10.1159/000519339

  View details for PubMedID 34644706

• Effect of dapagliflozin on the rate of decline in kidney function in patients with chronic kidney disease with and without type 2 diabetes: a prespecified analysis from the DAPA-CKD trial. The lancet. Diabetes & endocrinology Heerspink, H. J., Jongs, N., Chertow, G. M., Langkilde, A. M., McMurray, J. J., Correa-Rotter, R., Rossing, P., Sjostrom, C. D., Stefansson, B. V., Toto, R. D., Wheeler, D. C., Greene, T., DAPA-CKD Trial Committees and Investigators 2021

  Abstract

  BACKGROUND: Dapagliflozin reduced the risk of kidney failure in patients with chronic kidney disease with and without type 2 diabetes in the DAPA-CKD trial. In this pre-specified analysis, we assessed the effect of dapagliflozin on the rate of change in estimated glomerular filtration rate (eGFR)-ie, the eGFR slope.METHODS: DAPA-CKD was a randomised controlled trial that enrolled participants aged 18 years or older, with or without type 2 diabetes, with a urinary albumin-to-creatinine ratio (UACR) of 200-5000 mg/g, and an eGFR of 25-75 mL/min per 1·73m2. Participants were randomly assigned (1:1) to oral dapagliflozin 10 mg once daily or placebo, added to standard care. In this pre-specified analysis, we analysed eGFR slope using mixed-effect models with different slopes from baseline to week 2 (acute eGFR decline), week 2 to end of treatment (chronic eGFR slope), and baseline to end of treatment (total eGFR slope). DAPA-CKD is registered with ClinicalTrials.gov, NCT03036150, and is now complete.FINDINGS: Between Feb 2, 2017, and April 3, 2020, 4304 participants were recruited, of whom 2152 (50%) were assigned to dapagliflozin and 2152 (50%) were assigned to placebo. At baseline, the mean age was 62 years (SD 12), 1425 (33·1%) participants were women, 2906 (67·5%) participants had type 2 diabetes. The median on-treatment follow-up was 2·3 years (IQR 1·8-2·6). From baseline to the end of treatment, dapagliflozin compared with placebo slowed eGFR decline by 0·95 mL/min per 1·73 m2 per year (95% CI 0·63 to 1·27) in the overall cohort. Between baseline and week 2, dapagliflozin compared with placebo resulted in an acute eGFR decline of 2·61 mL/min per 1·73 m2 (2·16 to 3·06) in patients with type 2 diabetes and 2·01 mL/min per 1·73 m2 (1·36 to 2·66) in those without type 2 diabetes. Between week 2 and end of treatment, dapagliflozin compared with placebo reduced the mean rate of eGFR decline by a greater amount in patients with type 2 diabetes (mean difference in chronic eGFR slope 2·26 mL/min per 1·73 m2 per year [1·88 to 2·64]) than in those without type 2 diabetes (1·29 mL/min per 1·73 m2 per year [0·73 to 1·85]; pinteraction=0·0049). Between baseline and end of treatment, the effect of dapagliflozin compared with placebo on the decline of total eGFR slope in patients with type 2 diabetes was 1·18 mL/min per 1·73 m2 per year (0·79 to 1·56) and without type 2 diabetes was 0·46 mL/min per 1·73 m2 per year (-0·10 to 1·03; pinteraction=0·040). The total eGFR slope was steeper in patients with higher baseline HbA1c and UACR; the effect of dapagliflozin on eGFR slope was also more pronounced in patients with higher baseline HbA1c and UACR.INTERPRETATION: Dapagliflozin significantly slowed long-term eGFR decline in patients with chronic kidney disease compared with placebo. The mean difference in eGFR slope between patients treated with dapagliflozin versus placebo was greater in patients with type 2 diabetes, higher HbA1c, and higher UACR.FUNDING: AstraZeneca.

  View details for DOI 10.1016/S2213-8587(21)00242-4

  View details for PubMedID 34619108

• Effect of dapagliflozin on urinary albumin excretion in patients with chronic kidney disease with and without type 2 diabetes: a prespecified analysis from the DAPA-CKD trial. The lancet. Diabetes & endocrinology Jongs, N., Greene, T., Chertow, G. M., McMurray, J. J., Langkilde, A. M., Correa-Rotter, R., Rossing, P., Sjostrom, C. D., Stefansson, B. V., Toto, R. D., Wheeler, D. C., Heerspink, H. J., DAPA-CKD Trial Committees and Investigators 2021

  Abstract

  BACKGROUND: Reductions in albuminuria are associated with a subsequent lower risk of kidney failure in patients with chronic kidney disease. The SGLT2 inhibitor dapagliflozin significantly reduced albuminuria in patients with type 2 diabetes and normal or near-normal kidney function. Whether this effect persists in patients with chronic kidney disease with and without type 2 diabetes is unknown. We assessed the effects of dapagliflozin on albuminuria in patients with chronic kidney disease with and without type 2 diabetes in the dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trial.METHODS: DAPA-CKD was a multicentre, double-blind, placebo-controlled, randomised trial done at 386 sites in 21 countries. Patients were eligible for the trial if they had chronic kidney disease, defined as an estimated glomerular filtration rate (eGFR) between 25 mL/min per 1·73 m2 and 75 mL/min per 1·73 m2 and a urinary albumin-to-creatinine ratio (UACR) between 200 mg/g and 5000 mg/g (22·6 to 565·6 mg/mmol). Participants were randomly assigned to dapagliflozin 10 mg (AstraZeneca; Gothenburg, Sweden) once daily or matching placebo, in accordance with the sequestered, fixed randomisation schedule, using balanced blocks to ensure an approximate 1:1 ratio. Change in albuminuria was a pre-specified exploratory outcome of DAPA-CKD. Regression in UACR stage, defined as a transition from macroalbuminuria (≥300 mg/g) to microalbuminuria or normoalbuminuria (<300 mg/g), and progression in UACR stage, defined as a transition from less than 3000 mg/g to 3000 mg/g or greater, were additional discrete endpoints. The trial is registered with ClinicalTrials.gov, NCT03036150.FINDINGS: Between Feb 2, 2017, and April 3, 2020, 4304 patients were recruited and randomly assigned to either dapagliflozin (n=2152) or placebo (n=2152). Median UACR was 949 mg/g (IQR 477 to 1885). Overall, compared with placebo, dapagliflozin reduced geometric mean UACR by 29·3% (95% CI -33·1 to -25·2; p<0·0001); relative to placebo, treatment with dapagliflozin resulted in a geometric mean percentage change of -35·1% (95% CI -39·4 to -30·6; p<0·0001) in patients with type 2 diabetes and -14·8% (-22·9 to -5·9; p=0·0016) in patients without type 2 diabetes over the follow-up visits (pinteraction<0·0001) Among 3860 patients with UACR of 300 mg/g or greater at baseline, dapagliflozin increased the likelihood of regression in UACR stage (hazard ratio 1·81, 95% CI 1·60 to 2·05). Among 3820 patients with UACR less than 3000 mg/g at baseline, dapagliflozin decreased the risk of progression in UACR stage (0·41, 0·32 to 0·52). Larger reductions in UACR at day 14 during dapagliflozin treatment were significantly associated with attenuated eGFR decline during subsequent follow-up (beta per log unit UACR change -3·06, 95% CI -5·20 to -0·90; p=0·0056).INTERPRETATION: In patients with chronic kidney disease with and without type 2 diabetes, dapagliflozin significantly reduced albuminuria, with a larger relative reduction in patients with type 2 diabetes. The similar effects of dapagliflozin on clinical outcomes in patients with or without type 2 diabetes, but different effects on UACR, suggest that part of the protective effect of dapagliflozin in patients with chronic kidney disease might be mediated through pathways unrelated to reduction in albuminuria.FUNDING: AstraZeneca.

  View details for DOI 10.1016/S2213-8587(21)00243-6

  View details for PubMedID 34619106

• The effects of dapagliflozin on kidney and cardiovascular outcomes in patients with chronic kidney disease with and without heart failure Heerspink, J. L., Wheeler, D. C., Vart, P., Jongs, N., Hou, F. F., Langkilde, A. M., Correa-Rotter, R., Rossing, P., Sjostrom, C. D., Toto, R. D., Chertow, G. M., Stefansson, B. V., McMurray, J. V. OXFORD UNIV PRESS. 2021: 2913

  View details for Web of Science ID 000720456903214

• Inside CKD: modelling the clinical and economic impact of routine screening for albuminuria in people with type 2 diabetes Nolan, S., Arnlov, J., Batista, M. C., Chadban, S., Chertow, G. M., De Nicola, L., Halimi, J., Kanda, E., Li, G., Mennini, F. S., Navarro-Gonzalez, J. F., Power, A., Retat, L., Tangri, N., Wish, J. SPRINGER. 2021: 51

  View details for Web of Science ID 000696550100093

• TWENTY-FOUR HOUR URINE TESTING AND URINARY STONE DISEASE RECURRENCE IN VETERANS Song, S., Thomas, I., Ganesan, C., Velaer, K., Chertow, G., Pao, A., Leppert, J. LIPPINCOTT WILLIAMS & WILKINS. 2021: E374-E375

  Abstract

  To determine whether 24-hour urine testing in Veterans with USD (urinary stone disease) reduces or delays urinary stone recurrence.Cohort study of national health record data from Veterans Health Administration from 2007 through 2013. We utilized a study population of 130,129 Veterans with USD based on diagnostic or procedural codes and excluded those with USD claims in the two years before cohort entry. We then created a propensity-score matched cohort of 14,854 Veterans based on completion of 24-hour urine testing within 6 months of stone diagnosis. Primary outcome was time-to-next clinically significant stone event, defined as an emergency department visit, inpatient admission related to a urinary stone, or urologic stone procedure with 5-year follow up.Of 14,854 Veterans in the propensity-score matched cohort, 8,560 (57.6%) experienced a recurrent USD event. Completion of 24-hour urine testing was associated with a higher risk of developing a second stone event (hazard ratio (HR) 1.17, 95% confidence interval (95% CI) 1.12-1.22). Among Veterans with known recurrent disease, we examined time to a third stone event. In this cohort of 4,736 patients, completion of 24-hour urine testing was not associated with a higher risk of developing a third stone event (HR 1.06, 95% CI 0.99-1.12).Completion of 24-hour urine testing was not associated with a reduction in urinary stone recurrence. These findings challenge the validity of a longstanding recommendation in general medicine, nephrology, and urology practice.

  View details for Web of Science ID 000693688000745

  View details for PubMedID 34688771

• Efficacy and safety of dapagliflozin on kidney and cardiovascular outcomes by baseline albuminuria: a secondary analysis of the DAPA-CKD trial Heerspink, H., Waijer, S. W., Vart, P., Cherney, D. I., Chertow, G., Langkilde, A. M., McMurray, J. V., Rossing, P., Correa-Rotter, R., Stefansson, B. V., Toto, R., Wheeler, D. SPRINGER. 2021: 30

  View details for Web of Science ID 000696550100053

• Inside CKD: modelling the future global burden of chronic kidney disease in patients with type 2 diabetes Tangri, N., Arnlov, J., Batista, M. C., Chadban, S., Chertow, G. M., De Nicola, L., Halimi, J., Kanda, E., Li, G., Mennini, F. S., Navarro-Gonzalez, J. F., Power, A., Sultan, A. A., Webber, L., Wish, J. SPRINGER. 2021: 322

  View details for Web of Science ID 000696550100616

• Inside CKD: modelling the direct economic burden of concomitant chronic kidney disease and type 2 diabetes Power, A., Arnlov, J., Batista, M. C., Card-Gowers, J., Chadban, S., Chertow, G. M., De Nicola, L., Halimi, J., Kanda, E., Li, G., Mennini, F. S., Navarro-Gonzalez, J. F., Sanchez, J. G., Tangri, N., Wish, J. SPRINGER. 2021: 322-323

  View details for Web of Science ID 000696550100617

• The Contribution of Known Familial Cardiovascular Disease Genes to Sudden Cardiac Death in Patients Undergoing Hemodialysis CARDIORENAL MEDICINE Schwantes-An, T., Vatta, M., Abreu, M., Wetherill, L., Edenberg, H. J., Foroud, T. M., Chertow, G. M., Moe, S. M. 2021

  View details for DOI 10.1159/000517123

  View details for Web of Science ID 000684289700001

• The Contribution of Known Familial Cardiovascular Disease Genes to Sudden Cardiac Death in Patients Undergoing Hemodialysis. Cardiorenal medicine Schwantes-An, T. H., Vatta, M., Abreu, M., Wetherill, L., Edenberg, H. J., Foroud, T. M., Chertow, G. M., Moe, S. M. 2021; 11 (4): 174-183

  Abstract

  Patients with chronic kidney disease experience high rates of cardiovascular mortality and morbidity. When kidney disease progresses to the need for dialysis, sudden cardiac death (SCD) accounts for 25-35% of all cardiovascular deaths. The objective was to determine if rare genetic variants known to be associated with cardiovascular death in the general population are associated with SCD in patients undergoing hemodialysis.We performed a case-control study comparing 126 (37 African American [AfAn] and 89 European ancestry [EA]) SCD subjects and 107 controls (34 AfAn and 73 EA), matched for age, sex, self-reported race, dialysis duration (<2, 2-5 and >5 years), and the presence or absence of diabetes mellitus. To target the coding regions of genes previously reported to be associated with 15 inherited cardiac conditions (ICCs), we used the TruSight Cardio Kit (Illumina, San Diego, CA, USA) to capture the genetic regions of interest. In all, the kit targets 572-kb regions that include the protein-coding regions and 40-bp 5' and 3' end-flanking regions of 174 genes associated with the 15 ICCs. Using the sequence data, burden tests were conducted to identify genes with an increased number of variants among SCD cases compared to matched controls.Eleven genes were associated with SCD, but after correction for multiple testing, none of the 174 genes were identified as having more variants in the SCD cases than the matched controls, including previously identified genes. Secondary burden tests grouping variants based on diseases and gene function did not produce statistically significant associations.We found no associations between genes known to be associated with ICCs and SCD in our sample of patients undergoing hemodialysis. This suggests that genetic causes are unlikely to be a major pathogenic factor in SCD in hemodialysis patients, although our sample size limits definitive conclusions.

  View details for DOI 10.1159/000517123

  View details for PubMedID 34433165

  View details for PubMedCentralID PMC8393692

• Effects of Dapagliflozin in Patients With Kidney Disease, With and Without HeartFailure. JACC. Heart failure McMurray, J. J., Wheeler, D. C., Stefansson, B. V., Jongs, N., Postmus, D., Correa-Rotter, R., Chertow, G. M., Hou, F. F., Rossing, P., Sjostrom, C. D., Solomon, S. D., Toto, R. D., Langkilde, A. M., Heerspink, H. J., DAPA-CKD Trial Committees and Investigators 2021

  Abstract

  OBJECTIVES: The purpose of this paper was to investigate the effects of dapagliflozin in chronic kidney disease (CKD) patients, with and without heart failure (HF).BACKGROUND: Patients with CKD, with and without type 2 diabetes, were enrolled in the DAPA-CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease) trial. Some patients had HF at baseline.METHODS: A total of 4,304 participants were randomized to dapagliflozin 10mg daily or placebo. The primary composite endpoint was≥50% decline in estimated glomerular filtration rate, end-stage kidney disease, or kidney/cardiovascular death. Secondary endpoints were a kidney composite (primary endpoint minus cardiovascular death), the composite of cardiovascular death/HF hospitalization, and all-cause death. Analysis of outcomes according to HF history was prespecified.RESULTS: HF patients (n=468; 11%) were older and had more coronary disease, atrial fibrillation, and type 2 diabetes. Mean estimated glomerular filtration rate was similar in patients with and without HF. Rates of HF hospitalization/cardiovascular death and death from any cause were higher in HF patients, but the secondary kidney failure outcome occurred at the same rate in people with and without HF. Dapagliflozin reduced the risk of the primary outcome equally in patients with HF (HR: 0.58 [95%CI: 0.37-0.91]) and without HF (HR: 0.62 [95%CI: 0.51-0.75]) (P interaction=0.59). The proportional risk-reductions were similar in patients with and without HF for the cardiovascular death/HF hospitalization composite (HR: 0.68 [95%CI: 0.44-1.05] vs HR: 0.70 [95%CI: 0.51-0.97], respectively; P interaction=0.90), and all-cause death (HR: 0.56 [95%CI: 0.34-0.93] vs HR: 0.73 [95%CI: 0.54-0.97], respectively; P interaction=0.39), although absolute risk reductions were larger in HF patients. Adverse event rates were low and did not differ among patients with or without HF.CONCLUSIONS: Dapagliflozin reduced the risk of kidney failure and cardiovascular death/HF hospitalization and prolonged survival in CKD patients with or without type 2 diabetes, independently of history of HF. (A Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients With Chronic Kidney Disease [DAPA-CKD]; NCT03036150).

  View details for DOI 10.1016/j.jchf.2021.06.017

  View details for PubMedID 34446370

• Consensus-Based Recommendations for the Management of Hyperkalemia in the Hemodialysis Setting. Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation Fishbane, S., Charytan, D. M., Chertow, G. M., Ford, M., Kovesdy, C. P., Pergola, P. E., Pollock, C., Spinowitz, B. 2021

  Abstract

  Hyperkalemia (serum K+ >5.0mmol/L) is commonly observed among patients receiving maintenance hemodialysis and associated with increased risk of cardiac arrhythmias. Current international guidelines may not reflect the latest evidence on managing hyperkalemia in patients undergoing hemodialysis, and there is a lack of high-quality published studies in this area. This consensus guideline aims to provide recommendations in relation to clinical practice. Available published evidence was evaluated through a systematic literature review, and the nominal group technique was used to develop consensus recommendations from a panel of experienced nephrologists, covering monitoring, dietary restrictions, prescription of K+ binders, and concomitant prescription of renin-angiotensin-aldosterone system inhibitors. Recent studies have shown that K+ binders reduce the incidence of hyperkalemia, but further evidence is needed in areas including whether reduced-K+ diets or treatment with K+ binders improve patient-centered outcomes. Treatment of hyperkalemia in the hemodialysis setting is complex, and decisions need to be tailored for individual patients.

  View details for DOI 10.1053/j.jrn.2021.06.003

  View details for PubMedID 34364782

• THE EFFECT OF DAPAGLIFLOZIN IN PATIENTS WITH EGFR < 30 ML/MIN/1.73M2: FINDINGS FROM THE DAPA-CKD TRIAL Chertow, G., Vart, P., Jongs, N., Toto, R., Gorriz, J. L., Hou, F. F., Mcmurray, J., Correa-Rotter, R., Rossing, P., Sjostrom, C. D., Stefansson, B. V., Langkilde, A. M., Wheeler, D. C., Heerspink, H. L. WILEY. 2021: 33-34

  View details for Web of Science ID 000689277100097

• The potential roles of osmotic and non-osmotic sodium handling in mediating effects of SGLT2 inhibitors on heart failure. Journal of cardiac failure Bjornstad, P., Greasley, P. J., Wheeler, D. C., Chertow, G. M., Langkilde, A. M., Heerspink, H. J., van Raalte, D. H. 2021

  Abstract

  Concomitant type 2 diabetes and chronic kidney disease (CKD) increases the risk of heart failure (HF). Recent STUDIES: demonstrate beneficial effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on CKD progression and HF hospitalization in patients with and without diabetes. In addition to inhibiting glucose reabsorption, SGLT2i reduce proximal tubular sodium reabsorption, possibly leading to transient natriuresis. We review the hypothesis that SGLT2i's natriuretic and osmotic diuretic effects mediate their cardio-protective effects. The degree to which these benefits are related to changes in sodium, independent of the kidney, is currently unknown. Aside from effects on osmotically active sodium, we explore the intriguing possibility that SGLT2i could also modulate non-osmotic sodium storage. This alternative hypothesis is based on emerging literature that challenges the traditional two-compartment model of sodium balance to provide support for a three-compartment model that includes the binding of sodium to glycosaminoglycans, such as those in muscles and skin. This recent research on non-osmotic sodium storage, as well as direct cardiac effects of SGLT2i, provides possibilities for other ways in which SGLT2i might mitigate HF risk. Overall, we review the effects of SGLT2i on sodium balance and sensitivity, cardiac tissue, interstitial fluid and plasma volume, and non-osmotic sodium storage.

  View details for DOI 10.1016/j.cardfail.2021.07.003

  View details for PubMedID 34289398

• Effects of Dapagliflozin in Stage 4 Chronic Kidney Disease. Journal of the American Society of Nephrology : JASN Chertow, G., Vart, P., Jongs, N., Toto, R., Gorriz, J. L., Hou, F. F., McMurray, J., Correa-Rotter, R., Rossing, P., Sjostrom, C. D., Stefansson, B., Langkilde, A. M., Wheeler, D., Heerspink, H. 2021

  Abstract

  Background In the Dapagliflozin And Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) randomized placebo-controlled trial, the sodium-glucose cotransporter 2 inhibitor dapagliflozin significantly reduced risk of kidney failure and prolonged survival in CKD patients with or without type 2 diabetes. Methods In this prespecified analysis of dapagliflozin's effects in patients with stage 4 CKD (eGFR<30 mL/min per 1.73m2) at baseline, we randomized adults with eGFR of 25-75 mL/min per 1.73m2 and urinary albumin-to-creatinine ratio of 200-5000 mg/g to receive dapagliflozin 10 mg/day or placebo. The primary outcome was a composite of time to ≥50% sustained decline in eGFR, end-stage kidney disease, or kidney or cardiovascular death. Secondary outcomes were a kidney composite (same as the primary endpoint but without cardiovascular death), a composite of cardiovascular death or heart failure hospitalization, and all-cause death. Results A total of 293 participants received dapagliflozin and 331 received placebo. Relative to placebo, dapagliflozin was associated with reductions in the primary composite endpoint (hazard ratio [HR], 0.73; 95% confidence interval [95% CI], 0.53 to 1.0), the kidney endpoint (HR, 0.71; 95% CI, 0.49 to 1.02), the cardiovascular endpoint (HR, 0.83; 95% CI, 0.45 to 1.53), and the mortality endpoint (HR, 0.68; 95% CI, 0.39 to 1.21). The eGFR slope declined by 2.15 and 3.38 mL/min per 1.73m2 per year in the dapagliflozin and placebo groups, respectively (P=0.005). Patients treated with dapagliflozin or placebo had similar rates of serious adverse events and adverse events of interest. Conclusions Among patients with stage 4 CKD and albuminuria, dapagliflozin's benefits were consistent with those observed in the DAPA-CKD trial overall, with no evidence of increased risks.

  View details for DOI 10.1681/ASN.2021020167

  View details for PubMedID 34272327

• Utility of Phosphate Binder Equivalent Dose Concept Reply JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Pergola, P. E., Rosenbaum, D. P., Yang, Y., Chertow, G. M. 2021; 32 (7): 1824-1825

  View details for DOI 10.1681/ASN.2021050606

  View details for Web of Science ID 000753511400026

• Authors' Reply. Journal of the American Society of Nephrology : JASN Pergola, P. E., Rosenbaum, D. P., Yang, Y., Chertow, G. M. 2021; 32 (7): 1824-1825

  View details for DOI 10.1681/ASN.2021050606

  View details for PubMedID 36630522

  View details for PubMedCentralID PMC8425642

• SNF472: mechanism of action and results from clinical trials. Current opinion in nephrology and hypertension Sinha, S., Raggi, P., Chertow, G. M. 2021; 30 (4): 424-429

  Abstract

  PURPOSE OF REVIEW: Vascular calcification (VC) is associated with increased cardiovascular event rates, particularly in patients with end-stage kidney disease (ESKD). Dysregulated mineral metabolism and inflammation have been shown to promote VC, however, treatment options targeting VC specifically are not available. This review outlines the pathophysiological mechanisms contributing to VC in ESKD and describes recent studies evaluating the effects of the first-in-class inhibitor of VC, SNF472.RECENT FINDINGS: SNF472 directly inhibits calcium phosphate crystal formation and aggregation. SNF472 has completed early phase clinical trials with a favourable safety profile and Phase 2 clinical trial data have shown attenuation of coronary artery and aortic valve calcification in patients receiving hemodialysis.SUMMARY: Therapeutic agents that directly target VC may prevent the multiple complications associated with dystrophic calcification in patients with ESKD.

  View details for DOI 10.1097/MNH.0000000000000726

  View details for PubMedID 34027904

• Patient-Reported Experiences with Dialysis Care and Provider Visit Frequency. Clinical journal of the American Society of Nephrology : CJASN Brady, B. M., Zhao, B., Dang, B. N., Winkelmayer, W. C., Chertow, G. M., Erickson, K. F. 2021; 16 (7): 1052-1060

  Abstract

  New payment models resulting from the Advancing American Kidney Health initiative may create incentives for nephrologists to focus less on face-to-face in-center hemodialysis visits. This study aimed to understand whether more frequent nephrology practitioner dialysis visits improved patient experience and could help inform future policy.In a cross-sectional study of patients receiving dialysis from April 1, 2015 through January 31, 2016, we linked patient records from a national kidney failure registry to patient experience data from the In-Center Hemodialysis Consumer Assessment of Healthcare Providers and Systems survey. We used a multivariable mixed effects linear regression model to examine the association between nephrology practitioner visit frequency and patient-reported experiences with nephrologist care.Among 5125 US dialysis facilities, 2981 (58%) had ≥30 In-Center Hemodialysis Consumer Assessment of Healthcare Providers and Systems surveys completed between April 2015 and January 2016, and 243,324 patients receiving care within these facilities had Medicare Parts A/B coverage. Face-to-face practitioner visits per month were 71% with four or more visits, 17% with two to three visits, 4% with one visit, and 8% with no visits. Each 10% absolute greater proportion of patients seen by their nephrology practitioner(s) four or more times per month was associated with a modestly but statistically significant lower score of patient experience with nephrologist care by -0.3 points (95% confidence interval, -0.5 to -0.1) and no effect on experience with other domains of dialysis care.In an analysis of patient experiences at the dialysis facility level, frequent nephrology practitioner visits to facilities where patients undergo outpatient hemodialysis were not associated with better patient experiences.

  View details for DOI 10.2215/CJN.16621020

  View details for PubMedID 34597265

  View details for PubMedCentralID PMC8425623

• Karnofsky Performance Score-Failure to Thrive as a Frailty Proxy? Transplantation direct Stedman, M. R., Watford, D. J., Chertow, G. M., Tan, J. C. 2021; 7 (7): e708

  Abstract

  Among patients listed for kidney transplantation, the Karnofsky Performance Status (KPS) Scale has been used as a proxy for frailty and proposed as a predictor of long-term posttransplant outcomes. The KPS is required by the Organ Procurement and Transplantation Network for all transplants; however, the interrater reliability of KPS reporting in kidney transplant candidates has not been well investigated, and there is concern regarding limitations of using KPS that may influence transplant eligibility.Methods: We performed an observational study using existing Scientific Registry of Transplant Recipients data from 2006 to 2020 to examine the variability, reliability, and trends in the KPS among patients on the kidney transplant waitlist.Results: Our analysis included 8197 kidney transplant candidates with >1 KPS in a 3-mo period. We observed 2-7 scores per patient with an average score of 78.9 (SD = 12, 95% confidence interval, 78.8-79.1). We found substantial variability in KPS reporting, in which 27% of the patients had scores that varied widely with 20-80 points in difference. Interrater reliability in the 10-point scale was poor (30%). When using a condensed 4-category scale (disabled, requires assistance, capable of self-care, normal activity), 38% of patients experienced at least a 1-category shift in their score.Conclusions: The lack of reliability in KPS reporting raises concerns when applying the KPS as a proxy for frailty and a metric to be considered when evaluating candidacy for kidney transplantation.

  View details for DOI 10.1097/TXD.0000000000001164

  View details for PubMedID 34124344

• Chronic Inflammation in Chronic Kidney Disease Progression: Role of Nrf2 KIDNEY INTERNATIONAL REPORTS Stenvinkel, P., Chertow, G. M., Devarajan, P., Levin, A., Andreoli, S. P., Bangalore, S., Warady, B. A. 2021; 6 (7): 1775-1787

  View details for DOI 10.1016/j.ekir.2021.04.023

  View details for Web of Science ID 000671872900006

• Chronic Inflammation in Chronic Kidney Disease Progression: Role of Nrf2. Kidney international reports Stenvinkel, P., Chertow, G. M., Devarajan, P., Levin, A., Andreoli, S. P., Bangalore, S., Warady, B. A. 2021; 6 (7): 1775-1787

  Abstract

  Despite recent advances in the management of chronic kidney disease (CKD), morbidity and mortality rates in these patients remain high. Although pressure-mediated injury is a well-recognized mechanism of disease progression in CKD, emerging data indicate that an intermediate phenotype involving chronic inflammation, oxidative stress, hypoxia, senescence, and mitochondrial dysfunction plays a key role in the etiology, progression, and pathophysiology of CKD. A variety of factors promote chronic inflammation in CKD, including oxidative stress and the adoption of a proinflammatory phenotype by resident kidney cells. Regulation of proinflammatory and anti-inflammatory factors through NF-κB- and nuclear factor, erythroid 2 like 2 (Nrf2)-mediated gene transcription, respectively, plays a critical role in the glomerular and tubular cell response to kidney injury. Chronic inflammation contributes to the decline in glomerular filtration rate (GFR) in CKD. Whereas the role of chronic inflammation in diabetic kidney disease (DKD) has been well-elucidated, there is now substantial evidence indicating unresolved inflammatory processes lead to fibrosis and eventual end-stage kidney disease (ESKD) in several other diseases, such as Alport syndrome, autosomal-dominant polycystic kidney disease (ADPKD), IgA nephropathy (IgAN), and focal segmental glomerulosclerosis (FSGS). In this review, we aim to clarify the mechanisms of chronic inflammation in the pathophysiology and disease progression across the spectrum of kidney diseases, with a focus on Nrf2.

  View details for DOI 10.1016/j.ekir.2021.04.023

  View details for PubMedID 34307974

  View details for PubMedCentralID PMC8258499

• Estimated SARS-CoV-2 Seroprevalence in US Patients Receiving Dialysis 1 Year After the Beginning of the COVID-19 Pandemic. JAMA network open Anand, S., Montez-Rath, M., Han, J., Cadden, L., Hunsader, P., Kerschmann, R., Beyer, P., Boyd, S. D., Garcia, P., Dittrich, M., Block, G. A., Parsonnet, J., Chertow, G. M. 2021; 4 (7): e2116572

  Abstract

  Importance: Seroprevalence studies complement data on detected cases and attributed deaths in assessing the cumulative spread of the SARS-CoV-2 virus.Objective: To estimate seroprevalence of SARS-CoV-2 antibodies in patients receiving dialysis and adults in the US in January 2021 before the widespread introduction of COVID-19 vaccines.Design, Setting, and Participants: This cross-sectional study used data from the third largest US dialysis organization (US Renal Care), which has facilities located nationwide, to estimate SARS-CoV-2 seroprevalence among US patients receiving dialysis. Remainder plasma (ie, plasma that would have otherwise been discarded) of all patients receiving dialysis at US Renal Care facilities from January 1 to 31, 2021, was tested for SARS-CoV-2 antibodies. Patients were excluded if they had a documented dose of SARS-CoV-2 vaccination or if a residence zip code was missing from electronic medical records. Crude seroprevalence estimates from this sample (January 2021) were standardized to the US adult population using the 2018 American Community Survey 1-year estimates and stratified by age group, sex, self-reported race/ethnicity, neighborhood race/ethnicity composition, neighborhood income level, and urban or rural status. These data and case detection rates were then compared with data from a July 2020 subsample of patients who received dialysis at the same facilities.Exposures: Age, sex, race/ethnicity, and region of residence as well as neighborhood race/ethnicity composition, poverty, population density, and urban or rural status.Main Outcomes and Measures: The spike protein receptor-binding domain total antibody assay (Siemens Healthineers; manufacturer-reported sensitivity of 100% and specificity of 99.8%) was used to estimate crude SARS-CoV-2 seroprevalence in the unweighted sample, and then the estimated seroprevalence rates for the US dialysis and adult populations were calculated, adjusting for age, sex, and region.Results: A total of 21 464 patients (mean [SD] age, 63.1 [14.2] years; 12 265 men [57%]) were included in the unweighted sample from January 2021. The patients were disproportionately older (aged 65-79 years, 7847 [37%]; aged ≥80 years, 2668 [12%]) and members of racial/ethnic minority groups (Hispanic patients, 2945 [18%]; non-Hispanic Black patients, 4875 [29%]). Seroprevalence of SARS-CoV-2 antibodies was 18.9% (95% CI, 18.3%-19.5%) in the sample, with a seroprevalence of 18.7% (95% CI, 18.1%-19.2%) standardized to the US dialysis population, and 21.3% (95% CI, 20.3%-22.3%) standardized to the US adult population. In the unweighted sample, younger persons (aged 18-44 years, 25.9%; 95% CI, 24.1%-27.8%), those who self-identified as Hispanic or living in Hispanic neighborhoods (25.1%; 95% CI, 23.6%-26.4%), and those living in the lowest-income neighborhoods (24.8%; 95% CI, 23.2%-26.5%) were among the subgroups with the highest seroprevalence. Little variability was observed in seroprevalence by geographic region, population density, and urban or rural status in the January 2021 sample (largest regional difference, 1.2 [95% CI, 1.1-1.3] higher odds of seroprevalence in residents of the Northeast vs West).Conclusions and Relevance: In this cross-sectional study of patients receiving dialysis in the US, fewer than 1 in 4 patients had evidence of SARS-CoV-2 antibodies 1 year after the first case of SARS-CoV-2 infection was detected in the US. Results standardized to the US population indicate similar prevalence of antibodies among US adults. Vaccine introduction to younger individuals, those living in neighborhoods with a large population of racial/ethnic minority residents, and those living in low-income neighborhoods may be critical to disrupting the spread of infection.

  View details for DOI 10.1001/jamanetworkopen.2021.16572

  View details for PubMedID 34251441

• Patient-Reported Experiences with Dialysis Care and Provider Visit Frequency CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Brady, B. M., Zhao, B., Dang, B. N., Winkelmayer, W. C., Chertow, G. M., Erickson, K. F. 2021; 16 (7): 1052-1060

  View details for DOI 10.2215/CJN.16621020

  View details for Web of Science ID 000675905100012

• Efficacy and Safety of Dapagliflozin by Baseline Glycemic Status: A Prespecified Analysis From the DAPA-CKD Trial. Diabetes care Persson, F., Rossing, P., Vart, P., Chertow, G. M., Hou, F. F., Jongs, N., McMurray, J. J., Correa-Rotter, R., Bajaj, H. S., Stefansson, B. V., Toto, R. D., Langkilde, A. M., Wheeler, D. C., Heerspink, H. J., DAPA-CKD Trial Committees and Investigators 2021

  Abstract

  OBJECTIVE: The Dapagliflozin and Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD) study demonstrated risk reduction for kidney and cardiovascular outcomes with dapagliflozin versus placebo in participants with chronic kidney disease (CKD) with and without diabetes. We compared outcomes according to baseline glycemic status.RESEARCH DESIGN AND METHODS: We enrolled participants with CKD, estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73m2, and urinary albumin-to-creatinine ratio 200-5,000 mg/g. The primary composite end point was sustained eGFR decline ≥50%, end-stage kidney disease, or kidney or cardiovascular death.RESULTS: Of 4,304 participants, 738 had normoglycemia, 660 had prediabetes, and 2,906 had type 2 diabetes. The effect of dapagliflozin on the primary outcome was consistent (P for interaction = 0.19) in normoglycemia (hazard ratio [HR] 0.62 [95% CI 0.39, 1.01]), prediabetes (HR 0.37 [0.21, 0.66]), and type 2 diabetes (HR 0.64 [0.52, 0.79]). We found no evidence for effect modification on any outcome. Adverse events were similar, with no major hypoglycemia or ketoacidosis in participants with normoglycemia or prediabetes.CONCLUSIONS: Dapagliflozin safely reduced kidney and cardiovascular events independent of baseline glycemic status.

  View details for DOI 10.2337/dc21-0300

  View details for PubMedID 34183431

• Primary Nephrotic Syndrome and Risks of ESKD, Cardiovascular Events, and Death: The Kaiser Permanente Nephrotic Syndrome Study. Journal of the American Society of Nephrology : JASN Go, A. S., Tan, T. C., Chertow, G. M., Ordonez, J. D., Fan, D., Law, D., Yankulin, L., Wojcicki, J. M., Zheng, S., Chen, K. K., Khoshniat-Rad, F., Yang, J., Parikh, R. V. 2021

  Abstract

  BACKGROUND: Little population-based data exist about adults with primary nephrotic syndrome.METHODS: To evaluate kidney, cardiovascular, and mortality outcomes in adults with primary nephrotic syndrome, we identified adults within an integrated health care delivery system (Kaiser Permanente Northern California) with nephrotic-range proteinuria or diagnosed nephrotic syndrome between 1996 and 2012. Nephrologists reviewed medical records for clinical presentation, laboratory findings, and biopsy results to confirm primary nephrotic syndrome and assigned etiology. We identified a 1:100 time-matched cohort of adults without diabetes, diagnosed nephrotic syndrome, or proteinuria as controls to compare rates of ESKD, cardiovascular outcomes, and death through 2014, using multivariable Cox regression.RESULTS: We confirmed 907 patients with primary nephrotic syndrome (655 definite and 252 presumed patients with FSGS [40%], membranous nephropathy [40%], and minimal change disease [20%]). Mean age was 49 years; 43% were women. Adults with primary nephrotic syndrome had higher adjusted rates of ESKD (adjusted hazard ratio [aHR], 19.63; 95% confidence interval [95% CI], 12.76 to 30.20), acute coronary syndrome (aHR, 2.58; 95% CI, 1.89 to 3.52), heart failure (aHR, 3.01; 95% CI, 2.16 to 4.19), ischemic stroke (aHR, 1.80; 95% CI, 1.06 to 3.05), venous thromboembolism (aHR, 2.56; 95% CI, 1.35 to 4.85), and death (aHR, 1.34; 95% CI, 1.09 to 1.64) versus controls. Excess ESKD risk was significantly higher for FSGS and membranous nephropathy than for presumed minimal change disease. The three etiologies of primary nephrotic syndrome did not differ significantly in terms of cardiovascular outcomes and death.CONCLUSIONS: Adults with primary nephrotic syndrome experience higher adjusted rates of ESKD, cardiovascular outcomes, and death, with significant variation by underlying etiology in the risk for developing ESKD.

  View details for DOI 10.1681/ASN.2020111583

  View details for PubMedID 34362836

• Reply to the Editorial Comment on: Using an Automated Electronic Health Record Score To Estimate Life Expectancy In Men Diagnosed With Prostate Cancer In The Veterans Health Administration. Urology. 2021. Urology Soerensen, S. J., Thomas, I., Schmidt, B., Daskivich, T., Skolarus, T. A., Jackson, C., Osborne, T. F., Chertow, G. M., Brooks, J. D., Rehkopf, D., Leppert, J. T. 2021

  Abstract

  OBJECTIVES: To determine if an automatically calculated electronic health record score can estimate intermediate-term life expectancy in men with prostate cancer to provide guideline concordant care.METHODS: We identified all men (n=36,591) diagnosed with prostate cancer in 2013-2015 in the VHA. Of the 36,591, 35,364 (96.6%) had an available Care Assessment Needs (CAN) score (range: 0-99) automatically calculated in the 30 days prior to the date of diagnosis. It was designed to estimate short-term risks of hospitalization and mortality. We fit unadjusted and multivariable Cox proportional hazards regression models to determine the association between the CAN score and overall survival among men with prostate cancer. We compared CAN score performance to two established comorbidity measures: The Charlson Comorbidity Index and Prostate Cancer Comorbidity Index (PCCI).RESULTS: Among 35,364 men, the CAN score correlated with overall stage, with mean scores of 46.5 (±22.4), 58.0 (±24.4), and 68.1 (±24.3) in localized, locally advanced, and metastatic disease, respectively. In both unadjusted and adjusted models for prostate cancer risk, the CAN score was independently associated with survival (HR=1.23 95%CI 1.22-1.24 & adjusted HR=1.17 95%CI 1.16-1.18 per 5-unit change, respectively). The CAN score (overall C-Index 0.74) yielded better discrimination (AUC=0.76) than PCCI (AUC=0.65) or Charlson Comorbidity Index (AUC=0.66) for 5-year survival.CONCLUSIONS: The CAN score is strongly associated with intermediate-term survival following a prostate cancer diagnosis. The CAN score is an example of how learning health care systems can implement multi-dimensional tools to provide fully automated life expectancy estimates to facilitate patient-centered cancer care.

  View details for DOI 10.1016/j.urology.2021.05.056

  View details for PubMedID 34139251

• Antibody Response to COVID-19 Vaccination in Patients Receiving Dialysis. Journal of the American Society of Nephrology : JASN Anand, S., Montez-Rath, M., Han, J., Garcia, P., Cadden, L., Hunsader, P., Kerschmann, R., Beyer, P., Dittrich, M., Block, G., Boyd, S., Parsonnet, J., Chertow, G. 2021

  View details for DOI 10.1681/ASN.2021050611

  View details for PubMedID 34117129

• HOSPITALIZATION IN PATIENTS RECEIVING MAINTENANCE DIALYSIS WITH HYPERPHOSPHATEMIA RANDOMIZED TO TENAPANOR OR SEVELAMER Stephenson, B., Chertow, G., Yang, Y., Rosenbaum, D. ELSEVIER SCIENCE INC. 2021: S234

  View details for Web of Science ID 000660039401286

• Invasive Management of Coronary Artery Disease in Advanced Renal Disease. Kidney international reports Karimi Galougahi, K., Chadban, S., Mehran, R., Bangalore, S., Chertow, G. M., Ali, Z. A. 2021; 6 (6): 1513-1524

  Abstract

  Coronary artery disease (CAD) is highly prevalent in chronic kidney disease (CKD). CKD modifies the effects of traditional risk factors on atherosclerosis, with CKD-specific mechanisms, such as inflammation and altered mineral metabolism, playing a dominant pathophysiological role as kidney function declines. Traditional risk models and cardiovascular screening tests perform relatively poorly in the CKD population, and medical treatments including lipid-lowering therapies have reduced efficacy. Clinical presentation of cardiac ischemia in CKD is atypical, whereas invasive therapies are associated with higher rates of complications than in with patients with normal or near normal kidney function. The main focus of the present review is on the invasive approach to management of CAD in late-stage CKD, with an in-depth discussion of the findings of the International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA)-CKD trial, and their implications for therapeutic approach and future research in this area. We also briefly discuss the existing evidence in the epidemiology, pathogenesis, diagnosis, and medical management of CAD in late-stage CKD, end-stage kidney disease (ESKD), and kidney transplant recipients. We enumerate the evidence gap left by the frequent exclusion of patients with CKD from randomized controlled trials and highlight the priority areas for future research in the CKD population.

  View details for DOI 10.1016/j.ekir.2021.02.041

  View details for PubMedID 34169192

• Poor Reliability of Karnofsky Performance Score in Kidney Transplant Candidates Stedman, M. R., Watford, D. J., Chertow, G. M., Tan, J. C. WILEY. 2021: 662

  View details for Web of Science ID 000705310102383

• Performance versus Risk Factor-Based Approaches to Coronary Artery Disease Screening in Waitlisted Kidney Transplant Candidates. Cardiorenal medicine Cheng, X. S., Watford, D. J., Arashi, H., Stedman, M. R., Chertow, G. M., Tan, J. C., Fearon, W. F. 2021: 1-11

  Abstract

  INTRODUCTION: Current screening algorithms for coronary artery disease (CAD) before kidney transplantation result in many tests but few interventions.OBJECTIVE: The aim of this study was to study the utility of 6-minute walk test (6MWT), an office-based test of cardiorespiratory fitness, for risk stratification in this setting.METHODS: We enrolled 360 patients who are near the top of the kidney transplant waitlist at our institution. All patients underwent CAD evaluation irrespective of 6MWT results. We examined the association between 6MWT and time to CAD-related events (defined as cardiac death, revascularization, nonfatal myocardial infarction, and removal from the waitlist for CAD), treating noncardiac death and waitlist removal for non-CAD reasons as competing events.RESULTS: The 6MWT-based approach designated approximately 45% of patients as "low risk," whereas a risk factor- or symptom-based approach designated 14 and 81% of patients as "low risk," respectively. The 6MWT-based approach was not significantly associated with CAD-related events within 1 year (subproportional hazard ratio [sHR] 1.00 [0.90-1.11] per 50 m) but was significantly associated with competing events (sHR 0.70 [0.66-0.75] per 50 m). In a companion analysis, removing waitlist status from consideration, 6MWT result was associated with the development of CAD-related events (sHR 0.92 [0.84-1.00] per 50 m).CONCLUSIONS: The 6MWT designates fewer patients as high risk and in need of further testing (compared to risk factor-based approaches), but its utility as a pure CAD risk stratification tool is modulated by the background waitlist removal rate. CAD screening before kidney transplant should be tailored according to a patient's actual chance of receiving a transplant.

  View details for DOI 10.1159/000516158

  View details for PubMedID 34034263

• Serial SARS-CoV-2 Receptor-Binding Domain Antibody Responses in Patients Receiving Dialysis. Annals of internal medicine Anand, S., Montez-Rath, M. E., Han, J., Garcia, P., Cadden, L., Hunsader, P., Kerschmann, R., Beyer, P., Boyd, S. D., Chertow, G. M., Parsonnet, J. 2021

  Abstract

  BACKGROUND: Assessing the evolution of SARS-CoV-2 immune response among patients receiving dialysis can define its durability in a highly clinically relevant context because patients receiving dialysis share the characteristics of persons most susceptible to SARS-CoV-2 infection.OBJECTIVE: To evaluate the persistence of SARS-CoV-2 receptor-binding domain (RBD) IgG in seroprevalent patients receiving dialysis.DESIGN: Prospective.SETTING: Nationwide sample from dialysis facilities.PATIENTS: 2215 patients receiving dialysis who had evidence of SARS-CoV-2 infection as of July 2020.MEASUREMENTS: Remainder plasma from routine monthly laboratories was used to measure semiquantitative RBD IgG index value over 6 months.RESULTS: A total of 2063 (93%) seroprevalent patients reached an assay detectable response (IgG index value ≥1). Most (n = 1323, 60%) had responses in July with index values classified as high (IgG ≥10); 1003 (76%) remained within this stratum. Adjusted median index values declined slowly but continuously (July vs. December values were 21 vs. 13; P < 0.001). The trajectory of the response did not vary by age group, sex, race/ethnicity, or diabetes status. Patients without an assay detectable response (n = 137) were more likely to be White and in the younger (18 to 44 years) or older (≥80 years) age groups and less likely to have diabetes and hypoalbuminemia.LIMITATION: Lack of data on symptoms or reverse transcriptase polymerase chain reaction diagnosis, cohort of persons who survived infection, and use of a semiquantitative assay.CONCLUSION: Despite impaired immunity, most seropositive patients receiving dialysis maintained RBD antibody levels over 6 months. A slow and continual decline in median antibody levels over time was seen, but no indication that subgroups with impaired immunity had a shorter-lived humoral response was found.PRIMARY FUNDING SOURCE: Ascend Clinical Laboratories.

  View details for DOI 10.7326/M21-0256

  View details for PubMedID 34000201

• National Estimates of CKD Prevalence and Potential Impact of Estimating Glomerular Filtration Rate Without Race. Journal of the American Society of Nephrology : JASN Duggal, V., Thomas, I., Montez-Rath, M. E., Chertow, G. M., Kurella Tamura, M. 2021

  Abstract

  BACKGROUND: The implications of removing the adjustment for Black race in equations to eGFR on the prevalence of CKD and management strategies are incompletely understood.METHODS: We estimated changes in CKD prevalence and the potential effect on therapeutic drug prescriptions and prediction of kidney failure if race adjustment were removed from the CKD-EPI GFR estimating equation. We used cross-sectional and longitudinal data from adults aged ≥18 years in the National Health and Nutrition Examination Survey (NHANES) from 2015 to 2016, and the Veterans Affairs (VA) Health Care System in 2015. In the VA cohort, we assessed use of common medications that require dose adjustment on the basis of kidney function, and compared the prognostic accuracy of the Kidney Failure Risk Equation with versus without race adjustment of eGFR.RESULTS: The prevalence of CKD among Black adults increased from 5.2% to 10.6% in NHANES, and from 12.4% to 21.6% in the VA cohort after eliminating race adjustment. Among Black veterans, 41.0% of gabapentin users, 33.5% of ciprofloxacin users, 24.0% of metformin users, 6.9% of atenolol users, 6.6% of rosuvastatin users, and 5.8% of tramadol users were reclassified to a lower eGFR for which dose adjustment or discontinuation is recommended. Without race adjustment of eGFR, discrimination of the Kidney Failure Risk Equation among Black adults remained high and calibration was marginally improved overall, with better calibration at higher levels of predicted risk.CONCLUSIONS: Removal of race adjustment from CKD-EPI eGFR would double the estimated prevalence of CKD among Black adults in the United States. Such a change is likely to affect a sizeable number of drug-dosing decisions. It may also improve the accuracy of kidney failure risk prediction among higher-risk Black adults.

  View details for DOI 10.1681/ASN.2020121780

  View details for PubMedID 33958490

• Barriers to ACEI/ARB Use in Proteinuric Chronic Kidney Disease: An Observational Study. Mayo Clinic proceedings McCoy, I. E., Han, J., Montez-Rath, M. E., Chertow, G. M. 2021

  Abstract

  OBJECTIVE: To assess present angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) use among patients with proteinuric chronic kidney disease (CKD) and examine barriers limiting this guideline-concordant care.PATIENTS AND METHODS: Using a nationwide database containing patient-level claims and integrated clinical information, we examined current ACEI/ARB prescriptions on the index date (April 15, 2017) and prior ACEI/ARB use in 41,743 insured adults with proteinuric CKD. Using multivariable logistic regression, we estimated adjusted associations between current ACEI/ARB use and putative barriers including past acute kidney injury (AKI), hyperkalemia, advanced CKD, and lack of nephrology care.RESULTS: Only 49% (n=20,641) of patients had an active ACEI/ARB prescription on the index date, but 87% (n=36,199) had been previously prescribed an ACEI/ARB. Use was lower in patients with past AKI, hyperkalemia, CKD stages 4 or 5, and a lack of nephrology care (adjusted odds ratios were 0.61 [95% CI, 0.58 to 0.64], 0.76 [95% CI, 0.72 to 0.80], 0.48 [95% CI, 0.45 to 0.51], and 0.85 [95% CI, 0.81 to 0.89], respectively).CONCLUSION: Discontinuing, rather than never initiating, ACEI/ARB treatment limits guideline-concordant care in proteinuric CKD. Past AKI, hyperkalemia, advanced CKD, and lack of nephrology care were associated with lower use of ACEIs/ARBs, but these putative barriers may in many instances be inappropriate (AKI and advanced CKD) or modifiable (hyperkalemia and lack of nephrology care).

  View details for DOI 10.1016/j.mayocp.2020.12.038

  View details for PubMedID 33952396

• Body Composition Changes Following Dialysis Initiation and Cardiovascular and Mortality Outcomes in CRIC (Chronic Renal Insufficiency Cohort): A Bioimpedance Analysis Substudy. Kidney medicine Wang, K., Zelnick, L. R., Chertow, G. M., Himmelfarb, J., Bansal, N. 2021; 3 (3): 327

  Abstract

  Rationale & Objective: Bioelectrical impedance analysis (BIA) provides a noninvasive assessment of body composition. BIA measures of nutritional (phase angle) and hydration (vector length) status are associated with survival among individuals with chronic kidney disease (CKD), including those receiving maintenance dialysis. However, little is known regarding changes in these parameters with CKD following the high-risk transition to maintenance dialysis.Study Design: Observational study.Settings & Participants: 427 adults enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study, with BIA measurements performed within 1 year before and after initiation of maintenance dialysis.Exposures: We calculated the changes in vector length and phase angle for patients with CKD transitioning to maintenance dialysis.Outcomes: We examined the association of changes in vector length and phase angle during the transition to maintenance dialysis with risk for all-cause mortality or nonfatal myocardial infarction, stroke, or heart failure, adjusting for demographics, comorbid conditions, and nutritional parameters.Results: Mean age was 58 ± 12 years and mean estimated glomerular filtration rate using the CKD Epidemiology Collaboration equation before dialysis initiation was 17.0 ± 8.7 mL/min/1.73 m2. After covariate adjustment, mean changes in vector length and phase angle were 18 (95% CI, 7 to 30) Omega/m and-0.6 (95% CI,-1.3 to 0.1), respectively. Changes in both BIA parameters were not associated with risk for heart failure, stroke, myocardial infarction, or all-cause mortality: HR, 1.02 (95% CI, 0.91-1.14) per 1-SD increment in change for vector length and HR, 1.11 (95% CI, 0.88-1.41) per 1-SD increment in change for phase angle.Limitations: Observational study, relatively small sample size.Conclusions: In a multicenter cohort of patients with CKD who progressed to kidney failure, the transition to maintenance dialysis was associated with changes in body composition reflecting poorer cellular integrity and improved volume control. However, these longitudinal changes were not associated with adverse clinical events after dialysis initiation.

  View details for DOI 10.1016/j.xkme.2020.12.008

  View details for PubMedID 34136778

• SARS-COV-2 VACCINE ACCEPTABILITY IN PATIENTS ON DIALYSIS: A NATIONWIDE SURVEY Garcia, P., Montez-Rath, M., Moore, H., Flotte, J., Fults, C., Block, M., Han, J., Dittrich, M., Parsonnet, J., Chertow, G., Block, G., Anand, S. W B SAUNDERS CO-ELSEVIER INC. 2021: 831

  View details for Web of Science ID 000642322000031

• DAPAGLIFLOZIN DECREASES ALBUMINURIA IN PATIENTS WITH CHRONIC KIDNEY DISEASE WITH AND WITHOUT TYPE 2 DIABETES: INSIGHTS FROM THE DAPA-CKD TRIAL Jong, N., Chertow, G., Hou, F., McMurray, J., Correa-Rotter, R., Rossing, P., Sjostrom, D., Stefansson, B., Toto, R., Langkilde, A., Wheeler, D. C., Heerspink, H. OXFORD UNIV PRESS. 2021

  View details for Web of Science ID 000713465601391

• INSIDE CKD: MODELLING THE ECONOMIC BURDEN OF CHRONIC KIDNEY DISEASE IN THE AMERICAS AND THE ASIA-PACIFIC REGION USING PATIENT-LEVEL MICROSIMULATION Sultan, A., Batista, M., Cabrera, C., Card-Gowers, J., Chadban, S., Chertow, G., Sanchez, J., Kanda, E., Li, G., Nolan, S., Retat, L., Tangri, N., Webber, L., Wish, J., Xu, M. OXFORD UNIV PRESS. 2021

  View details for Web of Science ID 000713465600279

• INSIDE CKD: MODELLING THE IMPACT OF IMPROVED SCREENING FOR CHRONIC KIDNEY DISEASE IN THE AMERICAS AND ASIA-PACIFIC REGION Garcia Sanchez, J., Sultan, A., Batista, M., Cabrera, C., Card-Gowers, J., Chadban, S., Chertow, G., Kanda, E., Li, G., Nolan, S., Retat, L., Tangri, N., Webber, L., Wish, J., Xu, M. OXFORD UNIV PRESS. 2021

  View details for Web of Science ID 000713465600247

• SARS-CoV-2 Vaccine Acceptability in Patients on Hemodialysis: A Nationwide Survey. Journal of the American Society of Nephrology : JASN Garcia, P., Montez-Rath, M. E., Moore, H., Flotte, J., Fults, C., Block, M. S., Han, J., Dittrich, M., Parsonnet, J., Chertow, G. M., Block, G. A., Anand, S. 2021

  Abstract

  BACKGROUND: Patients on dialysis are at increased risk for COVID-19-related complications. However, a substantial fraction of patients on dialysis belong to groups more likely to be hesitant about vaccination.METHODS: With the goal of identifying strategies to increase COVID-19 vaccine uptake among patients on hemodialysis, we conducted a nationwide vaccine acceptability survey, partnering with a dialysis network to distribute an anonymized English and Spanish language online survey in 150 randomly selected facilities in the United States. We used logistic regression to evaluate characteristics of vaccine-hesitant persons.RESULTS: A total of 1515 (14% of eligible) patients responded; 20% of all responders, 29% of patients aged 18-44 years, and 29% of Black responders reported being hesitant to seek the COVID-19 vaccine, even if the vaccine was considered safe for the general population. Odds of vaccine hesitancy were higher among patients aged 18-44 years versus those 45-64 years (odds ratio [OR], 1.5; 95% confidence interval [95% CI], 1.0 to 2.3), Black patients versus non-Hispanic White patients (OR, 1.9; 95% CI, 1.3 to 2.7), Native Americans or Pacific Islanders versus non-Hispanic White patients (OR, 2.0; 95% CI, 1.1 to 3.7), and women versus men (OR, 1.6; 95% CI, 1.2 to 2.0). About half (53%) of patients who were vaccine hesitant expressed concerns about side effects. Responders' main information sources about COVID-19 vaccines were television news and dialysis staff (68% and 38%, respectively).CONCLUSIONS: A substantial proportion of patients receiving in-center hemodialysis in the United States are hesitant about seeking COVID-19 vaccination. Facilitating uptake requires outreach to younger patients, women, and Black, Native American, or Pacific Islander patients, and addressing concerns about side effects.

  View details for DOI 10.1681/ASN.2021010104

  View details for PubMedID 33927004

• Safety and Efficacy of Vadadustat for Anemia in Patients Undergoing Dialysis. The New England journal of medicine Eckardt, K., Agarwal, R., Aswad, A., Awad, A., Block, G. A., Bacci, M. R., Farag, Y. M., Fishbane, S., Hubert, H., Jardine, A., Khawaja, Z., Koury, M. J., Maroni, B. J., Matsushita, K., McCullough, P. A., Lewis, E. F., Luo, W., Parfrey, P. S., Pergola, P., Sarnak, M. J., Spinowitz, B., Tumlin, J., Vargo, D. L., Walters, K. A., Winkelmayer, W. C., Wittes, J., Zwiech, R., Chertow, G. M. 2021; 384 (17): 1601–12

  Abstract

  BACKGROUND: Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, a class of compounds that stimulate endogenous erythropoietin production.METHODS: We conducted two randomized, open-label, noninferiority phase 3 trials to evaluate the safety and efficacy of vadadustat, as compared with darbepoetin alfa, in patients with anemia and incident or prevalent dialysis-dependent chronic kidney disease (DD-CKD). The primary safety end point, assessed in a time-to-event analysis, was the first occurrence of a major adverse cardiovascular event (MACE, a composite of death from any cause, a nonfatal myocardial infarction, or a nonfatal stroke), pooled across the trials (noninferiority margin, 1.25). A key secondary safety end point was the first occurrence of a MACE plus hospitalization for either heart failure or a thromboembolic event. The primary and key secondary efficacy end points were the mean change in hemoglobin from baseline to weeks 24 to 36 and from baseline to weeks 40 to 52, respectively, in each trial (noninferiority margin, -0.75 g per deciliter).RESULTS: A total of 3923 patients were randomly assigned in a 1:1 ratio to receive vadadustat or darbepoetin alfa: 369 in the incident DD-CKD trial and 3554 in the prevalent DD-CKD trial. In the pooled analysis, a first MACE occurred in 355 patients (18.2%) in the vadadustat group and in 377 patients (19.3%) in the darbepoetin alfa group (hazard ratio, 0.96; 95% confidence interval [CI], 0.83 to 1.11). The mean differences between the groups in the change in hemoglobin concentration were -0.31 g per deciliter (95% CI, -0.53 to -0.10) at weeks 24 to 36 and -0.07 g per deciliter (95% CI, -0.34 to 0.19) at weeks 40 to 52 in the incident DD-CKD trial and -0.17 g per deciliter (95% CI, -0.23 to -0.10) and -0.18 g per deciliter (95% CI, -0.25 to -0.12), respectively, in the prevalent DD-CKD trial. The incidence of serious adverse events in the vadadustat group was 49.7% in the incident DD-CKD trial and 55.0% in the prevalent DD-CKD trial, and the incidences in the darbepoetin alfa group were 56.5% and 58.3%, respectively.CONCLUSIONS: Among patients with anemia and CKD who were undergoing dialysis, vadadustat was noninferior to darbepoetin alfa with respect to cardiovascular safety and correction and maintenance of hemoglobin concentrations. (Funded by Akebia Therapeutics and Otsuka Pharmaceutical; INNO2VATE ClinicalTrials.gov numbers, NCT02865850 and NCT02892149.).

  View details for DOI 10.1056/NEJMoa2025956

  View details for PubMedID 33913638

• Vadadustat in Patients with Anemia and Non-Dialysis-Dependent CKD. The New England journal of medicine Chertow, G. M., Pergola, P. E., Farag, Y. M., Agarwal, R., Arnold, S., Bako, G., Block, G. A., Burke, S., Castillo, F. P., Jardine, A. G., Khawaja, Z., Koury, M. J., Lewis, E. F., Lin, T., Luo, W., Maroni, B. J., Matsushita, K., McCullough, P. A., Parfrey, P. S., Roy-Chaudhury, P., Sarnak, M. J., Sharma, A., Spinowitz, B., Tseng, C., Tumlin, J., Vargo, D. L., Walters, K. A., Winkelmayer, W. C., Wittes, J., Eckardt, K., PRO2TECT Study Group, Porto, A., Glenny, J., Alvarisqueta, A., Vallejos, A., Cusumano, C., Chacon, C., Garcia, C., Goycoa, C., Stoppa, D., Otreras, F., Gorosito, G., Beresan, H., MacKinnon, I., Resk, J., Santos, J., Bittar, J., Schiavi, L., Rista, L., Maurich, M., Mansilla, M., Pelagagge, M., Garcia, N., Penalba, N., Ramallo, P., Calella, P., Leon de la Fuente, R., Visco, V., Irish, A., McMahon, L., Mathew, M., Suranyi, M., Boudville, N., Phoon, R., Ford, S., McDonald, S., Ludvik, B., Wiesholzer, M., Costa E Forti, A., Sousa, A., Goncalves, B., Teles Barretto, C., Fraga, C., Rinaldi Dos Santos, D., Miltersteiner, D., D'Avila, D., Contieri, F., Veronese, F., Neto, G., Sander, G., de Lourdes Noronha, I., Rodrigues Bacci, M., Gomes Bastos, M., Mara da Silva, M., Canziani, M., Paschoalin, N., Simoes Pires von Eye, O., Macedo de Souza, P., Silva, P., Armani, R., Barbieri, D., Paschoalin, R., Montenegro, R. J., Franco, R., Pecoits Filho, R., Yamada, S., Duro Garcia, V., Vasileva, A., Angelova, A., Kostadinova, A., Kundurdziev, A., Bogov, B., Kostadinova, D., Popov, I., Ashikova, K., Nikolova-Dimitrova, M., Petrova-Obretenova, P., Rangelov, R., Boyadzhieva, S., Vasilev, S., Bakardzhiev, T., Staykova, T., Atanasova, V., Hristov, V., Iliev, V., Simeonov, V., Todorova, V., Hristozov, V., Ting, R., Boltansky Brenner, A., Schneider Contreras, H., Garcia Lozada, H., Rueda Hernandez, J., Terront Lozano, M., Parikova, A., Dusilova Sulkova, S., Tesar, V., Mariat, C., Thervet, E., Fessi, H., Kazes, I., Lang, P., Rosenberger, C., Draganova, D., Toussaint, K., Krueger, T., Ladanyi, A., Palinkas, A., Csiky, B., Literati-Nagy, B., Pall, D., Magyar, K., Major, L., Zsom, M., Molnar, M., Keresztesi, S., Zolyomi, S., Szabo, T., Szelestei, T., Nemeth, Z., Szigeti, Z., Beberashvili, I., Hassan, K., Assady, S., Yagil, Y., Naticchia, A., Gambaro, G., Esposito, C., Aucella, F., Garibotto, G., Nicola, L. D., Vecchio, L. D., Zacchia, M., Ondei, P., David, S., Yang, C., Koh, E., Song, H., Chin, H., Joo, K., Han, S., Jo, S., Han, S., Yoo, S., An, W., Kim, Y., Kim, T., Kim, Y., Ching, C., Ong, L., Mohd, R., Lim, S., Leguizamo Dimas, A., Calvo Vargas, C., Tellez Chavez, E., Pelayo Orozco, E., Flores Lozano, F., Murguia Martin, F., Quintana Pina, F., Sanchez Mijangos, J., Tamayo Y Orozco, J., Herrara Jimenez, L., Nevarez Ruiz, L., Islas Guerrero, M., Vazquez Contreras, P., Austria Garcia, P., Banda Elizondo, R., Orozco Castellanos, R., Monreal Puente, R., Avila Pardo, S., Irizar Santana, S., Irigoyen Monroy, V., Limas Juarez, A., Pescador Martinez, Y., Achim, C., Bogeanu, C., David, C., Peride, I., Bako, G., Petrica, L., Vishnevsky, A., Smirnov, A., Pichkov, D., Reznik, E., Vaskina, E., Tsyba, L., Rossovskaya, M., Fomina, N., Barysheva, O., Kostitsina, O., Lesnyak, O., Sigitova, O., Ageeva, T., Marasaev, V., Tirmenstajn-Jankovic, B., Maksic, D., Maric, I., Velickovic-Radovanovic, R., Damjanovic, T., Dimkovic, N., Lazarevic, T., Lezaic, V., Krajnakova, A., Bobak, L., Vojtko, M., Muranda, A., Rayner, B., Malan, D., Engelbrecht, J., van Zyl, L., Van Jaarsveld, M., Mollentze, W., Sarvan, M., Nortje, M., Makanda, M. B., Ayoob, N., Chelin, N., Welkovics, N., Naiker, P., Moodley, R., Arnold, S., Govind, U., Naidoo, V., Galan Serrano, A., Garcia Carro, C., Hernandez Marrero, D., Gonzalez Martinez, F., Sanjuan, J., Ballarin Castan, J., Molas Coten, J., Torras Ambros, J., Hernandez-Jaras, J., Santos, J. P., Baro Salvador, M., Munar Vila, M., Slon Roblero, M., Yildiz, A., Kalender, B., Duranay, M., Tuglular, S., Ursol, G., Dudar, I., Rudyk, I., Vyshnyvetskyy, I., Kolesnyk, M., Tryshchuk, N., Pyvovarova, N., Sydor, N., Legun, O., Levchenko, O., Lyulko, O., Godlevska, O., Matushchak, O., Abrahamovych, O., Yatsyshyn, R., Kolupayev, S., Kostynenko, T., Vizir, V., Maslovskyi, V., Stus, V., Mostovoy, Y., Mikhail, A., Vilar, E., Yaqoob, M., Wilkie, M., El Kossi, M., Kalra, P., Shah, S., Nossuli, A. K., Jamal, A., Buridi, A., Murillo, A., Khan, A., Ijaz, A., Aswad, A., Awad, A., Sawhney, A., Esquenazi, A., Velar, A., Sprague, A., O'Shaughnessy, A., Agarwal, A., Parikh, S., Terrelonge, A., Dhandayuthapani, A., Chauhan, R., Silva, A., Mehta, A., Chaudhry, A., Bailey, A., Buerkert, J., Jones, A., Turk, T., Torres Consuegra, A., Sachdeva, B., Mehta, B., Thajudeen, B., Roy-Chaudhury, P., Spinowitz, B., Voinescu, C. G., Leon-Forero, C., Martinez, C., Ortiz-Butcher, C., Hernandez, C., Montoya, M., Arora, C., Sun, C., Argyropoulos, C., Galphin, C., Gadegbeku, C., Kovesdy, C., Christiano, C., Checketts, D., Arfaania, D., Goldfarb, D., Scott, D., Tietjen, D., Whittman, D., Price, D., Rizos, D., Dev, D., Belo, D., Brandon, D., Lanier, D., Hopkins, E., Linfert, D., Shemin, D., Gonzalez, E., Cosby, J., Rodriguez-Araya, E., Brown, E., Galindo-Ramos, E., Al-Saghir, F., Bangash, F., Castillo, F., Cid, J., Trespalacios, F., Finkelstein, F., Varghese, F., Vaz, G., Ramamurthy, G., Garcia Saez, G., Fadda, G., Hon, G., Nassar, G., Bueso, G., Diaz, G., Varallo, G., Pitone, J., Alvarez, G., Hernandez, G., Hadi, G., De La Calle, G., Krishna, G., Allen, G. J., Greenwood, G., Stewart, D., Toka, H., Boghara, H., Kumar, H., Niegos, F., Brar, H., Hubert, H., Szerlip, H., Farooq, H., Gonzalez, H., Martinez, L., Cosma, I., Drakakis, J., Shirazian, S., Reich, J., Tumlin, J., Colomar, J., Kumar, J., Moya, J., Rimmer, J., Navarro, J., Li, J., Meyer, J., Topf, J., Pullman, J., Alvarez-Moreno, J., Loredo, J., Posada, J., Fernandez, J., Gandhi, K., Servilla, K., Mootoo, K., Hendon, K., Choi, K., Bashir, K., Shah, K., Lalwani, T., Chaudhary, K., Thomas, K. V., Kooienga, L., Block, G., Forgosh, L., Spry, L., Adan, L., Glaser, L., Schneider, L., Seney, F., Lewy Alterbaum, L., Diaz-Secades, L., Perez, G., Garcia-Mayol, L., Bodell, M., Martinson, M., Sahani, M., Montero, M., Sanchez, M., Chang, M., Guillen, M., Henriquez, M., Lawrence, M., Vernace, M., Chan, M., Anger, M., Levey, S., Chang, I., Fredericks, M., Germain, M., Hassman, M., Levine, M., Patel, M., Issa, M., Dhillon, M., Moustafa, M., Siddiqui, N., Vo, N., Shahid, N., Atray, N., Khosla, N., Chronos, N., Stankus, N., Daboul, N., Frontela, O., Mendez, J., Ayodeji, O., Adler, O., Pergola, P., Kalirao, P., Peters, P., Santos, P., Van Buren, P., Lazowski, P., Ranjan, P., Krish, P., Suchinda, P., Gonzalez, R., Grillo, R., Abdullah, R., Zabaneh, R., Alappan, R., Yalavarthy, R., Patak, R., Berenji, R., Guadiz, R., Mendez, R., Sastre, R., Gaona, R., John, R., Sothinathan, R., Darwish, R., O'Donovan, R., Sandler, R., Szewc, R., Manllo-Karim, R., Gupta, R., Afsari, R., Raina, R., Benjamin, S., Kronfli, S., Sonbol, S., Butt, S., Sader, S., Kantor, S., Anand, S., Sharma, S., Dua, S., Kharait, S., Mandayam, S., Sitar, S., Zeig, S., Handelsman, S., Clarke, S., Joshi, S., Lalla-Reddy, S., Lee, S., Mustafa, E., Boone, T., Hart, T., Pillai, U., Subramanian, V., Prasad, V., Din, Z. 2021; 384 (17): 1589–1600

  Abstract

  BACKGROUND: Vadadustat is an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor, a class of drugs that stabilize HIF and stimulate erythropoietin and red-cell production.METHODS: In two phase 3, randomized, open-label, active-controlled, noninferiority trials, we compared vadadustat with the erythropoiesis-stimulating agent (ESA) darbepoetin alfa in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) not previously treated with an ESA who had a hemoglobin concentration of less than 10 g per deciliter and in patients with ESA-treated NDD-CKD and a hemoglobin concentration of 8 to 11 g per deciliter (in the United States) or 9 to 12 g per deciliter (in other countries). The primary safety end point, assessed in a time-to-event analysis, was the first major adverse cardiovascular event (MACE; a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke), pooled across the two trials. Secondary safety end points included expanded MACE (MACE plus hospitalization for either heart failure or a thromboembolic event). The primary and key secondary efficacy end points in each trial were the mean change in hemoglobin concentration from baseline during two evaluation periods: weeks 24 through 36 and weeks 40 through 52.RESULTS: A total of 1751 patients with ESA-untreated NDD-CKD and 1725 with ESA-treated NDD-CKD underwent randomization in the two trials. In the pooled analysis, in which 1739 patients received vadadustat and 1732 received darbepoetin alfa, the hazard ratio for MACE was 1.17 (95% confidence interval [CI], 1.01 to 1.36), which did not meet the prespecified noninferiority margin of 1.25. The mean between-group differences in the change in the hemoglobin concentration at weeks 24 through 36 were 0.05 g per deciliter (95% CI, -0.04 to 0.15) in the trial involving ESA-untreated patients and -0.01 g per deciliter (95% CI, -0.09 to 0.07) in the trial involving ESA-treated patients, which met the prespecified noninferiority margin of -0.75 g per deciliter.CONCLUSIONS: Vadadustat, as compared with darbepoetin alfa, met the prespecified noninferiority criterion for hematologic efficacy but not the prespecified noninferiority criterion for cardiovascular safety in patients with NDD-CKD. (Funded by Akebia Therapeutics and Otsuka Pharmaceutical; PRO2TECT ClinicalTrials.gov numbers, NCT02648347 and NCT02680574.).

  View details for DOI 10.1056/NEJMoa2035938

  View details for PubMedID 33913637

• Targeting Sedentary Behavior in CKD: A Pilot and Feasibility Randomized Controlled Trial. Clinical journal of the American Society of Nephrology : CJASN Lyden, K., Boucher, R., Wei, G., Zhou, N., Christensen, J., Chertow, G. M., Greene, T., Beddhu, S. 2021

  Abstract

  BACKGROUND AND OBJECTIVES: We tested the feasibility of reducing sedentary behavior common in CKD.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We carried out a Sit Less, Interact, Move More intervention in a 24-week parallel-group, randomized controlled trial in patients with stages 2-5 CKD. In the intervention group (n=54), accelerometry performed at baseline and repeated every 4 weeks was used to develop and monitor adherence to individualized plans targeting sedentary and stepping durations. The control group (n=52) was provided national physical activity recommendations; accelerometry was performed at baseline and every 8 weeks. Between-groups changes from baseline to the average follow-up values at weeks 8, 16, and 24 of the sedentary and stepping durations were the coprimary end points.RESULTS: The mean age was 69±13 years. Fourteen percent were on dialysis or received a kidney transplant. Eight percent of the control group and 17% of the intervention group were lost to follow-up. Sedentary and stepping durations did not change in the control group. Within the intervention group, the maximum decrease in sedentary duration (-43; 95% confidence interval, -69 to -17 min/d) and increase in stepping duration (16; 95% confidence interval, 7 to 24 min/d) and the number of steps per day (1265; 95% confidence interval, 518 to 2012) were seen at week 20. These attenuated at week 24. In mixed effects models, overall treatment effects between groups on sedentary (-17; 95% confidence interval, -43 to 8 min/d) and stepping (6; 95% confidence interval, -3 to 15 min/d) durations and the number of steps per day, a secondary end point (652; 95% confidence interval, -146 to 1449), were not significantly different. The intervention significantly reduced secondary end points of body mass index (-1.1; 95% confidence interval, -1.9 to -0.3 kg/m2) and body fat percentage (-2.1%; 95% confidence interval, -4.4% to -0.2%).CONCLUSIONS: It is feasible to reduce sedentary duration and increase stepping duration in patients with CKD, but these were not sustained.CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: National Health and Nutrition Examination Survey (NHANES), NCT02970123.

  View details for DOI 10.2215/CJN.12300720

  View details for PubMedID 33888536

• The Organ Procurement Costs of Expanding Deceased Donor Organ Acceptance Criteria: Evidence from a Cost Function Model. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons Cheng, X. S., Held, P. J., Dor, A., Bragg-Gresham, J. L., Tan, J. C., Scandling, J. D., Chertow, G. M., Roberts, J. P. 2021

  Abstract

  A potential solution to the deceased donor organ shortage is to expand donor acceptability criteria. The procurement cost implications of using non-standard donors is unknown. Using five years of United States (US) organ procurement organization (OPO) data, we built a cost function model to make cost projections: the total cost was the dependent variable; production outputs, including the number of donors and organs procured, were the independent variables. In the model, procuring one kidney from a donor (single-organ donor) or procuring both kidneys from double/en bloc transplantation resulted in a marginal cost of $55k (95% confidence interval [CI] $28k-$99k) per kidney, and procuring only the liver from a donor results in a marginal cost of $41k (95% CI $12k-69k) per liver. Procuring two kidneys for two candidates from a donor lowered the marginal cost to $36k (95% CI $22k-$66k) per kidney, and procuring two kidneys and a liver lowers the marginal cost to $24k per organ (95% CI $17k-$45k). Economies of scale were observed, where high OPO volume correlated with lower costs. Despite higher cost per organ than for standard donors, kidney transplantation from non-standard donors remained cost effective based on contemporary US data.

  View details for DOI 10.1111/ajt.16617

  View details for PubMedID 33884757

• Effects of Myo-inositol Hexaphosphate (SNF472) on Bone Mineral Density in Patients Receiving Hemodialysis: An Analysis of the Randomized, Placebo-Controlled CaLIPSO Study. Clinical journal of the American Society of Nephrology : CJASN Bushinsky, D. A., Raggi, P., Bover, J., Ketteler, M., Bellasi, A., Rodriguez, M., Sinha, S., Garg, R., Perello, J., Gold, A., Chertow, G. M., CaLIPSO Investigators, CaLIPSO Study Group Clinipace GmbH, I. I., Nash, K. W., Kaskas, M. O., Martin, E. R., Bernardo, M. V., Mehta, B., Hon, G., Meyer, J. M., Steer, D. L., Bhat, P., Kapoian, T., Sullivan, J. 3., Kopyt, N. P., Zeig, S., Cuellar, J. M., Lynn, R. I., Roer, D. A., Gandhi, N. D., Kleinman, K. S., Arenas Guadiz, R. N., Yan, J., Seek, M. M., Durham, W. T., Rakowski, D. A., Topf, J. M., Lehrner, L. M., Graham, S. L., Jamal, A. Z., Khawar, O. S., Dua, S., Patak, R. V., Navarro, J. O., Irby, B. P., Joshi, S. S., Darwish, R. Y., Anger, M. S., Gandhi, K. V., Al-Saghir, F., Jim, B., Singh, H., Belart Rodriguez, M. M., Parra, E. G., Planas Pons, A. F., Nieto, S. C., Ibeas Lopez, J. A., Escola, J. M., Marques, G. G., Diaz Gomez, J. M., Portillo, M. R., Buades Fuster, J. M., Terrades, N. R., Fernandez, I. M., Puchades Montesa, M. J., Vila, P. M., Vilaro, M. I., Lazo, M. S., Arnal, L. M., Varela, J. C., Sarro Sobrin, J. F., Canals, F. M., Sinha, S., Mitra, S., Hutchinson, A., Eardley, K. S., Balasubramaniam, G., Mikhail, A., Bansal, T. 2021

  Abstract

  BACKGROUND AND OBJECTIVES: In the CaLIPSO study, intravenous administration of SNF472 (300 or 600 mg) during hemodialysis significantly attenuated progression of coronary artery and aortic valve calcification. SNF472 selectively inhibits formation of hydroxyapatite, the final step in cardiovascular calcification. Because bone mineral is predominantly hydroxyapatite, we assessed changes in bone mineral density in CaLIPSO.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients with coronary artery calcification at screening (Agatston score of 100-3500 U) were randomized 1:1:1 to receive placebo, 300 mg SNF472, or 600 mg SNF472 as an intravenous infusion during hemodialysis three times weekly for 52 weeks. Dual-energy x-ray absorptiometry (DXA) scans were obtained at baseline (screening) and end of treatment, and between-group changes from baseline were compared using analysis of covariance.RESULTS: Among 274 randomized patients, 202 had evaluable DXA scans at baseline and postrandomization (the DXA-modified intention-to-treat population). Mean (95% confidence interval) changes in total-hip bone mineral density from baseline to week 52 were -1.5% (-2.7% to -0.3%), -1.5% (-2.7% to -0.4%), and -2.5% (-3.8% to -1.2%) in the placebo, 300 mg SNF472, and 600 mg SNF472 groups, respectively. Mean (95% confidence interval) changes in femoral-neck bone mineral density from baseline to week 52 were -0.3% (-1.6% to 1.0%), -1.0% (-2.3% to 0.2%), and -2.6% (-4.0% to -1.3%), respectively. Regression analyses showed no correlation between change in coronary artery calcium volume and change in bone mineral density at either location. Changes in serum alkaline phosphatase, calcium, magnesium, phosphate, and intact parathyroid hormone levels were similar across treatment groups. Clinical fracture events were reported for four of 90, three of 92, and six of 91 patients in the placebo, 300 mg SNF472, and 600 mg SNF472 groups, respectively.CONCLUSIONS: Bone mineral density decreased modestly in all groups over 1 year. In the 600 mg SNF472 group, the reduction appeared more pronounced. Reported fractures were infrequent in all groups.CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Effect of SNF472 on Progression of Cardiovascular Calcification in End-Stage-Renal-Disease (ESRD) Patients on Hemodialysis (HD), NCT02966028.

  View details for DOI 10.2215/CJN.16931020

  View details for PubMedID 33835939

• Effects of dapagliflozin on mortality in patients with chronic kidney disease: a pre-specified analysis from the DAPA-CKD randomized controlled trial. European heart journal Heerspink, H. J., Sjostrom, C. D., Jongs, N., Chertow, G. M., Kosiborod, M., Hou, F. F., McMurray, J. J., Rossing, P., Correa-Rotter, R., Kurlyandskaya, R., Stefansson, B. V., Toto, R. D., Langkilde, A. M., Wheeler, D. C., DAPA-CKD Trial Committees and Investigators, Heerspink, H. J., Wheeler, D. C., Chertow, G., Correa-Rotter, R., Greene, T., Fan Hou, F., McMurray, J., Rossing, P., Toto, R., Stefansson, B., Maria Langkilde, A., Maffei, L. E., Raffaele, P., Solis, S. E., Arias, C. A., Aizenberg, D., Luquez, C., Zaidman, C., Cluigt, N., Mayer, M., Alvarisqueta, A., Wassermann, A., Maldonado, R., Bittar, J., Maurich, M., Gaite, L. E., Garcia, N., Sivak, L., Ramallo, P. O., Santos, J. C., Garcia Duran, R., Oddino, J. A., Maranon, A., Maia, L. N., D Avila, D., Barros, E. J., Vidotti, M. H., Panarotto, D., Noronha, I. D., Turatti, L. A., Deboni, L., Canziani, M. E., Riella, M. C., Bacci, M. R., Paschoalin, R. P., Franco, R. J., Goldani, J. C., St-Amour, E., Steele, A. W., Goldenberg, R., Pandeya, S., Bajaj, H., Cherney, D., Kaiser, S. M., Conway, J. R., Chow, S. S., Bailey, G., Lafrance, J., Winterstein, J., Cournoyer, S., Gaudet, D., Madore, F., Houlden, R. L., Dowell, A., Langlois, M., Muirhead, N., Khandwala, H., Levin, A., Hou, F., Xue, Y., Zuo, L., Hao, C., Ni, Z., Xing, C., Chen, N., Dong, Y., Zhou, R., Xiao, X., Zou, Y., Wang, C., Liu, B., Chen, Q., Lin, M., Luo, Q., Zhang, D., Wang, J., Chen, M., Wang, X., Zhong, A., Dong, J., Zhu, C., Yan, T., Luo, P., Ren, Y., Pai, P., Li, D., Zhang, R., Zhang, J., Xu, M., Zhuang, Y., Kong, Y., Yao, X., Peng, X., Persson, F. I., Hansen, T. K., Borg, R., Pedersen Bjergaard, U., Hansen, D., Hornum, M., Haller, H., Klausmann, G., Tschope, D., Kruger, T., Gross, P., Hugo, C., Obermuller, N., Rose, L., Mertens, P., Zeller-Stefan, H., Fritsche, A., Renders, L., Muller, J., Budde, K., Schroppel, B., Wittmann, I., Voros, P., Dudas, M., Tabak, G. A., Kirschner, R., Letoha, A., Balku, I., Hermanyi, Z., Zakar, G., Mezei, I., Nagy, G. G., Lippai, J., Nemeth, A., Khullar, D., Gowdaiah, P. K., Fernando Mervin, E., Rao, V. A., Dewan, D., Maddi, V. S., Vyawahare, M. S., Pulichikkat, R. K., Sonkar, S. K., Gupta, V. K., Agarwal, S., Asirvatham, A. J., Ignatius, A., Chaubey, S., Melemadathil, S., Alva, H., Kadam, Y., Shimizu, H., Sueyoshi, A., Takeoka, H., Abe, Y., Imai, T., Onishi, Y., Fujita, Y., Tokita, Y., Makita, Y., Idogaki, A., Koyama, R., Kikuchi, H., Kashihara, N., Hayashi, T., Ando, Y., Tanaka, T., Shimizu, M., Hidaka, S., Gohda, T., Tamura, K., Abe, M., Kamijo, Y., Imasawa, T., Takahashi, Y., Nakayama, M., Tomita, M., Hirano, F., Nakayama, M., Fukushima, Y., Kiyosue, A., Kurioka, S., Imai, E., Kitagawa, K., Waki, M., Wada, J., Uehara, K., Iwatani, H., Ota, K., Shibazaki, S., Tamura, K., Katayama, K., Narita, I., Iinuma, M., Matsueda, S., Sasaki, S., Yokochi, A., Tsukamoto, T., Yoshimura, T., Kang, S., Lee, S., Lim, C. S., Chin, H., Joo, K. W., Han, S. Y., Chang, T. I., Park, S., Park, H., Park, C. W., Han, B. G., Cha, D. R., Yoon, S. A., Kim, W., Kim, S. W., Ryu, D., Correa Rotter, R., Irizar Santana, S. S., Hernandez Llamas, G., Valdez Ortiz, R., Secchi Nicolas, N. C., Gonzalez Galvez, G., Lazcano Soto, J. R., Bochicchio Riccardelli, T., Bayram Llamas, E. A., Ramos Ibarra, D. R., Melo, M. G., Gonzalez Gonzalez, J. G., Sanchez Mijangos, J. H., Madero Robalo, M., Garcia Castillo, A., Manrique, H. A., Farfan, J. C., Vargas, R., Valdivia, A., Dextre, A., Escudero, E., Calderon Ticona, J. R., Gonzales, L., Villena, J., Leon, L., Molina, G., Saavedra, A., Garrido, E., Arbanil, H., Vargas Marquez, S., Rodriguez, J., Isidto, R., Villaflor, A. J., Gumba, M. A., Tirador, L., Comia, R. S., Sy, R. A., Guanzon, M. L., Aquitania, G., De Asis, N. C., Silva, A. A., Lim, M. E., Danguilan, R. A., Nowicki, M., Rudzki, H., Landa, K., Kucharczyk-Bauman, I., Gogola-Migdal, B., Golski, M., Olech-Cudzik, A., Stompor, T., Szczepanik, T., Miklaszewicz, B., Sciborski, R., Kuzniewski, M., Ciechanowski, K., Wronska, D., Klatko, W., Mazur, S., Popenda, G., Myslicki, M., Bolieva, L. Z., Berns, S., Galyavich, A., Abissova, T., Karpova, I., Platonov, D., Koziolova, N., Kvitkova, L., Nilk, R., Medina, T., Rebrov, A., Rossovskaya, M., Sinitsina, I., Vishneva, E., Zagidullin, N., Novikova, T., Krasnopeeva, N., Magnitskaya, O., Antropenko, N., Batiushin, M., Escudero Quesada, V., Barrios Barrea, C., Espinel Garauz, E., Cruzado Garrit, J. M., Morales Portillo, C., Gorriz Teruel, J. L., Cigarran Guldris, S., Praga Terente, M., Robles Perez-Monteoliva, N. R., Infanta Cristina, H., Tinahones Madueno, F. J., Soto Gonzalez, A., Diaz Rodriguez, C., Furuland, H., Saeed, A., Dreja, K., Spaak, J., Bruchfeld, A., Kolesnyk, M., Levchenko, O., Pyvovarova, N., Stus, V., Doretskyy, V., Korobova, N., Horoshko, O., Katerenchuk, I., Mostovoy, Y. M., Orynchak, M., Legun, O., Dudar, I., Bilchenko, O., Andreychyn, S., Levchenko, A., Zub, L., Tereshchenko, N., Topchii, I., Ostapenko, T., Bezuglova, S., Kopytsya, M., Turenko, O., Mark, P., Barratt, J., Bhandari, S., Fraser, D., Kalra, P., Kon, S. P., Mccafferty, K., Mikhail, A., Kon, S. P., Alvarado, O. P., Anderson, R., Andrawis, N. S., Arif, A., Benjamin, S. A., Bueso, G., Busch, R. S., Carr, K. W., Carr, K. W., Crawford, P., Daboul, N., De La Calle, G. M., Delgado, B., Earl, J., El-Shahawy, M. A., Graf, R. J., Greenwood, G., Guevara, A., Wendland, E. M., Mayfield, R. K., Montero, M., Morin, D. J., Narayan, P., Numrungroad, V., Reddy, A. C., Reddy, R., Samson, M. B., Trejo, R., Butcher, M. B., Wise, J. K., Zemel, L. R., Raikhel, M., Weinstein, D., Hernandez, P., Wynne, A., Khan, B. V., Sterba, G. A., Jamal, A., Ross, D., Rovner, S. F., Tan, A., Ovalle, F., Patel, R. J., Talano, J., Patel, D. R., Burgner, A., Aslam, N., Elliott, M., Goral, S., Jovanovich, A., Umanath, K., Waguespack, D., Weiner, D., Yu, M., Schneider, L., Le, T., D, T., Nguyen, N., Nguyen, H., Nguyen, D., Nguyen, V., Do, T., Chu, P., Ta, D., Tran, N., Nguyen, D., Pfeffer, M. A., Pocock, S., Swedberg, K., Rouleau, J. L., Chaturvedi, N., Ivanovich, P., Levey, A. S., Held, C., Christersson, C., Mann, J., Varenhorst, C. 2021; 42 (13): 1216–27

  Abstract

  AIMS: Mortality rates from chronic kidney disease (CKD) have increased in the last decade. In this pre-specified analysis of the DAPA-CKD trial, we determined the effects of dapagliflozin on cardiovascular and non-cardiovascular causes of death.METHODS AND RESULTS: DAPA-CKD was an international, randomized, placebo-controlled trial with a median of 2.4years of follow-up. Eligible participants were adult patients with CKD, defined as a urinary albumin-to-creatinine ratio (UACR) 200-5000mg/g and an estimated glomerular filtration rate (eGFR) 25-75mL/min/1.73 m2. All-cause mortality was a key secondary endpoint. Cardiovascular and non-cardiovascular death was adjudicated by an independent clinical events committee. The DAPA-CKD trial randomized participants to dapagliflozin 10mg/day (n=2152) or placebo (n=2152). The mean age was 62years, 33% were women, the mean eGFR was 43.1mL/min/1.73 m2, and the median UACR was 949mg/g. During follow-up, 247 (5.7%) patients died, of whom 91 (36.8%) died due to cardiovascular causes, 102 (41.3%) due to non-cardiovascular causes, and in 54 (21.9%) patients, the cause of death was undetermined. The relative risk reduction for all-cause mortality with dapagliflozin (31%, hazard ratio [HR] [95% confidence interval (CI)] 0.69 [0.53, 0.88]; P=0.003) was consistent across pre-specified subgroups. The effect on all-cause mortality was driven largely by a 46% relative risk reduction of non-cardiovascular death (HR [95% CI] 0.54 [0.36, 0.82]). Deaths due to infections and malignancies were the most frequently occurring causes of non-cardiovascular deaths and were reduced with dapagliflozin vs. placebo.CONCLUSION: In patients with CKD, dapagliflozin prolonged survival irrespective of baseline patient characteristics. The benefits were driven largely by reductions in non-cardiovascular death.

  View details for DOI 10.1093/eurheartj/ehab094

  View details for PubMedID 33792669

• Removing Race from eGFR calculations: Implications for Urologic Care. Urology Vilson, F. L., Schmidt, B., White, L., Soerensen, S. J., Ganesan, C., Pao, A. C., Enemchukwu, E., Chertow, G. M., Leppert, J. T. 2021

  Abstract

  Equations estimating the glomerular filtration rate are important clinical tools in detecting and managing kidney disease. Urologists extensively use these equations in clinical decision making. For example, the estimated glomerular function rate is used when considering the type of urinary diversion following cystectomy, selecting systemic chemotherapy in managing urologic cancers, and deciding the type of cross-sectional imaging in diagnosing or staging urologic conditions. However, these equations, while widely accepted, are imprecise and adjust for race which is a social, not a biologic construct. The recent killings of unarmed Black Americans in the US have amplified the discussion of racism in healthcare and has prompted institutions to reconsider the role of race in eGFR equations and raced-based medicine. Urologist should be aware of the consequences of removing race from these equations, potential alternatives, and how these changes may affect Black patients receiving urologic care.

  View details for DOI 10.1016/j.urology.2021.03.018

  View details for PubMedID 33798557

• Effect of a Home-Based Exercise Program on Indices of Physical Function and Quality of Life in Elderly Maintenance Hemodialysis Patients. Kidney & blood pressure research Myers, J., Chan, K., Chen, Y., Lit, Y., Patti, A., Massaband, P., Kiratli, B. J., Tamura, M., Chertow, G. M., Rabkin, R. 2021: 1–11

  Abstract

  BACKGROUND: Patients on maintenance hemodialysis (MHD) exhibit muscle wasting and impaired physical function which can be reversed with regular exercise, but accessibility to exercise programs for this unique population is lacking. We assessed the efficacy of a home-based exercise program on a broad range of indices of physical function, quality of life (QoL), and cognitive decline in patients with MHD.DESIGN AND METHODS: Twenty-eight MHD patients, mean age 66 ± 7 years, were randomized to a 12-week home-based, case-managed aerobic and resistance exercise program or to usual care (13 exercise and 15 usual care). Comparisons were made for peak VO2, ventilatory inefficiency, 6-min walk test (6MWT), 1-min sit-to-stand (1STS), muscle strength, body composition, QoL, and cognitive measures.RESULTS: Peak VO2 improved significantly in the exercise group (p = 0.01 between groups); exercise time improved by 41 and 36% at the ventilatory threshold and peak exercise, respectively (p < 0.01 between groups), but there were no differences in ventilatory efficiency. Trends for improvements in 6MWT and 1STS in the exercise group were observed, but no differences were observed in strength or body composition. Among measures of QoL, general health determined by the SF-36 improved in the exercise group, but there were no differences between groups in cognitive function.CONCLUSIONS: MHD patients improved exercise capacity and some indices of QoL following a 12-week home-based exercise program. Home-based exercise is feasible for patients undergoing MHD and may help to obviate accessibility barriers to regular exercise.

  View details for DOI 10.1159/000514269

  View details for PubMedID 33774634

• A Randomized Trial of Tenapanor and Phosphate Binders as a Dual-Mechanism Treatment for Hyperphosphatemia in Patients on Maintenance Dialysis (AMPLIFY). Journal of the American Society of Nephrology : JASN Pergola, P. E., Rosenbaum, D. P., Yang, Y., Chertow, G. M. 2021

  Abstract

  BACKGROUND: Hyperphosphatemia is associated with cardiovascular morbidity and mortality in patients receiving maintenance dialysis. It is unknown whether combining two therapies with different mechanisms of action-tenapanor, an inhibitor of paracellular phosphate absorption, and phosphate binders-is safe and effective for the management of hyperphosphatemia in patients receiving maintenance dialysis.METHODS: This double-blind phase 3 trial enrolled 236 patients undergoing maintenance dialysis with hyperphosphatemia (defined in this trial as serum phosphorus 5.5-10 mg/dl inclusive) despite receiving phosphate binder therapy (sevelamer, nonsevelamer, sevelamer plus nonsevelamer, or multiple nonsevelamer binders). These participants were randomly assigned to receive oral tenapanor 30 mg twice daily or placebo for 4 weeks. The primary efficacy end point was the change in serum phosphorus concentration from baseline to week 4.RESULTS: Of the 236 randomized patients, 235 (99.6%) were included in the full analysis set; this included 116 in the tenapanor plus binder group and 119 in the placebo plus binder group. A total of 228 patients (96.6%) completed the 4-week treatment period. In the full analysis set (mean age 54.5 years, 40.9% women), patients treated with tenapanor plus binder achieved a larger mean change in serum phosphorus concentration from baseline to week 4 compared with placebo plus binder (-0.84 versus -0.19 mg/dl, P<0.001). Diarrhea was the most commonly reported adverse event, resulting in study drug discontinuation in four of 119 (3.4%) and two of 116 (1.7%) patients receiving tenapanor plus binder or placebo plus binder, respectively.CONCLUSIONS: A dual-mechanism treatment using both tenapanor and phosphate binders improved control of hyperphosphatemia in patients undergoing maintenance dialysis compared with phosphate binders alone.CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: AMPLIFY, NCT03824587.

  View details for DOI 10.1681/ASN.2020101398

  View details for PubMedID 33766811

• Estimated Impact of Novel Coronavirus-19 and Transplant Center Inactivity on ESRD-related Patient Mortality in the United States. Clinical transplantation Peters, T. G., Bragg-Gresham, J. L., Klopstock, A. C., Roberts, J. P., Chertow, G., McCormick, F., Held, P. J. 2021: e14292

  Abstract

  To predict if the COVID-19 pandemic and transplant center responses could have resulted in preventable deaths, we analyzed registry information of the U.S. ESRD patient population awaiting kidney transplantation. Data were from the Organ Procurement and Transplantation Network (OPTN), the U.S. Centers for Disease Control and Prevention, and the United States Renal Data System. Based on 2019 OPTN reports, annualized reduction in kidney transplantation of 25% to 100% could result in excess deaths of waitlisted (deceased donor) transplant candidates from 84 to 337 and living donor candidate excess deaths from 35 to 141 (total 119 to 478 potentially preventable deaths of transplant candidates). Changes in transplant activity due to COVID-19 varied with some centers shutting down while others simply heeded known or suspected pandemic risks. Understanding potential excess mortality for ESRD transplant candidates when circumstances compel curtailment of transplant activity may inform policy and procedural aspects of organ transplant systems allowing ways to best inform patients and families as to potential risks in shuttering organ transplant activity. Considering that more than 700,000 Americans have ESRD with 100,000 awaiting a kidney transplant, our highest annual estimate of 478 excess total deaths from postponing kidney transplantation seems modest.

  View details for DOI 10.1111/ctr.14292

  View details for PubMedID 33749935

• Osteoporosis, Fractures, and Bone Mineral Density Screening in Veterans With Kidney Stone Disease. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research Ganesan, C., Thomas, I., Romero, R., Song, S., Conti, S., Elliott, C., Chertow, G. M., Tamura, M. K., Leppert, J. T., Pao, A. C. 2021

  Abstract

  Whether a link exists between kidney stone disease and osteoporosis or fractures remains an open question. In this retrospective cohort study, we sought to determine the prevalence of osteoporosis and fractures and rate of bone mineral density screening by dual-energy X-ray absorptiometry (DXA) in patients with kidney stone disease. We examined nationwide data from the Veterans Health Administration and identified 531,431 patients with kidney stone disease between 2007 and 2015. Nearly 1 in 4 patients (23.6%, 95% confidence interval [CI] 23.5-23.7) with kidney stone disease had a prevalent diagnosis of osteoporosis or fracture. In patients with no prior history of osteoporosis or bone mineral density assessment before a kidney stone diagnosis, 9.1% were screened with DXA after their kidney stone diagnosis, of whom 20% were subsequently diagnosed with osteoporosis. Our findings provide support for wider use of bone mineral density screening in patients with kidney stone disease, including middle-aged and older men, a group less well recognized as at risk for osteoporosis or fractures. © 2021 American Society for Bone and Mineral Research (ASBMR).

  View details for DOI 10.1002/jbmr.4260

  View details for PubMedID 33655611

• Chronic kidney disease, atherosclerotic plaque characteristics on carotid magnetic resonance imaging, and cardiovascular outcomes. BMC nephrology Beddhu, S., Boucher, R. E., Sun, J., Balu, N., Chonchol, M., Navaneethan, S., Chertow, G. M., Townsend, R., Haley, W., Cheung, A. K., Conroy, M. B., Raj, D. S., Xu, D., George, T., Yunis, R., Wei, G., Canton, G., Bates, J., Chen, J., Papademetriou, V., Punzi, H., Wiggers, A., Wright, J. T., Greene, T., Yuan, C. 2021; 22 (1): 69

  Abstract

  BACKGROUND: It is unclear whether faster progression of atherosclerosis explains the higher risk of cardiovascular events in CKD. The objectives of this study were to 1. Characterize the associations of CKD with presence and morphology of atherosclerotic plaques on carotid magnetic resonance imaging (MRI) and 2. Examine the associations of baseline CKD and carotid atherosclerotic plaques with subsequent cardiovascular events.METHODS: In a subgroup (N=465) of Systolic Blood Pressure Intervention Trial. (SPRINT) participants, we measured carotid plaque presence and morphology at baseline and after 30-months with MRI. We examined the associations of CKD (baseline eGFR <60ml/min/1.73m2) with progression of carotid plaques and the SPRINT cardiovascular endpoint.RESULTS: One hundred and ninety six (42%) participants had CKD. Baseline eGFR in the non-CKD and CKD subgroups were 77±14 and 49±8ml/min/1.73m2, respectively. Lipid rich necrotic-core plaque was present in 137 (29.5%) participants. In 323 participants with both baseline and follow-up MRI measurements of maximum wall thickness, CKD was not associated with progression of maximum wall thickness (OR 0.62, 95% CI 0.36 to 1.07, p=0.082). In 96 participants with necrotic core plaque at baseline and with a valid follow-up MRI, CKD was associated with lower odds of progression of necrotic core plaque (OR 0.41, 95% CI 0.17 to 0.95, p=0.039). There were 28 cardiovascular events over 1764 person-years of follow-up. In separate Cox models, necrotic core plaque (HR 2.59, 95% CI 1.15 to 5.85) but not plaque defined by maximum wall thickness or presence of a plaque component (HR 1.79, 95% CI 0.73 to 4.43) was associated with cardiovascular events. Independent of necrotic core plaque, CKD (HR 3.35, 95% CI 1.40 to 7.99) was associated with cardiovascular events.CONCLUSIONS: Presence of necrotic core in carotid plaque rather than the presence of plaque per se was associated with increased risk of cardiovascular events. We did not find CKD to be associated with faster progression of necrotic core plaques, although both were independently associated with cardiovascular events. Thus, CKD may contribute to cardiovascular disease principally via mechanisms other than atherosclerosis such as arterial media calcification or stiffening.TRIAL REGISTRATION: NCT01475747 , registered on November 21, 2011.

  View details for DOI 10.1186/s12882-021-02260-x

  View details for PubMedID 33627066

• Urate Lowering With Combination Therapy in CKD: Reason for Optimism or Einstein's Definition of Insanity? American journal of kidney diseases : the official journal of the National Kidney Foundation Jalal, D. I., Chertow, G. M. 2021

  View details for DOI 10.1053/j.ajkd.2020.11.007

  View details for PubMedID 33568321

• Cost Structures of US Organ Procurement Organizations. Transplantation Held, P. J., Bragg-Gresham, J. L., Peters, T. G., McCormick, F., Chertow, G., Vaughan, W. P., Roberts, J. P. 2021

  Abstract

  BACKGROUND: The goal is to provide a national analysis of OPO costs.METHODS: Five years of data, for 51 of the 58 OPOs (2013-17, a near census) were obtained under a FOIA. OPOs are not-for-profit federal contractors with a geographic monopoly. A generalized 15-factor cost regression model was estimated with adjustments to precision of estimates (p-values) for repeated observations. Selected measures were validated by comparison to IRS forms.RESULTS: (p≤0.05) DD organ procurement is a $1B/yr. operation with over 26000 transplants/yr. Over 60 percent of the cost of an organ is overhead. Profits are $2.3M/OPO/yr. Total assets are $45M/OPO and growing at 9%/yr. "Tissue" (skin, bones) generates 2 to 3$M profit/OPO/yr.A comparison of the highest with the lower costing OPOs showed our model explained 75% of the cost difference. Comparing costs across OPOs showed that highest cost OPOs are smaller, import 44% more kidneys, face 6% higher labor costs, report 98% higher compensation for support personnel, spend 46% more on professional education, have 44% fewer assets, compensate their executive director 36% less, and have a lower procurement performance (SDRR) score.CONCLUSIONS: Profits and assets suggest that OPOs are fiscally secure and OPO finances are not a source of the organ shortage. Asset accumulation ($45M/OPO) of incumbents suggests establishing a competitive market with new entrants is unlikely. Kidney cost allocations support tissue procurements. Professional education spending does not reduce procurement costs. OPO importing of organs from other OPOs is a complex issue possibly increasing cost ($6K/kidney).Supplemental visual abstract; http://links.lww.com/TP/C135.

  View details for DOI 10.1097/TP.0000000000003667

  View details for PubMedID 33988344

• Race and Place in ESKD. Kidney international reports Watford, D. J., Chertow, G. M. 2021; 6 (2): 252–53

  View details for DOI 10.1016/j.ekir.2020.11.027

  View details for PubMedID 33617609

• And Then There Were Three: Effects of Pretransplant Dialysis on Multiorgan Transplantation. Transplantation direct Cheng, X. S., Han, J., Stedman, M. R., Chertow, G. M., Tan, J. C. 2021; 7 (2): e657

  Abstract

  Background: Simultaneous liver-kidney (SLK) and simultaneous heart-kidney (SHK) transplantation currently utilize 6% of deceased donor kidneys in the United States. To what extent residual kidney function accounts for apparent kidney allograft survival is unknown.Methods: We examined all adult SLK and SHK transplants in the United States during 1995-2014. We considered the duration of dialysis preceding SLK or SHK (≥90 d, 1-89 d, or none) as a proxy of residual kidney function. We used multinomial logistic regression to estimate the difference in the adjusted likelihood of 6- and 12-month apparent kidney allograft failure between the no dialysis versus ≥90 days dialysis groups.Results: Of 4875 SLK and 848 SHK recipients, 1775 (36%) SLK and 449 (53%) SHK recipients received no dialysis before transplant. The likelihood of apparent kidney allograft failure was 1%-3% lower at 12 months in SLK and SHK recipients who did not require pretransplant dialysis relative to recipients who required ≥90 days of pretransplant dialysis. Among 3978 SLK recipients who survived to 1 year, no pretransplant dialysis was associated with a lower risk of apparent kidney allograft failure over a median follow-up of 5.7 years (adjusted hazard ratio 0.73 [0.55-0.96]).Conclusions: Patients with residual kidney function at the time of multiorgan transplantation are less likely to have apparent failure of the kidney allograft. Whether residual kidney function facilitates function of the allograft or whether some SLK and SHK recipients have 3 functional kidneys is unknown. Sustained kidney function after SLK and SHK transplants does not necessarily indicate successful MOT.

  View details for DOI 10.1097/TXD.0000000000001112

  View details for PubMedID 33490382

• Association of 152 Biomarker Reference Intervals with All-Cause Mortality in Participants of a General United States Survey from 1999 to 2010. Clinical chemistry Pho, N. n., Manrai, A. K., Leppert, J. T., Chertow, G. M., Ioannidis, J. P., Patel, C. J. 2021; 67 (3): 500–507

  Abstract

  Physicians sometimes consider whether or not to perform diagnostic testing in healthy people, but it is unknown whether nonextreme values of diagnostic tests typically encountered in such populations have any predictive ability, in particular for risk of death. The goal of this study was to quantify the associations among population reference intervals of 152 common biomarkers with all-cause mortality in a representative, nondiseased sample of adults in the United States.The study used an observational cohort derived from the National Health and Nutrition Examination Survey (NHANES), a representative sample of the United States population consisting of 6 survey waves from 1999 to 2010 with linked mortality data (unweighted N = 30 651) and a median followup of 6.1 years. We deployed an X-wide association study (XWAS) approach to systematically perform association testing of 152 diagnostic tests with all-cause mortality.After controlling for multiple hypotheses, we found that the values within reference intervals (10-90th percentiles) of 20 common biomarkers used as diagnostic tests or clinical measures were associated with all-cause mortality, including serum albumin, red cell distribution width, serum alkaline phosphatase, and others after adjusting for age (linear and quadratic terms), sex, race, income, chronic illness, and prior-year healthcare utilization. All biomarkers combined, however, explained only an additional 0.8% of the variance of mortality risk. We found modest year-to-year changes, or changes in association from survey wave to survey wave from 1999 to 2010 in the association sizes of biomarkers.Reference and nonoutlying variation in common biomarkers are consistently associated with mortality risk in the US population, but their additive contribution in explaining mortality risk is minor.

  View details for DOI 10.1093/clinchem/hvaa271

  View details for PubMedID 33674838

• SARS-CoV-2 vaccine antibody response and breakthrough infection in dialysis. medRxiv : the preprint server for health sciences Anand, S., Montez-Rath, M. E., Han, J., Garcia, P., Cadden, L., Hunsader, P., Morgan, C., Kerschmann, R., Beyer, P., Dittrich, M., Block, G. A., Chertow, G. M., Parsonnet, J. 2021

  Abstract

  Patients receiving dialysis are a sentinel population for groups at high risk for death and disability from COVID-19. Understanding correlates of protection post-vaccination can inform immunization and mitigation strategies.Monthly since January 2021, we tested plasma from 4791 patients receiving dialysis for antibodies to the receptor-binding domain (RBD) of SARS-CoV-2 using a high-throughput assay. We qualitatively assessed the proportion without a detectable RBD response and among those with a response, semiquantitative median IgG index values. Using a nested case-control design, we matched each breakthrough case to five controls by age, sex, and vaccination-month to determine whether peak and pre-breakthrough RBD IgG index values were associated with risk for infection post-vaccination.Among 2563 vaccinated patients, the proportion without a detectable RBD response increased from 6.6% [95% CI 5.5-8.1] in 14-30 days post-vaccination to 20.2% [95% CI 17.1-23.8], and median index values declined from 92.7 (95% CI 77.8-107.5) to 3.7 (95% CI 3.1-4.3) after 5 months. Persons with SARS-CoV-2 infection prior-to-vaccination had higher peak index values than persons without prior infection, but values equalized by 5 months (p=0.230). Breakthrough infections occurred in 56 patients, with samples collected a median of 21 days pre-breakthrough. Peak and pre-breakthrough RBD values <23 (equivalent to <506 WHO BAU/mL) were associated with higher odds for breakthrough infection (OR: 3.7 [95% CI 2.0-6.8] and 9.8 [95% CI 2.9-32.8], respectively).The antibody response to SARS-CoV-2 vaccination wanes rapidly, and in persons receiving dialysis, the persisting antibody response is associated with risk for breakthrough infection.

  View details for DOI 10.1101/2021.10.12.21264860

  View details for PubMedID 34671782

  View details for PubMedCentralID PMC8528091

• Antibody Response to COVID-19 vaccination in Patients Receiving Dialysis. medRxiv : the preprint server for health sciences Anand, S., Montez-Rath, M. E., Han, J., Garcia, P., Cadden, L., Hunsader, P., Kerschmann, R., Beyer, P., Dittrich, M., Block, G. A., Boyd, S. D., Parsonnet, J., Chertow, G. M. 2021

  Abstract

  Patients receiving dialysis may mount impaired responses to COVID19 vaccination.We report antibody response to vaccination from 1140 patients without, and 493 patients with pre-vaccination SARS-CoV-2 RBD antibody. We used commercially available assays (Siemens) to test remainder plasma monthly in association with vaccination date and type, and assess prevalence of absent total receptor binding antibody, and absent or attenuated (index value < 10) semiquantitative receptor binding domain IgG index values. We used Poisson regression to evaluate risk factors for absent or attenuated response to vaccination.Among patients who were seronegative versus seropositive before vaccination, 62% and 56% were ≥65 years old, 20% and 24% were Hispanic, and 22% and 23% were Black. Median IgG index values rose steadily over time, and were higher among the seropositive than in the seronegative patients after completing vaccination (150 [25 th , 75 th percentile 23.2, 150.0] versus 41.6 [11.3, 150.0]). Among 610 patients who completed vaccination (assessed ≥14 days later, median 29 days later), the prevalence of absent total RBD response, and absent and attenuated semiquantitative IgG response was 4.4% (95% CI 3.1, 6.4%), 3.4% (2.4, 5.2%), and 14.3% (11.7, 17.3%) respectively. Risk factors for absent or attenuated response included longer vintage of end-stage kidney disease, and lower pre-vaccination serum albumin.More than one in five patients receiving dialysis had evidence of an attenuated immune response to COVID19 vaccination.Patients receiving dialysis face high likelihood of severe COVID19; at the same time, vaccination may be less efficacious, as prior data indicate impaired immune responses to influenza and Hepatitis B vaccination. We found that 22% of patients receiving dialysis had suboptimal responses to vaccination, irrespective of whether or not they had evidence of prior SARS-CoV-2 infection. Poorer health status and longer duration of end-stage kidney disease increased likelihood of suboptimal response. Ongoing vigilance for COVID19 in dialysis facilities and studies of modified vaccination dosing schedules will be critical to protecting patients receiving dialysis.

  View details for DOI 10.1101/2021.05.06.21256768

  View details for PubMedID 34013281

  View details for PubMedCentralID PMC8132255

• Kidney Disease, Hypertension Treatment, and Cerebral Perfusion and Structure. American journal of kidney diseases : the official journal of the National Kidney Foundation Kurella Tamura, M., Gaussoin, S., Pajewski, N. M., Zaharchuk, G., Freedman, B. I., Rapp, S. R., Auchus, A. P., Haley, W. E., Oparil, S., Kendrick, J., Roumie, C. L., Beddhu, S., Cheung, A. K., Williamson, J. D., Detre, J. A., Dolui, S., Bryan, R. N., Nasrallah, I. M. 2021

  Abstract

  The safety of intensive blood pressure (BP) targets is controversial for persons with chronic kidney disease (CKD). We studied the effects of hypertension treatment on cerebral perfusion and structure in those with and without CKD.Neuroimaging substudy of a randomized trial.A subset of participants in the Systolic Blood Pressure Intervention Trial who underwent brain MRI studies. Presence of baseline CKD was assessed by estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR).Participants were randomly assigned to intensive (systolic BP <120 mm Hg) versus standard (systolic BP <140 mm Hg) BP lowering.The magnetic resonance imaging outcome measures were the four-year change in global cerebral blood flow, white matter lesion (WML) volume, and total brain volume.A total of 716 randomized participants with mean age of 68 years were enrolled; follow-up imaging occurred after a median 3.9 years. Among participants with eGFR <60 ml/min/1.73m2 (N=234), the effects of intensive versus standard BP treatment on change in global cerebral blood flow, WMLs and total brain volume were 3.38 mL/100 g/min (95% CI 0.32, 6.44), -0.06 cm3 (asinh transformed, 95% CI -0.16, 0.04), and -3.8 cm3 (95% CI -8.3, 0.7), respectively. Among participants with UACR >30 mg/g (N=151), the effects of intensive versus standard BP treatment on change in global cerebral blood flow, WMLs and total brain volume were 1.91 ml/100g/min (95% CI -3.01, 6.82), 0.003 cm3 (asinh transformed, 95% CI -0.13, 0.13), and -7.0 cm3 (95% CI -13.3, -0.3), respectively. The overall treatment effects on cerebral blood flow and total brain volume were not modified by baseline eGFR or UACR; however the effect on WMLs was attenuated in participants with albuminuria (interaction p-value 0.04).Measurement variability due to multi-site design.Among hypertensive adults with primarily early kidney disease, intensive versus standard blood pressure treatment did not appear to have a detrimental effect on brain perfusion or structure. The findings support the safety of intensive blood pressure treatment targets on brain health in persons with early kidney disease.

  View details for DOI 10.1053/j.ajkd.2021.07.024

  View details for PubMedID 34543687

• AUTHOR REPLY. Urology Soerensen, S. J., Thomas, I. C., Schmidt, B., Daskivich, T. J., Skolarus, T. A., Jackson, C., Osborne, T. F., Chertow, G. M., Brooks, J. D., Rehkopf, D. H., Leppert, J. T. 2021; 155: 76

  View details for DOI 10.1016/j.urology.2021.05.058

  View details for PubMedID 34489006

• Clinical laboratory tests associated with survival in patients with metastatic renal cell carcinoma: A Laboratory Wide Association Study (LWAS). Urologic oncology Velaer, K., Thomas, I. C., Yang, J., Kapphahn, K., Metzner, T. J., Golla, A., Hoerner, C. R., Fan, A. C., Master, V., Chertow, G. M., Brooks, J. D., Patel, C. J., Desai, M., Leppert, J. T. 2021

  Abstract

  Prognostic models for patients with metastatic renal cell carcinoma (mRCC) include select laboratory values. These models have important limitations, including reliance on a limited array of laboratory tests, and use of dichotomous ("high-low") cutoffs. We applied a Laboratory-Wide Association Study (LWAS) framework to systematically evaluate common clinical laboratory results associated with survival for patients diagnosed with mRCC.We used laboratory data for 3,385 patients diagnosed with mRCC from 2002 to 2017. We developed a LWAS framework, to examine the association with 53 common clinical laboratory tests results (641,712 measurements) and overall survival. We employed false-discovery rate to test the association of multiple laboratory tests with survival, and validated these results using 3 separate cohorts to generate a standardized hazard ratio (sHR), reported for a 1 standard deviation unit change in each laboratory test.The LWAS approach confirmed the association of laboratory values currently used in prognostic models with survival, including calcium (HR 1.35, 95%CI 1.24-1.48), leukocyte count (HR 1.40, 95%CI 1.30-1.51), platelet count (HR 1.36, 95%CI 1.27-1.51), and hemoglobin (HR 0.79, 95%CI 0.72-0.86). Use of these tests as continuous variables improved model performance. LWAS also identified acute phase reactants associated with survival not typically included in prognostic models, including serum albumin (HR 0.66, 95%CI 0.61-0.72), ferritin (HR 1.25, 95%CI 1.08-1.45), alkaline phosphatase (HR 1.31, 95%CI 1.23-1.40), and C-reactive protein (HR 1.70, 95%CI 1.14-2.53).Routinely measured laboratory tests can refine current prognostic models, facilitate comparisons across clinical trial cohorts, and match patients with specific systemic therapies.

  View details for DOI 10.1016/j.urolonc.2021.08.011

  View details for PubMedID 34580027

• Vadadustat for Anemia in Patients with Dialysis-Dependent or Non-Dialysis-Dependent Chronic Kidney Disease. Reply. The New England journal of medicine Chertow, G. M., Eckardt, K. 2021; 385 (16): e56

  View details for DOI 10.1056/NEJMc2110095

  View details for PubMedID 34644482

• Population-based identification and temporal trend of children with primary nephrotic syndrome: The Kaiser Permanente nephrotic syndrome study. PloS one Parikh, R. V., Tan, T. C., Fan, D., Law, D., Salyer, A. S., Yankulin, L., Wojcicki, J. M., Zheng, S., Ordonez, J. D., Chertow, G. M., Khoshniat-Rad, F., Yang, J., Go, A. S. 2021; 16 (10): e0257674

  Abstract

  INTRODUCTION: Limited population-based data exist about children with primary nephrotic syndrome (NS).METHODS: We identified a cohort of children with primary NS receiving care in Kaiser Permanente Northern California, an integrated healthcare delivery system caring for >750,000 children. We identified all children <18 years between 1996 and 2012 who had nephrotic range proteinuria (urine ACR>3500 mg/g, urine PCR>3.5 mg/mg, 24-hour urine protein>3500 mg or urine dipstick>300 mg/dL) in laboratory databases or a diagnosis of NS in electronic health records. Nephrologists reviewed health records for clinical presentation and laboratory and biopsy results to confirm primary NS.RESULTS: Among 365 cases of confirmed NS, 179 had confirmed primary NS attributed to presumed minimal change disease (MCD) (72%), focal segmental glomerulosclerosis (FSGS) (23%) or membranous nephropathy (MN) (5%). The overall incidence of primary NS was 1.47 (95% Confidence Interval:1.27-1.70) per 100,000 person-years. Biopsy data were available in 40% of cases. Median age for patients with primary NS was 6.9 (interquartile range:3.7 to 12.9) years, 43% were female and 26% were white, 13% black, 17% Asian/Pacific Islander, and 32% Hispanic.CONCLUSION: This population-based identification of children with primary NS leveraging electronic health records can provide a unique approach and platform for describing the natural history of NS and identifying determinants of outcomes in children with primary NS.

  View details for DOI 10.1371/journal.pone.0257674

  View details for PubMedID 34648518

• A pre-specified analysis of the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) randomized controlled trial on the incidence of abrupt declines in kidney function. Kidney international Heerspink, H. J., Cherney, D., Postmus, D., Stefánsson, B. V., Chertow, G. M., Dwyer, J. P., Greene, T., Kosiborod, M., Langkilde, A. M., McMurray, J. J., Correa-Rotter, R., Rossing, P., Sjöström, C. D., Toto, R. D., Wheeler, D. C. 2021

  Abstract

  This pre-specified analysis of DAPA-CKD assessed the impact of sodium-glucose cotransporter 2 inhibition on abrupt declines in kidney function in high risk patients based on having chronic kidney disease (CKD) and severe albuminuria. DAPA-CKD was a randomized, double-blind, placebo-controlled trial had a median follow-up of 2.4 years. Adults with CKD (urinary albumin-to-creatinine ratio 200-5000 mg/g and estimated glomerular filtration rate 25-75 mL/min/1.73m2) were randomized to dapagliflozin 10 mg/day matched to placebo (2152 individuals each). An abrupt decline in kidney function was defined as a pre-specified endpoint of doubling of serum creatinine between two subsequent study visits. We also assessed a post-hoc analysis of investigator-reported acute kidney injury-related serious adverse events. Doubling of serum creatinine between two subsequent visits (median time-interval 100 days) occurred in 63 (2.9%) and 91 (4.2%) participants in the dapagliflozin and placebo groups, respectively (hazard ratio 0.68 [95% confidence interval 0.49, 0.94]). Accounting for the competing risk of mortality did not alter our findings. There was no heterogeneity in the effect of dapagliflozin on abrupt declines in kidney function based on baseline subgroups. Acute kidney injury-related serious adverse events were not significantly different and occurred in 52 (2.5%) and 69 (3.2%) participants in the dapagliflozin and placebo groups, respectively (0.77 [0.54, 1.10]). Thus, in patients with CKD and substantial albuminuria, dapagliflozin reduced the risk of abrupt declines in kidney function.

  View details for DOI 10.1016/j.kint.2021.09.005

  View details for PubMedID 34560136

• COVID19 vaccine type and humoral immune response in patients receiving dialysis. medRxiv : the preprint server for health sciences Garcia, P., Anand, S., Han, J., Montez-Rath, M., Sun, S., Shang, T., Parsonnet, J., Chertow, G. M., Schiller, B., Abra, G. 2021

  Abstract

  Patients on dialysis vaccinated with the attenuated adenovirus SARS-CoV-2 vaccine might mount an impaired response to vaccination.We evaluated the humoral vaccination response among 2,099 fully vaccinated patients receiving dialysis. We used commercially available assays (Siemens) to assess prevalence of no response or diminished response to COVID-19 vaccination by vaccine type. We defined "no seroconversion" as lack of change from negative to positive in total RBD Ig antibody, no detectable response on semiquantitative RBD IgG antibody (index value <1) as "no RBD IgG response", and a semiquantitative RBD IgG index value <10 as "diminished RBD IgG response".Of the 2,099 fully vaccinated patients on dialysis, the proportion receiving the mRNA1273, BNT162b2, and Ad26.COV2.S were 62% (n=1316), 20% (n=416) and 18% (n=367), respectively. A third (33.3%) of patients receiving the attenuated adenovirus Ad26.COV2.S vaccine failed to seroconvert and an additional 36% had no detectable or diminished IgG response even 28-60 days post vaccination.One in three fully vaccinated patients receiving dialysis had evidence of an impaired immune response to the attenuated adenovirus Ad26.COV2.S vaccine.

  View details for DOI 10.1101/2021.08.02.21261516

  View details for PubMedID 34373862

  View details for PubMedCentralID PMC8351784

• Laboratory correlates of SARS-CoV-2 seropositivity in a nationwide sample of patients on dialysis in the U.S. PloS one Anand, S., Montez-Rath, M. E., Han, J., Garcia, P., Bozeman, J., Kerschmann, R., Beyer, P., Parsonnet, J., Chertow, G. M. 2021; 16 (4): e0249466

  Abstract

  Patients on dialysis are at high risk for death due to COVID-19, yet a significant proportion do survive as evidenced by presence of SARS-CoV-2 antibodies in 8% of patients in the U.S. in July 2020. It is unclear whether patients with seropositivity represent the subgroup with robust health status, who would be more likely to mount a durable antibody response. Using data from a July 2020 sample of 28,503 patients receiving dialysis, we evaluated the cross-sectional association of SARS-CoV-2 seropositivity with laboratory surrogates of patient health. In separate logistic regression models, we assessed the association of SARS-CoV-2 seropositivity with seven laboratory-based covariates (albumin, creatinine, hemoglobin, sodium, potassium, phosphate, and parathyroid hormone), across the entire range of the laboratory and in comparison to a referent value. Models accounted for age, sex, region, race and ethnicity, and county-level COVID-19 deaths per 100,000. Odds of seropositivity for albumin 3 and 3.5 g/dL were 2.1 (95% CI 1.9-2.3) and 1.3 (1.2-1.4) respectively, compared with 4 g/dL. Odds of seropositivity for serum creatinine 5 and 8 mg/dL were 1.8 (1.6-2.0) and 1.3 (1.2-1.4) respectively, compared with 12.5 mg/dL. Lower values of hemoglobin, sodium, potassium, phosphate, and parathyroid hormone were associated with higher odds of seropositivity. Laboratory values associated with poorer health status and higher risk for mortality were also associated with higher likelihood of SARS-CoV-2 antibodies in patients receiving dialysis.

  View details for DOI 10.1371/journal.pone.0249466

  View details for PubMedID 33857168

• Study Design and Baseline Characteristics of the CARDINAL Trial: A Phase 3 Study of Bardoxolone Methyl in Patients with Alport Syndrome. American journal of nephrology Chertow, G. M., Appel, G. B., Andreoli, S. n., Bangalore, S. n., Block, G. A., Chapman, A. B., Chin, M. P., Gibson, K. L., Goldsberry, A. n., Iijima, K. n., Inker, L. A., Knebelmann, B. n., Mariani, L. H., Meyer, C. J., Nozu, K. n., O'Grady, M. n., Silva, A. L., Stenvinkel, P. n., Torra, R. n., Warady, B. A., Pergola, P. E. 2021: 1–10

  Abstract

  Alport syndrome is a rare genetic disorder that affects as many as 60,000 persons in the USA and a total of 103,000 persons (<5 per 10,000) in the European Union [1, 2]. It is the second most common inherited cause of kidney failure and is characterized by progressive loss of kidney function that often leads to end-stage kidney disease. Currently, there are no approved disease-specific agents for therapeutic use. We designed a phase 3 study (CARDINAL; NCT03019185) to evaluate the safety, tolerability, and efficacy of bardoxolone methyl in patients with Alport syndrome.The CARDINAL phase 3 study is an international, multicenter, double-blind, placebo-controlled, randomized registrational trial. Eligible patients were of ages 12-70 years with confirmed genetic or histologic diagnosis of Alport syndrome, eGFR 30-90 mL/min/1.73 m2, and urinary albumin to creatinine ratio (UACR) ≤3,500 mg/g. Patients with B-type natriuretic peptide values >200 pg/mL at baseline or with significant cardiovascular histories were excluded. Patients were randomized 1:1 to bardoxolone methyl or placebo, with stratification by baseline UACR.A total of 371 patients were screened, and 157 patients were randomly assigned to receive bardoxolone methyl (n = 77) or placebo (n = 80). The average age at screening was 39.2 years, and 23 (15%) were <18 years of age. Of the randomized population, 146 (93%) had confirmed genetic diagnosis of Alport syndrome, and 62% of patients had X-linked mode of inheritance. Mean baseline eGFR was 62.7 mL/min/1.73 m2, and the geometric mean UACR was 141.0 mg/g. The average annual rate of eGFR decline prior to enrollment in the study was -4.9 mL/min/1.73 m2 despite 78% of the patient population receiving ACE inhibitor (ACEi) or ARB therapy.CARDINAL is one of the largest interventional, randomized controlled trials in Alport syndrome conducted to date. Despite the use of ACEi or ARB, patients were experiencing significant loss of kidney function prior to study entry.

  View details for DOI 10.1159/000513777

  View details for PubMedID 33789284

• A pre-specified analysis of the DAPA-CKD trial indicates effects of dapagliflozin on major adverse kidney events in patients with IgA nephropathy. Kidney international Wheeler, D. C., Toto, R. D., Stefansson, B. V., Jongs, N. n., Chertow, G. M., Greene, T. n., Hou, F. F., McMurray, J. J., Pecoits-Filho, R. n., Correa-Rotter, R. n., Rossing, P. n., Sjöström, C. D., Umanath, K. n., Langkilde, A. M., Heerspink, H. J. 2021

  Abstract

  Immunoglobulin A (IgA) nephropathy is a common form of glomerulonephritis, which despite use of renin-angiotensin-aldosterone-system blockers and immunosuppressants, often progresses to kidney failure. In the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease trial, dapagliflozin reduced risk of kidney failure and prolonged survival in participants with chronic kidney disease with and without type 2 diabetes, including those with IgA nephropathy. Here we randomized participants with estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73m2 and urinary albumin-to-creatinine ratio 200-5000 mg/g (22.6-565 mg/mol) to dapagliflozin 10mg or placebo, as adjunct to standard care The primary composite endpoint was a sustained decline in eGFR of 50% or more, end-stage kidney disease, or death from a kidney disease-related or cardiovascular cause. Of 270 participants with IgA nephropathy (254 [94%] confirmed by previous biopsy), 137 were randomized to dapagliflozin and 133 to placebo, and followed for median 2.1 years. Overall, mean age was 51.2 years; mean eGFR, 43.8 mL/min/1.73m2; and median urinary albumin-to-creatinine ratio, 900 mg/g. The primary outcome occurred in six (4%) participants on dapagliflozin and 20 (15%) on placebo (hazard ratio, 0.29; 95% confidence interval, 0.12, 0.73). Mean rates of eGFR decline with dapagliflozin and placebo were -3.5 and -4.7 mL/min/1.73m2/year, respectively. Dapagliflozin reduced the urinary albumin-to-creatinine ratio by 26% relative to placebo. Adverse events leading to study drug discontinuation were similar with dapagliflozin and placebo. There were fewer serious adverse events with dapagliflozin. It had no new safety findings in this population. Thus, in participants with IgA nephropathy, dapagliflozin reduced the risk of chronic kidney disease progression with a favorable safety profile.

  View details for DOI 10.1016/j.kint.2021.03.033

  View details for PubMedID 33878338

• Aldosterone sensitivity: an opportunity for investigation into the pathogenesis of hypertension. American journal of physiology. Renal physiology Gray, Z. n., Tu, W. n., Chertow, G. M., Bhalla, V. n. 2021

  Abstract

  Aldosterone sensitivity is defined as an outcome variable for a given circulating level of aldosterone. In basic and translational studies, this has been measured in differential tissue responses, e.g. lower urine sodium and higher urine potassium, as an index of renal response; and in clinical studies has been measured in differential blood pressure. This concept of aldosterone sensitivity disrupts the conventional wisdom of the renin-angiotensin-aldosterone system and has the potential to uncover novel mechanisms of hypertension. We review basic and translational science studies that uncovered differential renal responses to aldosterone and connect this earlier work to more recent observational and randomized trials that have demonstrated differential blood pressure for a given level of aldosterone in healthy and hypertensive subjects. Black race and age are associated with higher aldosterone sensitivity and blood pressure. We also discuss gaps in the field and how future basic and clinical studies can inform mechanisms of differential sensitivity.

  View details for DOI 10.1152/ajprenal.00415.2020

  View details for PubMedID 33491565

• Combination treatment with tenapanor and sevelamer synergistically reduces urinary phosphorus excretion in rats. American journal of physiology. Renal physiology King, A. J., Kohler, J. n., Fung, C. n., Jiang, Z. n., Quach, A. n., Kumaraswamy, P. n., Chertow, G. M., Rosenbaum, D. P. 2021; 320 (1): F133–F144

  Abstract

  The majority of patients with chronic kidney disease (CKD) receiving dialysis do not achieve target serum phosphorus concentrations, despite treatment with phosphate binders. Tenapanor is a nonbinder, sodium/hydrogen exchanger isoform 3 (NHE3) inhibitor that reduces paracellular intestinal phosphate absorption. This preclinical study evaluated the effect of tenapanor and varying doses of sevelamer carbonate on urinary phosphorus excretion, a direct reflection of intestinal phosphate absorption. We measured 24-h urinary phosphorus excretion in male rats assigned to groups dosed orally with vehicle or tenapanor (0.3 mg/kg/day) and provided a diet containing varying amounts of sevelamer [0-3% (wt/wt)]. We also evaluated the effect of the addition of tenapanor or vehicle on 24-h urinary phosphorus excretion to rats on a stable dose of sevelamer [1.5% (wt/wt)]. When administered together, tenapanor and sevelamer decreased urinary phosphorus excretion significantly more than either tenapanor or sevelamer alone across all sevelamer dose levels. The Bliss statistical model of independence indicated that the combination was synergistic. A stable sevelamer dose [1.5% (wt/wt)] reduced mean ± SE urinary phosphorus excretion by 42 ± 3% compared with vehicle; together, tenapanor and sevelamer reduced residual urinary phosphorus excretion by an additional 37 ± 6% (P < 0.05). Although both tenapanor and sevelamer reduce intestinal phosphate absorption individually, administration of tenapanor and sevelamer together results in more pronounced reductions in intestinal phosphate absorption than if either agent is administered alone. Further evaluation of combination tenapanor plus phosphate binder treatment in patients receiving dialysis with hyperphosphatemia is warranted.

  View details for DOI 10.1152/ajprenal.00137.2020

  View details for PubMedID 33283643

• Effects of dapagliflozin on major adverse kidney and cardiovascular events in patients with diabetic and non-diabetic chronic kidney disease: a prespecified analysis from the DAPA-CKD trial. The lancet. Diabetes & endocrinology Wheeler, D. C., Stefánsson, B. V., Jongs, N. n., Chertow, G. M., Greene, T. n., Hou, F. F., McMurray, J. J., Correa-Rotter, R. n., Rossing, P. n., Toto, R. D., Sjöström, C. D., Langkilde, A. M., Heerspink, H. J. 2021; 9 (1): 22–31

  Abstract

  Dapagliflozin reduces the risk of kidney failure and heart failure in patients with chronic kidney disease. We aimed to investigate the effects of dapagliflozin on kidney, cardiovascular, and mortality outcomes according to presence or absence of type 2 diabetes and according to underlying cause of chronic kidney disease, reported as diabetic nephropathy, chronic glomerulonephritides, ischaemic or hypertensive chronic kidney disease, or chronic kidney disease of other or unknown cause.DAPA-CKD was a multicentre, double-blind, placebo-controlled, randomised trial done at 386 study sites in 21 countries, in which participants with a urinary albumin-to-creatinine ratio of 200-5000 mg/g and an estimated glomerular filtration rate (eGFR) of 25-75 mL/min per 1·73m2 were randomly assigned (1:1) to dapagliflozin 10 mg once daily or matching placebo, as an adjunct to standard care. The primary outcome was a composite of sustained decline in eGFR of at least 50%, end-stage kidney disease, or kidney-related or cardiovascular death. Secondary efficacy outcomes were a kidney-specific composite (the same as the primary outcome but excluding cardiovascular death), a composite of cardiovascular death or hospital admission for heart failure, and all-cause mortality. In this study, we conducted a prespecified subgroup analysis of the DAPA-CKD primary and secondary endpoints by presence or absence of type 2 diabetes and by aetiology of chronic kidney disease. DAPA-CKD is registered with ClinicalTrials.gov, NCT03036150.The study took place between Feb 2, 2017, and June 12, 2020. 4304 participants were randomly assigned (2152 to dapagliflozin and 2152 to placebo) and were followed up for a median of 2·4 years (IQR 2·0-2·7). Overall, 2906 (68%) participants had a diagnosis of type 2 diabetes, of whom 396 (14%) had chronic kidney disease ascribed to causes other than diabetic nephropathy. The relative risk reduction for the primary composite outcome with dapagliflozin was consistent in participants with type 2 diabetes (hazard ratio [HR] 0·64, 95% CI 0·52-0·79) and those without diabetes (0·50, 0·35-0·72; pinteraction=0·24). Similar findings were seen for the secondary outcomes: kidney-specific composite outcome (0·57 [0·45-0·73] vs 0·51 [0·34-0·75]; Pinteraction=0·57), cardiovascular death or hospital admission for heart failure (0·70 [0·53-0·92] vs 0·79 [0·40-1·55]; Pinteraction=0·78), and all-cause mortality (0·74 [0·56-0·98] vs 0·52 [0·29-0·93]; Pinteraction=0·25). The effect of dapagliflozin on the primary outcome was also consistent among patients with diabetic nephropathy (n=2510; HR 0·63, 95% CI 0·51-0·78), glomerulonephritides (n=695; 0·43, 0·26-0·71), ischaemic or hypertensive chronic kidney disease (n=687; 0·75, 0·44-1·26), and chronic kidney disease of other or unknown cause (n=412; 0·58, 0·29-1·19; Pinteraction=0·53), with similar consistency seen across the secondary outcomes. The proportions of participants in the dapagliflozin and placebo groups who had serious adverse events or discontinued study drug due to adverse events did not vary between those with and those without type 2 diabetes.Dapagliflozin reduces the risks of major adverse kidney and cardiovascular events and all-cause mortality in patients with diabetic and non-diabetic chronic kidney disease.AstraZeneca.

  View details for DOI 10.1016/S2213-8587(20)30369-7

  View details for PubMedID 33338413

• Trial design and baseline characteristics of CaLIPSO: a randomized, double-blind placebo-controlled trial of SNF472 in patients receiving haemodialysis with cardiovascular calcification. Clinical kidney journal Bellasi, A., Raggi, P., Bover, J., Bushinsky, D. A., Chertow, G. M., Ketteler, M., Rodriguez, M., Sinha, S., Salcedo, C., Garg, R., Gold, A., Perello, J. 2021; 14 (1): 366–74

  Abstract

  Background: The objective of CaLIPSO, a Phase 2b, randomized, double-blind, placebo-controlled clinical trial, is to test the hypothesis that myo-inositol hexaphosphate (SNF472) attenuates the progression of cardiovascular calcification in patients receiving maintenance haemodialysis. Here we report the trial design and baseline characteristics of trial participants.Methods: Adult patients on maintenance haemodialysis (≥6months) with an Agatston coronary artery calcium score, as measured by a multidetector computed tomography scanner, of 100-3500 U were enrolled. Patients were stratified by Agatston score (100-<400, 400-1000 or >1000 U) and randomized in a 1:1:1 ratio to receive placebo, SNF472 300mg or SNF472 600mg administered intravenously three times weekly during each haemodialysis session.Results: Overall, 274 patients were randomized. The mean age of trial participants was 63.6(standard deviation 8.9) years and 39% were women. The coronary artery, aorta and aortic valve median (25th-75th percentile) Agatston scores at baseline were 730 U (315-1435), 1728 U (625-4978) and 103 U (31-262), respectively, and the median (25th-75th percentile) calcium volume scores at baseline were 666 (310-1234), 1418 (536-4052) and 107 (38-278), respectively. Older age and diabetes mellitus were associated with higher calcium scores at baseline.Conclusions: The CaLIPSO trial enrolled patients on haemodialysis with pre-existent cardiovascular calcification to test the hypothesis that SNF472 attenuates its progression in the coronary arteries, aorta and aortic valve.

  View details for DOI 10.1093/ckj/sfz144

  View details for PubMedID 33564440

• Effects of dapagliflozin on major adverse kidney and cardiovascular events in patients with diabetic and non-diabetic chronic kidney disease: a prespecified analysis from the DAPA-CKD trial LANCET DIABETES & ENDOCRINOLOGY Wheeler, D. C., Stefansson, B., Jongs, N., Chertow, G. M., Greene, T., Hou, F., McMurray, J. J., Correa-Rotter, R., Rossing, P., Toto, R. D., Sjostrom, C., Langkilde, A., Heerspink, H. L., DAPA-CKD Trial Comm Investigators 2021; 9 (1): 22–31

  View details for Web of Science ID 000600606200011

• Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) McMurray, J. J., Wheeler, D. C., Stefansson, B. V., Rotter, R., Chertow, G. M., Greene, T., Hou, F., Lindberg, M. B., Rossing, P., Sjostrom, D., Toto, R. D., Langkilde, A., Heerspink, H., DAPA-CKD Comm Investigators LIPPINCOTT WILLIAMS & WILKINS. 2020: E482–E483

  View details for Web of Science ID 000598973900043

• Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) McMurray, J. J., Wheeler, D. C., Stefansson, B. V., Rotter, R., Chertow, G. M., Greene, T., Hou, F., Lindberg, M. B., Rossing, P., Sjostrom, D., Toto, R. D., Langkilde, A., Heerspink, H., DAPA-CKD Comm Investigators LIPPINCOTT WILLIAMS & WILKINS. 2020: E482–E483

  View details for Web of Science ID 000639226400043

• Dapagliflozin And Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD) McMurray, J. V., Wheeler, D. C., Stefansson, B. V., Correa-Rotter, R., Chertow, G. M., Greene, T., Hou, F., Lindberg, M. B., Rossing, P., Sjostrom, C., Toto, R. D., Langkilde, A., Heerspink, H. L. CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS. 2020: 1111

  View details for Web of Science ID 000599814300024

• Correlates and Consequences of High Serum Irisin Concentration in Patients on Hemodialysis: A Longitudinal Analysis. Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation Chiang, J. M., Delgado, C., Kaysen, G. A., Segal, M. R., Chertow, G. M., Johansen, K. L. 2020

  Abstract

  OBJECTIVE: Irisin is a hormone released by muscle in response to exercise that acts on white adipose cells to stimulate browning of adipose tissue. We aimed to examine irisin correlates and consequences of irisin in patients receiving hemodialysis.DESIGN AND METHODS: A prospective cohort study was conducted using data from 749 prevalent patients receiving hemodialysis. Multivariable linear regression and multivariable generalized estimating equations were used to determine correlates of baseline and change in serum irisin concentration. Proportional hazards (Cox) regression was used to assess the association between serum irisin concentration and time to death.RESULTS: Age and body mass index were inversely associated with baseline and change in serum irisin concentration. Lower muscle mass as estimated by serum creatinine concentration was associated with lower irisin concentration (-1.38% per mg/dL (95% confidence interval [CI]: -2.45, -0.21) and with a 0.72% decrease in irisin concentration (95% CI: -1.48, -0.04) from baseline to 12months. Each 50% higher serum interleukin-6 (IL-6) concentration was associated with 1.52% higher serum irisin concentration (95% CI: 0.38, 2.66) at baseline and an increase of 1.04% in irisin concentration over 1year (95% CI: 0.47, 1.61). Irisin concentration at baseline was associated with higher hazard of death (hazards ratio: 1.45, 95% CI: 1.05 2.00); an increase in irisin concentration over 1year was associated with a higher hazard of death (hazards ratio: 1.34, 95% CI: 1.01, 1.79). In formal mediation analysis, serum IL-6 was a mediator in the association between serum irisin and mortality.CONCLUSIONS: Lower serum creatinine (reflecting lower muscle mass) and higher serum IL-6 were associated with higher serum irisin concentrations. Higher serum irisin concentrations were associated with higher mortality, which may be mediated by inflammation.

  View details for DOI 10.1053/j.jrn.2020.05.005

  View details for PubMedID 33262071

• Laboratory-wide association study of survival with prostate cancer. Cancer Sohlberg, E. M., Thomas, I., Yang, J., Kapphahn, K., Velaer, K. N., Goldstein, M. K., Wagner, T. H., Chertow, G. M., Brooks, J. D., Patel, C. J., Desai, M., Leppert, J. T. 2020

  Abstract

  BACKGROUND: Estimates of overall patient health are essential to inform treatment decisions for patients diagnosed with cancer. The authors applied XWAS methods, herein referred to as "laboratory-wide association study (LWAS)", to evaluate associations between routinely collected laboratory tests and survival in veterans with prostate cancer.METHODS: The authors identified 133,878 patients who were diagnosed with prostate cancer between 2000 and 2013 in the Veterans Health Administration using any laboratory tests collected within 6 months of diagnosis (3,345,083 results). Using the LWAS framework, the false-discovery rate was used to test the association between multiple laboratory tests and survival, and these results were validated using training, testing, and validation cohorts.RESULTS: A total of 31 laboratory tests associated with survival met stringent LWAS criteria. LWAS confirmed markers of prostate cancer biology (prostate-specific antigen: hazard ratio [HR], 1.07 [95% confidence interval (95% CI), 1.06-1.08]; and alkaline phosphatase: HR, 1.22 [95% CI, 1.20-1.24]) as well laboratory tests of general health (eg, serum albumin: HR, 0.78 [95% CI, 0.76-0.80]; and creatinine: HR, 1.05 [95% CI, 1.03-1.07]) and inflammation (leukocyte count: HR, 1.23 [95% CI, 1.98-1.26]; and erythrocyte sedimentation rate: HR, 1.33 [95% CI, 1.09-1.61]). In addition, the authors derived and validated separate models for patients with localized and advanced disease, identifying 28 laboratory markers and 15 laboratory markers, respectively, in each cohort.CONCLUSIONS: The authors identified routinely collected laboratory data associated with survival for patients with prostate cancer using LWAS methodologies, including markers of prostate cancer biology, overall health, and inflammation. Broadening consideration of determinants of survival beyond those related to cancer itself could help to inform the design of clinical trials and aid in shared decision making.LAY SUMMARY: This article examined routine laboratory tests associated with survival among veterans with prostate cancer. Using laboratory-wide association studies, the authors identified 31 laboratory tests associated with survival that can be used to inform the design of clinical trials and aid patients in shared decision making.

  View details for DOI 10.1002/cncr.33341

  View details for PubMedID 33237577

• Global Phase 3 programme of vadadustat for treatment of anaemia of chronic kidney disease: rationale, study design and baseline characteristics of dialysis-dependent patients in the INNO2VATE trials. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association Eckardt, K., Agarwal, R., Farag, Y. M., Jardine, A. G., Khawaja, Z., Koury, M. J., Luo, W., Matsushita, K., McCullough, P. A., Parfrey, P., Ross, G., Sarnak, M. J., Vargo, D., Winkelmayer, W. C., Chertow, G. M. 2020

  Abstract

  BACKGROUND: Erythropoiesis-stimulating agents (ESAs) are currently the mainstay of treatment for anaemia of chronic kidney disease (CKD). Vadadustat is an investigational oral hypoxia-inducible factor prolyl-hydroxylase inhibitor that stimulates endogenous erythropoietin formation. The INNO2VATE programme comprises two studies designed to evaluate the safety and efficacy of vadadustat versus the ESA darbepoetin alfa in ameliorating anaemia in patients with dialysis-dependent CKD (DD-CKD). Here we describe the trial design along with patient demographics and baseline characteristics.METHODS: Two Phase 3, open-label, sponsor-blind, active-controlled trials enrolled adults with anaemia of CKD who recently initiated dialysis and had limited ESA exposure (incident DD-CKD trial) or were receiving maintenance dialysis with ESA treatment (prevalent DD-CKD trial). Study periods include correction/conversion (Weeks 0-23), maintenance (Weeks 24-52), long-term treatment (Weeks 53 to end of treatment) and safety follow-up. The primary safety endpoint is the time to the first major adverse cardiovascular event and the primary efficacy endpoint is the change in haemoglobin (baseline to Weeks 24-36).RESULTS: A total of 369 and 3554 patients were randomized in the incident DD-CKD and prevalent DD-CKD trials, respectively. Demographics and baseline characteristics were similar among patients in both trials and comparable to those typically observed in DD-CKD.CONCLUSIONS: The two INNO2VATE trials will provide important information on the safety and efficacy of a novel approach for anaemia management in a diverse DD-CKD population. Demographics and baseline characteristics of enrolled patients suggest that study results will be representative for a large proportion of the DD-CKD population.

  View details for DOI 10.1093/ndt/gfaa204

  View details for PubMedID 33188693

• Effect of Dapagliflozin on Clinical Outcomes in Patients with Chronic Kidney Disease, With and Without Cardiovascular Disease. Circulation McMurray, J. J., Wheeler, D. C., Stefansson, B. V., Jongs, N., Postmus, D., Correa-Rotter, R., Chertow, G. M., Greene, T., Held, C., Hou, F. F., Mann, J. F., Rossing, P., Sjostrom, C. D., Toto, R. D., Langkilde, A. M., Heerspink, H. J., DAPA-CKD Trial Committees and Investigators 2020

  Abstract

  Background: Dapagliflozin reduces the risk of end-stage renal disease in patients with chronic kidney disease. We examined the relative risk of cardiovascular and kidney events in these patients and the effect of dapagliflozin on either type of event, taking account of history of cardiovascular disease. Methods: In the DAPA-CKD trial (Dapagliflozin And Prevention of Adverse Outcomes in Chronic Kidney Disease), 4304 participants with chronic kidney disease were randomized to dapagliflozin 10 mg once daily or placebo. The primary endpoint was a composite of sustained decline in estimated GFR ≥50%, end-stage kidney disease, or kidney or cardiovascular death. The secondary endpoints were a kidney composite outcome (primary endpoint, minus cardiovascular death), the composite of hospitalization for heart failure or cardiovascular death and all-cause death. In a prespecified subgroup analysis, we divided patients into primary and secondary prevention subgroups according to history of cardiovascular disease. Results: Secondary prevention patients (n=1610; 37.4%) were older, more often male, had a higher blood pressure and body-mass index, and were more likely to have diabetes. Mean estimated glomerular filtration rate and median urinary albumin-to-creatinine ratio was similar in the primary and secondary prevention groups. The rates of adverse cardiovascular outcomes were higher in the secondary prevention group, but kidney failure occurred at the same rate in the primary and secondary prevention groups. Dapagliflozin reduced the risk of the primary composite outcome to a similar extent in both the primary (HR, 0.61 [95% CI, 0.48-0.78]) and secondary (0.61, 0.47-0.79) prevention groups (P-interaction=0.90). This was also true for the composite of heart failure hospitalization or cardiovascular death (0.67, 0.40-1.13 versus 0.70, 0.52-0.94, respectively, P-interaction=0.88), and all-cause (0.63, 0.41-0.98 versus 0.70, 0.51-0.95, respectively, P-interaction=0.71). Rates of adverse events were low overall and did not differ between patients with and without cardiovascular disease. Conclusions: Dapagliflozin reduced the risk of kidney failure, death from cardiovascular causes or hospitalization for heart failure, and prolonged survival, in people with chronic kidney disease, with or without type 2 diabetes, independently of the presence of concomitant cardiovascular disease Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT03036150.

  View details for DOI 10.1161/CIRCULATIONAHA.120.051675

  View details for PubMedID 33186054

• Factors Associated With Failure to Achieve the Intensive Blood Pressure Target in the Systolic Blood Pressure Intervention Trial (SPRINT). Hypertension (Dallas, Tex. : 1979) Wang, K. M., Stedman, M. R., Chertow, G. M., Chang, T. I. 2020: HYPERTENSIONAHA12016155

  Abstract

  SPRINT (Systolic Blood Pressure Intervention Trial) found that randomization of nondiabetic participants at high cardiovascular risk to an intensive (systolic blood pressure [SBP] <120 mm Hg) versus standard (SBP <140 mm Hg) target resulted in 25% risk reduction in the first cardiovascular composite event (ie, cardiovascular death or nonfatal myocardial infarction, stroke, or hospitalization for heart failure) and a 27% risk reduction in all-cause mortality. In this post hoc analysis, we sought to determine the factors associated with failure to achieve the SBP target in 4678 SPRINT participants randomized to the intensive treatment group. Using a generalized estimating equation model, we assessed variables associated with failure to achieve the intensive SBP target as a repeated outcome collected during serial follow-up visits, including the occurrence of serious adverse events. In the multivariable model adjusted for baseline demographic, clinical, and laboratory variables, older age, higher SBP, underlying chronic kidney disease, higher number of antihypertensives, and moderate cognitive impairment at screening were associated with failure to achieve the intensive SBP target. Occurrence of a serious adverse event during the trial was associated with 20% higher odds of failure to achieve the SBP target. Participants of Hispanic ethnicity had 47% lower odds of failure to achieve the intensive SBP target relative to non-Hispanic Whites. Understanding barriers to achieving intensive SBP targets should allow clinicians to optimize management of hypertension in patients at high risk for cardiovascular disease.

  View details for DOI 10.1161/HYPERTENSIONAHA.120.16155

  View details for PubMedID 33131314

• Pharmacokinetics of apixaban in patients with end stage renal disease on hemodialysis and atrial fibrillation: results from the RENAL-AF trial Pokorney, S., Garonzik, S., Chertow, G. M., Washam, J. B., Mussina, K., Bansal, N., Gadegbeku, C., Garcia, D., Lopes, R. D., Mahaffey, K. W., Middleton, J., Thadhani, R., Thomas, K. L., Winkelmayer, W., Granger, C. B., RENAL-AF Investigators OXFORD UNIV PRESS. 2020: 3373

  View details for Web of Science ID 000606106303380

• Cardiovascular Safety and Efficacy of Vadadust for the Treatment of Anemia in Non-Dialysis Dependent CKD: Design and Baseline Characteristics. American heart journal Chertow, G. M., Pergola, P. E., Agarwal, R., Block, G. A., Farag, Y. M., Jardine, A. G., Koury, M. J., Luo, W., Khawaja, Z., Lewis, E. F., Matsushita, K., McCullough, P. A., Parfrey, P. S., Wittes, J., Walters, K. A., Tseng, C., Lin, T., Sarnak, M. J., Vargo, D. L., Winkelmayer, W. C., Eckardt, K. 2020

  Abstract

  Current clinical practice guidelines for anemia management in non-dialysis dependent chronic kidney disease (NDD-CKD) recommend the use of erythropoiesis-stimulating agents (ESAs) as standard of care. Vadadustat, an investigational oral hypoxia-inducible factor prolyl hydroxylase inhibitor, stimulates endogenous erythropoietin production. The PRO2TECT program comprises two global, Phase 3, randomized, open-label, active-controlled, sponsor-blind clinical trials to evaluate safety and efficacy of vadadustat vs darbepoetin alfa in adult patients with anemia associated with NDD-CKD. Patients recruited into the ESA-untreated NDD-CKD trial (N=1751) had hemoglobin <10 g/dL and had not received an ESA within 8 weeks prior to inclusion in the study. Patients recruited into the ESA-treated NDD-CKD trial (N=1725) had hemoglobin between 8-11 g/dL (US) or 9-12 g/dL (non-US) and were actively treated with an ESA for anemia associated with CKD. Trial periods in both trials include 1) correction/conversion (weeks 0-23); 2) maintenance (weeks 24-52); 3) long-term treatment (week 53 to end of treatment); and 4) safety follow-up (end-of-treatment to 4 weeks later). The primary safety endpoint is time to first adjudicated major adverse cardiovascular event, defined as all-cause mortality, nonfatal myocardial infarction, or nonfatal stroke, pooled across both trials. The primary efficacy endpoint in each trial is change in hemoglobin from baseline to primary evaluation period (weeks 24-36), comparing vadadustat vs darbepoetin alfa treatment groups. Demographics and baseline characteristics were similar among patients in both trials and broadly representative of the NDD-CKD population. These trials will help to evaluate the safety and efficacy of vadadustat for management of anemia associated with NDD-CKD.

  View details for DOI 10.1016/j.ahj.2020.10.068

  View details for PubMedID 33129989

• Self-care training using the Tablo hemodialysis system. Hemodialysis international. International Symposium on Home Hemodialysis Plumb, T. J., Alvarez, L., Ross, D. L., Lee, J. J., Mulhern, J. G., Bell, J. L., Abra, G. E., Prichard, S. S., Chertow, G. M., Aragon, M. A. 2020

  Abstract

  INTRODUCTION: Recently published results of the investigational device exemption (IDE) trial using the Tablo hemodialysis system confirmed its safety and efficacy for home dialysis. This manuscript reports additional data from the Tablo IDE study on the training time required to be competent in self-care, the degree of dependence on health care workers and caregivers after training was complete, and participants' assessment of the ease-of-use of Tablo.METHODS: We collected data on the time required to set up concentrates and the Tablo cartridge prior to treatment initiation. We asked participants to rate system setup, treatment, and takedown on a Likert scale from 1 (very difficult) to 5 (very simple) and if they had required any assistance with any aspect of treatment over the prior 7days. In a subgroup of 15 participants, we recorded the number of training sessions required to be deemed competent to do self-care dialysis.FINDINGS: Eighteen men and 10 women with a mean age of 52.6years completed the study. Thirteen had previous self-care experience using a different dialysis system. Mean set up times for the concentrates and cartridge were 1.1 and 10.0minutes, respectively. Participants with or without previous self-care experience had similar set-up times. The mean ease-of-use score was 4.5 or higher on a scale from 1 to 5 during the in-home phase. Sixty-five percent required no assistance at home and on average required fewer than four training sessions to be competent in managing their treatments. Results were similar for participants with or without previous self-care experience.CONCLUSIONS: Participants in the Tablo IDE trial were able to quickly learn and manage hemodialysis treatments in the home, found Tablo easy to use, and were generally independent in performing hemodialysis.

  View details for DOI 10.1111/hdi.12890

  View details for PubMedID 33047477

• Fibroblast growth factor 23 as a risk factor for cardiovascular events and mortality in patients in the EVOLVE trial. Hemodialysis international. International Symposium on Home Hemodialysis Block, G. A., Chertow, G. M., Cooper, K., Xing, S., Fouqueray, B., Halperin, M., Danese, M. D. 2020

  Abstract

  INTRODUCTION: High mortality rates in patients with chronic kidney disease-mineral and bone disorder (CKD-MBD) receiving maintenance hemodialysis are largely due to cardiovascular (CV) events.METHODS: We evaluated associations between MBD parameters, fibroblast growth factor 23 (FGF23) concentrations, and clinically adjudicated CV events from the Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events (EVOLVE) trial. Patients enrolled in EVOLVE, who had not experienced any study endpoints between randomization and week 20 with evaluable baseline and week 20 values for key laboratory parameters (parathyroid hormone, calcium, phosphate, and FGF23), were assessed. We used adjusted Cox proportional hazards regression models to estimate relative risk of outcomes (primary composite, all-cause mortality, and CV events) based on FGF23 and MBD parameters. Laboratory values were modeled with linear terms and using natural cubic splines with two degrees of freedom.FINDINGS: For the primary endpoint, patients assessed (N = 2309) were followed up over a mean duration of 3.1years, during which 1037 CV events (497 deaths, 540 nonfatal events) occurred. Adjusted models showed an association between FGF23 and the risk of CV events. Hazard ratio per log unit of FGF23 at week 20 was 1.09 [95% CI: 1.03-1.16], and the hazard ratio per log unit change in FGF23 from week 0 to week 20 was 1.09 [95% CI: 1.00-1.17].DISCUSSION: Our data highlight FGF23 as an independent CV risk factor and potential biomarker and therapeutic target for patients with CKD-MBD receiving maintenance hemodialysis.

  View details for DOI 10.1111/hdi.12887

  View details for PubMedID 33016505

• One-year safety and efficacy of intravenous etelcalcetide in patients on hemodialysis with secondary hyperparathyroidism NEPHROLOGY DIALYSIS TRANSPLANTATION Bushinsky, D. A., Chertow, G. M., Cheng, S., Deng, H., Kopyt, N., Martin, K. J., Rastogi, A., Urena-Torres, P., Vervloet, M., Block, G. A. 2020; 35 (10): 1769–78

  View details for DOI 10.1093/ndt/gfz039

  View details for Web of Science ID 000607839600018

• Effects of Bardoxolone Methyl on Hepatic Enzymes in Patients with Type 2 Diabetes Mellitus and Stage 4 CKD. Clinical and translational science Lewis, J. H., Jadoul, M., Block, G. A., Chin, M. P., Ferguson, D. A., Goldsberry, A., Meyer, C. J., O'Grady, M., Pergola, P. E., Reisman, S. A., Wigley, W. C., Chertow, G. M. 2020

  Abstract

  In a multinational placebo-controlled phase 3 clinical trial in 2185 patients with type 2 diabetes mellitus [T2DM] and stage 4 chronic kidney disease [CKD], treatment with the Nrf2 activator bardoxolone methyl increased estimated glomerular filtration rate, a measure of kidney function, but also resulted in increases in serum alanine aminotransferase [ALT], aspartate aminotransferase [AST], and gamma glutamyl transferase [GGT]. These increases in liver enzyme level(s) were maximal after 4 weeks of treatment and reversible, trending back towards baseline through Week 48. Total bilirubin concentrations did not increase, and no cases met Hy's Law criteria, although two subjects had ALT concentrations that exceeded 10 * the upper limit of the population reference range leading to discontinuation of treatment. Animal and cell culture experiments suggested that the increases in ALT and AST induced by bardoxolone methyl may be related to its pharmacological activity. Bardoxolone methyl significantly induced the mRNA expression of ALT and AST isoforms in cultured cells. Expression of ALT and AST isoforms in liver and kidney also positively correlated with Nrf2 status in mice. Overall, these data suggest that the increases in ALT and AST observed clinically were at least in part, related to the pharmacological induction of aminotransferases via Nrf2 activation, rather than to any intrinsic form of hepatotoxicity.

  View details for DOI 10.1111/cts.12868

  View details for PubMedID 32860734

• Patient-reported outcomes from the investigational device exemption study of the Tablo hemodialysis system. Hemodialysis international. International Symposium on Home Hemodialysis Chertow, G. M., Alvarez, L., Plumb, T. J., Prichard, S. S., Aragon, M. 2020

  Abstract

  INTRODUCTION: We recently completed an Investigational Device Exemption (IDE) study in which 30 patients were enrolled (13 patients previously on home hemodialysis (HHD) and 17 patients new to HHD) and treated with the Tablo Hemodialysis System (Outset Medical, Inc., San Jose, CA) for 8weeks in-center and 8weeks in-home with an interim 2-4week transition period for home training.METHODS: In addition to assessments of urea kinetics, events related to safety, and operational issues (e.g., alarm resolution), we obtained data on several parameters of health-related quality of life, including time to recovery (TTR), the EQ-5D-5L (a well-validated measure of general health status), and the quality of sleep and related symptoms, to further assess the safety of HHD with Tablo. We compared results obtained during the in-center and in-home phases of the trial.RESULTS: Twenty-eight of 30 patients (93%) completed all trial periods. Adherence to the prescribed four treatments per week schedule was 96% in-center and 99% in-home. Median TTR was 1.5hours (10th, 90th percentile range 0.17 to 12, mean TTR 3.68±5.88hours) during the in-center and 2hours (10th, 90th percentile range 0 to 6.0, mean TTR 3.04±5.14hours) during the at-home phase (Wilcoxon signed rank p = 0.57). Median index values on the EQ-5D-5L were similar during the in-center (0.832, 10th, 90th percentile range 0.617 to 1, mean 0.817±0.165) and in-home (0.826, 10th, 90th percentile range 0.603 to 1, mean 0.821±0.163) trial phases (Wilcoxon signed rank p = 0.36). Patients reported feeling alert or well-rested with little difficulty falling or staying asleep or feeling tired and worn out when using Tablo in either environment.CONCLUSION: When using Tablo in-home, patients reported similar TTR, general health status, and sleep quality and related symptoms compared to using Tablo in-center. (294 words).

  View details for DOI 10.1111/hdi.12869

  View details for PubMedID 32851807

• Drug Development in Kidney Disease: Proceedings From a Multistakeholder Conference. American journal of kidney diseases : the official journal of the National Kidney Foundation Edmonston, D. L., Roe, M. T., Block, G., Conway, P. T., Dember, L. M., DiBattiste, P. M., Greene, T., Hariri, A., Inker, L. A., Isakova, T., Montez-Rath, M. E., Nkulikiyinka, R., Polidori, D., Roessig, L., Tangri, N., Wyatt, C., Chertow, G. M., Wolf, M. 2020

  Abstract

  Occasional bursts of discovery and innovation have appeared during the otherwise stagnant past several decades of drug development in nephrology. Among other recent drug discoveries, the unexpected kidney benefits observed with sodium-glucose cotransporter-2 inhibitors may herald a renaissance of drug development in kidney disease. This recent progress highlights the need to further promote and stimulate research and development of promising therapies that may ameliorate the morbidity and mortality associated with kidney disease. To help identify and address barriers to drug development in nephrology, the Duke Clinical Research Institute convened a think tank in April 2019 that included stakeholders from academia, industry, government agencies, and patient advocacy. From these discussions, several opportunities were identified to improve every stage of drug development for kidney disease from early discovery to implementation into practice. Key topics reviewed in this article are the utility of interconnected data and site research networks, surrogate endpoints, pragmatic and adaptive trial designs, the promising uses of real-world data, and methods to improve the generalizability of trial results and uptake of approved drugs for kidney-related diseases.

  View details for DOI 10.1053/j.ajkd.2020.05.026

  View details for PubMedID 32768631

• Does really central venous pressure affect the risk of diuretic-associated acute kidney injury after cardiac surgery? American heart journal McCoy, I., Montez-Rath, M., Chertow, G., Chang, T. 2020; 226: 252

  View details for DOI 10.1016/j.ahj.2020.04.002

  View details for PubMedID 32811639

• Analysis of Primary Hyperparathyroidism Screening Among US Veterans With Kidney Stones. JAMA surgery Ganesan, C., Weia, B., Thomas, I., Song, S., Velaer, K., Seib, C. D., Conti, S., Elliott, C., Chertow, G. M., Kurella Tamura, M., Leppert, J. T., Pao, A. C. 2020

  Abstract

  Importance: Approximately 3% to 5% of patients with kidney stones have primary hyperparathyroidism (PHPT), a treatable cause of recurrent stones. However, the rate of screening for PHPT in patients with kidney stones remains unknown.Objectives: To estimate the prevalence of parathyroid hormone (PTH) testing in veterans with kidney stones and hypercalcemia and to identify the demographic, geographic, and clinical characteristics of veterans who were more or less likely to receive PTH testing.Design, Setting, and Participants: This cohort study obtained Veterans Health Administration (VHA) health records from the Corporate Data Warehouse for veterans who received care in 1 of the 130 VHA facilities across the United States from January 1, 2008, through December 31, 2013. Historical encounters, medical codes, and laboratory data were assessed. Included patients had diagnostic or procedural codes for kidney or ureteral stones, and excluded patients were those with a previous serum PTH level measurement. Data were collected from January 1, 2006, to December 31, 2014. Data analysis was conducted from June 1, 2019, to January 31, 2020.Exposures: Elevated serum calcium concentration measurement between 6 months before and 6 months after kidney stone diagnosis.Main Outcomes and Measures: Proportion of patients with a serum PTH level measurement and proportion of patients with biochemical evidence of PHPT who underwent parathyroidectomy.Results: The final cohort comprised 7561 patients with kidney stones and hypercalcemia and a mean (SD) age of 64.3 (12.3) years. Of these patients, 7139 were men (94.4%) and 5673 were white individuals (75.0%). The proportion of patients who completed a serum PTH level measurement was 24.8% (1873 of 7561). Across the 130 VHA facilities included in the study, testing rates ranged from 4% to 57%. The factors associated with PTH testing included the magnitude of calcium concentration elevation (odds ratio [OR], 1.07 per 0.1 mg/dL >10.5 mg/dL; 95% CI, 1.05-1.08) and the number of elevated serum calcium concentration measurements (OR, 1.08 per measurement >10.5 mg/dL; 95% CI, 1.06-1.10) as well as visits to both a nephrologist and a urologist (OR, 6.57; 95% CI, 5.33-8.10) or an endocrinologist (OR, 4.93; 95% CI, 4.11-5.93). Of the 717 patients with biochemical evidence of PHPT, 189 (26.4%) underwent parathyroidectomy within 2 years of a stone diagnosis.Conclusions and Relevance: This cohort study found that only 1 in 4 patients with kidney stones and hypercalcemia were tested for PHPT in VHA facilities and that testing rates varied widely across these facilities. These findings suggest that raising clinician awareness to PHPT screening indications may improve evaluation for parathyroidectomy, increase the rates of detection and treatment of PHPT, and decrease recurrent kidney stone disease.

  View details for DOI 10.1001/jamasurg.2020.2423

  View details for PubMedID 32725208

• Early Delays in Insurance Coverage and Long-term Use of Home-based Peritoneal Dialysis. Medical care Lin, E., Chertow, G. M., Bhattacharya, J., Lakdawalla, D. 2020; 58 (7): 632–42

  Abstract

  BACKGROUND: Uninsured patients with end-stage renal disease face barriers to peritoneal dialysis (PD), a type of home dialysis that is associated with improved quality of life and reduced Medicare costs. Although uninsured patients using PD at dialysis start receive retroactive Medicare coverage for required predialysis services, coverage only applies for the calendar month of dialysis start. Thus, initiating dialysis later in the month yields longer retroactive coverage.OBJECTIVES: To examine whether differences in retroactive Medicare were associated with decreased long-term PD use.RESEARCH DESIGN: We exploited the dialysis start date using a regression discontinuity design on a national cohort from the US Renal Data System.SUBJECTS: 36,256 uninsured adults starting dialysis between January 1, 2006 and December 31, 2014.MEASURES: PD use at dialysis days 1, 90, 180, and 360.RESULTS: Starting dialysis on the first versus last day of the calendar month was associated with an absolute decrease in PD use of 2.7% [95% confidence interval (CI), 1.5%-3.9%], or a relative decrease of 20% (95% CI, 12%-27%) at dialysis day 360. The absolute decrease was 5.5% (95% CI, 3.5%-7.2%) after Medicare established provider incentives for PD in 2011 and 7.2% (95% CI, 2.5%-11.9%) after Medicaid expansion in 2014. Patients were unlikely to switch from hemodialysis to PD after the first month of dialysis (probability of 6.9% in month 1, 1.5% in month 2, and 0.9% in month 4).CONCLUSIONS: Extending retroactive coverage for preparatory dialysis services could increase PD use and reduce overall Medicare spending in the uninsured.

  View details for DOI 10.1097/MLR.0000000000001350

  View details for PubMedID 32520837

• SNF472 CONSISTENTLY SLOWS PROGRESSION OF CORONARY CALCIFICATION IN PATIENTS ON HEMODIALYSIS: SUBGROUP ANALYSIS OF THE CALIPSO STUDY Raggi, P., Bellasi, A., Bushinsky, D., Bover, J., Rodriguez, M., Ketteler, M., Sinha, S., Garg, R., Padgett, C., Perello, J., Gold, A., Chertow, G. OXFORD UNIV PRESS. 2020: 92

  View details for Web of Science ID 000554536200413

• SNF472 CONSISTENTLY SLOWS PROGRESSION OF CORONARY CALCIFICATION IN PATIENTS ON HEMODIALYSIS: SUBGROUP ANALYSIS OF THE CALIPSO STUDY Raggi, P., Bellasi, A., Bushinsky, D., Bover, J., Rodriquez, M., Ketteler, M., Sinha, S., Garg, R., Padgett, C., Perello, J., Gold, A., Chertow, G. OXFORD UNIV PRESS. 2020: 92

  View details for Web of Science ID 000562392100622

• Baseline Diastolic Blood Pressure and Cardiovascular Outcomes in SPRINT Participants with Chronic Kidney Disease. Kidney360 Chang, T. I., Wei, G., Boucher, R., Kramer, H., Chertow, G. M., Cheung, A. K., Greene, T., Whelton, P. K., Beddhu, S. 2020; 1 (5): 368-375

  Abstract

  We sought to determine whether intensive systolic BP (SBP) lowering was harmful in Systolic Blood Pressure Intervention Trial (SPRINT) participants with CKD (eGFR<60 ml/min per 1.73 m2) and lower baseline diastolic BP (DBP).We related baseline DBP with the SPRINT primary composite end point (myocardial infarction, acute coronary syndrome, stroke, acute decompensated heart failure, or cardiovascular death) and all-cause death. We examined the effect of intensive SBP lowering on these outcomes across the range of baseline DBPs using Cox regression with treatment by baseline DBP interaction terms.Among 2646 SPRINT participants with CKD, lower baseline DBP was associated with a higher adjusted hazard of the primary composite end point and all-cause death. For example, participants with baseline DBP of 61 mm Hg (mean baseline DBP in the lowest tertile) experienced a 37% (95% CI, 7% to 75%) higher hazard of the primary outcome relative to participants with baseline DBP of 75 mm Hg (mean baseline DBP for overall). The benefit of intensive SBP lowering was consistent across a range of baseline DBPs on rates of the primary composite end point (linear interaction P value =0.56) and all-cause death (linear interaction P value =0.20).Among SPRINT participants with baseline CKD, lower DBP was associated with higher rates of the primary composite end point and all-cause death. However, DBP did not seem to modify the benefit of intensive SBP lowering on the primary composite end point or all-cause death. Our results suggest that lower DBP should not necessarily impede more intensive SBP lowering in patients with mild to moderate CKD.

  View details for DOI 10.34067/KID.0000982019

  View details for PubMedID 35369376

  View details for PubMedCentralID PMC8809286

• The Influence of Baseline Diastolic Blood Pressure on the Effects of Intensive Blood Pressure Lowering on Cardiovascular Outcomes and All-Cause Mortality in Type 2 Diabetes. Diabetes care Ilkun, O. L., Greene, T., Cheung, A. K., Whelton, P. K., Wei, G., Boucher, R. E., Ambrosius, W., Chertow, G. M., Beddhu, S. 2020

  Abstract

  OBJECTIVE: To examine whether low baseline diastolic blood pressure (DBP) modifies the effects of intensive systolic blood pressure (SBP) lowering on cardiovascular outcomes in type 2 diabetes mellitus (T2DM).RESEARCH DESIGN AND METHODS: The Action to Control Cardiovascular Risk in Diabetes Blood Pressure trial (ACCORD BP), a two-by-two factorial randomized controlled trial, examined effects of SBP (<120 vs. <140 mmHg) and glycemic (HbA1c <6% vs. 7.0-7.9% [<42 vs. 53-63 mmol/mol]) control on cardiovascular events in T2DM (N = 4,731). We examined whether effects of SBP control on cardiovascular composite were modified by baseline DBP and glycemic control.RESULTS: Intensive SBP lowering decreased the risk of the cardiovascular composite (hazard ratio [HR] 0.76 [95% CI 0.59-0.98]) in the standard glycemic arm but not in the intensive glycemic arm (HR 1.06 [95% CI 0.81-1.40]). Spline regression models relating the effects of the intervention on the cardiovascular composite across the range of baseline DBP did not show evidence of effect modification by low baseline DBP for the cardiovascular composite in the standard or intensive glycemic arms. The relation between the effect of the intensive SBP intervention and baseline DBP was similar between glycemic arms for the cardiovascular composite three-way interaction (P = 0.83).CONCLUSIONS: In persons with T2DM, intensive SBP lowering decreased the risk of cardiovascular composite end point irrespective of baseline DBP in the setting of standard glycemic control. Hence, low baseline DBP should not be an impediment to intensive SBP lowering in patients with T2DM treated with guidelines recommending standard glycemic control.

  View details for DOI 10.2337/dc19-2047

  View details for PubMedID 32366577

• Targeting Vascular Calcification in Chronic Kidney Disease. JACC. Basic to translational science Nelson, A. J., Raggi, P., Wolf, M., Gold, A. M., Chertow, G. M., Roe, M. T. 2020; 5 (4): 398–412

  Abstract

  Cardiovascular (CV) disease remains an important cause of morbidity and mortality for patients with chronic kidney disease (CKD). Although clustering of traditional risk factors with CKD is well recognized, kidney-specific mechanisms are believed to drive the disproportionate burden of CV disease. One perturbation that is frequently observed at high rates in patients with CKD is vascular calcification, which may be a central mediator for an array of CV sequelae. This review summarizes the pathophysiological bases of intimal and medial vascular calcification in CKD, current strategies for diagnosis and management, and posits vascular calcification as a risk marker and therapeutic target.

  View details for DOI 10.1016/j.jacbts.2020.02.002

  View details for PubMedID 32368697

• OPEN-LABEL STUDY OF THE PHARMACOKINETICS, SAFETY, AND TOLERABILITY OF DM199 IN SUBJECTS WITH DIABETES AND CHRONIC KIDNEY DISEASE Marbury, T., Alcorn, H., Bakris, G., Bermudez, M., Agarwal, R., Herzog, C., Chertow, G., Canas, G. W B SAUNDERS CO-ELSEVIER INC. 2020: 542–43

  View details for Web of Science ID 000522408300035

• The Urine Albumin-Creatinine Ratio and Kidney Function after Nephrectomy. The Journal of urology Sun, A. J., Thomas, I., Velaer, K. N., Ganesan, C., Song, S., Pao, A. C., Wagner, T. H., Brooks, J. D., Chertow, G. M., Leppert, J. T. 2020: 101097JU0000000000001005

  Abstract

  BACKGROUND: Patients with kidney cancer are at risk of developing chronic kidney disease (CKD) after radical and partial nephrectomy. We sought to determine if the urine albumin-creatinine ratio (UACR) is independently associated with progressive CKD after nephrectomy.METHODS: We performed a cohort study based within a large, integrated health care system. We identified patients who underwent radical or partial nephrectomy from 2004 to 2014 with UACR measured in the 12 months prior to surgery. We fit multivariable models to determine if the UACR was associated with the time to CKD progression (defined as reaching stage 4 or 5 CKD, eGFR <30 mL/min/1.73m2). We performed a parallel analysis measuring the time to stage 3b, 4 or 5 CKD (eGFR <45 mL/min/1.73m2) among patients with normal or near-normal preoperative kidney function (eGFR ≥60 mL/min/1.73 m2). We also examined the association between UACR and survival.RESULTS: 1930 patients underwent radical or partial nephrectomy and had preoperative UACR and pre- and post-operative eGFR. Of these, 658 (34%) and 157 (8%) had moderate (UACR 30-300mg/g) or severe albuminuria (UACR > 300mg/g), respectively. Albuminuria severity was independently associated with progressive CKD after radical (moderate albuminuria HR 1.7, 95%CI 1.4-2.2; severe albuminuria HR 2.3, 95%CI 1.7-3.1) and partial nephrectomy (moderate albuminuria HR 1.8, 95%CI 1.2-2.7; severe albuminuria HR 4.3, 95%CI 2.7-7.0). Albuminuria was also associated with survival following radical and partial nephrectomy.CONCLUSIONS: In patients undergoing radical or partial nephrectomy, the severity of albuminuria can stratify risk of progressive CKD.

  View details for DOI 10.1097/JU.0000000000001005

  View details for PubMedID 32125227

• The ongoing search for a robust clinical prediction model of ICU AKI CLINICAL NEPHROLOGY McCoy, I. E., Chertow, G. M. 2020; 93 (3): 160–62

  View details for DOI 10.5414/CN109968

  View details for Web of Science ID 000512950000008

  View details for PubMedID 31933475

• AKI-A Relevant Safety End Point? American journal of kidney diseases : the official journal of the National Kidney Foundation McCoy, I. E., Chertow, G. M. 2020

  Abstract

  Acute kidney injury (AKI) is a common outcome evaluated in clinical studies, often as a safety end point in a variety of cardiovascular, kidney disease, and other clinical trials. AKI end points that include modest increases in serum creatinine levels from baseline may not associate with patient-centered outcomes such as initiation of dialysis, sustained decline in kidney function, or death. Surprisingly, data from several randomized controlled trials have suggested that in certain settings, the development of AKI may be associated with favorable outcomes. AKI safety end points that are nonspecific and may not associate with patient-centered outcomes could result in beneficial therapies being inappropriately withheld or never developed for commercial use. We review several issues related to commonly used AKI definitions and suggest that future work in AKI use more patient-centered AKI end points such as major adverse kidney events at 30 days or other later time points.

  View details for DOI 10.1053/j.ajkd.2019.11.010

  View details for PubMedID 32037098

• Screening Rates for Primary Aldosteronism in Resistant Hypertension: A Cohort Study. Hypertension (Dallas, Tex. : 1979) Jaffe, G., Gray, Z., Krishnan, G., Stedman, M., Zheng, Y., Han, J., Chertow, G. M., Leppert, J. T., Bhalla, V. 2020: HYPERTENSIONAHA11914359

  Abstract

  Resistant hypertension is associated with higher rates of cardiovascular disease, kidney disease, and death than primary hypertension. Although clinical practice guidelines recommend screening for primary aldosteronism among persons with resistant hypertension, rates of screening are unknown. We identified 145 670 persons with hypertension and excluded persons with congestive heart failure or advanced chronic kidney disease. Among this cohort, we studied 4660 persons ages 18 to <90 from the years 2008 to 2014 with resistant hypertension and available laboratory tests within the following 24 months. The screening rate for primary aldosteronism in persons with resistant hypertension was 2.1%. Screened persons were younger (55.9±13.3 versus 65.5±11.6 years; P<0.0001) and had higher systolic (145.1±24.3 versus 139.6±20.5 mm Hg; P=0.04) and diastolic blood pressure (81.8±13.6 versus 74.4±13.8 mm Hg; P<0.0001), lower rates of coronary artery disease (5.2% versus 14.2%; P=0.01), and lower serum potassium concentrations (3.9±0.6 versus 4.1±0.5 mmol/L; P=0.04) than unscreened persons. Screened persons had significantly higher rates of prescription for calcium channel blockers, mixed alpha/beta-adrenergic receptor antagonists, sympatholytics, and vasodilators, and lower rates of prescription for loop, thiazide, and thiazide-type diuretics. The prescription of mineralocorticoid receptor antagonists or other potassium-sparing diuretics was not significantly different between groups (P=0.20). In conclusion, only 2.1% of eligible persons received a screening test within 2 years of meeting criteria for resistant hypertension. Low rates of screening were not due to the prescription of antihypertensive medications that may potentially interfere with interpretation of the screening test. Efforts to highlight guideline-recommended screening and targeted therapy are warranted.

  View details for DOI 10.1161/HYPERTENSIONAHA.119.14359

  View details for PubMedID 32008436

• Outcomes after left ventricular assist device implantation in patients with acute kidney injury JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Silver, S. A., Long, J., Zheng, Y., Goldstone, A. B., Franz, D., Chang, T. I., Chertow, G. M. 2020; 159 (2): 477-+

  View details for DOI 10.1016/j.jtcvs.2019.03.064

  View details for Web of Science ID 000507380200052

• Effects of etelcalcetide on fibroblast growth factor 23 in patients with secondary hyperparathyroidism receiving hemodialysis. Clinical kidney journal Wolf, M., Block, G. A., Chertow, G. M., Cooper, K., Fouqueray, B., Moe, S. M., Sun, Y., Tomlin, H., Vervloet, M., Oberbauer, R. 2020; 13 (1): 75–84

  Abstract

  Background: Etelcalcetide is an intravenous calcimimetic approved for treatment of secondary hyperparathyroidism (sHPT) in patients receiving hemodialysis. Besides lowering parathyroid hormone (PTH), etelcalcetide also significantly reduces fibroblast growth factor 23 (FGF23), but the mechanisms are unknown.Methods: To investigate potential mediators of etelcalcetide-induced FGF23 reduction, we performed secondary analyses of the 26-week randomized trials that compared the effects on PTH of etelcalcetide (n=509) versus placebo (n=514) and etelcalcetide (n=340) versus cinacalcet (n=343) in adults with sHPT receiving hemodialysis. We analyzed changes in FGF23 in relation to changes in PTH, calcium, phosphate and bone turnover markers. We also investigated how concomitant treatments aimed at mitigating hypocalcemia altered the FGF23-lowering effects of etelcalcetide.Results: Etelcalcetide reduced FGF23 [median % change (quartile 1-quartile 3)] from baseline to the end of the trial significantly more than placebo [-56% (-85 to -7) versus +2% (-40 to +65); P<0.001] and cinacalcet [-68% (-87 to -26) versus -41% (-76 to +25); P<0.001]. Reductions in FGF23 correlated strongly with reductions in calcium and phosphate, but not with PTH; correlations with bone turnover markers were inconsistent and of borderline significance. Increases in concomitant vitamin D administration partially attenuated the FGF23-lowering effect of etelcalcetide, but increased dialysate calcium concentration versus no increase and increased dose of calcium supplementation versus no increase did not attenuate the FGF23-lowering effects of etelcalcetide.Conclusion: These data suggest that etelcalcetide potently lowers FGF23 in patients with sHPT receiving hemodialysis and that the effect remains detectable among patients who receive concomitant treatments aimed at mitigating treatment-associated decreases in serum calcium.

  View details for DOI 10.1093/ckj/sfz034

  View details for PubMedID 32082556

• Rationale and protocol of the Dapagliflozin And Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD) randomized controlled trial. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association Heerspink, H. J., Stefansson, B. V., Chertow, G. M., Correa-Rotter, R. n., Greene, T. n., Hou, F. F., Lindberg, M. n., McMurray, J. n., Rossing, P. n., Toto, R. n., Langkilde, A. M., Wheeler, D. C. 2020; 35 (2): 274–82

  Abstract

  Recent cardiovascular outcome trials have shown that sodium-glucose co-transporter 2 (SGLT2) inhibitors slow the progression of chronic kidney disease (CKD) in patients with type 2 diabetes at high cardiovascular risk. Whether these benefits extend to CKD patients without type 2 diabetes or cardiovascular disease is unknown. The Dapagliflozin and Prevention of Adverse Outcomes in CKD (DAPA-CKD) trial (NCT03036150) will assess the effect of the SGLT2 inhibitor dapagliflozin on renal and cardiovascular events in a broad range of patients with CKD with and without diabetes.DAPA-CKD is a randomized, double-blind, placebo-controlled, trial in which ∼4300 patients with CKD Stages 2-4 and elevated urinary albumin excretion will be enrolled. The vast majority will be receiving a maximum tolerated dose of a renin-angiotensin system inhibitor at enrolment.After a screening assessment, eligible patients with a urinary albumin:creatinine ratio ≥200 mg/g and estimated glomerular filtration rate (eGFR) between 25 and 75 mL/min/1.73 m2 are randomly assigned to placebo or dapagliflozin 10 mg/day. Enrolment is monitored to ensure that at least 30% of patients do not have diabetes and that no more than 10% have an eGFR >60 mL/min/1.73 m2. The primary endpoint is a composite of a sustained decline in eGFR of ≥50%, end-stage renal disease, renal death or cardiovascular death. The trial will conclude when 681 primary renal events have occurred, providing 90% power to detect a 22% relative risk reduction (α level of 0.05).DAPA-CKD will determine whether the SGLT2 inhibitor dapagliflozin, added to guideline-recommended therapies, safely reduces the rate of renal and cardiovascular events in patients across multiple CKD stages with and without diabetes.

  View details for DOI 10.1093/ndt/gfz290

  View details for PubMedID 32030417

• The "Advancing American Kidney Health" Executive Order: Challenges and Opportunities for the Large Dialysis Organizations. American journal of kidney diseases : the official journal of the National Kidney Foundation Lin, E. n., Ginsburg, P. B., Chertow, G. M., Berns, J. S. 2020

  View details for DOI 10.1053/j.ajkd.2020.07.007

  View details for PubMedID 32763259

• Dedicated kidney disease-focused outcome trials with sodium-glucose cotransporter-2 inhibitors: Lessons from CREDENCE and expectations from DAPA-HF, DAPA-CKD, and EMPA-KIDNEY. Diabetes, obesity & metabolism Rhee, J. J., Jardine, M. J., Chertow, G. M., Mahaffey, K. W. 2020; 22 Suppl 1: 46–54

  Abstract

  In the past decade, many cardiovascular outcome trials (CVOT) on the efficacy and safety of glucose-lowering agents have been completed. Amongst newer agents available for treatment of type 2 diabetes mellitus (T2DM), sodium-glucose cotransporter-2 (SGLT2) inhibitors have garnered much attention in contemporary clinical practice due to observed benefits on cardiovascular and kidney outcomes among patients with T2DM, as reported in large randomized controlled trials (RCT). These findings are reflected in the updated clinical guidelines of several major professional societies. Herein, we briefly review the mechanism of action of SGLT2 inhibitors and their pleiotropic effects, summarize key findings and limitations of initial CVOTs, then discuss three major kidney disease-focused outcome trials, including the Canagliflozin and Renal Events in Diabetes and Established Nephropathy Clinical Evaluation (CREDENCE) trial as well as two ongoing RCTs: Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure-chronic kidney disease and EMPA-KIDNEY.

  View details for DOI 10.1111/dom.13987

  View details for PubMedID 32267076

• Innovation in hemodialysis: Using the Biodesign process to identify unmet needs. The journal of vascular access Augustin, D. A., Chertow, G. M., Azagury, D. E. 2020: 1129729820913692

  Abstract

  There is renewed demand to accelerate innovation in nephrology; public and private sectors are creating programs to support its growth. The Stanford Biodesign innovation process, first developed in 2000, provides a roadmap for health technology and device innovation. There is insufficient published guidance on the application of the Biodesign process in the generation of novel devices to address nephrology- and/or dialysis-related clinical unmet needs. We present "needs finding," the initial part of the identify phase in the Biodesign innovation process and how it may be utilized for nephrology- and/or dialysis-related innovation. We describe here how to apply the Biodesign process to identify unmet dialysis-related needs, with the use of specific case-based examples based on observations within a hemodialysis unit. We then explore how to develop these needs using background research, direct clinical observations, interviews, documentation of observations and interview findings, and development of multiple needs statements. We conclude that there is an opportunity for nephrology innovators to use this methodology broadly in order to identify areas for innovation and initiated the development on novel solutions to be introduced into patient care.

  View details for DOI 10.1177/1129729820913692

  View details for PubMedID 32306842

• Differential effects of phosphate binders on vitamin D metabolism in chronic kidney disease. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association Ginsberg, C. n., Zelnick, L. R., Block, G. A., Chertow, G. M., Chonchol, M. n., Hoofnagle, A. n., Kestenbaum, B. n., de Boer, I. H. 2020

  Abstract

  Phosphate binders are commonly used in the treatment of patients with hyperphosphatemia. While phosphate binders are used to lower phosphate, the effects of specific phosphate binder types on vitamin D metabolism are unknown.We performed a secondary analysis of the Phosphate Normalization Trial in which patients with moderate to advanced chronic kidney disease were randomized to receive either placebo, sevelamer carbonate, lanthanum carbonate or calcium acetate for 9 months. We evaluated changes in serum concentrations of vitamin D metabolites including 24,25-dihydroxyvitamin D3 [24,25(OH)2D3], 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the ratio of 24,25(OH)2D3 to 25-hydroxyvitamin D [the vitamin D metabolite ratio (VMR)] and the ratio of serum 1,25(OH)2D to 25-hydroxyvitamin D.Compared with placebo, randomization to the calcium acetate arm was associated with a 0.6 ng/mL (95% CI 0.2, 1) and 13.5 pg/ng (95% CI 5.5, 21.5) increase in 24,25(OH)2D and VMR, respectively, and a 5.2 pg/mL (95% CI 1.1, 9.4) reduction in 1,25(OH)2D. Randomization to sevelamer carbonate was associated with a 0.5 ng/mL (95% CI -0.9, -0.1) and 11.8 pg/ng (95% CI -20, -3.5) reduction in 24,25(OH)2D3 and VMR, respectively. There was no association of the sevelamer arm with the change in 1,25(OH)2D3, and randomization to lanthanum carbonate was not associated with a change in any of the vitamin D metabolites.Administration of different phosphate binders to patients with moderate to severe CKD results in unique changes in vitamin D metabolism.

  View details for DOI 10.1093/ndt/gfaa010

  View details for PubMedID 32160298

• Apixaban versus Warfarin in Patients with Atrial Fibrillation and Advanced Chronic Kidney Disease. Circulation Stanifer, J. W., Pokorney, S. D., Chertow, G. M., Hohnloser, S. H., Wojdyla, D. M., Garonzik, S. n., Byon, W. n., Hijazi, Z. n., Lopes, R. D., Alexander, J. H., Wallentin, L. n., Granger, C. B. 2020

  Abstract

  Background: Compared with the general population, patients with advanced chronic kidney disease (CKD) have a >10-fold higher burden of atrial fibrillation (AF). Limited data are available guiding the use of non-vitamin K antagonist oral anticoagulants in this population. Methods: We compared the safety of apixaban with warfarin in 269 patients with AF and advanced CKD (defined as creatinine clearance [CrCl] 25-30 mL/min) enrolled in ARISTOTLE. Cox proportional models were used to estimate hazard ratios (HRs) for major bleeding and major or clinically relevant non-major (CRNM) bleeding. We characterized the pharmacokinetic profile of apixaban by assessing differences in exposure using non-linear mixed effects models. Results: Among patients with CrCl 25-30 mL/min, apixaban caused less major bleeding (HR 0.34, 95% confidence interval [CI] 0.14-0.80) and major or CRNM bleeding (HR 0.35, 95% CI 0.17-0.72) compared with warfarin. Patients with CrCl 25-30 mL/min randomized to apixaban demonstrated a trend towards lower rates of major bleeding when compared with those with CrCl >30 mL/min (p interaction=0.08) and major or CRNM bleeding (p interaction=0.05). Median daily steady state areas under the curve (AUCss) for apixaban 5 mg twice daily were 5512 ng/mL*hr and 3406 ng/mL*hr for patients with CrCl 25-30 mL/min or >30 mL/min, respectively. For apixaban 2.5 mg twice daily, the median exposure was 2780 ng/mL*hr for patients with CrCl 25-30 mL/min. The AUC values for patients with CrCl 25-30 mL/min fell completely within the ranges demonstrated for patients with CrCl >30 mL/min. Conclusions: Among patients with AF and CrCl 25-30 mL/min, apixaban caused less bleeding than warfarin, with even greater reductions in bleeding than in patients with CrCl >30 mL/min. We observed substantial overlap in the range of exposure to apixaban 5 mg twice daily for patients with or without advanced CKD, supporting conventional dosing in patients with CrCl 25-30 mL/min. Randomized controlled studies evaluating the safety and efficacy of apixaban are urgently needed in patients with advanced CKD, including those receiving dialysis. Clinical Trial Registration: URL: https://ClinicalTrials.gov Unique Identifier: NCT00412984.

  View details for DOI 10.1161/CIRCULATIONAHA.119.044059

  View details for PubMedID 32160801

• The dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trial: baseline characteristics. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association Wheeler, D. C., Stefansson, B. V., Batiushin, M. n., Bilchenko, O. n., Cherney, D. Z., Chertow, G. M., Douthat, W. n., Dwyer, J. P., Escudero, E. n., Pecoits-Filho, R. n., Furuland, H. n., Górriz, J. L., Greene, T. n., Haller, H. n., Hou, F. F., Kang, S. W., Isidto, R. n., Khullar, D. n., Mark, P. B., McMurray, J. J., Kashihara, N. n., Nowicki, M. n., Persson, F. n., Correa-Rotter, R. n., Rossing, P. n., Toto, R. D., Umanath, K. n., Van Bui, P. n., Wittmann, I. n., Lindberg, M. n., Sjöström, C. D., Langkilde, A. M., Heerspink, H. J. 2020

  Abstract

  The Dapagliflozin and Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD; NCT03036150) trial was designed to assess the effect of the sodium-glucose co-transporter 2 (SGLT2) inhibitor dapagliflozin on kidney and cardiovascular events in participants with CKD with and without type 2 diabetes (T2D). This analysis reports the baseline characteristics of those recruited, comparing them with those enrolled in other trials.In DAPA-CKD, 4304 participants with a urinary albumin:creatinine ratio (UACR) ≥200 mg/g and estimated glomerular filtration rate (eGFR) between 25 and 75 mL/min/1.73 m2 were randomized to dapagliflozin 10 mg once daily or placebo. Mean eGFR was 43.1 mL/min/1.73 m2 and median UACR was 949 mg/g (108 mg/mmol).Overall, 2906 participants (68%) had a diagnosis of T2D and of these, 396 had CKD ascribed to a cause other than diabetes. The most common causes of CKD after diabetes (n = 2510) were ischaemic/hypertensive nephropathy (n = 687) and chronic glomerulonephritis (n = 695), of which immunoglobulin A nephropathy (n = 270) was the most common. A total of 4174 participants (97%) were receiving an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, 1882 (43.7%) diuretics, 229 (5.3%) mineralocorticoid receptor antagonists and 122 (2.8%) glucagon-like peptide 1 receptor agonists. In contrast to the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE), the DAPA-CKD trial enrolled participants with CKD due to diabetes and to causes other than diabetes. The mean eGFR of participants in the DAPA-CKD trial was 13.1 mL/min/1.73 m2 lower than in CREDENCE, similar to that in the Finerenone in Reducing Kidney Failure and Disease Progression in DKD (FIDELIO-DKD) trial and the Study Of diabetic Nephropathy with AtRasentan (SONAR).Participants with a wide range of underlying kidney diseases receiving renin-angiotensin system blocking therapy have been enrolled in the DAPA-CKD trial. The trial will examine the efficacy and safety of dapagliflozin in participants with CKD Stages 2-4 and increased albuminuria, with and without T2D.

  View details for DOI 10.1093/ndt/gfaa234

  View details for PubMedID 32862232

• Toward telemedicine-compatible physical functioning assessments in kidney transplant candidates. Clinical transplantation Watford, D. J., Cheng, X. S., Han, J. n., Stedman, M. R., Chertow, G. M., Tan, J. C. 2020: e14173

  Abstract

  Frailty is associated with adverse kidney transplant outcomes and can be assessed by subjective and objective metrics. There is increasing recognition of the value of metrics obtainable remotely. We compared the self-reported SF-36 physical functioning subscale score (SF-36 PF) with in-person physical performance tests (6-minute walk and sit-to-stand) in a prospective cohort of kidney transplant candidates. We assessed each metric's ability to predict time to the composite outcome of waitlist removal or death, censoring at transplant. We built time-dependent receiver operating characteristic curves and calculated the area under the curve [AUC(t)] at 1 year, using bootstrapping for internal validation. In 199 patients followed for a median of 346 days, 41 reached the composite endpoint. Lower SF-36 PF scores were associated with higher risk of waitlist removal/death, with every 10-point decrease corresponding to a 16% increase in risk. All models showed an AUC(t) of 0.83-0.84 that did not contract substantially after internal validation. Among kidney transplant candidates, SF-36 PF, obtainable remotely, can help to stratify the risk of waitlist removal or death, and may be used as a screening tool for poor physical functioning in ongoing candidate evaluation, particularly where travel, increasing patient volume, or other restrictions challenge in-person assessment.

  View details for DOI 10.1111/ctr.14173

  View details for PubMedID 33247983

• Prolonged Hospitalization Following Acute Respiratory Failure. Chest Marmor, M. n., Liu, S. n., Long, J. n., Chertow, G. M., Rogers, A. J. 2020

  Abstract

  A better understanding of the clinical features associated with prolonged hospitalization in acute respiratory failure may allow for better informed care planning.To assess the incidence, mortality, cost and clinical determinants of prolonged hospitalization among patients with acute respiratory failure (ARF).Using the National Inpatient Sample (NIS) data from 2004 to 2014, we identified adults 18 years and older with International Classification of Disease, 9th Edition (ICD-9), codes for ARF requiring mechanical ventilation for at least two days (ICD-9 518.81 or 518.82, 96.7 or 96.04, and 96.05). Outcomes studied included incidence, in-hospital mortality, cost of hospitalization, and associated patient-level and hospital-level characteristics. Trends were assessed by logistic regression, linear regression and general linear modeling with Poisson distribution.Of the 5,539,567 patients with ARF, 77,665 (1.4%) had a prolonged length of stay, defined as ≥60 days (pLOS). Among pLOS, 52,776 (68%) survived to discharge. Over the study period, incidence of pLOS decreased by 48%, in-patient mortality decreased by 18%, per patient cost-of-care rose, but percent of the total cost of ARF care consumed by patients with pLOS did not significantly decrease (p=0.06). PLOS was more likely to occur in urban teaching hospitals (OR 6.8, CI 4.6-10.2, p<0.001), hospitals located in the Northeastern US (OR 3.6, CI 3.0-4.3, p<0.001), and among patients with Medicaid insurance coverage (OR 2.1, CI 1.9-2.4, p<0.001).From 2004-2014, incidence and mortality decreased among patients with ARF and pLOS, and while per patient costs rose, percent of total cost of care remained stable. There is substantial variation in length-of-stay for patients with ARF by US region, hospital teaching status and patient insurance coverage.

  View details for DOI 10.1016/j.chest.2020.11.023

  View details for PubMedID 33333057

• Physical Performance Testing in Kidney Transplant Candidates at the Top of the Waitlist. American journal of kidney diseases : the official journal of the National Kidney Foundation Cheng, X. S., Myers, J. n., Han, J. n., Stedman, M. R., Watford, D. J., Lee, J. n., Discipulo, K. V., Chan, K. N., Chertow, G. M., Tan, J. C. 2020

  Abstract

  Frailty and poor physical function are associated with adverse kidney transplant outcomes, but how to incorporate this knowledge into clinical practice is uncertain. We studied the association between measured physical performance and clinical outcomes among patients on kidney transplant waitlists.Prospective observational cohort study.We studied consecutive patients evaluated in our Transplant Readiness Assessment Clinic, a top-of-the-waitlist management program, from May 2017 through December 2018 (N=305). We incorporated physical performance testing, including the 6-minute walk test (6MWT) and the sit-to-stand (STS) test, into routine clinical assessments.6MWT and STS test results.Primary - Time to adverse waitlist outcomes (removal from waitlist or death). Secondary - Time to transplantation, time to death.We used linear regression to examine the relationship between clinical characteristics and physical performance test results. We used subdistribution hazards models to examine the association between physical performance test results and outcomes.Median 6MWT and STS results were 393 meters (25th- 75th percentile range 305-455) and 17 repetitions (25th- 75th percentile range 12-21), respectively. Clinical characteristics and Estimated Post-Transplant Survival scores only accounted for 14-21% of the variance in 6MWT/STS results. 6MWT/STS results were associated with adverse waitlist outcomes (adjusted subdistribution hazard ratio [sHR] of 1.42 [95% confidence interval 1.30-1.56 per 50-meter lower in 6MWT and 1.53 [95% confidence interval 1.33-1.75] per 5-repetition lower in STS), and with transplantation (adjusted sHR of 0.80 [95% confidence interval 0.72-0.88] per 50-meter lower in 6MWT and 0.80 [95% confidence interval 0.71-0.89] per 5-repetition lower in STS). Addition of either STS or 6MWT to survival models containing clinical characteristics enhanced fit (likelihood ratio test p<0.001).Single-center observational study. Other measures of global health status (e.g., Fried frailty index or short physical performance battery) were not examined.Among waitlisted kidney transplant candidates with high Kidney Allocation Scores, standardized and easily performed physical performance test results are associated with waitlist outcomes and contain information beyond what is currently routinely collected in clinical practice.

  View details for DOI 10.1053/j.ajkd.2020.04.009

  View details for PubMedID 32512039

• Health Status after Invasive or Conservative Care in Coronary and Advanced Kidney Disease. The New England journal of medicine Spertus, J. A., Jones, P. G., Maron, D. J., Mark, D. B., O'Brien, S. M., Fleg, J. L., Reynolds, H. R., Stone, G. W., Sidhu, M. S., Chaitman, B. R., Chertow, G. M., Hochman, J. S., Bangalore, S. n. 2020

  Abstract

  In the ISCHEMIA-CKD trial, the primary analysis showed no significant difference in the risk of death or myocardial infarction with initial angiography and revascularization plus guideline-based medical therapy (invasive strategy) as compared with guideline-based medical therapy alone (conservative strategy) in participants with stable ischemic heart disease, moderate or severe ischemia, and advanced chronic kidney disease (an estimated glomerular filtration rate of <30 ml per minute per 1.73 m2 or receipt of dialysis). A secondary objective of the trial was to assess angina-related health status.We assessed health status with the Seattle Angina Questionnaire (SAQ) before randomization and at 1.5, 3, and 6 months and every 6 months thereafter. The primary outcome of this analysis was the SAQ Summary score (ranging from 0 to 100, with higher scores indicating less frequent angina and better function and quality of life). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate the treatment effect with the invasive strategy.Health status was assessed in 705 of 777 participants. Nearly half the participants (49%) had had no angina during the month before randomization. At 3 months, the estimated mean difference between the invasive-strategy group and the conservative-strategy group in the SAQ Summary score was 2.1 points (95% credible interval, -0.4 to 4.6), a result that favored the invasive strategy. The mean difference in score at 3 months was largest among participants with daily or weekly angina at baseline (10.1 points; 95% credible interval, 0.0 to 19.9), smaller among those with monthly angina at baseline (2.2 points; 95% credible interval, -2.0 to 6.2), and nearly absent among those without angina at baseline (0.6 points; 95% credible interval, -1.9 to 3.3). By 6 months, the between-group difference in the overall trial population was attenuated (0.5 points; 95% credible interval, -2.2 to 3.4).Participants with stable ischemic heart disease, moderate or severe ischemia, and advanced chronic kidney disease did not have substantial or sustained benefits with regard to angina-related health status with an initially invasive strategy as compared with a conservative strategy. (Funded by the National Heart, Lung, and Blood Institute; ISCHEMIA-CKD ClinicalTrials.gov number, NCT01985360.).

  View details for DOI 10.1056/NEJMoa1916374

  View details for PubMedID 32227754

• Management of Coronary Disease in Patients with Advanced Kidney Disease. The New England journal of medicine Bangalore, S. n., Maron, D. J., O'Brien, S. M., Fleg, J. L., Kretov, E. I., Briguori, C. n., Kaul, U. n., Reynolds, H. R., Mazurek, T. n., Sidhu, M. S., Berger, J. S., Mathew, R. O., Bockeria, O. n., Broderick, S. n., Pracon, R. n., Herzog, C. A., Huang, Z. n., Stone, G. W., Boden, W. E., Newman, J. D., Ali, Z. A., Mark, D. B., Spertus, J. A., Alexander, K. P., Chaitman, B. R., Chertow, G. M., Hochman, J. S. 2020

  Abstract

  Clinical trials that have assessed the effect of revascularization in patients with stable coronary disease have routinely excluded those with advanced chronic kidney disease.We randomly assigned 777 patients with advanced kidney disease and moderate or severe ischemia on stress testing to be treated with an initial invasive strategy consisting of coronary angiography and revascularization (if appropriate) added to medical therapy or an initial conservative strategy consisting of medical therapy alone and angiography reserved for those in whom medical therapy had failed. The primary outcome was a composite of death or nonfatal myocardial infarction. A key secondary outcome was a composite of death, nonfatal myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest.At a median follow-up of 2.2 years, a primary outcome event had occurred in 123 patients in the invasive-strategy group and in 129 patients in the conservative-strategy group (estimated 3-year event rate, 36.4% vs. 36.7%; adjusted hazard ratio, 1.01; 95% confidence interval [CI], 0.79 to 1.29; P = 0.95). Results for the key secondary outcome were similar (38.5% vs. 39.7%; hazard ratio, 1.01; 95% CI, 0.79 to 1.29). The invasive strategy was associated with a higher incidence of stroke than the conservative strategy (hazard ratio, 3.76; 95% CI, 1.52 to 9.32; P = 0.004) and with a higher incidence of death or initiation of dialysis (hazard ratio, 1.48; 95% CI, 1.04 to 2.11; P = 0.03).Among patients with stable coronary disease, advanced chronic kidney disease, and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of death or nonfatal myocardial infarction. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA-CKD ClinicalTrials.gov number, NCT01985360.).

  View details for DOI 10.1056/NEJMoa1915925

  View details for PubMedID 32227756

• Alport Syndrome Classification and Management. Kidney medicine Warady, B. A., Agarwal, R. n., Bangalore, S. n., Chapman, A. n., Levin, A. n., Stenvinkel, P. n., Toto, R. D., Chertow, G. M. 2020; 2 (5): 639–49

  Abstract

  Alport syndrome affects up to 60,000 people in the United States. The proposed reclassification of thin basement membrane nephropathy and some cases of focal segmental glomerulosclerosis as Alport syndrome could substantially increase the affected population. The reclassification scheme categorizes Alport syndrome as 3 distinct diseases of type IV collagen α3/4/5 based on a genetic evaluation: X-linked, autosomal, and digenic. This approach has the advantage of identifying patients at risk for progressive loss of kidney function. Furthermore, the shared molecular cause of Alport syndrome and thin basement membrane nephropathy arises from mutations in the COL4A3, COL4A4, and COL4A5 genes, which contribute to downstream pathophysiologic consequences, including chronic kidney inflammation. Recent evidence indicates that chronic inflammation and its regulation through anti-inflammatory nuclear factor erythroid 2-related factor 2 (Nrf2) and proinflammatory nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) transcription factors plays a central role in renal tubular and glomerular cell responses to injury. Crosstalk between the Nrf2 and NF-κB pathways is important in the regulation of inflammation in patients with chronic kidney disease; moreover, there is evidence that an insufficient Nrf2 response to inflammation contributes to disease progression. Given the association between type IV collagen abnormalities and chronic inflammation, there is renewed interest in targeted anti-inflammatory therapies in Alport syndrome and other forms of progressive chronic kidney disease.

  View details for DOI 10.1016/j.xkme.2020.05.014

  View details for PubMedID 33094278

  View details for PubMedCentralID PMC7568086

• Effects of SNF472, a Novel Inhibitor of Hydroxyapatite Crystallization in Patients Receiving Hemodialysis - Subgroup Analyses of the CALIPSO Trial. Kidney international reports Raggi, P. n., Bellasi, A. n., Sinha, S. n., Bover, J. n., Rodriguez, M. n., Ketteler, M. n., Bushinsky, D. A., Garg, R. n., Perelló, J. n., Gold, A. n., Chertow, G. M. 2020; 5 (12): 2178–82

  Abstract

  Coronary artery calcium (CAC) is highly prevalent and linked with poor outcomes in patients receiving maintenance hemodialysis, and its reduction may improve patient prognosis. SNF472, a selective inhibitor of hydroxyapatite crystallization, slows CAC progression in patients receiving maintenance hemodialysis. In this analysis, we assessed the efficacy of SNF472 in prespecified patient subgroups.In a randomized clinical trial SNF472 300 mg, SNF472 600 mg, or placebo were infused thrice weekly in 91, 92, and 91 patients receiving maintenance hemodialysis and with CAC at baseline, respectively. In prespecified subanalyses, the percent change in CAC volume score (CACvs) from baseline to week 52 in modified intention-to-treat (mITT) and per-protocol (PP) populations was calculated in the following subgroups: age, sex, diabetes mellitus, dialysis vintage, prior atherosclerotic cardiovascular disease, baseline use of non-calcium and calcium-based phosphate binders, calcimimetics, activated vitamin D, warfarin, and statins.In the main trial, SNF472 significantly reduced CACvs progression compared with placebo (11% versus 20% mITT analyses; P = 0.016; 8% vs. 24% PP analyses; P < 0.001). Treatment differences for CACvs progression were similar across all subgroups, and all interaction P values were non-significant in mITT and PP analyses.SNF472 treatment for 52 weeks reduced CACvs progression compared with placebo in a broad range of patients receiving maintenance hemodialysis. Future studies will determine the impact of SNF472 on cardiovascular events in this population.

  View details for DOI 10.1016/j.ekir.2020.09.032

  View details for PubMedID 33305110

  View details for PubMedCentralID PMC7710828

• Preparing for Hemodialysis CHRONIC RENAL DISEASE, 2ND EDITION Isom, R. T., Chertow, G. M., Kimmel, P. L., Rosenberg, M. E. 2020: 1157–73

  View details for DOI 10.1016/B978-0-12-815876-0.00070-X

  View details for Web of Science ID 000489824100070

• Reducing the Shortage of Transplant Kidneys: A Lost Opportunity for the US Health Resources and Services Administration (HRSA). American journal of kidney diseases : the official journal of the National Kidney Foundation McCormick, F. n., Held, P. J., Chertow, G. M., Peters, T. G., Roberts, J. P. 2020

  View details for DOI 10.1053/j.ajkd.2020.10.007

  View details for PubMedID 33271212

• Dapagliflozin in Patients with Chronic Kidney Disease. The New England journal of medicine Heerspink, H. J., Stefánsson, B. V., Correa-Rotter, R. n., Chertow, G. M., Greene, T. n., Hou, F. F., Mann, J. F., McMurray, J. J., Lindberg, M. n., Rossing, P. n., Sjöström, C. D., Toto, R. D., Langkilde, A. M., Wheeler, D. C. 2020

  Abstract

  Patients with chronic kidney disease have a high risk of adverse kidney and cardiovascular outcomes. The effect of dapagliflozin in patients with chronic kidney disease, with or without type 2 diabetes, is not known.We randomly assigned 4304 participants with an estimated glomerular filtration rate (GFR) of 25 to 75 ml per minute per 1.73 m2 of body-surface area and a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of 200 to 5000 to receive dapagliflozin (10 mg once daily) or placebo. The primary outcome was a composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes.The independent data monitoring committee recommended stopping the trial because of efficacy. Over a median of 2.4 years, a primary outcome event occurred in 197 of 2152 participants (9.2%) in the dapagliflozin group and 312 of 2152 participants (14.5%) in the placebo group (hazard ratio, 0.61; 95% confidence interval [CI], 0.51 to 0.72; P<0.001; number needed to treat to prevent one primary outcome event, 19 [95% CI, 15 to 27]). The hazard ratio for the composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal causes was 0.56 (95% CI, 0.45 to 0.68; P<0.001), and the hazard ratio for the composite of death from cardiovascular causes or hospitalization for heart failure was 0.71 (95% CI, 0.55 to 0.92; P = 0.009). Death occurred in 101 participants (4.7%) in the dapagliflozin group and 146 participants (6.8%) in the placebo group (hazard ratio, 0.69; 95% CI, 0.53 to 0.88; P = 0.004). The effects of dapagliflozin were similar in participants with type 2 diabetes and in those without type 2 diabetes. The known safety profile of dapagliflozin was confirmed.Among patients with chronic kidney disease, regardless of the presence or absence of diabetes, the risk of a composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes was significantly lower with dapagliflozin than with placebo. (Funded by AstraZeneca; DAPA-CKD ClinicalTrials.gov number, NCT03036150.).

  View details for DOI 10.1056/NEJMoa2024816

  View details for PubMedID 32970396

• Prevalence of SARS-CoV-2 antibodies in a large nationwide sample of patients on dialysis in the USA: a cross-sectional study. Lancet (London, England) Anand, S. n., Montez-Rath, M. n., Han, J. n., Bozeman, J. n., Kerschmann, R. n., Beyer, P. n., Parsonnet, J. n., Chertow, G. M. 2020

  Abstract

  Many patients receiving dialysis in the USA share the socioeconomic characteristics of underserved communities, and undergo routine monthly laboratory testing, facilitating a practical, unbiased, and repeatable assessment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence.For this cross-sectional study, in partnership with a central laboratory that receives samples from approximately 1300 dialysis facilities across the USA, we tested the remainder plasma of 28 503 randomly selected adult patients receiving dialysis in July, 2020, using a spike protein receptor binding domain total antibody chemiluminescence assay (100% sensitivity, 99·8% specificity). We extracted data on age, sex, race and ethnicity, and residence and facility ZIP codes from the anonymised electronic health records, linking patient-level residence data with cumulative and daily cases and deaths per 100 000 population and with nasal swab test positivity rates. We standardised prevalence estimates according to the overall US dialysis and adult population, and present estimates for four prespecified strata (age, sex, region, and race and ethnicity).The sampled population had similar age, sex, and race and ethnicity distribution to the US dialysis population, with a higher proportion of older people, men, and people living in majority Black and Hispanic neighbourhoods than in the US adult population. Seroprevalence of SARS-CoV-2 was 8·0% (95% CI 7·7-8·4) in the sample, 8·3% (8·0-8·6) when standardised to the US dialysis population, and 9·3% (8·8-9·9) when standardised to the US adult population. When standardised to the US dialysis population, seroprevalence ranged from 3·5% (3·1-3·9) in the west to 27·2% (25·9-28·5) in the northeast. Comparing seroprevalent and case counts per 100 000 population, we found that 9·2% (8·7-9·8) of seropositive patients were diagnosed. When compared with other measures of SARS-CoV-2 spread, seroprevalence correlated best with deaths per 100 000 population (Spearman's ρ=0·77). Residents of non-Hispanic Black and Hispanic neighbourhoods experienced higher odds of seropositivity (odds ratio 3·9 [95% CI 3·4-4·6] and 2·3 [1·9-2·6], respectively) compared with residents of predominantly non-Hispanic white neighbourhoods. Residents of neighbourhoods in the highest population density quintile experienced increased odds of seropositivity (10·3 [8·7-12·2]) compared with residents of the lowest density quintile. County mobility restrictions that reduced workplace visits by at least 5% in early March, 2020, were associated with lower odds of seropositivity in July, 2020 (0·4 [0·3-0·5]) when compared with a reduction of less than 5%.During the first wave of the COVID-19 pandemic, fewer than 10% of the US adult population formed antibodies against SARS-CoV-2, and fewer than 10% of those with antibodies were diagnosed. Public health efforts to limit SARS-CoV-2 spread need to especially target racial and ethnic minority and densely populated communities.Ascend Clinical Laboratories.

  View details for DOI 10.1016/S0140-6736(20)32009-2

  View details for PubMedID 32987007

• Patient and Provider Characteristics Associated With Sodium-Glucose Cotransporter 2 Inhibitor Prescription in Patients With Diabetes and Proteinuric Chronic Kidney Disease. Clinical diabetes : a publication of the American Diabetes Association McCoy, I. E., Han, J. n., Montez-Rath, M. E., Chertow, G. M., Rhee, J. J. 2020; 38 (3): 240–47

  Abstract

  Despite accumulating evidence of cardiorenal benefits from sodium-glucose cotransporter 2 (SGLT2) inhibitors, prescription of agents in this drug class may be limited by concerns regarding adverse effects and interdisciplinary care coordination. To investigate these potential barriers, we performed a cross-sectional study of SGLT2 inhibitor prescriptions in 2017 in 3,779 adults with type 2 diabetes and proteinuric chronic kidney disease from a nationwide database. Only 173 (5%) of these patients received an SGLT2 inhibitor in 2017. Younger age, renin-angiotensin-aldosterone system inhibitor prescription, and higher estimated glomerular filtration rate were associated with SGLT2 inhibitor prescription. Primary care providers were responsible for the majority of the prescriptions. Continued efforts should be made to track and improve SGLT2 inhibitor use in indicated populations.

  View details for DOI 10.2337/cd19-0087

  View details for PubMedID 32699472

  View details for PubMedCentralID PMC7364452

• Effect of Intensive vs Standard Blood Pressure Treatment Upon Erectile Function in Hypertensive Men: Findings From the Systolic Blood Pressure Intervention Trial. The journal of sexual medicine Foy, C. G., Newman, J. C., Russell, G. B., Berlowitz, D. R., Bates, J. T., Burgner, A. M., Carson, T. Y., Chertow, G. M., Doumas, M. N., Hughes, R. Y., Kostis, J. B., Buren, P. v., Wadley, V. G., SPRINT Study Research Group 2019

  Abstract

  INTRODUCTION: The effect of intensive blood pressure control upon erectile function in men with hypertension, but without diabetes, is largely unknown.AIM: To examine the effects of intensive systolic blood pressure (SBP) lowering on erectile function in a multiethnic clinical trial of men with hypertension.METHODS: We performed subgroup analyses from the Systolic Blood Pressure Intervention Trial ([SPRINT]; ClinicalTrials.gov: NCT120602, in a sample of 1255 men aged 50 years or older with hypertension and increased cardiovascular disease risk. Participants were randomly assigned to an intensive treatment group (SBP goal of <120 mmHg) or a standard treatment group (SBP goal of <140 mmHg).MAIN OUTCOME MEASURE: The main outcome measure was change in erectile function from baseline, using the 5-item International Index of Erectile Function (IIEF-5) total score, and erectile dysfunction ([ED]; defined as IIEF-5 score ≤21) after a median follow-up of 3 years.RESULTS: At baseline, roughly two-thirds (66.1%) of the sample had self-reported ED. At 48 months after randomization, we determined that the effects of more intensive blood pressure lowering were significantly moderated by race-ethnicity (p for interaction= 0.0016), prompting separate analyses stratified by race-ethnicity. In non-Hispanic whites, participants in the intensive treatment group reported slightly, but significantly better change in the IIEF-5 score than those in the standard treatment group (mean difference= 0.67; 95% CI= 0.03, 1.32; P= 0.041). In non-Hispanic blacks, participants in the intensive group reported slightly worse change in the IIEF-5 score than those in the standard group (mean difference=-1.17; 95% CI=-1.92,-0.41; P= 0.0025). However, in non-Hispanic whites and non-Hispanic blacks, further adjustment for the baseline IIEF-5 score resulted in nonsignificant differences (P > 0.05) according to the treatment group. In Hispanic/other participants, there were no significant differences in change in the IIEF-5 score between the two treatment groups (P= 0.40). In a subgroup of 280 participants who did not report ED at baseline, the incidence of ED did not differ in the two treatment groups (P= 0.53) and was without interaction by race-ethnicity.CLINICAL IMPLICATIONS: The effect of intensive treatment of blood pressure on erectile function was very small overall and likely not of great clinical magnitude.STRENGTH & LIMITATIONS: Although this study included a validated measure of erectile function, testosterone, other androgen, and estrogen levels were not assessed.CONCLUSION: In a sample of male patients at high risk for cardiovascular events but without diabetes, targeting a SBP of less than 120 mm Hg, as compared with less than 140 mm Hg, resulted in statistically significant effects on erectile function that differed in accordance with race-ethnicity, although the clinical importance of the differences may be of small magnitude. Foy CG, Newman JC, Russell GB, etal. Effect of Intensive vs Standard Blood Pressure Treatment Upon Erectile Function in Hypertensive Men: Findings From the Systolic Blood Pressure Intervention Trial. J Sex Med 2019;XX:XXX-XXX.

  View details for DOI 10.1016/j.jsxm.2019.11.256

  View details for PubMedID 31862174

• Apixaban versus Warfarin for Stroke Prevention in Patients With End Stage Renal Disease on Hemodialysis and Atrial Fibrillation: Results of a Randomized Clinical Trial Assessing Safety Pokorney, S. D., Chertow, G. M., Al-Khalidi, H., Gallup, D., Dignacco, P., Mussina, K., Bansal, N., Gadegbeku, C. A., Garcia, D., Jones-Burton, C., Lopes, R. D., Mahaffey, K. W., Middleton, J., Mills, D., Rymer, J. A., Thadhani, R., Thomas, K. L., Winkelmayer, W. C., Granger, C. B. LIPPINCOTT WILLIAMS & WILKINS. 2019: E988–E989

  View details for Web of Science ID 000508228600062

• Effect of SNF472 on Progression of Cardiovascular Calcification in Patients on Hemodialysis (Results of a Phase 2 Randomized Controlled Study: CaLIPSO) Raggi, P., Bellasi, A., Bover, J., Rodriguez, M., Ketteler, M., Sinha, S., Chertow, G., Bushinsky, D., Gillotti, K., Carroll, K., Salcedo, C., Garg, R., Gold, A., Perello, J. LIPPINCOTT WILLIAMS & WILKINS. 2019: E967

  View details for Web of Science ID 000508228600011

• A double-blind, randomized, placebo-controlled pilot trial to evaluate safety and efficacy of vorapaxar on arteriovenous fistula maturation. The journal of vascular access Olivier, C. B., Sundaram, V., Chertow, G. M., Shashidhar, S., McDonnell, L. K., Ding, V. Y., Desai, M., Mahaffey, K. W., Mell, M. 2019: 1129729819887269

  Abstract

  BACKGROUND: Protease-activated receptor-1 antagonism by vorapaxar could facilitate arteriovenous fistula maturation but may increase bleeding risk.OBJECTIVE: The primary objective of the Vorapaxar Study for Maturation of arteriovenous fistula for Hemodialysis Access (VorapAccess) was to determine if vorapaxar improves arteriovenous fistula functional maturation in patients with end-stage renal disease.METHODS: VorapAccess was a randomized, placebo-controlled, double-blind pilot trial comparing 2.5mg vorapaxar per day with placebo for twelve weeks starting on day two after arteriovenous fistula creation. The primary outcome was time to functional maturation defined as successful cannulation for six hemodialysis sessions within three weeks. The planned sample size was 50 participants. The study was terminated early after withdrawal of planned financial support. Given the small number of randomized patients, we performed descriptive analyses without inference testing.RESULTS: A total of 13 participants were randomly allocated study drug (six vorapaxar and seven placebo). The median age was 56years and seven participants (54%) were female. The median (minimum-maximum) days to functional maturation were 169 (77-287)days in the vorapaxar group and 145 (48-198)days in the placebo group. Six of the 13 (46%) participants had arteriovenous fistula functional maturation within 180days; two of six (33%) in the vorapaxar group and four of seven (57%) in the placebo group. There was one bleeding event in the placebo group.CONCLUSION: Fewer than half of participants had functional maturation within 180days after surgery, suggesting a major need for agents or strategies that enhance arteriovenous fistula maturation.

  View details for DOI 10.1177/1129729819887269

  View details for PubMedID 31774037

• Acute Kidney Injury in Children Hospitalized With Diarrheal Illness in the United States. Hospital pediatrics Bradshaw, C., Han, J., Chertow, G. M., Long, J., Sutherland, S. M., Anand, S. 2019

  Abstract

  OBJECTIVES: To determine the incidence, correlates, and consequences of acute kidney injury (AKI) among children hospitalized with diarrheal illness in the United States.METHODS: Using data from Kids' Inpatient Database in 2009 and 2012, we studied children hospitalized with a primary diagnosis of diarrheal illness (weighted N = 113195). We used the International Classification of Diseases, Ninth Revision, Clinical Modification, diagnosis codes 584.5 to 584.9 to capture AKI. We calculated the incidence, correlates, and consequences (mortality, length of stay [LOS], and costs) of AKI associated with hospitalized diarrheal illness using stepwise logistic regression and generalized linear models.RESULTS: The average incidence of AKI in children hospitalized with diarrheal illness was 0.8%. Hospital location and teaching status were associated with the odds of AKI, as were older age, solid organ transplant, hypertension, chronic kidney disease, and rheumatologic and hematologic conditions. The development of AKI in hospitalized diarrheal illness was associated with an eightfold increase in the odds of in-hospital mortality (odds ratio 8.0; 95% confidence interval [CI] 4.2-15.4). AKI was associated with prolonged LOS (mean increase 3.0 days; 95% CI 2.3-3.8) and higher hospital cost (mean increase $9241; 95% CI $4661-$13820).CONCLUSIONS: Several demographic factors and comorbid conditions are associated with the risk of AKI in children hospitalized with diarrheal illness. Although rare, development of AKI in this common pediatric condition is associated with increased mortality, LOS, and hospital cost.

  View details for DOI 10.1542/hpeds.2019-0220

  View details for PubMedID 31771950

• Urinary Stone Disease in Pregnancy: A Claims-Based Analysis of 1.4 Million Patients. The Journal of urology Sohlberg, E. M., Brubaker, W. D., Zhang, C. A., Anderegg, L. D., Dallas, K., Song, S., Ganesan, C., Chertow, G., Pao, A., Liao, J., Leppert, J. T., Elliott, C. S., Conti, S. L. 2019: 101097JU0000000000000657

  Abstract

  PURPOSE: Urinary stone disease during pregnancy is poorly understood but is thought to be associated with increased maternal and fetal morbidity. We sought to determine the prevalence of urinary stone disease in pregnancy and whether urinary stone disease during pregnancy is associated with adverse pregnancy outcomes.MATERIALS AND METHODS: We identified all pregnant women from 2003 through 2017 in the Optum national insurance claims database. We used diagnosis claims to identify urinary stone disease and assess medical comorbidity. We established the prevalence of urinary stone disease during pregnancy, stratified by week of pregnancy. We further evaluated associations among urinary stone disease and maternal complications and pregnancy outcomes in both univariable and multivariable analyses.RESULTS: Urinary stone disease affects 8/1000 pregnancies and is more common in white women and women with more comorbid conditions. In fully adjusted models, pregnancies complicated by urinary stone disease had higher rates of adverse fetal outcomes, including prematurity and spontaneous abortions. This analysis is limited by its retrospective administrative claims design.CONCLUSIONS: The rate of urinary stone disease during pregnancy is higher than previously reported. Urinary stone disease is associated with adverse pregnancy outcomes.

  View details for DOI 10.1097/JU.0000000000000657

  View details for PubMedID 31738114

• Slowing Progression of Cardiovascular Calcification with SNF472 in Patients on Hemodialysis: Results of a Randomized, Phase 2b Study. Circulation Raggi, P., Bellasi, A., Bushinsky, D., Bover, J., Rodriguez, M., Ketteler, M., Sinha, S., Salcedo, C., Gillotti, K., Padgett, C., Garg, R., Gold, A., Perello, J., Chertow, G. M. 2019

  Abstract

  Background: The high cardiovascular morbidity and mortality in patients with end-stage kidney disease (ESKD) could be partially due to extensive cardiovascular calcification. SNF472, intravenous myo-inositol hexaphosphate, selectively inhibits formation and growth of hydroxyapatite. Methods: This double-blind, placebo-controlled phase 2b trial compared progression of coronary artery calcium (CAC) volume score and other measurements of cardiovascular calcification by CT scan during 52 weeks of treatment with SNF472 or placebo, in addition to standard therapy, in adult patients with ESKD receiving hemodialysis. Patients were randomized 1:1:1 to SNF472 300 mg (n=92), SNF472 600 mg (n=91), or placebo (n=91) by infusion in the hemodialysis lines thrice weekly during hemodialysis sessions. The primary end point was change in log CAC volume score from baseline to week 52. The primary efficacy analysis combined the SNF472 treatment groups and included all patients who received at least one dose of SNF472 or placebo and had an evaluable CT scan post-randomization. Results: The mean change in CAC volume score was 11% (95% CI, 7%-15%) for the combined SNF472 dose group and 20% (95% CI, 14%-26%) for placebo (P=0.016). SNF472 compared to placebo attenuated progression of calcium volume score in the aortic valve (14% [95% CI, 5%-24%] vs 98% [95% CI, 77%-123%], P<0.001), but not in the thoracic aorta (23% [95% CI, 16%-30%] vs 28% [95% CI, 19%-38%], P=0.40). Death occurred in 7 patients (4%) who received SNF472 and 5 patients (6%) who received placebo. At least one treatment-emergent adverse event occurred in 86%, 92%, and 87% of patients treated with SNF472 300 mg, SNF472 600 mg and placebo, respectively. Most adverse events were mild. Adverse events resulted in discontinuation of SNF472 300 mg, SNF472 600 mg, and placebo for 14%, 29%, and 20% of patients, respectively. Conclusions: Compared with placebo, SNF472 significantly attenuated progression of CAC and aortic valve calcification in patients with ESKD receiving hemodialysis in addition to standard care. Future studies are needed to determine the effects of SNF472 on cardiovascular events. Clinical Trial Registration: URL: https://www.clinicaltrials.gov Unique identifier: NCT02966028.

  View details for DOI 10.1161/CIRCULATIONAHA.119.044195

  View details for PubMedID 31707860

• Safety and efficacy of the Tablo hemodialysis system for in-center and home hemodialysis. Hemodialysis international. International Symposium on Home Hemodialysis Plumb, T. J., Alvarez, L., Ross, D. L., Lee, J. J., Mulhern, J. G., Bell, J. L., Abra, G., Prichard, S. S., Chertow, G. M., Aragon, M. A. 2019

  Abstract

  INTRODUCTION: Home hemodialysis remains underutilized despite observational data indicating more favorable outcomes with home compared with in-center hemodialysis. The Tablo Hemodialysis system is designed to be easy to learn and use and to facilitate adoption of home hemodialysis. The objective of the current investigational device exemption (IDE) study was to evaluate the safety and efficacy of Tablo managed in-center by health care professionals and in-home by patients and/or caregivers.METHODS: A prospective, multicenter, open-label, crossover trial comparing in-center and in-home hemodialysis using Tablo. There were 4 treatment periods during which hemodialysis was prescribed 4 times per week: 1-week Run-In, 8-week In-Center, 4-week Transition, and 8-week In-Home. The primary efficacy endpoint was weekly standard Kt/Vurea ≥2.1. The secondary efficacy endpoint was delivery of ultrafiltration (UF) within 10% of prescribed UF. We collected safety and usability data.FINDINGS: Thirty participants enrolled and 28 completed all trial periods. Adherence to the protocol requirement of 4 treatments per week was 96% in-center and 99% in-home. The average prescribed and delivered session lengths were 3.4hours for both the In-Center and the In-Home periods. The primary efficacy endpoint for the intention-to-treat cohort was achieved in 199/200 (99.5%) of measurements during the In-Center period and 168/171 (98.3%) In-Home. The average weekly standard Kt/Vurea was 2.8 in both periods. The secondary efficacy UF endpoint was achieved in the ITT cohort in 94% in both in-center and in-home. Two prespecified adverse events (AEs) occurred during the In-Center period and 6 in the In-Home period. None of the AEs were deemed by investigators as related to Tablo. The median resolution time of alarms was 8seconds in-center and 5seconds in-home.CONCLUSION: Primary and secondary efficacy and safety endpoints were achieved during both In-Center and In-Home trial periods. This study confirms that Tablo is safe and effective for home hemodialysis use.

  View details for DOI 10.1111/hdi.12795

  View details for PubMedID 31697042

• Antidiabetic medication use in patients with type 2 diabetes and chronic kidney disease JOURNAL OF DIABETES AND ITS COMPLICATIONS Rhee, J. J., Han, J., Montez-Rath, M. E., Kim, S. H., Cullen, M. R., Stafford, R. S., Winkelmayer, W. C., Chertow, G. M. 2019; 33 (11)

  View details for DOI 10.1016/j.jdiacomp2019.107423

  View details for Web of Science ID 000497890000003

• Angiotensin-related genetic determinants of cardiovascular disease in patients undergoing hemodialysis NEPHROLOGY DIALYSIS TRANSPLANTATION Moe, S. M., Long, J., Schwantes-An, T., Decker, B. S., Wetherill, L., Edenberg, H. J., Xuei, X., Vatta, M., Foroud, T. M., Chertow, G. M. 2019; 34 (11): 1924–31

  View details for DOI 10.1093/ndt/gfy191

  View details for Web of Science ID 000498168100018

• Chronic Kidney Disease and the Adiposity Paradox: Valid or Confounded? JOURNAL OF RENAL NUTRITION Ziolkowski, S. L., Long, J., Baker, J. F., Chertow, G. M., Leonard, M. B. 2019; 29 (6): 521–28

  View details for DOI 10.1053/j.jrn.2018.11.011

  View details for Web of Science ID 000493897600010

• Current Status of Angiotensin Receptor Blocker Recalls. Hypertension (Dallas, Tex. : 1979) Gunasekaran, P. M., Chertow, G. M., Bhalla, V., Byrd, J. B. 2019: HYPERTENSIONAHA11913955

  Abstract

  Losartan was the ninth most prescribed drug in the United States in 2016, and several other angiotensin-II receptor blockers (ARBs) are widely prescribed. Since July 2018, >2 dozen specific ARB products have been recalled owing to the presence of potentially carcinogenic nitrosamine impurities in selected lots. As is the case with all U.S. drug recalls, the ARB recalls have been voluntary on the part of the companies involved. In April 2019, the Food and Drug Administration categorized marketed ARB products with respect to nitrosamine impurities: (1) not present, (2) to be determined with no prior lots removed from the market (TBD), or (3) to be determined in the context of prior lots having been removed from the market (TBD*). The data were structured as hundreds of rows of products. Owing to the complexity of these data, more than a year into the recalls, it remains difficult for clinicians to understand which ARB products are free of impurities.

  View details for DOI 10.1161/HYPERTENSIONAHA.119.13955

  View details for PubMedID 31630573

• Percutaneous Kidney Biopsy and the Utilization of Blood Transfusion and Renal Angiography Among Hospitalized Adults KIDNEY INTERNATIONAL REPORTS Charu, V., O'Shaughnessy, M. M., Chertow, G. M., Kambham, N. 2019; 4 (10): 1435–45

  View details for DOI 10.1016/j.ekir.2019.07.008

  View details for Web of Science ID 000488859300010

• Percutaneous Kidney Biopsy and the Utilization of Blood Transfusion and Renal Angiography Among Hospitalized Adults. Kidney international reports Charu, V., O'Shaughnessy, M. M., Chertow, G. M., Kambham, N. 2019; 4 (10): 1435-1445

  Abstract

  Data on percutaneous kidney biopsy (KBx) incidence and frequencies of hemorrhagic complications among inpatients are limited.Using nationally representative US hospitalization discharge data, we report temporal trends in inpatient KBx rates from 2007 to 2014 and estimate frequencies of, and risk factors for, utilization of packed red blood cell (pRBC) transfusion and renal angiography.From 2007 to 2014, rates of native KBx among adult inpatients increased from 8.2 to 10.0 per 100,000, while transplant KBx rates declined from 3.6 to 3.1 per 100,000. We studied 35,183 and 14,266 discharge records with native and transplant KBx. We found that 5.7% (95% confidence interval [CI]: 5.3%-6.0%) of inpatients undergoing native KBx and 4.9% (4.2%-5.5%) of those undergoing transplant KBx received a pRBC transfusion within 2 days of biopsy. Similarly, 0.6% (0.5%-0.7%) of inpatients undergoing native KBx and 0.4% (0.2%-0.5%) undergoing transplant KBx received a renal angiogram within 2 days of KBx. For inpatient native KBx, female sex, older age, higher chronic kidney disease stage, acute renal failure, lupus, vasculitis, cirrhosis, multiple myeloma/paraproteinemia, and anemia of chronic disease were independently associated with increased odds of pRBC transfusion; cirrhosis and end-stage renal disease (ESRD) were associated with increased odds, and nephrotic syndrome was associated with decreased odds, of renal angiography.In this large population-based study of inpatient KBx practices, we demonstrate increasing rates of inpatient native KBx among US adults and provide accurate estimates of the frequencies of, and risk factors for, pRBC transfusion and renal angiography following inpatient KBx.

  View details for DOI 10.1016/j.ekir.2019.07.008

  View details for PubMedID 31701053

  View details for PubMedCentralID PMC6829181

• Effects of Selonsertib in Patients with Diabetic Kidney Disease. Journal of the American Society of Nephrology : JASN Chertow, G. M., Pergola, P. E., Chen, F., Kirby, B. J., Sundy, J. S., Patel, U. D., GS-US-223-1015 Investigators, Pergola, Chow, S., Elliott, T., Jolly, S. S., Steele, A., Ting, R., Ahmad, A., Aiello, J., Ailani, R., Ajani, D., Alvarez, L., Arif, A., Atta, M., Ayesu, K., Bays, H. E., Belo, D., Berenji, R., Bernardo, M. V., Betts, J., Bloomberg, R., Blumenthal, S., Bretton, E., Buxton, S., Chan, M., Chappel, C., Darwish, R., Daudjee, M., De La Rosa, R., Diamond, S., El Asmar, I., Elliott, K., Ellison, H., El-Shahawy, M., Feldman, M., Fidelholtz, J., Fluck, P., Fogelfeld, L., Fonseca, V., Fraser, N., Galvez, O., Gandhi, K., Gaona, R. E., Gold, M., Goreja, A., Guadiz, R., Gupta, A., Hammoud, J., Hansen, V., Hendon, K., Hole, S., Houchin, V., Hura, C., Jain, M., Jamal, A., Jere, C., Jones, S., Judd, E., Karimjee, N., Kaskas, M., Kusnir, G., Lee, S., Lee, S. K., Lloyd-Turney, C., Lund, R., Maheshawri, H., Marar, I., Martin, E., Medina, J., Mehta, B., Moustafa, M., Nammour, T. M., Naseeruddin, S., Nica, R., Nossuli, A., Numrungroad, V., Nwakoby, I., Pitone, J., Pullman, J., Qureshi, J., Rabiei, A., Raikhel, M., Rastogi, A., Rendell, M. S., Rodriguez-Araya, E., Ross, D., Sandoval, J., Schlau, A., Seyoum, B., Shafik, S., Shah, S., Sholer, C., Solomon, R., Spinowitz, B., Sun, C., Terrelonge, A. E., Thompson, C., Toke, A., Trespalacios, F., Tumlin, J., Varghese, F., Vaz, G., Weiss, D., Whittman, D., Wiegmann, T., Wise, J., Zeig, S. 2019

  Abstract

  BACKGROUND: Apoptosis signal-regulating kinase 1 (ASK1) activation in glomerular and tubular cells resulting from oxidative stress may drive kidney disease progression. Findings in animal models identified selonsertib, a selective ASK1 inhibitor, as a potential therapeutic agent.METHODS: In a phase 2 trial evaluating selonsertib's safety and efficacy in adults with type 2 diabetes and treatment-refractory moderate-to-advanced diabetic kidney disease, we randomly assigned 333 adults in a 1:1:1:1 allocation to selonsertib (oral daily doses of 2, 6, or 18 mg) or placebo. Primary outcome was change from baseline eGFR at 48 weeks.RESULTS: Selonsertib appeared safe, with no dose-dependent adverse effects over 48 weeks. Although mean eGFR for selonsertib and placebo groups did not differ significantly at 48 weeks, acute effects related to inhibition of creatinine secretion by selonsertib confounded eGFR differences at 48 weeks. Because of this unanticipated effect, we used piecewise linear regression, finding two dose-dependent effects: an acute and more pronounced eGFR decline from 0 to 4 weeks (creatinine secretion effect) and an attenuated eGFR decline between 4 and 48 weeks (therapeutic effect) with higher doses of selonsertib. A post hoc analysis (excluding data for 20 patients from two sites with Good Clinical Practice compliance-related issues) found that between 4 and 48 weeks, rate of eGFR decline was reduced 71% for the 18-mg group relative to placebo (difference 3.11±1.53 ml/min per 1.73 m2 annualized over 1 year; 95% confidence interval, 0.10-6.13; nominal P=0.043). Effects on urine albumin-to-creatinine ratio did not differ between selonsertib and placebo.CONCLUSIONS: Although the trial did not meet its primary endpoint, exploratory post hoc analyses suggest that selonsertib may slow diabetic kidney disease progression.

  View details for DOI 10.1681/ASN.2018121231

  View details for PubMedID 31506292

• Modification of eGFR-Based CKD Definitions: Perfect, or Enemy of the Good? Journal of the American Society of Nephrology : JASN Chertow, G. M., Beddhu, S. 2019

  View details for DOI 10.1681/ASN.2019070743

  View details for PubMedID 31506290

• Understanding the role of the cytoprotective transcription factor nuclear factor erythroid 2-related factor 2-lessons from evolution, the animal kingdom and rare progeroid syndromes. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association Stenvinkel, P., Meyer, C. J., Block, G. A., Chertow, G. M., Shiels, P. G. 2019

  Abstract

  The cytoprotective transcriptor factor nuclear factor erythroid 2- related factor 2 (NRF2) is part of a complex regulatory network that responds to environmental cues. To better understand its role in a cluster of inflammatory and pro-oxidative burden of lifestyle diseases that accumulate with age, lessons can be learned from evolution, the animal kingdom and progeroid syndromes. When levels of oxygen increased in the atmosphere, mammals required ways to protect themselves from the metabolic toxicity that arose from the production of reactive oxygen species. The evolutionary origin of the NRF2-Kelch-like ECH-associated protein 1 (KEAP1) signalling pathway from primitive origins has been a prerequisite for a successful life on earth, with checkpoints in antioxidant gene expression, inflammation, detoxification and protein homoeostasis. Examples from the animal kingdom suggest that superior antioxidant defense mechanisms with enhanced NRF2 expression have been developed during evolution to protect animals during extreme environmental conditions, such as deep sea diving, hibernation and habitual hypoxia. The NRF2-KEAP1 signalling pathway is repressed in progeroid (accelerated ageing) syndromes and a cluster of burden of lifestyle disorders that accumulate with age. Compelling links exist between tissue hypoxia, senescence and a repressed NRF2 system. Effects of interventions that activate NRF2, including nutrients, and more potent (semi)synthetic NRF2 agonists on clinical outcomes are of major interest. Given the broad-ranging actions of NRF2, we need to better understand the mechanisms of activation, biological function and regulation of NRF2 and its inhibitor, KEAP1, in different clinical conditions to ensure that modulation of this thiol-based system will not result in major adverse effects. Lessons from evolution, the animal kingdom and conditions of accelerated ageing clarify a major role of a controlled NRF2-KEAP1 system in healthy ageing and well-being.

  View details for DOI 10.1093/ndt/gfz120

  View details for PubMedID 31302696

• A Pilot Randomized Trial of Ferric Citrate Coordination Complex for the Treatment of Advanced CKD. Journal of the American Society of Nephrology : JASN Block, G. A., Block, M. S., Smits, G., Mehta, R., Isakova, T., Wolf, M., Chertow, G. M. 2019

  Abstract

  BACKGROUND: Researchers have yet to determine the optimal care of patients with advanced CKD. Evidence suggests that anemia and CKD-related disordered mineral metabolism (including abnormalities in phosphate and fibroblast growth factor 23 [FGF23]) contribute to adverse outcomes in this population.METHODS: To investigate whether fixed-dose ferric citrate coordination complex favorably affects multiple biochemical parameters in patients with advanced CKD, we randomly assigned 203 patients with eGFR≤20 ml/min per 1.73 m2 2:1 to receive a fixed dose of ferric citrate coordination complex (two tablets per meal, 210 mg ferric iron per tablet) or usual care for 9 months or until 3 months after starting dialysis. No single biochemical end point was designated as primary; sample size was determined empirically.RESULTS: The two groups had generally similar baseline characteristics, although diabetes and peripheral vascular disease were more common in the usual-care group. Ferric citrate coordination complex significantly increased hemoglobin, transferrin saturation, and serum ferritin, and it significantly reduced serum phosphate and intact FGF23 (P<0.001 for all). Of the 133 patients randomized to ferric citrate coordination complex, 31 (23%) initiated dialysis during the study period, as did 32 of 66 (48%) patients randomized to usual care (P=0.001). Compared with usual care, ferric citrate coordination complex treatment resulted in significantly fewer annualized hospital admissions, fewer days in hospital, and a lower incidence of the composite end point of death, provision of dialysis, or transplantation (P=0.002).CONCLUSIONS: The beneficial effects of fixed-dose ferric citrate coordination complex on biochemical parameters, as well as the exploratory results regarding the composite end point and hospitalization, suggest that fixed-dose ferric citrate coordination complex has an excellent safety profile in an unselected population with advanced CKD and merits further study.

  View details for DOI 10.1681/ASN.2018101016

  View details for PubMedID 31278194

• A phase II trial showing improvements in calcific uraemic arteriolopathy wound healing, pain and quality of life during SNF472 treatment McMullen, E., Sinha, S., Gould, L., Brandenburg, V., Chertow, G., Miller, S., Canals, A., Bahr, D., Salcedo, C., Garg, R., Gold, A., Perello, J. WILEY. 2019: 39–40

  View details for Web of Science ID 000474478800062

• Testing two (of several) intravenous iron dosing strategies in hemodialysis ANNALS OF TRANSLATIONAL MEDICINE Yu, M. K., Chertow, G. M. 2019; 7

  View details for DOI 10.21037/atm.2019.05.75

  View details for Web of Science ID 000483693200055

• Asymmetric dimethylarginine, erythropoietin resistance, and anemia in CKD ANNALS OF TRANSLATIONAL MEDICINE Sirich, T. L., Chertow, G. M. 2019; 7

  View details for DOI 10.21037/atm.2019.04.22

  View details for Web of Science ID 000483693200012

• Challenges in Assessing the Burden of Hospitalized Heart Failure in End-Stage Kidney Disease JOURNAL OF CARDIAC FAILURE Wang, K. M., Chertow, G. M. 2019; 25 (7): 534–36

  View details for DOI 10.1016/j.cardfail.2019.05.001

  View details for Web of Science ID 000479183600006

• Effect of ferric citrate on serum phosphate and fibroblast growth factor 23 among patients with nondialysis-dependent chronic kidney disease: path analyses NEPHROLOGY DIALYSIS TRANSPLANTATION Block, G. A., Pergola, P. E., Fishbane, S., Martins, J. G., LeWinter, R. D., Uhlig, K., Neylan, J. F., Chertow, G. M. 2019; 34 (7): 1115–24

  View details for DOI 10.1093/ndt/gfy318

  View details for Web of Science ID 000484368300011

• Asymmetric dimethylarginine, erythropoietin resistance, and anemia in CKD. Annals of translational medicine Sirich, T. L., Chertow, G. M. 2019; 7 (Suppl 3): S86

  View details for DOI 10.21037/atm.2019.04.22

  View details for PubMedID 31576295

  View details for PubMedCentralID PMC6685898

• Testing two (of several) intravenous iron dosing strategies in hemodialysis. Annals of translational medicine Yu, M. K., Chertow, G. M. 2019; 7 (Suppl 3): S129

  View details for DOI 10.21037/atm.2019.05.75

  View details for PubMedID 31576336

  View details for PubMedCentralID PMC6685907

• Influence of prediabetes on the effects of intensive systolic blood pressure control on kidney events. American journal of hypertension Rathi, N., Whelton, P. K., Chertow, G. M., Cushman, W. C., Cheung, A. K., Wei, G., Boucher, R., Kimmel, P. L., Bress, A., Kramer, H. J., Al-Marji, C., Greene, T., Beddhu, S. 2019

  Abstract

  BACKGROUND: More than one-third of US adults have prediabetes which is typically accompanied by hypertension.METHODS: We examined whether prediabetes modified the effects of intensive SBP lowering on the incidence of chronic kidney disease (CKD) and acute kidney injury (AKI) events in a post-hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT). Diabetes was a SPRINT exclusion criterion. We defined normoglycemia and prediabetes as fasting plasma glucose < 100 mg/dl and ≥ 100 mg/dl, respectively.RESULTS: Of the 9323 participants included in the current analysis, 3898 (41.8%) had prediabetes and the rest (5425) had normoglycemia. In participants with baseline eGFR ≥60 ml/min/1.73m2, incident CKD was defined as a ≥30% decline in estimated glomerular filtration rate (eGFR) to below 60 mL/min/1.73m2 with repeat confirmation. AKI events were identified clinically. In the non-CKD participants (N= 6678), there were 164 incident CKD events. The hazard ratios (HR) for incident CKD for intensive SBP goal (< 120 mmHg) versus standard SBP goal (< 140 mmHg) in the normoglycemia (HR 3.25, 95% 2.03, 5.19) and prediabetes (HR 3.90, 95% CI 2.17, 7.02) groups were similar (interaction p-value 0.64). In the entire analytic cohort (N= 9323), there were 310 AKI events. AKI hazard ratios for intensive versus standard SBP in the normoglycemia (HR 1.59, 95% 1.17, 2.15) and prediabetes (HR 1.74, 95% CI 1.22, 2.48) groups were also similar (interaction p-value 0.71).CONCLUSIONS: Prediabetes was highly prevalent but there was no evidence that prediabetes modified the effects of SPRINT intervention on kidney events.

  View details for DOI 10.1093/ajh/hpz105

  View details for PubMedID 31257407

• Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy NEW ENGLAND JOURNAL OF MEDICINE Perkovic, V., Jardine, M. J., Neal, B., Bompoint, S., Heerspink, H. L., Charytan, D. M., Edwards, R., Agarwal, R., Bakris, G., Bull, S., Cannon, C. P., Capuano, G., Chu, P., De Zeeuw, D., Greene, T., Levin, A., Pollock, C., Wheeler, D. C., Yavin, Y., Zhang, H., Zinman, B., Meininger, G., Brenner, B. M., Mahaffey, K. W., CREDENCE Trial Investigators 2019; 380 (24): 2295–2306

  View details for DOI 10.1056/NEJMoa1811744

  View details for Web of Science ID 000471299100008

• A DOUBLE-BLIND, RANDOMISED, PLACEBO-CONTROLLED PHASE 2B STUDY TO ASSESS THE EFFECT OF SNF472 ADDED TO STANDARD OF CARE ON PROGRESSION OF CARDIOVASCULAR CALCIFICATION IN PATIENTS WITH END-STAGE RENAL DISEASE ON MAINTENANCE HAEMODIALYSIS (CALIPSO STUDY) Raggi, P., Bellasi, A., Bover Sanjuan, J., Mariano Rodriguez, J., Ketteler, M., Sinha, S., Chertow, G., Bushinsky, D. A., Salcedo, C., Garg, R., Gold, A., Perello, J. OXFORD UNIV PRESS. 2019

  View details for Web of Science ID 000495412900718

• DESIGN OF A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO ASSESS THE EFFICACY AND SAFETY OF SNF472 FOR THE TREATMENT OF CALCIFIC UREMIC ARTERIOLOPATHY (CALCIPHYLAXIS) Sinha, S., Chertow, G., Brandenburg, V., Gould, L., Miller, S., Salcedo, C., Garg, R., Gold, A., Perello, J. OXFORD UNIV PRESS. 2019

  View details for Web of Science ID 000495412902046

• The effect of increased frequency of hemodialysis on vitamin C concentrations: an ancillary study of the randomized Frequent Hemodialysis Network (FHN) daily trial BMC NEPHROLOGY Raimann, J. G., Abbas, S. R., Liu, L., Larive, B., Beck, G., Kotanko, P., Levin, N. W., Handelman, G., Kliger, A., Eggers, P., Briggs, J., Hostetter, T., Narva, A., Star, R., Augustine, B., Mohr, P., Beck, G., Fu, Z., Gassman, J., Greene, T., Daugirdas, J., Hunsicker, L., Larive, B., Li, M., MacKrell, J., Wiggins, K., Sherer, S., Weiss, B., Rajagopalan, S., Sanz, J., Dellagrottaglie, S., Kariisa, M., Tran, T., West, J., Unruh, M., Keene, R., Schlarb, J., Chan, C., McGrath-Chong, M., Frome, R., Higgins, H., Ke, S., Mandaci, O., Owens, C., Snell, C., Eknoyan, G., Appel, L., Cheung, A., Derse, A., Kramer, C., Geller, N., Grimm, R., Henderson, L., Prichard, S., Roecker, E., Chertow, G., James, S., Tamura, M., Hall, Y., McCulloch, C., Painter, P., Gorodetskaya, Tichy, M., Humphreys, M., Luan, J., Escalada, R., Rodriquez, R., Depner, T., Kaysen, G., Suter, M., Sonico, J., Anderson, S., Ting, G., Schiller, B., Coplon, N., Doss, S., Rogers, J., Dominguez, A., Atwal, J., Lemus, D., Rastogi, A., Nissenson, A., Goodman, W., Salusky, Schweitzer, S., Rivas, M., Smith, M., Gayda, P., Hernandez, A., Rashid, M., Mehta, R., Pepas, J., Bharti, B., Nabali, A., Manaster, R., Mathew, R., Shah, S., Sanz, G., Wei, J., Ayus, J., Achinger, S., Gutierrez, M., Levin, N., Bay, W., Carter, M., Geronemus, R., Kuhlmann, M., Handelman, G., Gotch, F., Finkelstein, F., Kimmel, P., Lacson, E., Ornt, D., Greenwood, R., Vassalotti, J., Burrowes, J., Kotanko, P., Kaufman, A., Winchester, J., Meisels, Radbill, B., Chang, J., Fofie, Y., Ramos, R., Sergeyeva, O., Callegari, J., Arthur, B., Tarallo, M., Ulloa, D., Apruzzese, R., Lindsay, R., Suri, R., Garg, A., Mazzorato, B. A., Rocco, M., Burkart, J., Moossavi, S., Mauck, Kaufman, T., Coppley, A., Schulman, G., McLeroy, S., Sika, M., Leavell, E., Miller, B., Schussler, R., Bardsley, J., Skelton, R., Riley, J., Schuessler, R., Lockridge, R., Pipkin, M., Peterson, C., Hoy, C., Fensterer, A., Steigerwald, D., Stokes, J., Somers, D., Hilkin, A., Lilli, K., Wallace, W., Franzwa, B., Waterman, E., Copland, M., Levin, A., Sioson, L., Cabezon, E., Kwan, S., Roger, D., Champagne, J., Bullas, R., Mazzorato, A., Spanner, E., Pierratos, A., Chan, W., Regozo, K., Kwok, S., FHN Trial 2019; 20: 179

  Abstract

  Reports on vitamin C in HD patients have shown effects of vitamin C deficiency in association with scurvy symptoms. Dialyzability of water soluble vitamins is high, and substantial losses in those who are dialyzed more frequently were hypothesized. The randomized FHN Daily Trial compared the effects of in-center HD six versus three times per week. We studied baseline correlations between vitamin C and potentially associated parameters, and the effect of more frequent HD on circulating vitamin C concentrations.We studied vitamin C levels at baseline and months, 3, 5 and 11. Patients enrolled between 2007 and 2009 into the randomized FHN Daily trial in the East Coast consortium were approached for participation. Predialysis plasma samples were processed with metaphosphoric acid and frozen at - 70 °C for measurement with HPLC. Regression models between baseline log-transformed vitamin C and hemoglobin, CRP, eKt/V, ePCR and PTH, and a linear mixed-effects model to estimate the effect size of more frequent HD on plasma vitamin C, were constructed.We studied 44 subjects enrolled in the FHN Daily trial (50 ± 12 years, 36% female, 29% Hispanics and 64% blacks, 60% anuric). Vitamin C correlated significantly with predialysis hemoglobin (r = 0.3; P = 0.03) and PTH (r = - 0.3, P = 0.04), respectively. Vitamin C did not significantly differ at baseline (6×/week, 25.8 ± 25.9 versus 3×/week, 32.6 ± 39.4 μmol/L) and no significant treatment effect on plasma vitamin C concentrations was found [- 26.2 (95%CI -57.5 to 5.1) μmol/L at Month 4 and - 2.5 (95%CI -15.6 to 10.6) μmol/L at Month 12.Based on data from this large randomized-controlled trial no significant effect of the intervention on circulating plasma vitamin C concentrations was found, allaying the concerns that more frequent HD would affect the concentrations of water-soluble vitamins and adversely affect patient's well-being. Correlations between vitamin C and hemoglobin and PTH support the importance of vitamin C for normal bone and mineral metabolism, and anemia management.

  View details for DOI 10.1186/s12882-019-1311-4

  View details for Web of Science ID 000468306900004

  View details for PubMedID 31101018

• Low testosterone is associated with frailty, muscle wasting and physical dysfunction among men receiving hemodialysis: a longitudinal analysis NEPHROLOGY DIALYSIS TRANSPLANTATION Chiang, J. M., Kaysen, G. A., Segal, M., Chertow, G. M., Delgado, C., Johansen, K. L. 2019; 34 (5): 802–10

  View details for DOI 10.1093/ndt/gfy252

  View details for Web of Science ID 000473748300012

• Association of Hospitalization and Mortality Among Patients Initiating Dialysis With Hemodialysis Facility Ownership and Acquisitions JAMA NETWORK OPEN Erickson, K. F., Zhao, B., Niu, J., Winkelmayer, W. C., Bhattacharya, J., Chertow, G. M., Ho, V. 2019; 2 (5)

  View details for DOI 10.1001/jamanetworkopen.2019.3987

  View details for Web of Science ID 000476806200060

• Hypertension Hot Potato - Anatomy of the Angiotensin-Receptor Blocker Recalls NEW ENGLAND JOURNAL OF MEDICINE Byrd, J., Chertow, G. M., Bhalla, V. 2019; 380 (17): 1589–91

  View details for DOI 10.1056/NEJMp1901657

  View details for Web of Science ID 000465598600004

• Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. The New England journal of medicine Perkovic, V., Jardine, M. J., Neal, B., Bompoint, S., Heerspink, H. J., Charytan, D. M., Edwards, R., Agarwal, R., Bakris, G., Bull, S., Cannon, C. P., Capuano, G., Chu, P., de Zeeuw, D., Greene, T., Levin, A., Pollock, C., Wheeler, D. C., Yavin, Y., Zhang, H., Zinman, B., Meininger, G., Brenner, B. M., Mahaffey, K. W., CREDENCE Trial Investigators 2019

  Abstract

  BACKGROUND: Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium-glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes.METHODS: In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin-angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically.RESULTS: The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture.CONCLUSIONS: In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years. (Funded by Janssen Research and Development; CREDENCE ClinicalTrials.gov number, NCT02065791.).

  View details for PubMedID 30990260

• Treatment of metabolic acidosis with an intestinal binder LANCET Song, S., Chertow, G. M. 2019; 393 (10179): 1387–88

  View details for DOI 10.1016/S0140-6736(19)30230-2

  View details for Web of Science ID 000463561000005

• Outcomes after left ventricular assist device implantation in patients with acute kidney injury. The Journal of thoracic and cardiovascular surgery Silver, S. A., Long, J., Zheng, Y., Goldstone, A. B., Franz, D., Chang, T. I., Chertow, G. M. 2019

  Abstract

  OBJECTIVE: The study objective was to compare outcomes for patients with and without acute kidney injury during hospitalizations when left ventricular assist devices are implanted.METHODS: By using the National Inpatient Sample from 2008 to 2013, we identified patients with an International Classification of Diseases, Ninth Revision procedure code for left ventricular assist device implantation (37.66). We ascertained the presence of acute kidney injury and acute kidney injury requiring dialysis using validated International Classification of Diseases, Ninth Revision codes. We used logistic regression to examine the association of nondialysis-requiring acute kidney injury and acute kidney injury requiring dialysis with mortality, procedural complications, and discharge destination.RESULTS: We identified 8362 patients who underwent left ventricular assist device implantation, of whom 3760 (45.0%) experienced nondialysis-requiring acute kidney injury and 426 (5.1%) experienced acute kidney injury requiring dialysis. In-hospital mortality was 3.9% for patients without acute kidney injury, 12.2% for patients with nondialysis-requiring acute kidney injury, and 47.4% for patients with acute kidney injury requiring dialysis. Patients with nondialysis-requiring acute kidney injury and acute kidney injury requiring dialysis had higher adjusted odds of mortality (3.24, 95% confidence interval [CI], 2.04-5.13 and 20.8, 95% CI, 9.7-44.2), major bleeding (1.38, 95% CI, 1.08-1.77 and 2.44, 95% CI, 1.47-4.04), sepsis (2.69, 95% CI, 1.93-3.75 and 5.75, 95% CI, 3.46-9.56), and discharge to a nursing facility (2.15, 95% CI, 1.51-3.07 and 5.89, 95% CI, 2.67-12.99).CONCLUSIONS: More than 1 in 10 patients with acute kidney injury and approximately 1 in 2 patients with acute kidney injury requiring dialysis died during their hospitalization, with only 30% of patients with acute kidney injury requiring dialysis discharged to home. This information is necessary to support shared decision-making for patients with advanced heart failure and acute kidney injury.

  View details for PubMedID 31053433

• Efficacy and Safety of Tenapanor in Patients with Hyperphosphatemia Receiving Maintenance Hemodialysis: A Randomized Phase 3 Trial JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Block, G. A., Rosenbaum, D. P., Yan, A., Chertow, G. M. 2019; 30 (4): 641–52

  View details for DOI 10.1681/ASN.2018080832

  View details for Web of Science ID 000463913200013

• Updates in Management and Timing of Dialysis in Acute Kidney Injury JOURNAL OF HOSPITAL MEDICINE Yu, M. K., Kamal, F., Chertow, G. M. 2019; 14 (4): 232–38

  View details for DOI 10.12788/jhm.3105

  View details for Web of Science ID 000462532700007

• Relative sarcopenia and mortality and the modifying effects of chronic kidney disease and adiposity JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE Ziolkowski, S. L., Long, J., Baker, J. F., Chertow, G. M., Leonard, M. B. 2019; 10 (2): 338–46

  View details for DOI 10.1002/jcsm.12396

  View details for Web of Science ID 000465092100008

• An integrated analysis of safety and tolerability of etelcalcetide in patients receiving hemodialysis with secondary hyperparathyroidism PLOS ONE Block, G. A., Chertow, G. M., Sullivan, J. T., Deng, H., Mather, O., Tomlin, H., Serenko, M. 2019; 14 (3)

  View details for DOI 10.1371/journal.pone.0213774

  View details for Web of Science ID 000461316400029

• Hypertension Hot Potato - Anatomy of the Angiotensin-Receptor Blocker Recalls. The New England journal of medicine Byrd, J. B., Chertow, G. M., Bhalla, V. 2019

  View details for PubMedID 30865819

• One-year safety and efficacy of intravenous etelcalcetide in patients on hemodialysis with secondary hyperparathyroidism. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association Bushinsky, D. A., Chertow, G. M., Cheng, S., Deng, H., Kopyt, N., Martin, K. J., Rastogi, A., Urena-Torres, P., Vervloet, M., Block, G. A. 2019

  Abstract

  BACKGROUND: Secondary hyperparathyroidism (sHPT), a common complication of chronic kidney disease, is characterized by elevated serum parathyroid hormone (PTH). Etelcalcetide is an intravenous calcimimetic that increases sensitivity of the calcium-sensing receptor to calcium and decreases PTH secretion. This open-label extension (OLE) trial evaluated the long-term effects of etelcalcetide for sHPT treatment in patients receiving hemodialysis.METHODS: This 52-week, multicenter, single-arm OLE enrolled patients from three parent trials: two randomized, double-blind, placebo-controlled trials and one open-label, single-arm, 'switch' study from cinacalcet to etelcalcetide. The primary endpoint was to investigate the nature, frequency, severity and relation to treatment of all adverse events (AEs) reported throughout the trial. Secondary endpoints included the proportion of patients with >30% reduction from baseline in PTH and the percentage change from baseline in PTH, albumin-corrected calcium (Ca), phosphate (P) and the calcium-phosphate product (Ca*P).ClinicalTrials.gov identifier: NCT01785875; Amgen study: 20120231.RESULTS: Overall, 89.8% of the patients experienced one or more treatment-emergent AE. The most common were decreased blood Ca (43.3%), diarrhea (10.8%), vomiting (10.4%) and nausea (9.6%); symptomatic hypocalcemia occurred in 3.7% of the patients. Approximately 68% of patients achieved >30% reduction in PTH, and 56% achieved PTH ≤300pg/mL. Mean percent changes from baseline ranged from -25.4% to -26.1% for PTH, -8.3% to -9.1% for Ca, -3.6% to -4.1% for P and -12.0% to -12.6% for Ca*P.CONCLUSIONS: Etelcalcetide effectively lowered PTH and its effect was sustained, while no new safety concerns emerged over a 1-year treatment period.

  View details for PubMedID 30859218

• Treatment of metabolic acidosis with an intestinal binder. Lancet (London, England) Song, S., Chertow, G. M. 2019

  View details for PubMedID 30857645

• Efficacy and Safety of Tenapanor in Patients with Hyperphosphatemia Receiving Maintenance Hemodialysis: A Randomized Phase 3 Trial. Journal of the American Society of Nephrology : JASN Block, G. A., Rosenbaum, D. P., Yan, A., Chertow, G. M. 2019

  Abstract

  BACKGROUND: Guidelines recommend reducing elevated serum phosphate in patients with CKD. Tenapanor, a minimally absorbed inhibitor of gastrointestinal sodium/hydrogen exchanger 3 (NHE3), reduces paracellular phosphate transport.METHODS: In this phase 3 randomized, double-blind trial, we randomly assigned patients with hyperphosphatemia receiving maintenance hemodialysis to receive twice-daily oral tenapanor (3, 10, or 30 mg [the latter down-titrated, if needed]) for 8 weeks. Patients were then rerandomized 1:1 to receive either their previously assigned dose or placebo for a 4-week 'withdrawal' period. We measured serum phosphate levels over the course of the trial. The primary end point was mean change in serum phosphate over the 4-week withdrawal period for the tenapanor group (using pooled data) versus the placebo group.RESULTS: Of 219 patients randomized, 152 completed both study phases. During the initial 8-week treatment period, all three treatment groups experienced significant decreases in mean serum phosphate (reductions of 1.00, 1.02, and 1.19 mg/dl, corresponding to the 3, 10, and 30 mg [down-titrated] dose groups, respectively). Tenapanor also showed a significant benefit over placebo during the withdrawal period, with a mean increase of 0.85 mg/dl in the placebo group versus a mean increase of 0.02 mg/dl in the pooled tenapanor group. Adverse events were largely limited to softened stool and a modest increase in bowel movement frequency, resulting from increased stool sodium and water content, stemming from tenapanor's mechanism of action.CONCLUSIONS: Tenapanor significantly reduced elevated serum phosphate in patients with hyperphosphatemia receiving maintenance hemodialysis. Adverse effects were limited to those induced by its known mechanism of action, which increases stool sodium and water content.

  View details for PubMedID 30846557

• Treatment of Anemia With Darbepoetin Prior to Dialysis Initiation and Clinical Outcomes: Analyses From the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT) AMERICAN JOURNAL OF KIDNEY DISEASES Mc Causland, F. R., Claggett, B., Burdmann, E. A., Chertow, G. M., Cooper, M. E., Eckardt, K., Ivanovich, P., Levey, A. S., Lewis, E. F., McGill, J. B., McMurray, J. V., Parfrey, P., Parving, H., Remuzzi, G., Singh, A. K., Solomon, S. D., Toto, R. D., Pfeffer, M. A. 2019; 73 (3): 309–15

  View details for DOI 10.1053/j.ajkd.2018.10.006

  View details for Web of Science ID 000459248200005

• Long-term Trends and Clinical Outcomes of Inpatient Percutaneous Renal Biopsies in the United States, 2001-2013 Charu, V., O'Shaughnessy, M., Chertow, G., Kambham, N. NATURE PUBLISHING GROUP. 2019

  View details for Web of Science ID 000478915503209

• Long-term Trends and Clinical Outcomes of Inpatient Percutaneous Renal Biopsies in the United States, 2001-2013 Charu, V., O'Shaughnessy, M., Chertow, G., Kambham, N. NATURE PUBLISHING GROUP. 2019

  View details for Web of Science ID 000478081103084

• Paying for Hemodialysis in Kerala, India: A Description of Household Financial Hardship in the Context of Medical Subsidy KIDNEY INTERNATIONAL REPORTS Bradshaw, C., Gracious, N., Narayanan, R., Narayanan, S., Safeer, M., Nair, G. M., Murlidharan, P., Sundaresan, A., Santhi, S., Prabhakaran, D., Tamura, M., Jha, V., Chertow, G. M., Jeemon, P., Anand, S. 2019; 4 (3): 390–98

  View details for DOI 10.1016/j.ekir.2018.12.007

  View details for Web of Science ID 000460067100007

• Paying for Hemodialysis in Kerala, India: A Description of Household Financial Hardship in the Context of Medical Subsidy. Kidney international reports Bradshaw, C., Gracious, N., Narayanan, R., Narayanan, S., Safeer, M., Nair, G. M., Murlidharan, P., Sundaresan, A., Retnaraj Santhi, S., Prabhakaran, D., Kurella Tamura, M., Jha, V., Chertow, G. M., Jeemon, P., Anand, S. 2019; 4 (3): 390-398

  Abstract

  Many low- and middle-income countries are implementing strategies to increase dialysis availability as growing numbers of people reach end-stage renal disease. Despite efforts to subsidize care, the economic sustainability of chronic dialysis in these settings remains uncertain. We evaluated the association of medical subsidy with household financial hardship related to hemodialysis in Kerala, India, a state with high penetrance of procedure-based subsidies for patients on dialysis.Patients on maintenance hemodialysis at 15 facilities in Kerala were administered a questionnaire that ascertained demographics, dialysis details, and household finances. We estimated direct and indirect costs of hemodialysis, and described the use of medical subsidy. We evaluated whether presence of subsidy (private, charity, or government-sponsored) was associated with lower catastrophic health expenditure (defined as ≥40% of nonsubsistence expenditure spent on dialysis) or distress financing.Of the 835 patients surveyed, 759 (91%) reported their households experienced catastrophic health expenditure, and 644 (77%) engaged in distress financing. Median dialysis-related expenditure was 80% (25th-75th percentile: 60%-90%) of household nonsubsistence expenditure. Government subsidies were used by 238 (29%) of households, 139 (58%) of which were in the lowest income category. Catastrophic health expenditure was present in 215 (90%) of households receiving government subsidy and 332 (93%) without subsidy.Provision of medical subsidy in Kerala, India was not associated with lower rates of household financial hardship related to long-term hemodialysis therapy. Transparent counseling on impending costs and innovative strategies to mitigate household financial distress are necessary for persons with end-stage renal disease in resource-limited settings.

  View details for DOI 10.1016/j.ekir.2018.12.007

  View details for PubMedID 30899866

  View details for PubMedCentralID PMC6409432

• Frailty Among Patients Receiving Hemodialysis: Evolution of Components and Associations With Mortality JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Johansen, K. L., Delgado, C., Kaysen, G. A., Chertow, G. M., Chiang, J., Dalrymple, L. S., Segal, M. R., Grimes, B. A. 2019; 74 (3): 380–86

  View details for DOI 10.1093/gerona/gly206

  View details for Web of Science ID 000462192600014

• Updates in Management and Timing of Dialysis in Acute Kidney Injury. Journal of hospital medicine Yu, M. K., Kamal, F., Chertow, G. M. 2019; 14: E1–E7

  Abstract

  Acute kidney injury (AKI) is a common complication in hospitalized patients and is associated with mortality, prolonged hospital length of stay, and increased healthcare costs. This paper reviews several areas of controversy in the identification and management of AKI. Serum creatinine and urine output are used to identify and stage AKI by severity. Although standardized definitions of AKI are used in research settings, these definitions do not account for individual patient factors or clinical context which are necessary components in the assessment of AKI. After treatment of reversible causes of AKI, patients with AKI should receive adequate volume resuscitation with crystalloid solutions. Balanced crystalloid solutions generally prevent severe hyperchloremia and could potentially reduce the risk of AKI, but additional studies are needed to demonstrate a clinical benefit. Intravenous albumin may be beneficial in patients with chronic liver disease either to prevent or attenuate the severity of AKI; otherwise, the use of albumin or other colloids (eg, hydroxyethyl starch) is not recommended. Diuretics should be used to treat volume overload, but they do not facilitate AKI recovery or reduce mortality. Nutrition consultation may be helpful to ensure that patients receive adequate, but not excessive, dietary protein intake, as the latter can lead to azotemia and electrolyte disturbances disproportionate to the patient's kidney failure. The optimal timing of dialysis initiation in AKI remains controversial, with conflicting results from two randomized controlled trials.

  View details for PubMedID 30794134

• Relative sarcopenia and mortality and the modifying effects of chronic kidney disease and adiposity. Journal of cachexia, sarcopenia and muscle Ziolkowski, S. L., Long, J., Baker, J. F., Chertow, G. M., Leonard, M. B. 2019

  Abstract

  BACKGROUND: Conventional definitions of sarcopenia based on lean mass may fail to capture low lean mass relative to higher fat mass, that is, relative sarcopenia. The objective of this study is to determine the associations of sarcopenia and relative sarcopenia with mortality independent of co-morbidities, and whether chronic kidney disease (CKD) and adiposity alter these associations.METHODS: Dual energy X-ray absorptiometry-derived appendicular lean mass index (ALMI, kg/m2 ) and fat mass index (FMI, kg/m2 ) were assessed in 14850 National Health and Nutrition Examination Survey participants from 1999 to 2006 and were linked to death certificate data in the National Death Index with follow-up through 2011. Sarcopenia was defined using sex-specific and race/ethnicity-specific standard deviation scores compared with young adults (T-scores) as an ALMI T-score<-2 and relative sarcopenia as fat-adjusted ALMI (ALMIFMI ) T-score<-2. Glomerular filtration rate (GFR) was estimated using creatinine-based (eGFRCr ) and cystatin C-based (eGFRCys ) regression equations.RESULTS: Three (3.0) per cent of National Health and Nutrition Examination Survey participants met criteria for sarcopenia and 8.7% met criteria for relative sarcopenia. Sarcopenia and relative sarcopenia were independently associated with mortality (HR sarcopenia 2.20, 95% CI 1.69 to 2.86; HR relative sarcopenia 1.60, 95% CI 1.31 to 1.96). The corresponding population attributable risks were 5.2% (95% CI 3.4% to 6.4%) and 8.4% (95% CI 4.8% to 11.2%), respectively. Relative sarcopenia remained significantly associated with mortality (HR 1.32, 95% CI 1.08 to 1.61) when limited to the subset who did not meet the criteria for sarcopenia. The risk of mortality associated with relative sarcopenia was attenuated among persons with higher FMI (P for interaction <0.01) and was not affected by CKD status for either sarcopenia or relative sarcopenia.CONCLUSIONS: Sarcopenia and relative sarcopenia are significantly associated with mortality regardless of CKD status. Relative sarcopenia is nearly three-fold more prevalent amplifying its associated mortality risk at the population level. The association between relative sarcopenia and mortality is attenuated in persons with higher FMI.

  View details for PubMedID 30784237

• Frailty Among Patients Receiving Hemodialysis: Evolution of Components and Associations With Mortality. The journals of gerontology. Series A, Biological sciences and medical sciences Johansen, K. L., Delgado, C., Kaysen, G. A., Chertow, G. M., Chiang, J., Dalrymple, L. S., Segal, M. R., Grimes, B. A. 2019; 74 (3): 380–86

  Abstract

  BACKGROUND: Understanding how components of frailty change over time and how they can be modeled as time-dependent predictors of mortality could lead to better risk prediction in the dialysis population.METHODS: We measured frailty at baseline, 12 months, and 24 months among 727 patients receiving hemodialysis in Northern California and Atlanta. We examined the likelihood of meeting frailty components (weight loss, exhaustion, low physical activity, weak grip strength, and slow gait speed) as a function of time in logistic regression analysis and association of frailty components with mortality in time-updated multivariable Cox models.RESULTS: Physical activity and gait speed declined, exhaustion and grip strength did not change, and the odds of meeting the weight loss criterion declined with time. All five components were associated with higher mortality in multivariable analyses, but gait speed was the strongest individual predictor. All frailty components except physical inactivity were independently associated with mortality when all five components were included in the same model. The number of frailty components met was associated with mortality in a gradient that ranged from a hazard ratio of 2.73 for one component to 10.07 for five components met; the model including all five components was the best model based on Akaike information criterion.CONCLUSIONS: Measurement of all frailty components was necessary for optimal mortality prediction, and the number of components met was strongly associated with mortality in this cohort.

  View details for PubMedID 30192916

• Trimethylamine N-Oxide and Cardiovascular Outcomes in Patients with ESKD Receiving Maintenance Hemodialysis CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Stubbs, J. R., Stedman, M. R., Liu, S., Long, J., Franchetti, Y., West, R. E., Prokopienko, A. J., Mahnken, J. D., Chertow, G. M., Nolin, T. D. 2019; 14 (2): 261–67

  View details for DOI 10.2215/CJN.06190518

  View details for Web of Science ID 000458400200015

• Prospective Biopsy-Based Study of CKD of Unknown Etiology in Sri Lanka CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Anand, S., Montez-Rath, M. E., Adasooriya, D., Ratnatunga, N., Kambham, N., Wazil, A., Wijetunge, S., Badurdeen, Z., Ratnayake, C., Karunasena, N., Schensul, S. L., Valhos, P., Haider, L., Bhalla, V., Levin, A., Wise, P. H., Chertow, G. M., Barry, M., Fire, A. Z., Nanayakkara, N. 2019; 14 (2): 224–32

  View details for DOI 10.2215/CJN.07430618

  View details for Web of Science ID 000458400200011

• Excess Deaths Attributable to Influenza-Like Illness in the ESRD Population JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Gilbertson, D. T., Rothman, K. J., Chertow, G. M., Bradbury, B. D., Brookhart, M., Liu, J., Winkelmayer, W. C., Stuermer, T., Monda, K. L., Herzog, C. A., Ashfaq, A., Collins, A. J., Wetmore, J. B. 2019; 30 (2): 346–53

  View details for DOI 10.1681/ASN.2018060581

  View details for Web of Science ID 000458398100014

• The effects of tenapanor on serum fibroblast growth factor 23 in patients receiving hemodialysis with hyperphosphatemia NEPHROLOGY DIALYSIS TRANSPLANTATION Block, G. A., Rosenbaum, D. P., Yan, A., Greasley, P. J., Chertow, G. M., Wolf, M. 2019; 34 (2): 339–46

  Abstract

  Elevated serum fibroblast growth factor 23 (FGF23) is strongly associated with cardiovascular risk and mortality. Tenapanor, an inhibitor of gastrointestinal sodium/hydrogen exchanger isoform 3, decreased serum phosphate in a randomized, double-blind, placebo-controlled Phase 2 trial (ClinicalTrials.gov identifier NCT02081534) of patients receiving hemodialysis with hyperphosphatemia. Here, we report a secondary analysis of effects on serum FGF23 during that study.After 1-3 weeks of washout of phosphate binders, 162 patients were randomized to receive 4 weeks of treatment with placebo or one of six tenapanor regimens (3 or 30 mg once daily, or 1, 3, 10 or 30 mg twice daily). Intact FGF23 concentrations were determined from serum samples collected at screening, post-washout and end of treatment, assayed in duplicate in a single batch at the end of the study.After phosphate-binder washout, serum FGF23 concentrations increased in all groups [range of geometric means: 1430-2605 pg/mL before, to 2601-6294 pg/mL after washout (P < 0.001 for all patients analyzed as a single group)]. Serum FGF23 concentrations subsequently decreased in tenapanor-treated patients (2030-3563 pg/mL), whereas they increased further in placebo-treated patients (6930 pg/mL). In an analysis of covariance, FGF23 decreased by 9.1-27.9% in tenapanor-treated patients and increased by 21.9% in placebo-treated patients (P ≤ 0.001-0.04).Following a marked increase in serum FGF23 in response to withdrawal of phosphate binders, tenapanor significantly decreased serum FGF23 in patients receiving hemodialysis with hyperphosphatemia. Further studies are required to explore the long-term effects of controlling FGF23 with tenapanor.

  View details for PubMedID 29617976

• Prior Hospitalization Burden and the Relatedness of 30-Day Readmissions in Patients Receiving Hemodialysis JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Lin, E., Bhattacharya, J., Chertow, G. M. 2019; 30 (2): 323–35

  View details for DOI 10.1681/ASN.2018080858

  View details for Web of Science ID 000458398100012

• Differential Molecular Modeling Predictions of Mid and Conventional Dialysate Flows. Blood purification Leypoldt, J. K., Prichard, S., Chertow, G. M., Alvarez, L. 2019: 1–8

  Abstract

  BACKGROUND: High dialysate flow rates (QD) of500-800 mL/min are used to maximize urea removal during conventional hemodialysis. There are few data describing hemodialysis with use of mid-rate QD (300 mL/min).METHODS: We constructed uremic solute (urea, beta2-microglobulin and phosphate) kinetic models at varying volumes of distribution and blood flow rates to predict solute clearances at QD of 300 and 500 mL/min.RESULTS: Across a range of volumes of distribution a QD of 300 mL/min generally yields a predicted urea spKt/V greater than 1.2 during typical treatment times with a small difference in urea spKt/V between a QD of 300 and 500 mL/min. A larger urea KoA dialyzer and 15 min of additional time narrows the urea spKt/V difference. No substantial differences were observed regarding the kinetics of beta2-microglobulin and phosphate for QD of 300 vs. 500 mL/min.CONCLUSION: A QD of 300 mL/min can achieve urea clearance targets. Hemodialysis systems using mid-rate QD can be expected to provide adequate hemodialysis, as currently defined.

  View details for PubMedID 30699416

• Chronic Kidney Disease and the Adiposity Paradox: Valid or Confounded? Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation Ziolkowski, S. L., Long, J., Baker, J. F., Chertow, G. M., Leonard, M. B. 2019

  Abstract

  OBJECTIVE: Obesity, defined by body mass index (BMI), is associated with lower mortality risk in patients with chronic kidney disease (CKD). BMI and % body fat (%BF) are confounded by muscle mass, while DXA derived fat mass index (FMI) overcomes this limitation. We compared the associations between obesity and mortality in persons with CKD using multiple estimates of adiposity, and determined whether muscle mass, inflammation and weight loss modify these associations.METHODS: Obesity was defined using BMI and DXA-derived FMI and %BF cut-offs in 2,852 NHANES participants with CKD from 1999-2006 and linked to the National Death Index with follow up through 2011. Cox proportional hazards models assessed associations between mortality and measures of obesity.RESULTS: Obesity based on FMI and continuous variables, FMI, BMI and %BF were associated with lower mortality. The protective association of obesity was less pronounced among participants with higher muscle mass and was no longer significant after adjustment for prior weight loss. Inflammation did not modify these associations.CONCLUSIONS: We observed lower mortality associated with higher fat mass, particularly among persons with lower muscle mass. The prevalence of >10% weight loss was half as common among obese compared to non-obese participants and confounded these associations.

  View details for PubMedID 30709713

• Excess Deaths Attributable to Influenza-Like Illness in the ESRD Population. Journal of the American Society of Nephrology : JASN Gilbertson, D. T., Rothman, K. J., Chertow, G. M., Bradbury, B. D., Brookhart, M. A., Liu, J., Winkelmayer, W. C., Sturmer, T., Monda, K. L., Herzog, C. A., Ashfaq, A., Collins, A. J., Wetmore, J. B. 2019

  Abstract

  BACKGROUND: Morbidity and mortality vary seasonally. Timing and severity of influenza seasons contribute to those patterns, especially among vulnerable populations such as patients with ESRD. However, the extent to which influenza-like illness (ILI), a syndrome comprising a range of potentially serious respiratory tract infections, contributes to mortality in patients with ESRD has not been quantified.METHODS: We used data from the Centers for Disease Control and Prevention (CDC) Outpatient Influenza-like Illness Surveillance Network and Centers for Medicare and Medicaid Services ESRD death data from 2000 to 2013. After addressing the increasing trend in deaths due to the growing prevalent ESRD population, we calculated quarterly relative mortality compared with average third-quarter (summer) death counts. We used linear regression models to assess the relationship between ILI data and mortality, separately for quarters 4 and 1 for each influenza season, and model parameter estimates to predict seasonal mortality counts and calculate excess ILI-associated deaths.RESULTS: An estimated 1% absolute increase in quarterly ILI was associated with a 1.5% increase in relative mortality for quarter 4 and a 2.0% increase for quarter 1. The average number of annual deaths potentially attributable to ILI was substantial, about 1100 deaths per year.CONCLUSIONS: We found an association between community ILI activity and seasonal variation in all-cause mortality in patients with ESRD, with ILI likely contributing to >1000 deaths annually. Surveillance efforts, such as timely reporting to the CDC of ILI activity within dialysis units during influenza season, may help focus attention on high-risk periods for this vulnerable population.

  View details for PubMedID 30679380

• Fibroblast Growth Factor 23 Genotype and Cardiovascular Disease in Patients Undergoing Hemodialysis. American journal of nephrology Schwantes-An, T., Liu, S., Stedman, M., Decker, B. S., Wetherill, L., Edenberg, H. J., Vatta, M., Foroud, T. M., Chertow, G. M., Moe, S. M. 2019; 49 (2): 125–32

  Abstract

  BACKGROUND: Elevated serum concentrations of fibroblast growth factor 23 (FGF23) are associated with cardiovascular mortality in patients with chronic kidney disease and those undergoing dialysis.OBJECTIVES: We tested the hypotheses that polymorphisms in FGF23, its co-receptor alpha-klotho (KL), and/or FGF23 receptors (FGFR) are associated with cardiovascular events and/or mortality.METHODS: We used 1,494 DNA samples collected at baseline from the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events Trial, in which patients were randomized to the calcimimetic cinacalcet or placebo for the treatment of secondary hyperparathyroidism. We analyzed European and African Ancestry samples separately and then combined summary statistics to perform a meta-analysis. We evaluated single-nucleotide polymorphisms (SNPs) in FGF23, KL, and FGFR4 as the key exposures of interest in proportional hazards (Cox) regression models using adjudicated endpoints (all-cause and cardiovascular mortality, sudden cardiac death, and heart failure [HF]) as the outcomes of interest.RESULTS: rs11063112 in FGF23 was associated with cardiovascular mortality (risk allele = A, hazard ratio [HR] 1.32, meta-p value = 0.004) and HF (HR 1.40, meta-p value = 0.007). No statistically significant associations were observed between FGF23 rs13312789 and SNPs in FGFR4 or KL genes and the outcomes of interest.CONCLUSIONS: rs11063112 was associated with HF and cardiovascular mortality in patients receiving dialysis with moderate to severe secondary hyperparathyroidism.

  View details for PubMedID 30669147

• Trimethylamine N-Oxide and Cardiovascular Outcomes in Patients with End-stage Kidney Disease Receiving Maintenance Hemodialysis. Clinical journal of the American Society of Nephrology : CJASN Stubbs, J. R., Stedman, M. R., Liu, S., Long, J., Franchetti, Y., West, R. E., Prokopienko, A. J., Mahnken, J. D., Chertow, G. M., Nolin, T. D. 2019

  Abstract

  BACKGROUND AND OBJECTIVES: Trimethylamine N-oxide (TMAO), a compound derived from byproducts of intestinal bacteria, has been shown to accelerate atherosclerosis in rodents. To date, there are conflicting data regarding the association of serum TMAO with cardiovascular outcomes in patients with ESKD, a population exhibiting both high serum TMAO and excessive atherosclerosis.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We measured baseline serum TMAO concentrations in a subset of participants (n=1243) from the Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events (EVOLVE) trial and conducted post hoc analyses evaluating the association between baseline serum TMAO and cardiovascular outcomes.RESULTS: We observed a wide distribution of serum TMAO in our cohort, with approximately 80% of participants exhibiting TMAO concentrations ≥56 M and a maximum TMAO concentration of 1103.1 M. We found no association between TMAO and our primary outcome, a composite of cardiovascular mortality, myocardial infarction, peripheral vascular event, stroke, and hospitalization for unstable angina. Moreover, in unadjusted and adjusted analyses, we observed no relation between TMAO and all-cause mortality, the independent components of our composite outcome, or the original EVOLVE primary outcome. Although we did observe higher TMAO concentrations in white participants, further subgroup analyses did not confirm the previously identified interaction between TMAO and race observed in a prior study in patients receiving dialysis.CONCLUSIONS: We found no evidence linking TMAO to adverse clinical outcomes in patients receiving maintenance hemodialysis with moderate to severe secondary hyperparathyroidism.

  View details for PubMedID 30665924

• Prospective Biopsy-Based Study of Chronic Kidney Disease of Unknown Etiology in Sri Lanka. Clinical journal of the American Society of Nephrology : CJASN Anand, S., Montez-Rath, M. E., Adasooriya, D., Ratnatunga, N., Kambham, N., Wazil, A., Wijetunge, S., Badurdeen, Z., Ratnayake, C., Karunasena, N., Schensul, S. L., Valhos, P., Haider, L., Bhalla, V., Levin, A., Wise, P. H., Chertow, G. M., Barry, M., Fire, A. Z., Nanayakkara, N. 2019

  Abstract

  BACKGROUND AND OBJECTIVES: A kidney disease of unknown cause is common in Sri Lanka's lowland (dry) region. Detailed clinical characterizations of patients with biopsy-proven disease are limited, and there is no current consensus on criteria for a noninvasive diagnosis.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We designed a prospective study in a major Sri Lankan hospital servicing endemic areas to ascertain pathologic and clinical characteristics of and assess risk factors for primary tubulointerstitial kidney disease. We used logistic regression to determine whether common clinical characteristics could be used to predict the presence of primary tubulointerstitial kidney disease on kidney biopsy.RESULTS: From 600 new patients presenting to a tertiary nephrology clinic over the course of 1 year, 87 underwent kidney biopsy, and 43 (49%) had a biopsy diagnosis of primary tubulointerstitial kidney disease. On detailed biopsy review, 13 (30%) had evidence of moderate to severe active kidney disease, and six (15%) had evidence of moderate to severe chronic tubulointerstitial kidney disease. Patients with tubulointerstitial kidney disease were exclusively born in endemic provinces; 91% spent a majority of their lifespan there. They were more likely men and farmers (risk ratio, 2.0; 95% confidence interval, 1.2 to 2.9), and they were more likely to have used tobacco (risk ratio, 1.7; 95% confidence interval, 1.0 to 2.3) and well water (risk ratio, 1.5; 95% confidence interval, 1.1 to 2.0). Three clinical characteristics-age, urine dipstick for protein, and serum albumin-could predict likelihood of tubulointerstitial kidney disease on biopsy (model sensitivity of 79% and specificity of 84%). Patients referred for kidney biopsy despite comorbid diabetes or hypertension did not experience lower odds of tubulointerstitial kidney disease.CONCLUSIONS: A primary tubulointerstitial kidney disease occurs commonly in specific regions of Sri Lanka with characteristic environmental and lifestyle exposures.PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_01_18_CJASNPodcast_19_02_.mp3.

  View details for PubMedID 30659059

• Prior Hospitalization Burden and the Relatedness of 30-Day Readmissions in Patients Receiving Hemodialysis. Journal of the American Society of Nephrology : JASN Lin, E., Bhattacharya, J., Chertow, G. M. 2019

  Abstract

  BACKGROUND: Thirty-day readmissions are common in patients receiving hemodialysis and costly to Medicare. Because patients on hemodialysis have a high background hospitalization rate, 30-day readmissions might be less likely related to the index hospitalization than in patients with other conditions.METHODS: In adults with Medicare receiving hemodialysis in the United States, we used multinomial logistic regression to evaluate whether prior hospitalization burden was associated with increased 30-day readmissions unrelated to index hospitalizations with a discharge date from January 1, 2013 to December 31, 2014. We categorized a hospitalization, 30-day readmission pair as "related" if the principal diagnoses came from the same organ system.RESULTS: The adjusted probability of unrelated 30-day readmission after any index hospitalization was 19.1% (95% confidence interval [95% CI] 18.9% to 19.3%), 22.6% (95% CI, 22.4% to 22.8%), and 31.2% (95% CI, 30.8% to 31.5%) in patients with 0-1, 2-4, and ≥5 hospitalizations, respectively. Cardiovascular index hospitalizations had the highest adjusted probability of related 30-day readmission: 10.4% (95% CI, 10.2% to 10.7%), 13.6% (95% CI, 13.4% to 13.9%), and 20.8% (95% CI, 20.2% to 21.4%), respectively. Renal index hospitalizations had the lowest adjusted probability of related 30-day readmission: 2.0% (95% CI, 1.8% to 2.3%), 3.9% (95% CI, 3.4% to 4.4%), and 5.1% (95% CI, 4.3% to 5.9%), respectively.CONCLUSIONS: High prior hospitalization burden increases the likelihood that patients receiving hemodialysis experience a 30-day readmission unrelated to the index hospitalization. Health care payers such as Medicare should consider incorporating clinical relatedness into 30-day readmission quality measures.

  View details for PubMedID 30606782

• Safety-Net Care for Maintenance Dialysis in the United States. Journal of the American Society of Nephrology : JASN Erickson, K. F., Shen, J. I., Zhao, B. n., Winkelmayer, W. C., Chertow, G. M., Ho, V. n., Bhattacharya, J. n. 2019

  Abstract

  Although most American patients with ESKD become eligible for Medicare by their fourth month of dialysis, some never do. Information about where patients with limited health insurance receive maintenance dialysis has been lacking.We identified patients initiating maintenance dialysis (2008-2015) from the US Renal Data System, defining patients as "safety-net reliant" if they were uninsured or had only Medicaid coverage at dialysis onset and had not qualified for Medicare by the fourth dialysis month. We examined four dialysis facility ownership categories according to for-profit/nonprofit status and ownership (chain versus independent). We assessed whether patients who were safety-net reliant were more likely to initiate dialysis at certain facility types. We also examined hospital-based affiliation.The proportion of patients <65 years initiating dialysis who were safety-net reliant increased significantly over time, from 11% to 14%; 73% of such patients started dialysis at for-profit/chain-owned facilities compared to 76% of all patients starting dialysis. Patients who were safety-net reliant had a 30% higher relative risk of initiating dialysis at nonprofit/independently owned versus for-profit/independently owned facilities (odds ratio, 1.30; 95% CI, 1.24 to 1.36); they had slightly lower relative risks of initiating dialysis at for-profit and non-profit chain-owned facilities, and were more likely to receive dialysis at hospital-based facilities. These findings primarily reflect increased likelihood of dialysis among patients without insurance at certain facility types.Although most patients who were safety-net reliant received care at for-profit/chain-owned facilities, they were disproportionately cared for at nonprofit/independently owned and hospital-based facilities. Ongoing loss of market share of nonprofit/independently owned outpatient dialysis facilities may affect safety net-reliant populations.

  View details for DOI 10.1681/ASN.2019040417

  View details for PubMedID 31857351

• The cost of procuring deceased donor kidneys: Evidence from OPO cost reports 2013-2017. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons Held, P. J., Bragg-Gresham, J. L., Peters, T. n., Chertow, G. M., McCormick, F. n., Roberts, J. P. 2019

  Abstract

  Using 5-years of US organ procurement organization (OPO) data, we determined the cost of recovering a viable (i.e., transplanted) kidney for each of 51 OPOs. We also examined the effects on OPO costs of the recovery of non-viable (i.e., discarded) kidneys and other OPO metrics. Annual cost reports from 51 independent OPOs were used to determine the cost per recovered kidney for each OPO. A quadratic regression model was employed to estimate the relationship between the cost of kidneys and the number of viable kidneys recovered, as well as other OPO performance indicators. The cost of transplanted kidneys at individual OPOs ranged widely from $24,000 to $56,000, and the average was $36,000. The cost of a viable kidney tended to decline with the number of kidneys procured up to 549 kidneys per year and then increase. Of the total 81,401 kidneys recovered, 66,454 were viable and 14,947 (18.4%) were non-viable. The costs of kidneys varied widely over the OPOs studied, and costs were a function of the recovered number of viable and non-viable organs, local cost levels, donation after cardiac death (DCD), year, and Standardized Donor Rate Ratio (SDRR). Cost increases were 3% per year.

  View details for DOI 10.1111/ajt.15669

  View details for PubMedID 31667990

• Antidiabetic medication use in patients with type 2 diabetes and chronic kidney disease. Journal of diabetes and its complications Rhee, J. J., Han, J. n., Montez-Rath, M. E., Kim, S. H., Cullen, M. R., Stafford, R. S., Winkelmayer, W. C., Chertow, G. M. 2019: 107423

  Abstract

  To quantify patterns of conventional and newer antidiabetic medication use in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD).We used data from a large claims and integrated dataset that includes employed and commercially insured patients in the US to select patients who had T2DM and CKD with information on laboratory values and prescriptions for antidiabetic medications from January 1, 2014 to January 1, 2015. We stratified the analyses by sociodemographic variables.In a cohort of 38,577 patients with T2DM and CKD, we found wide variation in the treatment of T2DM by CKD stage as well as by several sociodemographic factors. Although metformin was the most commonly prescribed medication, only about half of patients in the cohort and fewer than two-thirds of patients with early stage CKD were prescribed metformin. Approximately 10.6% of patients with CKD stage 4 and 2.1% of the patients with CKD stage 5 were prescribed metformin. Sulfonylureas with active metabolites that accumulate with impaired kidney function were prescribed in more than one-third of patients with CKD stages 3b, 4, and 5. Only 3.4% and 12.3% of patients were prescribed GLP-1 and DPP-4 respectively.Prescriptions for metformin were lower than expected among patients with mild to moderate CKD. Prescriptions for newer antidiabetic medications with known safety and efficacy across the spectrum of CKD remained low. Prescriptions for agents contraindicated in advanced CKD continued to be written in a sizeable fraction of patients.

  View details for DOI 10.1016/j.jdiacomp.2019.107423

  View details for PubMedID 31537413

• Central venous pressure and the risk of diuretic-associated acute kidney injury in patients after cardiac surgery. American heart journal McCoy, I. E., Montez-Rath, M. E., Chertow, G. M., Chang, T. I. 2019; 221: 67–73

  Abstract

  When prescribing diuretics in the postcardiac surgical intensive care unit (ICU), clinicians may use central venous pressure (CVP) to assess volume status and the risk of acute kidney injury (AKI). In this study, we examined how the risk of diuretic-associated AKI varied with CVP in patients undergoing cardiac surgery.We used the Medical Information Mart for Intensive Care database to study adults admitted to the postcardiac surgical ICU at an urban, academic medical center between 2001 and 2012. We examined the odds of AKI per 1-mm Hg increase in CVP among patients receiving intravenous loop diuretics using multivariable adjusted logistic regression. We examined the risk of AKI among patients with diuretic use (vs nonuse) across tertiles of CVP using inverse probability treatment weighting.Among 4,164 patients receiving intravenous loop diuretics, the adjusted odds of subsequent AKI were 1.11 (95% CI 1.08-1.13) times higher per mm Hg increase in mean CVP. This association was log-linear across the entire range of CVPs observed. In the analysis of diuretic use (n = 5,396), the adjusted risk ratio for AKI with diuretic use (vs nonuse) was 1.33 (95% CI 1.21-1.47) and did not materially differ across tertile of CVP.Higher rather than lower CVP is an independent marker of AKI risk. The risk of AKI associated with diuretic use may not be influenced by CVP. Novel methods of assessing volume status and AKI risk are needed to guide patient selection for diuretic therapy.

  View details for DOI 10.1016/j.ahj.2019.12.013

  View details for PubMedID 31931418

• Twenty-Four Hour Urine Testing and Prescriptions for Urinary Stone Disease-Related Medications in Veterans. Clinical journal of the American Society of Nephrology : CJASN Song, S. n., Thomas, I. C., Ganesan, C. n., Sohlberg, E. M., Chertow, G. M., Liao, J. C., Conti, S. n., Elliott, C. S., Pao, A. C., Leppert, J. T. 2019

  Abstract

  Current guidelines recommend 24-hour urine testing in the evaluation and treatment of persons with high-risk urinary stone disease. However, how much clinicians use information from 24-hour urine testing to guide secondary prevention strategies is unknown. We sought to determine the degree to which clinicians initiate or continue stone disease-related medications in response to 24-hour urine testing.We examined a national cohort of 130,489 patients with incident urinary stone disease in the Veterans Health Administration between 2007 and 2013 to determine whether prescription patterns for thiazide diuretics, alkali therapy, and allopurinol changed in response to 24-hour urine testing.Stone formers who completed 24-hour urine testing (n=17,303; 13%) were significantly more likely to be prescribed thiazide diuretics, alkali therapy, and allopurinol compared with those who did not complete a 24-hour urine test (n=113,186; 87%). Prescription of thiazide diuretics increased in patients with hypercalciuria (9% absolute increase if urine calcium 201-400 mg/d; 21% absolute increase if urine calcium >400 mg/d, P<0.001). Prescription of alkali therapy increased in patients with hypocitraturia (24% absolute increase if urine citrate 201-400 mg/d; 34% absolute increase if urine citrate ≤200 mg/d, P<0.001). Prescription of allopurinol increased in patients with hyperuricosuria (18% absolute increase if urine uric acid >800 mg/d, P<0.001). Patients who had visited both a urologist and a nephrologist within 6 months of 24-hour urine testing were more likely to have been prescribed stone-related medications than patients who visited one, the other, or neither.Clinicians adjust their treatment regimens in response to 24-hour urine testing by increasing the prescription of medications thought to reduce risk for urinary stone disease. Most patients who might benefit from targeted medications remain untreated.

  View details for DOI 10.2215/CJN.03580319

  View details for PubMedID 31712387

• Estimated effects of early diuretic use in critical illness. Critical care explorations McCoy, I. E., Montez-Rath, M. E., Chertow, G. M., Chang, T. I. 2019; 1 (7)

  Abstract

  To estimate the effects of diuretic use during the first 24 hours of an intensive care unit stay on in-hospital mortality and other clinical outcomes including acute kidney injury and duration of mechanical ventilation.Retrospective cohort study.Urban, academic medical center.Adult patients admitted to medical or cardiac ICUs between 2001 and 2012, excluding those on maintenance dialysis or with ICU length of stay < 24 hours.None.We included 13,589 patients: 2,606 with and 10,983 without early diuretic use (loop diuretic exposure during the first 24 hours of an ICU stay). Propensity score matching generated 2523 pairs with well-balanced baseline characteristics. Early diuretic use was unassociated with in-hospital mortality (risk ratio 1.01, 99.5% confidence interval 0.83-1.22). We found no evidence of associations with ICU or hospital length of stay, or duration or provision of mechanical ventilation. Early diuretic use was associated with higher rates of subsequent acute kidney injury (risk ratio 1.41, 99.5% confidence interval 1.25 to 1.59) and electrolyte abnormalities. Results were not materially different in subgroups of patients with heart failure, chronic kidney disease, or acute lung injury.Early diuretic use in critical illness was unassociated with in-hospital mortality, ICU or hospital length of stay, or duration of mechanical ventilation, but risks of acute kidney injury and electrolyte abnormalities were higher.

  View details for DOI 10.1097/CCE.0000000000000021

  View details for PubMedID 31440746

  View details for PubMedCentralID PMC6705600

• Prevalence of twenty-four hour urine testing in Veterans with urinary stone disease. PloS one Ganesan, C. n., Thomas, I. C., Song, S. n., Sun, A. J., Sohlberg, E. M., Kurella Tamura, M. n., Chertow, G. M., Liao, J. C., Conti, S. n., Elliott, C. S., Leppert, J. T., Pao, A. C. 2019; 14 (8): e0220768

  Abstract

  The American Urological Association guidelines recommend 24-hour urine testing in patients with urinary stone disease to decrease the risk of stone recurrence; however, national practice patterns for 24-hour urine testing are not well characterized. Our objective is to determine the prevalence of 24-hour urine testing in patients with urinary stone disease in the Veterans Health Administration and examine patient-specific and facility-level factors associated with 24-hour urine testing. Identifying variations in clinical practice can inform future quality improvement efforts in the management of urinary stone disease in integrated healthcare systems.We accessed national Veterans Health Administration data through the Corporate Data Warehouse (CDW), hosted by the Veterans Affairs Informatics and Computing Infrastructure (VINCI), to identify patients with urinary stone disease. We defined stone formers as Veterans with one inpatient ICD-9 code for kidney or ureteral stones, two or more outpatient ICD-9 codes for kidney or ureteral stones, or one or more CPT codes for kidney or ureteral stone procedures from 2007 through 2013. We defined a 24-hour urine test as a 24-hour collection for calcium, oxalate, citrate or sulfate. We used multivariable regression to assess demographic, geographic, and selected clinical factors associated with 24-hour urine testing.We identified 130,489 Veterans with urinary stone disease; 19,288 (14.8%) underwent 24-hour urine testing. Patients who completed 24-hour urine testing were younger, had fewer comorbidities, and were more likely to be White. Utilization of 24-hour urine testing varied widely by geography and facility, the latter ranging from 1 to 40%.Fewer than one in six patients with urinary stone disease complete 24-hour urine testing in the Veterans Health Administration. In addition, utilization of 24-hour urine testing varies widely by facility identifying a target area for improvement in the care of patients with urinary stone disease. Future efforts to increase utilization of 24-hour urine testing and improve clinician awareness of targeted approaches to stone prevention may be warranted to reduce the morbidity and cost of urinary stone disease.

  View details for DOI 10.1371/journal.pone.0220768

  View details for PubMedID 31393935

• Exploring Care Attributes of Nephrologists Ranking Favorably on Measures of Value. Journal of the American Society of Nephrology : JASN Brady, B. M., Ragavan, M. V., Simon, M. n., Chertow, G. M., Milstein, A. n. 2019

  Abstract

  Despite growth in value-based payment, attributes of nephrology care associated with payer-defined value remains unexplored.Using national health insurance claims data from private preferred provider organization plans, we ranked nephrology practices using total cost of care and a composite of common quality metrics. Blinded to practice rankings, we conducted site visits at four highly ranked and three average ranked practices to identify care attributes more frequently present in highly ranked practices. A panel of nephrologists used a modified Delphi method to score each distinguishing attribute on its potential to affect quality and cost of care and ease of transfer to other nephrology practices.Compared with average-value peers, high-value practices were located in areas with a relatively higher proportion of black and Hispanic patients and a lower proportion of patients aged >65 years. Mean risk-adjusted per capita monthly total spending was 24% lower for high-value practices. Twelve attributes comprising five general themes were observed more frequently in high-value nephrology practices: preventing near-term costly health crises, supporting patient self-care, maximizing effectiveness of office visits, selecting cost-effective diagnostic and treatment options, and developing infrastructure to support high-value care. The Delphi panel rated four attributes highly on effect and transferability: rapidly adjustable office visit frequency for unstable patients, close monitoring and management to preserve kidney function, early planning for vascular access, and education to support self-management at every contact.Findings from this small-scale exploratory study may serve as a starting point for nephrologists seeking to improve on payer-specified value measures.

  View details for DOI 10.1681/ASN.2019030219

  View details for PubMedID 31727849

• Intradialytic Symptoms and Recovery Time in Patients on Thrice-Weekly In-Center Hemodialysis: A Cross-sectional Online Survey. Kidney medicine Alvarez, L. n., Brown, D. n., Hu, D. n., Chertow, G. M., Vassalotti, J. A., Prichard, S. n. 2019; 2 (2): 125–30

  Abstract

  Patients experience various symptoms during hemodialysis. We aimed to assess the frequency and severity of symptoms during hemodialysis and whether intradialytic symptoms are associated with recovery time postdialysis.An online questionnaire was sent to 10,000 patients in a National Kidney Foundation database.Adult patients receiving in-center hemodialysis 3 times weekly for 3 or more months.Online questionnaire.Tabulation of frequency and severity of events and recovery time as percent of respondents, construction of a total symptom score, followed by rank correlation analysis of symptom characteristics with total recovery time.Patient-reported intradialytic symptoms and recovery time postdialysis.359 patients met screening criteria and completed the questionnaire. Mean age was 62.5 ± 13.8 years, 207 (58%) were men, 74 (21%) were black/African American, 132 (37%) had diabetes, 252 (70%) had hypertension, and 102 (28%) had a history of myocardial infarction, heart surgery, or stent placement. 311 (87%) patients had symptoms during dialysis in the previous week, with mean severity of 2.7 (range for each symptom, 1-5). The most common symptoms were fatigue/feeling washed out (62%), cramps (44%), and symptoms of low blood pressure (42%). Median time to recovery was 3 (range, 0-24) hours, and this correlated with the incidence and severity of intradialytic symptoms (P < 0.0001). 40% of patients had time to recovery times of 4 hours or longer. 1 in 3 patients reported having stopped dialysis early for intradialytic symptoms and 6% reported skipping dialysis at least once because of intradialytic symptoms.Recall-based self-reported data with a relatively low response rate.A majority of patients receiving in-center hemodialysis experience symptoms such as feeling washed out, fatigue, and cramping; these may be severe and are correlated with longer recovery time following hemodialysis, as well as shortened and skipped hemodialysis sessions.

  View details for DOI 10.1016/j.xkme.2019.10.010

  View details for PubMedID 32734233

  View details for PubMedCentralID PMC7380355

• Market Consolidation and Mortality in Patients Initiating Hemodialysis. Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research Erickson, K. F., Winkelmayer, W. C., Ho, V., Bhattacharya, J., Chertow, G. M. 2019; 22 (1): 69–76

  Abstract

  BACKGROUND: It is uncertain whether consolidation in health care markets affects the quality of care provided and health outcomes.OBJECTIVES: To examine whether changes in market competition resulting from acquisitions by two large national for-profit dialysis chains were associated with patient mortality.METHODS: We identified patients initiating in-center hemodialysis between 2001 and 2009 from a registry of patients with end-stage renal disease in the United States. We considered two scenarios when evaluating consolidation from dialysis facility acquisitions: one in which we considered only those patients receiving dialysis in markets that became substantially more concentrated to have been affected by consolidation, and the other in which all patients living in hospital service areas where a facility was acquired were potentially affected. We used a difference-in-differences study design to examine the associations between market consolidation and changes in mortality rates.RESULTS: When we considered the 12,065 patients living in areas that became substantially more consolidated to have been affected by consolidation, we found a nominally significant (8%; 95% confidence interval 0%-17%) increase in likelihood of death after consolidation. Nevertheless, when we considered all 186,158 patients living in areas where an acquisition occurred to have been affected by consolidation, there was no observable effect of market consolidation on mortality.CONCLUSIONS: Decreased market competition may have led to increased mortality among a relatively small subset of patients initiating in-center hemodialysis in areas that became substantially more concentrated after two large dialysis acquisitions, but not for most of the patients living in affected areas.

  View details for PubMedID 30661636

• Effects of vadadustat on hemoglobin concentrations in patients receiving hemodialysis previously treated with erythropoiesis-stimulating agents NEPHROLOGY DIALYSIS TRANSPLANTATION Haase, V. H., Chertow, G. M., Block, G. A., Pergola, P. E., deGoma, E. M., Khawaja, Z., Sharma, A., Maroni, B. J., McCullough, P. A. 2019; 34 (1): 90–99

  Abstract

  Vadadustat, an inhibitor of hypoxia-inducible factor prolyl-4-hydroxylase domain dioxygenases, is an oral investigational agent in development for the treatment of anemia secondary to chronic kidney disease.In this open-label Phase 2 trial, vadadustat was evaluated in 94 subjects receiving hemodialysis, previously maintained on epoetin alfa. Subjects were sequentially assigned to one of three vadadustat dose cohorts by starting dose: 300 mg once daily (QD), 450 mg QD or 450 mg thrice weekly (TIW). The primary endpoint was mean hemoglobin (Hb) change from pre-baseline average to midtrial (Weeks 7-8) and end-of-trial (Weeks 15-16) and was analyzed using available data (no imputation).Overall, 80, 73 and 68% of subjects in the 300 mg QD, 450 mg QD, and 450 mg TIW dose cohorts respectively, completed the study. For all dose cohorts no statistically significant mean change in Hb from pre-baseline average was observed, and mean Hb concentrations-analyzed using available data-remained stable at mid- and end-of-trial. There was one subject with an Hb excursion >13 g/dL. Overall, 83% of subjects experienced an adverse event (AE); the proportion of subjects who experienced at least one AE was similar among the three dose cohorts. The most frequently reported AEs were nausea (11.7%), diarrhea (10.6%) and vomiting (9.6%). No deaths occurred during the study. No serious AEs were attributed to vadadustat.Vadadustat maintained mean Hb concentrations in subjects on hemodialysis previously receiving epoetin. These data support further investigation of vadadustat to assess its long-term safety and efficacy in subjects on hemodialysis.

  View details for PubMedID 29672740

  View details for PubMedCentralID PMC6322440

• An integrated analysis of safety and tolerability of etelcalcetide in patients receiving hemodialysis with secondary hyperparathyroidism. PloS one Block, G. A., Chertow, G. M., Sullivan, J. T., Deng, H., Mather, O., Tomlin, H., Serenko, M. 2019; 14 (3): e0213774

  Abstract

  BACKGROUND: Calcimimetics have been shown to be effective and safe therapies for the treatment of secondary hyperparathyroidism (sHPT), a serious complication of disordered mineral metabolism associated with dialysis-dependent chronic kidney disease. Etelcalcetide, a recently approved intravenous calcimimetic, reduces serum parathyroid hormone (PTH), calcium, phosphorus, and fibroblast growth factor-23 concentrations. Here we report the first integrated safety profile of etelcalcetide using pooled data from five pivotal clinical trials.METHODS: This analysis included data from patients receiving hemodialysis with moderate to severe sHPT enrolled in two randomized, placebo-controlled trials; a randomized active-controlled (with cinacalcet) trial; and two single-arm, open-label extension trials. Patients initially received etelcalcetide intravenously 5 mg three times weekly (TIW) after hemodialysis; with potential dose increases of 2.5 or 5 mg at 4-week intervals to a maximum dose of 15 mg TIW, depending on serum PTH and calcium levels. The nature, frequency, and severity of treatment-emergent adverse events (AEs) and changes in laboratory parameters were assessed.RESULTS: Overall, we evaluated 1023 patients from the placebo-controlled trials, 683 from the active-controlled trial, and 1299 from open-label extensions. The frequency and nature of common treatment-emergent AEs reported for the etelcalcetide arm were consistent among the placebo-controlled and active-controlled trials. The most common AEs were those related to mineral metabolism (decreased blood calcium, hypophosphatemia, muscle spasms) or gastrointestinal abnormalities (diarrhea, nausea, vomiting). Hypocalcemia leading to discontinuation of either calcimimetic was experienced in ≤ 1% of patients.CONCLUSIONS: This integrated safety assessment of etelcalcetide across placebo- and active-controlled trials showed an overall favorable risk/benefit profile, with safety similar to that of cinacalcet. Consistent with its mechanism of action, the most important risks associated with etelcalcetide were serum calcium reductions and hypocalcemia-related AEs; no new safety findings were identified in the pooled long-term extension trials.

  View details for PubMedID 30875390

• Patterns of diuretic use in the intensive care unit. PloS one McCoy, I. E., Chertow, G. M., Chang, T. I. 2019; 14 (5): e0217911

  Abstract

  To inform future outcomes research on diuretics, we sought to describe modern patterns of diuretic use in the intensive care unit (ICU), including diuretic type, combination, and dosing. We also investigated two possible quality improvement targets: furosemide dosing in renal impairment and inclusion of an initial bolus with continuous furosemide infusions.In this descriptive study, we retrospectively studied 46,037 adult ICU admissions from a publicly available database of patients in an urban, academic medical center.Diuretics were employed in nearly half (49%, 22,569/46,037) of ICU admissions. Mechanical ventilation, a history of heart failure, and admission to the post-cardiac surgery unit were associated with a higher frequency of diuretic use. Combination use of different diuretic classes was uncommon. Patients with severely impaired kidney function were less likely to receive diuretics. Furosemide was by far the most common diuretic given and the initial intravenous dose was only 20 mg in more than half of ICU admissions. Among patients treated with a continuous infusion, 30% did not receive a bolus on the day of infusion initiation.Patterns of diuretic use varied by patient-specific factors and by ICU type. Diuretic dosing strategies may be suboptimal.

  View details for DOI 10.1371/journal.pone.0217911

  View details for PubMedID 31150512

• Association of Hospitalization and Mortality Among Patients Initiating Dialysis With Hemodialysis Facility Ownership and Acquisitions. JAMA network open Erickson, K. F., Zhao, B. n., Niu, J. n., Winkelmayer, W. C., Bhattacharya, J. n., Chertow, G. M., Ho, V. n. 2019; 2 (5): e193987

  Abstract

  Mergers and acquisitions among health care institutions are increasingly common, and dialysis markets have undergone several decades of mergers and acquisitions.To examine the outcomes of hemodialysis facility acquisitions independent of associated changes in market competition resulting from acquisitions.Cohort study using difference-in-differences (DID) analyses to compare changes in health outcomes over time among in-center US dialysis facilities that were acquired by a hemodialysis chain with facilities located nearby but not acquired. Multivariable Cox proportional hazards regression models and negative binomial models with predicted marginal effects were developed to examine health outcomes, controlling for patient, facility, and geographic characteristics. All facility ownership types were examined together and stratified analyses were conducted of facilities that were independently owned and chain owned prior to acquisitions. The study was conducted from January 2001 to September 2015; 174 905 patients starting in-center dialysis in the 3 years before and following dialysis facility acquisitions were included. Data were analyzed from March 2017 to December 2018.Acquisition by a hemodialysis chain.Twelve-month hazard of death and hospital days per patient-year were the primary outcomes.Of the 174 905 patients included in the study, 79 705 were women (45.6%), 24 409 (14.0%) were of Hispanic ethnicity, 61 815 (35.3%) were black, 105 272 (60.2%) were white, and 1247 (0.7%) were Native American. Mean (SD) age was 65 (15) years. Before acquisitions, adjusted mortality and hospitalization rates were 10% (95% CI, -16% to -5%) and 2.9 days per patient-year (95% CI, -3.8 to -2.0) lower, respectively, at independently owned facilities that were acquired compared with those that were not acquired, while hospitalization rates were 0.7 days (95% CI, -1.2 to -2.0) lower at chain-owned facilities that were acquired compared with those that were not acquired. In stratified analyses of independently owned facilities, mortality decreases were smaller at acquired (-8.4%; 95% CI, -14% to -25%) vs nonacquired (-20.3%; 95% CI, -25.8% to -14.3%) facilities (DID P < .001). Similarly, hospitalization rates did not change at acquired facilities and decreased by 2.6 days per patient-year (95% CI, -3.6 to -1.7 days) at nonacquired facilities (DID P < .001). Acquisitions were not associated with changes in health outcomes at chain-owned facilities. Slower reductions in mortality and hospitalization rates at independently owned facilities contributed to significant differences in hospitalizations (-2.0 days; 95% CI, -2.5 to -1.6, at nonacquired vs 0.9 days; 95% CI, -1.3 to -0.5, at acquired facilities; DID, P < .001) across all ownership types but not mortality (DID, P = .28) with regard to acquisitions.Acquisition of independently owned dialysis facilities by larger dialysis organizations was associated with slower decreases in mortality and hospitalization rates, as nonacquired facilities appeared to experience more rapid improvements in outcomes over time.

  View details for PubMedID 31099872

• Market Consolidation and Mortality in Patients Initiating Hemodialysis VALUE IN HEALTH Erickson, K. F., Winkelmayer, W. C., Ho, V., Bhattacharya, J., Chertow, G. M. 2019; 22 (1): 69–76

  View details for DOI 10.1016/j.jval.2018.06.008

  View details for Web of Science ID 000456090600010

• Fibroblast Growth Factor 23 Genotype and Cardiovascular Disease in Patients Undergoing Hemodialysis AMERICAN JOURNAL OF NEPHROLOGY Schwantes-An, T., Liu, S., Stedman, M., Decker, B. S., Wetherill, L., Edenberg, H. J., Vatta, M., Foroud, T. M., Chertow, G. M., Moe, S. M. 2019; 49 (2): 125–32

  View details for DOI 10.1159/000496060

  View details for Web of Science ID 000459402800005

• Differential Molecular Modeling Predictions of Mid and Conventional Dialysate Flows BLOOD PURIFICATION Leypoldt, J. K., Prichard, S., Chertow, G. M., Alvarez, L. 2019; 47 (4): 369–76

  View details for DOI 10.1159/000495022

  View details for Web of Science ID 000468935700009

• Removing Disincentives to Kidney Donation: A Quantitative Analysis. Journal of the American Society of Nephrology : JASN McCormick, F. n., Held, P. J., Chertow, G. M., Peters, T. G., Roberts, J. P. 2019

  View details for DOI 10.1681/ASN.2019030242

  View details for PubMedID 31345987

• Defining a willingness-to-transplant threshold in an era of organ scarcity: Simultaneous liver-kidney transplant as a case example. Transplantation Cheng, X. S., Goldhaber-Fiebert, J. n., Tan, J. C., Chertow, G. M., Kim, W. R., Wall, A. E. 2019

  Abstract

  Organ scarcity continues in solid organ transplantation, such that the availability of organs limits the number of people able to benefit from transplantation. Medical advancements in managing end-stage organ disease have led to an increasing demand for multi-organ transplant, wherein a patient with multi-organ disease receives more than one organ from the same donor. Current allocation schemes give priority to multi-organ recipients over single-organ transplant recipients, which raises ethical questions regarding equity and utility.We use simultaneous liver-kidney (SLK) transplant, a type of multi-organ transplant, as a case study to examine the tension between equity and utility in multi-organ allocation. We adapt the health economics willingness-to-pay threshold to a solid organ transplant setting by coining a new metric: the willingness-to-transplant (WTT) threshold.We demonstrate how the WTT threshold can be used to evaluate different SLK allocation strategies by synthesizing utility and equity perspectives.We submit that this new framework enables us to distill the question of SLK allocation down to: what is the minimum amount of benefit we require from a deceased donor kidney to allocate it for a particular indication? Addressing the above question will prove helpful to devising a rational system of SLK allocation and is applicable to other transplant settings.

  View details for DOI 10.1097/TP.0000000000002788

  View details for PubMedID 31107820

• Toward Greater Scrutiny of Dialysate Flow: Reply to the Letter to the Editor of Dr. Molano-Triviño and Colleagues. Blood purification Alvarez, L. n., Leypoldt, J. K., Prichard, S. n., Chertow, G. M. 2019: 1–2

  View details for DOI 10.1159/000501842

  View details for PubMedID 31340211

• Implications of Early Decline in eGFR due to Intensive BP Control for Cardiovascular Outcomes in SPRINT. Journal of the American Society of Nephrology : JASN Beddhu, S. n., Shen, J. n., Cheung, A. K., Kimmel, P. L., Chertow, G. M., Wei, G. n., Boucher, R. E., Chonchol, M. n., Arman, F. n., Campbell, R. C., Contreras, G. n., Dwyer, J. P., Freedman, B. I., Ix, J. H., Kirchner, K. n., Papademetriou, V. n., Pisoni, R. n., Rocco, M. V., Whelton, P. K., Greene, T. n. 2019

  Abstract

  The Systolic BP Intervention Trial (SPRINT) found that intensive versus standard systolic BP control (targeting <120 or <140 mm Hg, respectively) reduced the risks of death and major cardiovascular events in persons with elevated cardiovascular disease risk. However, the intensive intervention was associated with an early decline in eGFR, and the clinical implications of this early decline are unclear.In a post hoc analysis of SPRINT, we defined change in eGFR as the percentage change in eGFR at 6 months compared with baseline. We performed causal mediation analyses to separate the overall effects of the randomized systolic BP intervention on the SPRINT primary cardiovascular composite and all-cause mortality into indirect effects (mediated by percentage change in eGFR) and direct effects (mediated through pathways other than percentage change in eGFR).About 10.3% of the 4270 participants in the intensive group had a ≥20% eGFR decline versus 4.4% of the 4256 participants in the standard arm (P<0.001). After the 6-month visit, there were 591 cardiovascular composite events during 27,849 person-years of follow-up. The hazard ratios for total effect, direct effect, and indirect effect of the intervention on the cardiovascular composite were 0.67 (95% confidence interval [95% CI], 0.56 to 0.78), 0.68 (95% CI, 0.57 to 0.79), and 0.99 (95% CI, 0.95 to 1.03), respectively. All-cause mortality results were similar.Although intensive systolic BP lowering resulted in greater early decline in eGFR, there was no evidence that the reduction in eGFR owing to intensive systolic BP lowering attenuated the beneficial effects of this intervention on cardiovascular events or all-cause mortality.

  View details for DOI 10.1681/ASN.2018121261

  View details for PubMedID 31324734

• Correction of hypomagnesemia by dapagliflozin in patients with type 2 diabetes: A post hoc analysis of 10 randomized, placebo-controlled trials. Journal of diabetes and its complications Toto, R. D., Goldenberg, R. n., Chertow, G. M., Cain, V. n., Stefánsson, B. V., Sjöström, C. D., Sartipy, P. n. 2019: 107402

  Abstract

  Hypomagnesemia (serum magnesium [Mg] <0.74 mmol/L [<1.8 mg/dL]) is commonly observed in patients with type 2 diabetes (T2D). This study investigated the effect of treatment with dapagliflozin 10 mg on Mg concentrations in patients with T2D.In this post hoc analysis, we used pooled data from 10 placebo-controlled studies of dapagliflozin over 24 weeks of treatment in patients with T2D. We evaluated the change in Mg in patients receiving dapagliflozin vs. placebo overall, and in subgroups with baseline hypomagnesemia and normal/hypermagnesemia (≥0.74 mmol/L [≥1.8 mg/dL]). We determined the proportion of patients with baseline hypomagnesemia who achieved Mg ≥0.74 mmol/L (≥1.8 mg/dL).A total of 4398 patients with T2D were included. The mean change from baseline to week 24 in Mg was significantly larger with dapagliflozin vs. placebo; difference, 0.06 mmol/L (95% confidence interval [CI]: 0.05, 0.06). The proportion of patients with Mg within the population reference range after 24 weeks of treatment was significantly higher with dapagliflozin vs. placebo; difference, 47.8% (95% CI: 41.4, 53.9). The proportion of patients displaying hypermagnesemia did not increase with dapagliflozin treatment.Treatment with dapagliflozin 10 mg resulted in correction of Mg concentrations in patients with T2D and hypomagnesemia.

  View details for DOI 10.1016/j.jdiacomp.2019.06.007

  View details for PubMedID 31375422

• Effect of bardoxolone methyl on the urine albumin-to-creatinine ratio in patients with type 2 diabetes and stage 4 chronic kidney disease. Kidney international Rossing, P. n., Block, G. A., Chin, M. P., Goldsberry, A. n., Heerspink, H. J., McCullough, P. A., Meyer, C. J., Packham, D. n., Pergola, P. E., Spinowitz, B. n., Sprague, S. M., Warnock, D. G., Chertow, G. M. 2019

  Abstract

  Bardoxolone methyl attenuates inflammation by inducing nuclear factor erythroid-derived 2-related factor 2 and suppressing nuclear factor κB. The Bardoxolone Methyl Evaluation in Patients With Chronic Kidney Disease and Type 2 Diabetes (BEACON) trial was a phase 3 placebo-controlled, randomized, double-blind, parallel-group, international, multicenter trial in 2185 patients with type 2 diabetes mellitus and stage 4 chronic kidney disease (CKD). BEACON was terminated because of safety concerns, largely related to a significant increase in early heart failure events in patients randomized to bardoxolone methyl. Bardoxolone methyl resulted in increased estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio. Herein, we present post hoc analyses characterizing the relation between the urine albumin-to-creatinine ratio and eGFR. The urine albumin-to-creatinine ratio and eGFR were assessed every four weeks through Week 12, followed by assessments every eight weeks thereafter, and 4 weeks after the last dose of bardoxolone methyl was administered. The initial increases in urine albumin-to-creatinine ratio observed in patients randomized to bardoxolone methyl were attenuated after six months. Multivariable regression analysis identified baseline eGFR and eGFR over time as the dominant factors associated with change in the urine albumin-to-creatinine ratio. Relative to placebo, bardoxolone methyl resulted in a significant decrease in albuminuria when indexed to eGFR (least-squared means: -0.035 [95% confidence interval -0.031 to -0.039]). Thus, among patients with type 2 diabetes mellitus and stage 4 CKD treated with bardoxolone methyl, changes in albuminuria are directly related to changes in eGFR, challenging the conventional construct that increases in albuminuria universally reflect kidney injury and denote harm.

  View details for DOI 10.1016/j.kint.2019.04.027

  View details for PubMedID 31377056

• Etelcalcetide Is Effective at All Levels of Severity of Secondary Hyperparathyroidism in Hemodialysis Patients. Kidney international reports Cunningham, J. n., Block, G. A., Chertow, G. M., Cooper, K. n., Evenepoel, P. n., Iles, J. n., Sun, Y. n., Ureña-Torres, P. n., Bushinsky, D. A. 2019; 4 (7): 987–94

  Abstract

  Calcimimetics improve parameters of secondary hyperparathyroidism (sHPT) but are mostly initiated when patients have severe disease, potentially limiting effectiveness. We evaluated the effects of etelcalcetide on lowering intact parathyroid hormone, calcium, and phosphate at different disease severity levels.This analysis examined data from 2 parallel, phase 3, randomized, placebo-controlled, 26-week trials conducted in 1023 adult (≥18 years old) patients with sHPT on maintenance hemodialysis. Etelcalcetide effects by baseline intact parathyroid hormone stratum (<600, 600-1000, and >1000 ng/l) on mean percentage change in intact parathyroid hormone; changes in calcium and phosphate; and achieving serum intact parathyroid hormone ≤300 ng/l, phosphate <1.78 mmol/l, and both combined, were assessed.Etelcalcetide reduced serum intact parathyroid hormone by a similar percentage across baseline strata. A similar proportion achieved >30% intact parathyroid hormone reduction across strata for the etelcalcetide arms. Parathyroid hormone increased modestly in each placebo-group stratum, most prominently in the lowest stratum. Serum calcium and phosphate concentrations decreased across strata in etelcalcetide-treated patients, with the most pronounced reductions in patients with highest baseline parathyroid hormone. However, the proportion of patients achieving parathyroid hormone, phosphate, and both targets was highest in the lowest baseline parathyroid hormone stratum, where etelcalcetide dose requirements were lowest. Etelcalcetide dose requirement was lowest among patients in the lowest intact parathyroid hormone stratum.Etelcalcetide effectively lowered serum intact parathyroid hormone, calcium, and phosphate, irrespective of the severity of secondary hyperparathyroidism. The ability to achieve target goals was greatest, and dose requirement smallest, when etelcalcetide was initiated among patients with the lowest level of disease severity.

  View details for DOI 10.1016/j.ekir.2019.04.010

  View details for PubMedID 31317120

  View details for PubMedCentralID PMC6611952

• Challenges in Assessing the Burden of Hospitalized Heart Failure in End-stage Kidney Disease. Journal of cardiac failure Wang, K. M., Chertow, G. M. 2019

  View details for PubMedID 31063825

• Treatment of Anemia With Darbepoetin Prior to Dialysis Initiation and Clinical Outcomes: Analyses From the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT). American journal of kidney diseases : the official journal of the National Kidney Foundation Mc Causland, F. R., Claggett, B., Burdmann, E. A., Chertow, G. M., Cooper, M. E., Eckardt, K., Ivanovich, P., Levey, A. S., Lewis, E. F., McGill, J. B., McMurray, J. J., Parfrey, P., Parving, H., Remuzzi, G., Singh, A. K., Solomon, S. D., Toto, R. D., Pfeffer, M. A. 2018

  Abstract

  RATIONALE & OBJECTIVE: Evidence from clinical trials to guide patient preparation for maintenance dialysis therapy is limited. Although anemia is associated with mortality and cardiovascular (CV) disease in individuals initiating maintenance dialysis therapy, it is not known if treatment of anemia before dialysis therapy initiation with erythropoiesis-stimulating agents alters outcomes.STUDY DESIGN: Post hoc analysis of a randomized controlled trial.SETTING & PARTICIPANTS: Participants with type 2 diabetes and chronic kidney disease who progressed to dialysis therapy (n=590) in the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT).EXPOSURE: Randomized treatment assignment (darbepoetin vs placebo).OUTCOMES: All-cause mortality, CV mortality, nonfatal myocardial infarction, heart failure, and stroke within the first 180 days of dialysis therapy initiation.ANALYTICAL APPROACH: Proportional hazards regression.RESULTS: Overall, 590 of 4,038 (14.6%) participants initiated dialysis therapy during the trial (n=298 and 292 in the darbepoetin and placebo groups, respectively). Corresponding hemoglobin levels were 11.3±1.6 and 9.5±1.5g/dL (P<0.001). Death from any cause occurred in 31 (10.4%) participants assigned to darbepoetin and 28 (9.6%) assigned to placebo (HR, 1.16; 95% CI, 0.69-1.93), while death from CV causes occurred in 15 (5.0%) and 13 (4.5%) participants, respectively (HR, 1.21; 95% CI, 0.58-1.93). There were no differences in risk for nonfatal myocardial infarction or heart failure. Stroke occurred in 8 (2.8%) participants assigned to darbepoetin and 1 (0.3%) assigned to placebo (HR, 8.6; 95% CI, 1.1-68.7).LIMITATIONS: Post hoc analyses of a subgroup of study participants.CONCLUSIONS: Despite initiating dialysis therapy with a higher hemoglobin level, prior treatment with darbepoetin was not associated with a reduction in mortality, myocardial infarction, or heart failure in the first 180 days, but a higher frequency of stroke was observed. In the absence of more definitive data, this may inform decisions regarding the use of erythropoiesis-stimulating agents to treat mild to moderate anemia in patients with type 2 diabetes and chronic kidney disease nearing dialysis therapy initiation.

  View details for PubMedID 30578152

• PTH, FGF23, and Intensive Blood Pressure Lowering in Chronic Kidney Disease Participants in SPRINT CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Ginsberg, C., Craven, T. E., Chonchol, M. B., Cheung, A. K., Sarnak, M. J., Ambrosius, W. T., Killeen, A. A., Raphael, K. L., Bhatt, U. Y., Chen, J., Chertow, G. M., Freedman, B. I., Oparil, S., Papademetriou, V., Wall, B. M., Wright, C. B., Ix, J. H., Shlipak, M. G., SPRINT Res Grp 2018; 13 (12): 1816–24

  View details for DOI 10.2215/CJN.05390518

  View details for Web of Science ID 000452863400010

• Randomized trial of intravenous iron-induced hypophosphatemia. JCI insight Wolf, M., Chertow, G. M., Macdougall, I. C., Kaper, R., Krop, J., Strauss, W. 2018; 3 (23)

  Abstract

  BACKGROUND: Hypophosphatemia can complicate intravenous iron therapy, but no head-to-head trials compared the effects of newer intravenous iron formulations on risks and mediators of hypophosphatemia.METHODS: In a randomized, double-blinded, controlled trial of adults with iron deficiency anemia from February 2016 to January 2017, we compared rates of hypophosphatemia in response to a single FDA-approved course of ferric carboxymaltose (n = 1,000) or ferumoxytol (n = 997). To investigate pathophysiological mediators of intravenous iron-induced hypophosphatemia, we nested within the parent trial a physiological substudy (ferric carboxymaltose, n = 98; ferumoxytol, n = 87) in which we measured fibroblast growth factor 23 (FGF23), calcitriol, and parathyroid hormone (PTH) at baseline and 1, 2, and 5 weeks later.RESULTS: The incidence of hypophosphatemia was significantly higher in the ferric carboxymaltose versus the ferumoxytol group (<2.0 mg/dl, 50.8% vs. 0.9%; <1.3 mg/dl, 10.0% vs. 0.0%; P < 0.001), and hypophosphatemia persisted through the end of the 5-week study period in 29.1% of ferric carboxymaltose-treated patients versus none of the ferumoxytol-treated patients (P < 0.001). Ferric carboxymaltose, but not ferumoxytol, increased circulating concentrations of biologically active FGF23 (mean within-patient percentage change from baseline to week 2 peak: +302.8 ± 326.2% vs. +10.1 ± 61.0%; P < 0.001), which was significantly associated with contemporaneous hypophosphatemia, renal phosphate wasting, and decreased serum calcitriol and calcium, and increased PTH concentrations.CONCLUSIONS: Ferric carboxymaltose rapidly increases biologically active FGF23 in patients with iron deficiency anemia. Paralleling hereditary and other acquired syndromes of hypophosphatemic rickets/osteomalacia, ferric carboxymaltose-induced FGF23 elevation triggers a pathophysiological cascade of renal phosphate wasting, calcitriol deficiency, and secondary hyperparathyroidism that frequently culminates in hypophosphatemia.TRIAL REGISTRATION: ClinicalTrials.gov, NCT02694978FUNDING. AMAG Pharmaceuticals, Inc.Role of the funding source: This study was supported by AMAG Pharmaceuticals, Inc. The academic investigators designed the clinical trial, performed the analyses, and authored the manuscript with input from the coauthors from AMAG Pharmaceuticals, Inc.

  View details for PubMedID 30518682

• Randomized trial of intravenous iron-induced hypophosphatemia JCI INSIGHT Wolf, M., Chertow, G. M., Macdougall, L. C., Kaper, R., Krop, J., Strauss, W. 2018; 3 (23)

  View details for DOI 10.1172/jci.insight.124486

  View details for Web of Science ID 000452436000011

• Effects of bardoxolone methyl on body weight, waist circumference and glycemic control in obese patients with type 2 diabetes mellitus and stage 4 chronic kidney disease JOURNAL OF DIABETES AND ITS COMPLICATIONS Chertow, G. M., Appel, G. B., Block, G. A., Chin, M. P., Coyne, D. W., Goldsberry, A., Kalantar-Zadeh, K., Meyer, C. J., Molitch, M. E., Pergola, P. E., Raskin, P., Silva, A. L., Spinowitz, B., Sprague, S. M., Rossing, P. 2018; 32 (12): 1113–17

  View details for DOI 10.1016/j.jdiacomp.2018.09.005

  View details for Web of Science ID 000455073400006

• The Terrible Toll of the Kidney Shortage JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY McCormick, F., Held, P. J., Chertow, G. M. 2018; 29 (12): 2775–76

  View details for PubMedID 30420419

• Would government compensation of living kidney donors exploit the poor? An empirical analysis PLOS ONE Held, P. J., McCormick, F., Chertow, G. M., Peters, T. G., Roberts, J. P. 2018; 13 (11)

  View details for DOI 10.1371/journal.pone.0205655

  View details for Web of Science ID 000451755800009

• Payer Type, Race/Ethnicity, and the Timing of Surgical Management of Urinary Stone Disease JOURNAL OF ENDOUROLOGY Brubaker, W. D., Dallas, K. B., Elliott, C. S., Pao, A. C., Chertow, G. M., Leppert, J. T., Conti, S. L. 2019; 33 (2): 152–58

  View details for DOI 10.1089/end.2018.0614

  View details for Web of Science ID 000450757000001

• PTH, FGF23, and Intensive Blood Pressure Lowering in Chronic Kidney Disease Participants in SPRINT. Clinical journal of the American Society of Nephrology : CJASN Ginsberg, C., Craven, T. E., Chonchol, M. B., Cheung, A. K., Sarnak, M. J., Ambrosius, W. T., Killeen, A. A., Raphael, K. L., Bhatt, U. Y., Chen, J., Chertow, G. M., Freedman, B. I., Oparil, S., Papademetriou, V., Wall, B. M., Wright, C. B., Ix, J. H., Shlipak, M. G., SPRINT Research Group 2018

  Abstract

  BACKGROUND AND OBJECTIVES: The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated that intensive BP lowering reduced the risk of cardiovascular disease, but increased eGFR decline. Serum parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF23) concentrations are elevated in CKD and are associated with cardiovascular disease. We evaluated whether intact PTH or intact FGF23 concentrations modify the effects of intensive BP control on cardiovascular events, heart failure, and all-cause mortality in SPRINT participants with CKD.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We measured PTH and FGF23 in 2486 SPRINT participants with eGFR<60 ml/min per 1.73 m2 at baseline. Cox models were used to evaluate whether serum PTH and FGF23 concentrations were associated with cardiovascular events, heart failure, and all-cause mortality, and whether PTH and FGF23 modified the effects of intensive BP control.RESULTS: The mean age of this subcohort was 73 years, 60% were men, and mean eGFR was 46±11 ml/min per 1.73 m2. Median PTH was 48 (interquartile range [IQR], 35-67) pg/ml and FGF23 was 66 (IQR, 52-88) pg/ml. There were 261 composite cardiovascular events, 102 heart failure events, and 179 deaths within the subcohort. The adjusted hazard ratio (HR) per doubling of PTH concentration for cardiovascular events, heart failure, and all-cause mortality were 1.29 (95% confidence interval [95% CI], 1.06 to 1.57), 1.32 (95% CI, 0.96 to 1.83), and 1.04 (95% CI, 0.82 to 1.31), respectively. There were significant interactions between PTH and BP arm for both the cardiovascular (P-interaction=0.01) and heart failure (P-interaction=0.004) end points. Participants with a PTH above the median experienced attenuated benefits of intensive BP control on cardiovascular events (adjusted HR, 1.02; 95% CI, 0.72 to 1.42) compared with participants with a PTH below the median (adjusted HR, 0.67; 95% CI, 0.45 to 1.00). FGF23 was not independently associated with any outcome and did not modify the effects of the intervention.CONCLUSIONS: SPRINT participants with CKD and a high serum PTH received less cardiovascular protection from intensive BP therapy than participants with a lower serum PTH.

  View details for PubMedID 30425104

• Prognostic relevance of visit-to-visit office blood pressure variability in Systolic Blood Pressure Intervention Trial: Same data, different conclusions? JOURNAL OF CLINICAL HYPERTENSION Chang, T. I., Reboussin, D. M., Chertow, G. M., Cheung, A. K., Cushman, W. C., Kostis, W. J., Parati, G., Riessen, E., Shapiro, B., Stergiou, G. S., Tsioufis, K., Whelton, P. K., Whittle, J., Wright, J. T., Papademetriou, V. 2018; 20 (11): 1644–45

  View details for DOI 10.1111/jch.13395

  View details for Web of Science ID 000449560100013

• Prognostic relevance of visit-to-visit office blood pressure variability in Systolic Blood Pressure Intervention Trial: Same data, different conclusions? Journal of clinical hypertension (Greenwich, Conn.) Chang, T. I., Reboussin, D. M., Chertow, G. M., Cheung, A. K., Cushman, W. C., Kostis, W. J., Parati, G., Riessen, E., Shapiro, B., Stergiou, G. S., Tsioufis, K., Whelton, P. K., Whittle, J., Wright, J. T., Papademetriou, V. 2018; 20 (11): 1644–45

  View details for PubMedID 30328272

• Bioelectrical Impedance Analysis Measures and Clinical Outcomes in CKD AMERICAN JOURNAL OF KIDNEY DISEASES Bansal, N., Zelnick, L. R., Himmelfarb, J., Chertow, G. M. 2018; 72 (5): 662–72

  Abstract

  Bioelectrical impedance analysis (BIA) provides a noninvasive assessment of body composition. BIA measures of cell integrity (phase angle) and hydration (vector length) have been associated with mortality among patients receiving dialysis. Whether these measures are associated with clinical outcomes in patients with chronic kidney disease (CKD) is unknown.Observational study.We studied 3,751 participants with CKD in the prospective multicenter Chronic Renal Insufficiency Cohort (CRIC) who had baseline single-frequency BIA performed.Predictors included phase angle and vector length, which were calculated from measurements of resistance and reactance from BIA. We ranked phase angle and vector length into quartiles and compared the 2 narrower quartiles of phase angle and shorter quartiles of vector length with the 2 upper quartiles.Mortality, heart failure, atherosclerotic cardiovascular disease, and progression of CKD (30% decline in estimated glomerular filtration rate or end-stage kidney disease).We tested associations of phase angle and vector length with risks for mortality and progression of CKD using Cox proportional hazard models and the association with heart failure and atherosclerotic cardiovascular disease using Fine and Gray models. All models were adjusted for demographics, comorbid conditions, and kidney function.Mean phase angle and vector length were 6.6°±1.8° and 470 ± 96 Ω/m, respectively. Relative to phase angle ≥ 6.40o, narrower phase angle (<5.59o) was significantly associated with mortality (HR, 1.31; 95% CI, 1.09-1.58). Relative to vector length ≥ 459 Ω/m, shorter vector length (<401 Ω/m) was significantly associated with heart failure (HR, 1.28; 95% CI, 1.01-1.61). Neither measure was associated with atherosclerotic cardiovascular disease or a composite renal end point.Observational study.Adjusted for key confounders, BIA-derived measures of cellular integrity and tissue hydration were significantly associated with death and incident heart failure, respectively.

  View details for PubMedID 29885923

• International Study of Comparative Health Effectiveness with Medical and Invasive Approaches-Chronic Kidney Disease (ISCHEMIA-CKD): Rationale and design AMERICAN HEART JOURNAL Bangalore, S., Maron, D. J., Fleg, J. L., O'Brien, S. M., Herzog, C. A., Stone, G. W., Mark, D. B., Spertus, J. A., Alexander, K. P., Sidhu, M. S., Chertow, G. M., Boden, W. E., Hochman, J. S., ISCHEMIA-CKD Res Grp 2018; 205: 42–52

  Abstract

  Patients with chronic kidney disease (CKD) and stable ischemic heart disease are at markedly increased risk of cardiovascular events. Prior trials comparing a strategy of optimal medical therapy (OMT) with or without revascularization have largely excluded patients with advanced CKD. Whether a routine invasive approach when compared with a conservative strategy is beneficial in such patients is unknown.ISCHEMIA-CKD is a National Heart, Lung, and Blood Institute-funded randomized trial designed to determine the comparative effectiveness of an initial invasive strategy (cardiac catheterization and optimal revascularization [percutaneous coronary intervention or coronary artery bypass graft surgery, if suitable] plus OMT) versus a conservative strategy (OMT alone, with cardiac catheterization and revascularization [percutaneous coronary intervention or coronary artery bypass graft surgery, if suitable] reserved for failure of OMT) on long-term clinical outcomes in 777 patients with advanced CKD (defined as those with estimated glomerular filtration rate <30 mL/min/1.73m2 or on dialysis) and moderate or severe ischemia on stress testing. Participants were randomized in a 1:1 fashion to the invasive or a conservative strategy. The primary end point is a composite of death or nonfatal myocardial infarction. Major secondary endpoints are a composite of death, nonfatal myocardial infarction, hospitalization for unstable angina, hospitalization for heart failure, or resuscitated cardiac arrest; angina control; and disease-specific quality of life. Safety outcomes such as initiation of maintenance dialysis and a composite of initiation of maintenance dialysis or death will be reported. The trial is projected to have 80% power to detect a 22% to 24% reduction in the primary composite end point with the invasive strategy when compared with the conservative strategy.ISCHEMIA-CKD will determine whether an initial invasive management strategy improves clinical outcomes when added to OMT in patients with advanced CKD and stable ischemic heart disease.

  View details for PubMedID 30172098

• Effect of ferric citrate on serum phosphate and fibroblast growth factor 23 among patients with nondialysis-dependent chronic kidney disease: path analyses. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association Block, G. A., Pergola, P. E., Fishbane, S., Martins, J. G., LeWinter, R. D., Uhlig, K., Neylan, J. F., Chertow, G. M. 2018

  Abstract

  Background: Among patients with nondialysis-dependent chronic kidney disease (NDD-CKD) and iron-deficiency anemia (IDA), ferric citrate increases hemoglobin and iron parameters and reduces serum phosphate and fibroblast growth factor 23 (FGF23), a key phosphate-regulating hormone. We conducted post hoc analyses of a phase 3 trial to explore associations between iron replacement, serum phosphate changes and FGF23 regulation.Methods: We employed multivariable regression and longitudinal mixed-effects models to identify and confirm, respectively, whether baseline demographic and laboratory variables were associated with ferric citrate-induced changes in serum phosphate or FGF23 concentrations. We employed path analyses to determine whether changes in FGF23 concentrations were mediated via changes in serum phosphate and/or transferrin saturation (TSAT).Results: We analyzed a total of 117 and 115 ferric citrate-treated and placebo-treated patients, respectively. At 16weeks, ferric citrate significantly reduced serum phosphate versus placebo (P=0.006) only among patients with elevated baseline serum phosphate (≥4.5mg/dL) and did not reduce serum phosphate among patients with baseline serum phosphate within the population reference range. Ferric citrate reduced intact FGF23 and C-terminal FGF23 partially via changes in TSAT (for C-terminal FGF23) and serum phosphate (for intact FGF23) and partially via unknown/unmeasured mechanisms.Conclusions: Ferric citrate reduced serum FGF23 concentrations (partially via effects on serum phosphate and iron balance) and did not reduce serum phosphate among patients with baseline serum phosphate concentrations within the population reference range.

  View details for PubMedID 30380116

• Payer Type, Race/Ethnicity, and the Timing of Surgical Management of Urinary Stone Disease. Journal of endourology Brubaker, W. D., Dallas, K., Elliott, C. S., Pao, A. C., Chertow, G., Leppert, J. T., Conti, S. L. 2018

  Abstract

  PURPOSE: Surgery for upper tract urinary stone disease is often reserved for symptomatic patients and those whose stone does not spontaneously pass after a trial of passage. Our objective was to determine whether payer type or race/ethnicity is associated with the timeliness of kidney stone surgery.MATERIALS AND METHODS: Population-based cohort study using the California Office of Statewide Health Planning and Development dataset from 2010 to 2012. We identified patients who were discharged from an emergency department with a stone diagnosis and who subsequently underwent a stone surgery. Primary outcome was time from emergency department discharge to urinary stone surgery in days. Secondary outcomes included potential harms resulting from delayed stone surgery.RESULTS: Over the study period, 15,193 patients met the inclusion criteria. Median time from emergency department discharge to stone surgery was 28 days. On multivariable analysis patients with Medicaid, Medicare, and self-pay coverage experienced adjusted mean increases of 46%, 42%, and 60% in time to surgery, respectively, when compared with private insurance. Additionally, patients of Black and Hispanic race/ethnicity, respectively experienced adjusted mean increases of 36% and 20% in time to surgery relative to their white counterparts. Prior to a stone surgery, underinsured patients were more likely to revisit an emergency department three or more times, undergo two or more CT imaging studies, and receive upper urinary tract decompression.CONCLUSIONS: Underinsured and minority patients are more likely to experience a longer time to stone surgery after presenting to an emergency department and experience potential harm from this delay.

  View details for PubMedID 30343603

• Market Competition and Health Outcomes in Heniodialysis HEALTH SERVICES RESEARCH Erickson, K. F., Zheng, Y., Ho, V., Winkelmayer, W. C., Bhattacharya, J., Chertow, G. M. 2018; 53 (5): 3680–3703

  Abstract

  To examine whether market competition is associated with improved health outcomes in hemodialysis.Secondary analysis of data from a national dialysis registry between 2001 and 2011.We conducted one- and two-part linear regression models, using each hospital service area (HSA) as its own control, to examine the independent associations among market concentration and health outcomes.We selected cohorts of patients receiving in-center hemodialysis in the United States at the start of each calendar year. We used information about dialysis facility ownership and the location where patients received dialysis to measure an index of market concentration-the Hirschman-Herfindahl Index (HHI)-for HSA and year, which ranges from near zero (perfect competition) to one (monopoly).An average reduction in HHI by 0.2 (one standard deviation in 2011) was associated with 2.9 fewer hospitalizations per 100 patient-years (95 percent CI, 0.4 to 5.4). If these findings were generalized to the entire in-center hemodialysis population, this would translate to 8,100 (95 percent CI 1,200 to 15,000) fewer hospitalizations in 2011. There was no association between change in market competition and mortality.Market competition in dialysis may lead to improved health outcomes.

  View details for PubMedID 29468675

  View details for PubMedCentralID PMC6153181

• Patient-Reported Experiences of Dialysis Care Within a National Pay-for-Performance System JAMA INTERNAL MEDICINE Brady, B. M., Zhao, B., Niu, J., Winkelmayer, W. C., Milstein, A., Chertow, G. M., Erickson, K. F. 2018; 178 (10): 1358–67

  View details for DOI 10.1001/jamainternmed.2018.3756

  View details for Web of Science ID 000446453500012

• Small increases in serum magnesium levels by dapagliflozin and normalisation of hypomagnesaemia in patients with type 2 diabetes Toto, R., Goldenberg, R., Chertow, G. M., Cain, V., Stefansson, B. V., Sjostrom, C. D., Sartipy, P. SPRINGER. 2018: S316

  View details for Web of Science ID 000443556004017

• Pulse wave velocity and central aortic pressure in systolic blood pressure intervention trial participants PLOS ONE Supiano, M. A., Lovato, L., Ambrosius, W. T., Bates, J., Beddhu, S., Drawz, P., Dwyer, J. P., Hamburg, N. M., Kitzman, D., Lash, J., Lustigova, E., Miracle, C. M., Oparil, S., Raj, D. S., Weiner, D. E., Taylor, A., Vita, J. A., Yunis, R., Chertow, G. M., Chonchol, M. 2018; 13 (9): e0203305

  Abstract

  Arterial stiffness, typically assessed as the aortic pulse wave velocity (PWV), and central blood pressure levels may be indicators of cardiovascular disease (CVD) risk. This ancillary study to the Systolic Blood Pressure Intervention Trial (SPRINT) obtained baseline assessments (at randomization) of PWV and central systolic blood pressure (C-SBP) to: 1) characterize these vascular measurements in the SPRINT cohort, and 2) test the hypotheses that PWV and C-SBP are associated with glucose homeostasis and markers of chronic kidney disease (CKD). The SphygmoCor® CPV device was used to assess carotid-femoral PWV and its pulse wave analysis study protocol was used to obtain C-SBP. Valid results were obtained from 652 participants. Mean (±SD) PWV and C-SBP for the SPRINT cohort were 10.7 ± 2.7 m/s and 132.0 ± 17.9 mm Hg respectively. Linear regression analyses for PWV and C-SBP results adjusted for age, sex, and race/ethnicity in relation to several markers of glucose homeostasis and CKD did not identify any significant associations with the exception of a marginally statistically significant and modest association between PWV and urine albumin-to-creatinine ratio (linear regression estimate ± SE, 0.001 ± 0.0006; P-value 0.046). In a subset of SPRINT participants, PWV was significantly higher than in prior studies of normotensive persons, as expected. For older age groups in the SPRINT cohort (age > 60 years), PWV was compared with a reference population of hypertensive individuals. There were no compelling associations noted between PWV or C-SBP and markers of glucose homeostasis or CKD.NCT01206062.

  View details for PubMedID 30256784

• Effects of Intensive Systolic Blood Pressure Lowering on Cardiovascular Events and Mortality in Patients With Type 2 Diabetes Mellitus on Standard Glycemic Control and in Those Without Diabetes Mellitus: Reconciling Results From ACCORD BP and SPRINT JOURNAL OF THE AMERICAN HEART ASSOCIATION Beddhu, S., Chertow, G. M., Greene, T., Whelton, P. K., Ambrosius, W. T., Cheung, A. K., Cutler, J., Fine, L., Boucher, R., Wei, G., Zhang, C., Kramer, H., Bress, A. P., Kimmel, P. L., Oparil, S., Lewis, C. E., Rahman, M., Cushman, W. C. 2018; 7 (18)

  View details for DOI 10.1161/JAHA.118.009326

  View details for Web of Science ID 000452805400017

• Effects of Intensive Systolic Blood Pressure Lowering on Cardiovascular Events and Mortality in Patients With Type 2 Diabetes Mellitus on Standard Glycemic Control and in Those Without Diabetes Mellitus: Reconciling Results From ACCORD BP and SPRINT. Journal of the American Heart Association Beddhu, S., Chertow, G. M., Greene, T., Whelton, P. K., Ambrosius, W. T., Cheung, A. K., Cutler, J., Fine, L., Boucher, R., Wei, G., Zhang, C., Kramer, H., Bress, A. P., Kimmel, P. L., Oparil, S., Lewis, C. E., Rahman, M., Cushman, W. C. 2018; 7 (18): e009326

  Abstract

  Background Intensive systolic blood pressure ( SBP ) lowering significantly reduced cardiovascular disease ( CVD ) events in SPRINT (Systolic Blood Pressure Intervention Trial) but not in ACCORD BP (Action to Control Cardiovascular Risk in Diabetes Blood Pressure). Methods and Results SPRINT tested the effects of intensive (<120mmHg) versus standard (<140mmHg) SBP goals on CVD events and all-cause mortality. Using 2*2 factorial design, ACCORD BP tested the same SBP intervention in addition to an intensive versus standard glycemia intervention. We compared the effects of intensive SBP lowering on the composite CVD end point and all-cause mortality in SPRINT with its effects within each of the glycemia arms in ACCORD BP . Intensive SBP lowering decreased the hazard of the composite CVD end point similarly in SPRINT (hazard ratio: 0.75; 95% confidence interval, 0.64-0.89) and in the ACCORD BP standard glycemia arm (hazard ratio: 0.77; 95% confidence interval, 0.63-0.95; interaction P=0.87). However, the effect of intensive SBP lowering on the composite CVD end point in the ACCORD BP intensive glycemia arm (hazard ratio: 1.04; 95% confidence interval, 0.83-1.29) was significantly different from SPRINT (interaction P=0.023). Patterns were similar for all-cause mortality. Conclusions The effects of intensive SBP control on CVD events and all-cause mortality were similar in patients without diabetes mellitus and in those with diabetes mellitus on standard glycemic control. An interaction between intensive SBP lowering and intensive glycemic control may have masked beneficial effects of intensive SBP lowering in ACCORD BP . Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifiers: NCT 01206062, NCT 00000620.

  View details for PubMedID 30371182

• Effects of bardoxolone methyl on body weight, waist circumference and glycemic control in obese patients with type 2 diabetes mellitus and stage 4 chronic kidney disease. Journal of diabetes and its complications Chertow, G. M., Appel, G. B., Block, G. A., Chin, M. P., Coyne, D. W., Goldsberry, A., Kalantar-Zadeh, K., Meyer, C. J., Molitch, M. E., Pergola, P. E., Raskin, P., Silva, A. L., Spinowitz, B., Sprague, S. M., Rossing, P. 2018

  Abstract

  AIMS: Obesity is associated with progression of chronic kidney disease (CKD). Treatment with bardoxolone methyl in a multinational phase 3 trial, Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes (BEACON), resulted in increases in estimated glomerular filtration rate (eGFR) with concurrent reductions in body weight. We performed post-hoc analyses to further characterize reductions in body weight with bardoxolone methyl.METHODS: Eligible patients with type 2 diabetes (T2DM) and CKD stage 4 (eGFR 15 to <30 mL/min/1.73 m2) were randomized 1:1 to receive once-daily oral dose of bardoxolone methyl (20 mg) or placebo.RESULTS: BEACON enrolled 2185 patients. Patients randomized to bardoxolone methyl experienced significant reductions in body weight from baseline relative to patients randomized to placebo (-5.7 kg; 95% CI: -6.0 to -5.3 kg; p < 0.001). In patients randomized to bardoxolone methyl, rate and magnitude of body weight loss were proportional to baseline BMI. Bardoxolone methyl resulted in significant reductions in waist circumference and improved glycemic control.CONCLUSIONS: Bardoxolone methyl resulted in significant weight loss in a generally obese patient population with T2DM and stage 4 CKD, with the magnitude and rate dependent on baseline BMI.

  View details for PubMedID 30318163

• Patient-Reported Experiences of Dialysis Care Within a National Pay-for-Performance System. JAMA internal medicine Brady, B. M., Zhao, B., Niu, J., Winkelmayer, W. C., Milstein, A., Chertow, G. M., Erickson, K. F. 2018

  Abstract

  Importance: Medicare's End-Stage Renal Disease Quality Incentive Program incorporates measures of perceived value into reimbursement calculations. In 2016, patient experience became a clinical measure in the Quality Incentive Program scoring system. Dialysis facility performance in patient experience measures has not been studied at the national level to date.Objective: To examine associations among dialysis facility performance with patient experience measures and patient, facility, and geographic characteristics.Design: In this cross-sectional analysis, patients from a national end-stage renal disease registry receiving in-center hemodialysis in the United States on December 31, 2014, were linked with dialysis facility scores on the In-Center Hemodialysis Consumer Assessment of Healthcare Providers and Systems (ICH-CAHPS) survey. Of 4977 US dialysis facilities, 2939 (59.1%) reported ICH-CAHPS scores from April 8, 2015, through January 11, 2016. Multivariable linear regression models with geographic random effects were used to examine associations of facility ICH-CAHPS scores with patient, dialysis facility, and geographic characteristics and to identify the amount of total between-facility variation in patient experience scores explained by these categories. Data were analyzed from September 15, 2017, through June 1, 2018.Exposures: Dialysis facility, geographic characteristic, and 10% change in patient characteristics.Main Outcomes and Measures: Dialysis facility ICH-CAHPS scores and the total between-facility variation explained by different categories of characteristics.Results: Of the 2939 facilities included in the analysis, adjusted mean ICH-CAHPS scores were 2.6 percentage points (95% CI, 1.5-3.7) lower in for-profit facilities, 1.6 percentage points (95% CI, 0.9-2.2) lower in facilities owned by large dialysis organizations, and 2.3 percentage points (95% CI, 0.5-4.2) lower in free-standing facilities compared with their counterparts. More nurses per patient was associated with 0.2 percentage points (95% CI, 0.03-0.3) higher scores; a privately insured patient population was associated with 1.2 percentage points (95% CI, 0.2-2.2) higher scores. Facilities with higher proportions of black patients had 0.95 percentage points (95% CI, 0.78-1.12) lower scores; more Native American patients, 1.00 percentage point (95% CI, 0.39-1.60) lower facility scores. Geographic location and dialysis facility characteristics explained larger proportions of the overall between-facility variation in ICH-CAHPS scores than did patient characteristics.Conclusions and Relevance: This study suggests that for-profit operation, free-standing status, and large dialysis organization designation were associated with less favorable patient-reported experiences of care. Patient experience scores varied geographically, and black and Native American populations reported less favorable experiences. The study findings suggest that perceived quality of care delivered in these settings are of concern, and that there may be opportunities for improved implementation of patient experience surveys as is highlighted.

  View details for PubMedID 30208398

• Acute Kidney Injury Due to Diarrheal Illness Requiring Hospitalization: Data from the National Inpatient Sample JOURNAL OF GENERAL INTERNAL MEDICINE Bradshaw, C., Zheng, Y., Silver, S. A., Chertow, G. M., Long, J., Anand, S. 2018; 33 (9): 1520–27

  View details for DOI 10.1007/s11606-018-4531-6

  View details for Web of Science ID 000442642300024

• A response by Strauss et al. to "a comment on the comparative safety of intravenous ferumoxytol versus ferric carboxymaltose in iron deficiency anemia" AMERICAN JOURNAL OF HEMATOLOGY Strauss, W. E., Adkinson, N., Macdougall, I. C., Auerbach, M., Kaper, R. F., Chertow, G. M., Krop, J. S. 2018; 93 (9): E232–E233

  View details for PubMedID 30016554

• Risk-benefit profile of intensive blood pressure treatment reply LANCET DIABETES & ENDOCRINOLOGY Beddhu, S., Greene, T., Boucher, R., Cushman, W. C., Wei, G., Cheung, A. K., Whelton, P. K., Chertow, G. M. 2018; 6 (8): 602

  View details for PubMedID 30053986

• Low testosterone is associated with frailty, muscle wasting and physical dysfunction among men receiving hemodialysis: a longitudinal analysis. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association Chiang, J. M., Kaysen, G. A., Segal, M., Chertow, G. M., Delgado, C., Johansen, K. L. 2018

  Abstract

  Background: Despite the high prevalence of frailty among patients receiving hemodialysis, few preventable or treatable contributing causes have been identified. Hypogonadism is also common in this population and low serum testosterone concentrations share several clinical phenotypes with frailty. We hypothesized that low serum testosterone concentrations would be associated with frailty and several of its individual components.Methods: We used data from 440 men from A Cohort Study To Investigate the Value of Exercise in ESRD/Analysis Designed to Investigate the Paradox of Obesity and Survival in ESRD, a longitudinal study that recruited participants from 14 dialysis centers in Atlanta, GA and the San Francisco, CA Bay Area from 2009 to 2011. We assessed frailty using the Fried Frailty Phenotype. We examined the association between free testosterone (as a continuous and dichotomous variable) and frailty, individual frailty components, sarcopenia, lower extremity function and muscle mass estimation by creatinine and body impedance spectroscopy over 12months using generalized estimating equations.Results: The mean age was 56.1±14.2 years and 27% were white. A 50% lower concentration of free testosterone was associated with 1.40-fold higher odds of being frail [95% confidence interval (CI) 1.05-1.53] and 1.40-fold higher odds of becoming frail over 12months (95% CI 1.07-1.73). This association was mainly due to an association with two components of frailty: grip strength and gait speed. In addition, 50% lower free testosterone concentration was associated with a 1.55-fold higher odds of having sarcopenia (95% CI 1.09-2.02) and 1.72-fold higher odds for developing sarcopenia (95% CI 1.13-2.33) as well as with lower muscle mass and a decrease in muscle mass over 12months as estimated by serum creatinine and by bioelectrical impedance spectroscopy.Conclusion: Serum free testosterone concentration was associated with frailty, physical function, sarcopenia and muscle mass as well as with changes in these outcomes over 12months. Testosterone replacement may be a feasible therapeutic target toward prevention of frailty, although clinical trials are needed to test this possibility.

  View details for PubMedID 30085235

• Dialysis versus Medical Management at Different Ages and Levels of Kidney Function in Veterans with Advanced CKD JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Tamura, M., Desai, M., Kapphahn, K. I., Thomas, I., Asch, S. M., Chertow, G. M. 2018; 29 (8): 2169–77

  View details for DOI 10.1681/ASN.2017121273

  View details for Web of Science ID 000445764500017

• Use of Estimating Equations for Dosing Antimicrobials in Patients with Acute Kidney Injury Not Receiving Renal Replacement Therapy JOURNAL OF CLINICAL MEDICINE Awdishu, L., Connor, A., Bouchard, J., Macedo, E., Chertow, G. M., Mehta, R. L. 2018; 7 (8)

  Abstract

  Acute kidney injury (AKI) can potentially lead to the accumulation of antimicrobial drugs with significant renal clearance. Drug dosing adjustments are commonly made using the Cockcroft-Gault estimate of creatinine clearance (CLcr). The Modified Jelliffe equation is significantly better at estimating kidney function than the Cockcroft-Gault equation in the setting of AKI. The objective of this study is to assess the degree of antimicrobial dosing discordance using different glomerular filtration rate (GFR) estimating equations. This is a retrospective evaluation of antimicrobial dosing using different estimating equations for kidney function in AKI and comparison to Cockcroft-Gault estimation as a reference. Considering the Cockcroft-Gault estimate as the criterion standard, antimicrobials were appropriately adjusted at most 80.7% of the time. On average, kidney function changed by 30 mL/min over the course of an AKI episode. The median clearance at the peak serum creatinine was 27.4 (9.3⁻66.3) mL/min for Cockcroft Gault, 19.8 (9.8⁻47.0) mL/min/1.73 m² for MDRD and 20.5 (4.9⁻49.6) mL/min for the Modified Jelliffe equations. The discordance rate for antimicrobial dosing ranged from a minimum of 8.6% to a maximum of 16.4%. In the event of discordance, the dose administered was supra-therapeutic 100% of the time using the Modified Jelliffe equation. Use of estimating equations other than the Cockcroft Gault equation may significantly alter dosing of antimicrobials in AKI.

  View details for PubMedID 30103503

• Mandating Staffing Ratios in Hemodialysis Facilities California SB 349 and Unintended Consequences CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Rastogi, A., Chertow, G. M. 2018; 13 (7): 1110–12

  View details for PubMedID 29875201

  View details for PubMedCentralID PMC6032581

• Angiotensin-related genetic determinants of cardiovascular disease in patients undergoing hemodialysis. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association Moe, S. M., Long, J., Schwantes-An, T. L., Decker, B. S., Wetherill, L., Edenberg, H. J., Xuei, X., Vatta, M., Foroud, T. M., Chertow, G. M. 2018

  Abstract

  Background: Cardiovascular mortality in patients receiving dialysis remains unacceptably high, with unexplained ancestry differences suggesting a genetic component.Methods: We analyzed DNA samples from 37% of subjects enrolled in the EValuation Of Cinacalcet Hydrochloride (HCl) Therapy to Lower CardioVascular Events (EVOLVE) trial, a randomized trial conducted in patients receiving hemodialysis with secondary hyperparathyroidism, comparing cinacalcet to placebo on a background of usual care. DNA was analyzed for single-nucleotide polymorphisms (SNPs) in the genes encoding the angiotensin-converting enzyme receptor type I (AGTR1) and angiotensin-converting enzyme (ACE). Survival analyses were conducted separately in European Ancestry (EA) and African Ancestry (AfAn) due to known differences in cardiovascular events, minor alleles for the same variant and the frequency of minor alleles. Our primary determination was a meta-analysis across both races.Results: Meta-analysis showed significant associations between rs5186 in AGTR1 and increased rates by 25-34% for the primary endpoint (composite of death or nonfatal myocardial infarction, hospitalization for unstable angina, heart failure or peripheral vascular event), all-cause mortality, cardiovascular mortality and heart failure; all P<0.001. Three correlated SNPs in ACE were associated with lower rates of sudden cardiac death (SCD) in EA samples. One ACE SNP, rs4318, only found in the AfAn samples, was associated with a lower rate of SCD in the AfAn samples.Conclusions: The C allele in rs5186 in AGTR1 was associated with higher rates of death and major cardiovascular events in a meta-analysis of EA and AfAn patients with end-stage kidney disease. SNPs in ACE were associated with SCD.

  View details for PubMedID 29982608

• Intensive systolic blood pressure control and incident chronic kidney disease in people with and without diabetes mellitus: secondary analyses of two randomised controlled trials LANCET DIABETES & ENDOCRINOLOGY Beddhu, S., Greene, T., Boucher, R., Cushman, W. C., Wei, G., Stoddard, G., Ix, J. H., Chonchol, M., Kramer, H., Cheung, A. K., Kimmel, P. L., Whelton, P. K., Chertow, G. M. 2018; 6 (7): 555–63

  Abstract

  Guidelines, including the 2017 American College of Cardiology and American Heart Association blood pressure guideline, recommend tighter control of systolic blood pressure in people with type 2 diabetes. However, it is unclear whether intensive lowering of systolic blood pressure increases the incidence of chronic kidney disease in this population. We aimed to compare the effects of intensive systolic blood pressure control on incident chronic kidney disease in people with and without type 2 diabetes.The Systolic Blood Pressure Intervention Trial (SPRINT) tested the effects of a systolic blood pressure goal of less than 120 mm Hg (intensive intervention) versus a goal of less than 140 mm Hg (standard intervention) in people without diabetes. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) blood pressure trial tested a similar systolic blood pressure intervention in people with type 2 diabetes. Our study is a secondary analysis of limited access datasets from SPRINT and the ACCORD trial obtained from the National Institutes of Health. In participants without chronic kidney disease at baseline (n=4311 in the ACCORD trial; n=6715 in SPRINT), we related systolic blood pressure interventions (intensive vs standard) to incident chronic kidney disease (defined as >30% decrease in estimated glomerular filtration rate [eGFR] to <60 mL/min per 1·73 m2). These trials are registered with ClinicalTrials.gov, numbers NCT01206062 (SPRINT) and NCT00000620 (ACCORD trial).The average difference in systolic blood pressure between intensive and standard interventions was 13·9 mm Hg (95% CI 13·4-14·4) in the ACCORD trial and 15·2 mm Hg (14·8-15·6) in SPRINT. At 3 years, the cumulative incidence of chronic kidney disease in the ACCORD trial was 10·0% (95% CI 8·8-11·4) with the intensive intervention and 4·1% (3·3-5·1) with the standard intervention (absolute risk difference 5·9%, 95% CI 4·3-7·5). Corresponding values in SPRINT were 3·5% (95% CI 2·9-4·2) and 1·0% (0·7-1·4; absolute risk difference 2·5%, 95% CI 1·8-3·2). The absolute risk difference was significantly higher in the ACCORD trial than in SPRINT (p=0·0001 for interaction).Intensive lowering of systolic blood pressure increased the risk of incident chronic kidney disease in people with and without type 2 diabetes. However, the absolute risk of incident chronic kidney disease was higher in people with type 2 diabetes. Our findings suggest the need for vigilance in monitoring kidney function during intensive antihypertensive drug treatment, particularly in adults with diabetes. Long-term studies are needed to understand the clinical implications of antihypertensive treatment-related reductions in eGFR.National Institutes of Health.

  View details for PubMedID 29685860

• Unplanned Emergency Department Visits and Hospital Admissions Following Ureteroscopy: Do Ureteral Stents Make a Difference? UROLOGY Mittakanti, H. R., Conti, S. L., Pao, A. C., Chertow, G. M., Liao, J. C., Leppert, J. T., Elliott, C. S. 2018; 117: 44–49

  View details for DOI 10.1016/j.urology.2018.03.019

  View details for Web of Science ID 000437729900013

• Effects of calcimimetics on long-term outcomes in dialysis patients: literature review and Bayesian meta-analysis JOURNAL OF COMPARATIVE EFFECTIVENESS RESEARCH Lozano-Ortega, G., Waser, N., Bensink, M. E., Goring, S., Bennett, H., Block, G. A., Chertow, G. M., Trotman, M., Cooper, K., Levy, A. R., Belozeroff, V. 2018; 7 (7): 693–707

  Abstract

  Randomized controlled trials (RCTs) with clinical outcomes are considered the gold standard for regulatory approval. However, by design they are only able to answer a small number of clinical questions. Other high-quality studies are required for clinical decision-making. The EVOLVE was the largest RCT, evaluating the effects of cinacalcet on clinical outcomes among adult patients receiving maintenance dialysis suffering from secondary hyperparathyroidism. While the EVOLVE trial did not reach its primary end point, imbalance in subjects' age at randomization and discontinuation rates are two of the reasons that the lack of mortality benefit is in question. We undertook a systematic literature review and Bayesian meta-analysis combining randomized and observational studies on the estimated effects of the oral calcimimetic cinacalcet on clinical outcomes including all-cause mortality, cardiovascular-related mortality, hospitalization for cardiovascular events, fracture and parathyroidectomy among patients on maintenance dialysis.Data sources included MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials databases. RCTs and observational studies were included. Data extraction was completed by two authors independently and in duplicate determined the methodological quality of the studies and extracted data.Of 564 unique citations identified, 16 studies were included: six observational studies and ten RCTs. Four high-quality studies (two observational and two RCTs) were deemed suitable for meta-analysis. Results indicated a statistically significant reduction in the risk of death associated with cinacalcet (hazard ratio: 0.83; 95% credible interval: 0.78-0.89).The results of this meta-analysis indicate that treatment of secondary hyperparathyroidism with calcimimetic therapy may in fact reduce mortality among patients receiving maintenance dialysis. This finding provides justification for a well-designed and adequately powered randomized trial to definitively address the question.

  View details for PubMedID 29762046

• Benefits and risks of intensive blood-pressure lowering in advanced chronic kidney disease JOURNAL OF INTERNAL MEDICINE Cheung, A. K., Chertow, G. M., Greene, T., Kimmel, P. L., Rahman, M., Reboussin, D., Rocco, M., SPRINT Res Grop 2018; 284 (1): 106–7

  View details for PubMedID 29385288

• Acute Kidney Injury Due to Diarrheal Illness Requiring Hospitalization: Data from the National Inpatient Sample. Journal of general internal medicine Bradshaw, C., Zheng, Y., Silver, S. A., Chertow, G. M., Long, J., Anand, S. 2018

  Abstract

  BACKGROUND: Diarrheal illness is a major reason for hospitalization, but data on consequent acute kidney injury (AKI) are sparse.OBJECTIVE: To determine the incidence of AKI in infectious and non-infectious diarrheal illness requiring hospitalization and to identify correlates and outcomes of diarrhea-associated AKI.DESIGN: Using data from the 2012 National Inpatient Sample (NIS), we created a cohort of patients with a primary diagnosis of diarrheal illness. Diarrheal illness, disease correlates, and AKI were defined by ICD-9 diagnosis codes. We used logistic regression with backward variable selection to determine factors independently associated with AKI in infectious and non-infectious diarrheal illness, as well as to determine the association of AKI with in-hospital mortality. We used generalized linear models to assess differences in length of stay and costs of hospitalization.MAIN MEASURES: The primary outcome was AKI in hospitalized diarrheal illness. Secondary outcomes were in-hospital mortality, length of stay, and cost of hospitalization associated with AKI.KEY RESULTS: One in ten adults hospitalized with diarrheal illness experienced AKI, with higher incidence rates in older adults. Chronic kidney disease (CKD) and hypertension were associated with increased odds of AKI (all diarrhea OR 4.81, 95% CI 4.52 to 5.12 and OR 1.33, 95% CI 1.27 to 1.40, respectively). AKI in diarrheal illness was associated with substantial increase in mortality (OR 5.05, 95% CI 4.47 to 5.72), length of stay (mean increase 1.7days [95% CI 1.6 to 1.8]), and cost of hospitalization (mean increase $4411 [95% CI 4023 to 4800]).CONCLUSION: Acute kidney injury is common and consequential among patients hospitalized for diarrheal illness. Persons with CKD and hypertension are the most susceptible, possibly due to diminished renal reserve and exacerbating effects of treatment with diuretics and renin-angiotensin-aldosterone system blockers. Proactive management of these unique pharmacologic and physiologic factors is necessary to prevent AKI in this vulnerable population.

  View details for PubMedID 29916026

• Response by Beddhu et al to Letters Regarding Article, "Influence of Baseline Diastolic Blood Pressure on Effects of Intensive Compared With Standard Blood Pressure Control" CIRCULATION Beddhu, S., Chertow, G. M., Cheung, A. K., Cushman, W. C., Greene, T., Wei, G., Boucher, R., Whelton, P. K., SPRINT Res Grp 2018; 137 (24): 2668–69

  View details for PubMedID 29891628

  View details for PubMedCentralID PMC6003621

• Hemoglobin response to ferric citrate in patients with nondialysis-dependent chronic kidney disease and iron deficiency anemia AMERICAN JOURNAL OF HEMATOLOGY Pergola, P. E., Fishbane, S., LeWinter, R. D., Neylan, J. F., Uhlig, K., Block, G. A., Chertow, G. M. 2018; 93 (6): E154–E156

  View details for PubMedID 29575100

• Hyperuricemia, Acute and Chronic Kidney Disease, Hypertension, and Cardiovascular Disease: Report of a Scientific Workshop Organized by the National Kidney Foundation AMERICAN JOURNAL OF KIDNEY DISEASES Johnson, R. J., Bakris, G. L., Borghi, C., Chonchol, M. B., Feldman, D., Lanaspa, M. A., Merriman, T. R., Moe, O. W., Mount, D. B., Sanchez Lozada, L., Stahl, E., Weiner, D. E., Chertow, G. M. 2018; 71 (6): 851–65

  Abstract

  Urate is a cause of gout, kidney stones, and acute kidney injury from tumor lysis syndrome, but its relationship to kidney disease, cardiovascular disease, and diabetes remains controversial. A scientific workshop organized by the National Kidney Foundation was held in September 2016 to review current evidence. Cell culture studies and animal models suggest that elevated serum urate concentrations can contribute to kidney disease, hypertension, and metabolic syndrome. Epidemiologic evidence also supports elevated serum urate concentrations as a risk factor for the development of kidney disease, hypertension, and diabetes, but differences in methodologies and inpacts on serum urate concentrations by even subtle changes in kidney function render conclusions uncertain. Mendelian randomization studies generally do not support a causal role of serum urate in kidney disease, hypertension, or diabetes, although interpretation is complicated by nonhomogeneous populations, a failure to consider environmental interactions, and a lack of understanding of how the genetic polymorphisms affect biological mechanisms related to urate. Although several small clinical trials suggest benefits of urate-lowering therapies on kidney function, blood pressure, and insulin resistance, others have been negative, with many trials having design limitations and insufficient power. Thus, whether uric acid has a causal role in kidney and cardiovascular diseases requires further study.

  View details for PubMedID 29496260

• Incidence, predictors and therapeutic consequences of hypocalcemia in patients treated with cinacalcet in the EVOLVE trial KIDNEY INTERNATIONAL Floege, J., Tsirtsonis, K., Iles, J., Drueke, T. B., Chertow, G. M., Parfrey, P. 2018; 93 (6): 1475–82

  Abstract

  The calcimimetic cinacalcet is used to treat secondary hyperparathyroidism in patients receiving dialysis, and asymptomatic hypocalcemia is often observed following its initiation. Here we investigated the incidence, predictors and therapeutic consequences of hypocalcemia by a post hoc analysis of the randomized, double-blind, placebo-controlled EValuation Of Cinacalcet Hydrochloride Therapy to Lower CardioVascular Events (EVOLVE) trial. Hypocalcemia was classified as mild (total serum calcium 8.0-8.39 mg/dL), moderate (7.5-7.99 mg/dL) or severe (under 7.5 mg/dL). At least one episode of hypocalcemia developed within 16 weeks after the first administered dose among 58.3% of 1938 patients randomized to cinacalcet versus 14.9% of 1923 patients randomized to placebo. Hypocalcemia in the cinacalcet group was severe in 18.4% of the patients versus 4.4% in the placebo group. Severe hypocalcemia following administration of cinacalcet was associated with higher baseline plasma parathyroid hormone, lower corrected total serum calcium, higher serum alkaline phosphatase, geographic region (patients from Latin America and Russia had a higher risk relative to the United States) and higher body mass index. The median cinacalcet dose immediately prior to the first hypocalcemic episode was 54-58 mg/day and similar in the three hypocalcemia categories. In the majority of patients, hypocalcemia resolved spontaneously within 14 days without modification of background therapy. Among patients who received an intervention, the most common was an increase in the active vitamin D sterol dose. Thus, the occurrence of hypocalcemia is frequent following initiation of cinacalcet and the likelihood of developing hypocalcemia was related to the severity of secondary hyperparathyroidism. Hypocalcemia was generally asymptomatic and self-limited.

  View details for PubMedID 29525393

• Dialysis versus Medical Management at Different Ages and Levels of Kidney Function in Veterans with Advanced CKD. Journal of the American Society of Nephrology : JASN Kurella Tamura, M., Desai, M., Kapphahn, K. I., Thomas, I., Asch, S. M., Chertow, G. M. 2018

  Abstract

  Background Appropriate patient selection and optimal timing of dialysis initiation among older adults with advanced CKD are uncertain. We determined the association between dialysis versus medical management and survival at different ages and levels of kidney function.Methods We assembled a nationally representative 20% sample of United States veterans with eGFR<30 ml/min per 1.73 m2 between 2005 and 2010 (n=73,349), with follow-up through 2012. We used an extended Cox model to determine associations among the time-varying exposures, age (<65, 65-74, 75-84, and ≥85 years), eGFR (<6, 6-<9, 9-<12, 12-<15, and 15-<29 ml/min per 1.73 m2), and provision of dialysis, and survival.Result Over the mean±SEM follow-up of 3.4±2.2 years, 15% of patients started dialysis and 52% died. The eGFR at which dialysis, compared with medical management, associated with lower mortality varied by age (P<0.001). For patients aged <65, 65-74, 75-84, and ≥85 years, dialysis associated with lower mortality for those with eGFR not exceeding 6-<9, <6, 9-<12, and 9-<12 ml/min per 1.73 m2, respectively. Dialysis initiation at eGFR<6 ml/min per 1.73 m2 associated with a higher median life expectancy of 26, 25, and 19 months for patients aged 65, 75, and 85 years, respectively. When dialysis was initiated at eGFR 9-<12 ml/min per 1.73 m2, the estimated difference in median life expectancy was <1 year for these patients.Conclusions Provision of dialysis at higher levels of kidney function may extend survival for some older patients.

  View details for PubMedID 29789430

• EFFECT OF BARDOXOLONE METHYL TREATMENT ON URINARY ALBUMIN IN PATIENTS WITH TYPE 2 DIABETES AND CHRONIC KIDNEY DISEASE - POST-HOC ANALYSIS FROM BEAM AND BEACON Rossing, P., Block, G., Chertow, G., Chin, M., Goldsberry, A., McCullough, P., Meyer, C., Packham, D., Spinowitz, B., Sprague, S., Warnock, D., Pergola, P. OXFORD UNIV PRESS. 2018

  View details for Web of Science ID 000433059800076

• Comparing Simultaneous Liver-Kidney Transplant Strategies: A Modified Cost-Effectiveness Analysis TRANSPLANTATION Cheng, X. S., Kim, W., Tan, J. C., Chertow, G. M., Goldhaber-Fiebert, J. 2018; 102 (5): E219–E228

  View details for DOI 10.1097/TP.0000000000002148

  View details for Web of Science ID 000431423600006

• Comparative safety of intravenous ferumoxytol versus ferric carboxymaltose in iron deficiency anemia: A randomized trial AMERICAN JOURNAL OF HEMATOLOGY Adkinson, N., Strauss, W. E., Macdougall, I. C., Bernard, K. E., Auerbach, M., Kaper, R. F., Chertow, G. M., Krop, J. S. 2018; 93 (5): 683–90

  Abstract

  Few trials have examined rates of hypersensitivity reactions (HSRs) with intravenous iron formulations used to treat iron deficiency anemia (IDA). This randomized, multicenter, double-blind clinical trial compared the safety, and efficacy of ferumoxytol versus ferric carboxymaltose (FCM), focusing on rates of HSRs and hypotension as the primary end point. Patients with IDA of any etiology in whom oral iron was unsatisfactory or intolerable received ferumoxytol (n = 997) or FCM (n = 1000) intravenously over ≥15 minutes on days 1 and 8 or 9 for total respective doses of 1.02 g and 1.50 g. Composite incidences of moderate-to-severe HSRs, including anaphylaxis, or moderate-to-severe hypotension from baseline to week 5 (primary safety end point) were 0.6% and 0.7% in the ferumoxytol and FCM groups, respectively, with ferumoxytol noninferior to FCM. No anaphylaxis was reported in either group. The secondary safety end point of incidences of moderate-to-severe HSRs, including anaphylaxis, serious cardiovascular events, and death from baseline to week 5 were 1.3% and 2.0% in the ferumoxytol and FCM groups, respectively (noninferiority test P < .0001). Least-squares mean changes in hemoglobin at week 5 were 1.4 g/dL and 1.6 g/dL in the ferumoxytol and FCM groups, respectively (noninferiority test P < .0001). Incidence of hypophosphatemia was 0.4% for ferumoxytol and 38.7% for FCM.

  View details for PubMedID 29417614

• DECREASES IN WEIGHT WITH BARDOXOLONE METHYL IN OBESE PATIENTS WITH CHRONIC KIDNEY DISEASE STAGE 4 AND TYPE 2 DIABETES - POST-HOC ANALYSES FROM BEACON Rossing, P., Appel, G., Block, G., Chertow, G., Chin, M., Coyne, D., Goldsberry, A., Meyer, C., Molitch, M., Pergola, P., Spinowitz, B., Sprague, S., Raskin, P. OXFORD UNIV PRESS. 2018

  View details for Web of Science ID 000433059801225

• BARDOXOLONE METHYL PREVENTS EGFR DECLINE IN PATIENTS WITH CHRONIC KIDNEY DISEASE STAGE 4 AND TYPE 2 DIABETES - POST-HOC ANALYSES FROM BEACON Wanner, C., Bakris, G., Block, G., Chin, M., Goldsberry, A., Inker, L., Meyer, C., O'Grady, M., Pergola, P., Warnock, D., Chertow, G. OXFORD UNIV PRESS. 2018

  View details for Web of Science ID 000433059800023

• BASELINE LEVELS OF FGF23 AND EFFECTS OF ETELCALCETIDE Vervloet, M., Cooper, K., Block, G., Chertow, G., Fouqueray, B., Moe, S., Sun, Y., Tomlin, H., Wolf, M., Oberbauer, R. OXFORD UNIV PRESS. 2018

  View details for Web of Science ID 000433059800443

• Associations of lipoproteins with cardiovascular and infection-related outcomes in patients receiving hemodialysis JOURNAL OF CLINICAL LIPIDOLOGY Kaysen, G. A., Grimes, B., Dalrymple, L. S., Chertow, G. M., Ishida, J. H., Delgado, C., Segal, M., Chiang, J., Dwyer, T., Johansen, K. L. 2018; 12 (2): 481–87

  Abstract

  In hemodialysis (HD) patients, higher lipid levels are associated with lower mortality. Lipid-lowering therapy does not reduce all-cause mortality or cardiovascular (CV) mortality. Lipoproteins play a role in the innate immune system. Our objective was to determine whether protection from infection might counterbalance adverse CV outcomes associated with lipoproteins.We examined associations between serum apolipoprotein (Apo) A1, B, C2, C3, high-density lipoprotein and low-density lipoprotein (LDL) cholesterol and triglyceride levels and infectious mortality or hospitalization, CV mortality or hospitalization, and all-cause mortality in 433 prevalent HD patients. Cox models with time-varying apolipoprotein concentrations collected every 6 months for up to 2 years were used for analyses.Median follow-up time for all-cause mortality was 2.7 years (25th-75th percentile range: 2.2-3.4 years). One hundred seventy-nine (41%) patients had an infection-related event. In multivariable models, higher Apo B and LDL were associated with lower risks of infection-related outcomes (hazard ratio Apo B 0.92 [95% confidence interval 0.86-0.99 per 10 mg/dL, P = .03]; hazard ratio LDL 0.93 [95% confidence interval 0.87-1.00 per 10 mg/dL, P = .05]). Sixty-three (15%) participants had a CV-related event. No significant associations were observed between lipoproteins and CV outcomes. Eighty-seven (20%) participants died. Higher Apo A1, Apo B, and Apo C3 were associated with lower risks of all-cause mortality. There was no interaction between the use of lipid-lowering medication and any of the outcomes.Associations of lipoproteins with lower risk of serious infection accompanied by no significant association with CV events may help to explain the paradoxical association between lipids and survival and lack of benefit of lipid-lowering therapies in HD.

  View details for PubMedID 29361496

  View details for PubMedCentralID PMC5880742

• PREOPERATIVE KIDNEY FUNCTION TRENDS: IMPROVING ESTIMATES OF BASELINE KIDNEY FUNCTION PRIOR TO KIDNEY CANCER SURGERY Sun, A., Thomas, C., Ganesan, C., Sylman, J., Pao, A., Wagner, T., Brooks, J., Chertow, G., Leppert, J. ELSEVIER SCIENCE INC. 2018: E362

  View details for Web of Science ID 000429166601066

• Updated guidelines for the diagnosis and management of high blood pressure: implications for clinical practice in nephrology KIDNEY INTERNATIONAL Wyatt, C. M., Chertow, G. M. 2018; 93 (4): 768–70

  View details for DOI 10.1016/j.kint.2018.01.017

  View details for Web of Science ID 000428169200001

  View details for PubMedID 29475561

• Comparing Simultaneous Liver-Kidney Transplant Strategies: A Modified Cost-Effectiveness Analysis. Transplantation Cheng, X. S., Kim, W. R., Tan, J. C., Chertow, G. M., Goldhaber-Fiebert, J. 2018

  Abstract

  BACKGROUND: The proportion of patients with kidney failure at time of liver transplantation is at an historic high in the United States. The optimal timing of kidney transplantation with respect to the liver transplant is unknown.METHODS: We used a modified cost-effectiveness analysis to compare four strategies: the old system ("pre-OPTN"), the new Organ Procurement Transplant Network (OPTN) system since August 10, 2017 ("OPTN"), and two strategies which restrict simultaneous liver-kidney transplants ("safety net" and "stringent"). We measured "cost" by deployment of deceased donor kidneys (DDKs) to liver transplant recipients and effectiveness by life years (LYs) and quality-adjusted life years (QALYs) in liver transplant recipients. We validated our model against Scientific Registry for Transplant Recipients data.RESULTS: The OPTN, safety net and stringent strategies were on the efficient frontier. By rank order, OPTN > safety net > stringent strategy in terms of LY, QALY and DDK deployment. The pre-OPTN system was dominated, or outperformed, by all alternative strategies. The incremental LY per DDK between the strategies ranged from 1.30 to 1.85. The incremental QALY per DDK ranged from 1.11 to 2.03.CONCLUSION: These estimates quantify the "organ"-effectiveness of various kidney allocation strategies for liver transplant candidates. The OPTN system will likely deliver better liver transplant outcomes at the expense of more frequent deployment of DDKs to liver transplant recipients.

  View details for PubMedID 29554056

• Chronic kidney disease care models in low- and middle-income countries: a systematic review BMJ GLOBAL HEALTH Stanifer, J. W., Von Isenburg, M., Chertow, G. M., Anand, S. 2018; 3 (2): e000728

  Abstract

  The number of persons with chronic kidney disease (CKD) living in low- and middle-income countries (LMIC) is increasing rapidly; yet systems built to care for them have received little attention. In order to inform the development of scalable CKD care models, we conducted a systematic review to characterise existing CKD care models in LMICs.We searched PubMed, Embase and WHO Global Health Library databases for published reports of CKD care models from LMICs between January 2000 and 31 October 2017. We used a combination of database-specific medical subject headings and keywords for care models, CKD and LMICs as defined by the World Bank.Of 3367 retrieved articles, we reviewed the full text of 104 and identified 17 articles describing 16 programmes from 10 countries for inclusion. National efforts (n=4) focused on the prevention of end-stage renal disease through enhanced screening, public awareness campaigns and education for primary care providers. Of the 12 clinical care models, nine focused on persons with CKD and the remaining on persons at risk for CKD; a majority in the first category implemented a multidisciplinary clinic with allied health professionals or primary care providers (rather than nephrologists) in lead roles. Four clinical care models used a randomised control design allowing for assessment of programme effectiveness, but only one was assessed as having low risk for bias; all four showed significant attenuation of kidney function decline in the intervention arms.Overall, very few rigorous CKD care models have been reported from LMICs. While preliminary data indicate that national efforts or clinical CKD care models bolstering primary care are successful in slowing kidney function decline, limited data on regional causes of CKD to inform national campaigns, and on effectiveness and affordability of local programmes represent important challenges to scalability.

  View details for PubMedID 29629191

• IgA nephropathy: toward more specific diagnosis (and rescue of snails) KIDNEY INTERNATIONAL Floege, J. 2018; 93 (3): 542–44

  Abstract

  The diagnosis of IgA nephropathy relies on the histologic demonstration of glomerular mesangial IgA deposits. However, only a very small fraction of IgA, namely, galactose-deficient IgA1, seems to induce the disease. So far, this type of IgA could only be detected using mass spectrometry or lectins, which are relatively difficult to standardize. A novel monoclonal antibody, KM55, specifically recognizing galactose-deficient IgA1, may now change this.

  View details for DOI 10.1016/j.kint.2017.10.028

  View details for Web of Science ID 000425713400005

  View details for PubMedID 29475546

• Effects of Intensive Blood Pressure Treatment on Acute Kidney Injury Events in the Systolic Blood Pressure Intervention Trial (SPRINT) AMERICAN JOURNAL OF KIDNEY DISEASES Rocco, M. V., Sink, K. M., Lovato, L. C., Wolfgram, D. F., Wiegmann, T. B., Wall, B. M., Umanath, K., Rahbari-Oskoui, F., Porter, A. C., Pisoni, R., Lewis, C. E., Lewis, J. B., Lash, J. P., Katz, L. A., Hawfield, A. T., Haley, W. E., Freedman, B. I., Dwyer, J. P., Drawz, P. E., Dobre, M., Cheung, A. K., Campbell, R. C., Bhatt, U., Beddhu, S., Kimmel, P. L., Reboussin, D. M., Chertow, G. M., SPRINT Res Grp 2018; 71 (3): 352–61

  Abstract

  Treating to a lower blood pressure (BP) may increase acute kidney injury (AKI) events.Data for AKI resulting in or during hospitalization or emergency department visits were collected as part of the serious adverse events reporting process of the Systolic Blood Pressure Intervention Trial (SPRINT).9,361 participants 50 years or older with 1 or more risk factors for cardiovascular disease.Participants were randomly assigned to a systolic BP target of <120 (intensive arm) or <140mmHg (standard arm).Primary outcome was the number of adjudicated AKI events. Secondary outcomes included severity of AKI and degree of recovery of kidney function after an AKI event. Baseline creatinine concentration was defined as the most recent SPRINT outpatient creatinine value before the date of the AKI event.There were 179 participants with AKI events in the intensive arm and 109 in the standard arm (3.8% vs 2.3%; HR, 1.64; 95% CI, 1.30-2.10; P<0.001). Of 288 participants with an AKI event, 248 (86.1%) had a single AKI event during the trial. Based on modified KDIGO (Kidney Disease: Improving Global Outcomes) criteria for severity of AKI, the number of AKI events in the intensive versus standard arm by KDIGO stage was 128 (58.5%) versus 81 (62.8%) for AKI stage 1, 42 (19.2%) versus 18 (14.0%) for AKI stage 2, and 42 (19.2%) versus 25 (19.4%) for AKI stage 3 (P=0.5). For participants with sufficient data, complete or partial resolution of AKI was seen for 169 (90.4%) and 9 (4.8%) of 187 AKI events in the intensive arm and 86 (86.9%) and 4 (4.0%) of 99 AKI events in the standard arm, respectively.Trial results are not generalizable to patients with diabetes mellitus or without risk factors for cardiovascular disease.More intensive BP lowering resulted in more frequent episodes of AKI. Most cases were mild and most participants had complete recovery of kidney function.Registered at ClinicalTrials.gov with study number NCT01206062.

  View details for PubMedID 29162340

  View details for PubMedCentralID PMC5828778

• Cost-effectiveness of multidisciplinary care in mild to moderate chronic kidney disease in the United States: A modeling study PLOS MEDICINE Lin, E., Chertow, G. M., Yan, B., Malcolm, E., Goldhaber-Fiebert, J. D. 2018; 15 (3): e1002532

  Abstract

  Multidisciplinary care (MDC) programs have been proposed as a way to alleviate the cost and morbidity associated with chronic kidney disease (CKD) in the US.We assessed the cost-effectiveness of a theoretical Medicare-based MDC program for CKD compared to usual CKD care in Medicare beneficiaries with stage 3 and 4 CKD between 45 and 84 years old in the US. The program used nephrologists, advanced practitioners, educators, dieticians, and social workers. From Medicare claims and published literature, we developed a novel deterministic Markov model for CKD progression and calibrated it to long-term risks of mortality and progression to end-stage renal disease. We then used the model to project accrued discounted costs and quality-adjusted life years (QALYs) over patients' remaining lifetime. We estimated the incremental cost-effectiveness ratio (ICER) of MDC, or the cost of the intervention per QALY gained. MDC added 0.23 (95% CI: 0.08, 0.42) QALYs over usual care, costing $51,285 per QALY gained (net monetary benefit of $23,100 at a threshold of $150,000 per QALY gained; 95% CI: $6,252, $44,323). In all subpopulations analyzed, ICERs ranged from $42,663 to $72,432 per QALY gained. MDC was generally more cost-effective in patients with higher urine albumin excretion. Although ICERs were higher in younger patients, MDC could yield greater improvements in health in younger than older patients. MDC remained cost-effective when we decreased its effectiveness to 25% of the base case or increased the cost 5-fold. The program costed less than $70,000 per QALY in 95% of probabilistic sensitivity analyses and less than $87,500 per QALY in 99% of analyses. Limitations of our study include its theoretical nature and being less generalizable to populations at low risk for progression to ESRD. We did not study the potential impact of MDC on hospitalization (cardiovascular or other).Our model estimates that a Medicare-funded MDC program could reduce the need for dialysis, prolong life expectancy, and meet conventional cost-effectiveness thresholds in middle-aged to elderly patients with mild to moderate CKD.

  View details for PubMedID 29584720

• Causes of Death after a Hospitalization with AKI JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Silver, S. A., Harel, Z., McArthur, E., Nash, D. M., Acedillo, R., Kitchlu, A., Garg, A. X., Chertow, G. M., Bell, C. M., Wald, R. 2018; 29 (3): 1001–10

  Abstract

  Mortality after AKI is high, but the causes of death are not well described. To better understand causes of death in patients after a hospitalization with AKI and to determine patient and hospital factors associated with mortality, we conducted a population-based study of residents in Ontario, Canada, who survived a hospitalization with AKI from 2003 to 2013. Using linked administrative databases, we categorized cause of death in the year after hospital discharge as cardiovascular, cancer, infection-related, or other. We calculated standardized mortality ratios to compare the causes of death in survivors of AKI with those in the general adult population and used Cox proportional hazards modeling to estimate determinants of death. Of the 156,690 patients included, 43,422 (28%) died in the subsequent year. The most common causes of death were cardiovascular disease (28%) and cancer (28%), with respective standardized mortality ratios nearly six-fold (5.81; 95% confidence interval [95% CI], 5.70 to 5.92) and eight-fold (7.87; 95% CI, 7.72 to 8.02) higher than those in the general population. The highest standardized mortality ratios were for bladder cancer (18.24; 95% CI, 17.10 to 19.41), gynecologic cancer (16.83; 95% CI, 15.63 to 18.07), and leukemia (14.99; 95% CI, 14.16 to 15.85). Along with older age and nursing home residence, cancer and chemotherapy strongly associated with 1-year mortality. In conclusion, cancer-related death was as common as cardiovascular death in these patients; moreover, cancer-related deaths occurred at substantially higher rates than in the general population. Strategies are needed to care for and counsel patients with cancer who experience AKI.

  View details for PubMedID 29242248

  View details for PubMedCentralID PMC5827605

• Outcomes after Angiography with Sodium Bicarbonate and Acetylcysteine NEW ENGLAND JOURNAL OF MEDICINE Weisbord, S. D., Gallagher, M., Jneid, H., Garcia, S., Cass, A., Thwin, S., Conner, T. A., Chertow, G. M., Bhatt, D. L., Shunk, K., Parikh, C. R., McFalls, E. O., Brophy, M., Ferguson, R., Wu, H., Androsenko, M., Myles, J., Kaufman, J., Palevsky, P. M., PRESERVE Trial Grp 2018; 378 (7): 603–14

  Abstract

  Intravenous sodium bicarbonate and oral acetylcysteine are widely used to prevent acute kidney injury and associated adverse outcomes after angiography without definitive evidence of their efficacy.Using a 2-by-2 factorial design, we randomly assigned 5177 patients at high risk for renal complications who were scheduled for angiography to receive intravenous 1.26% sodium bicarbonate or intravenous 0.9% sodium chloride and 5 days of oral acetylcysteine or oral placebo; of these patients, 4993 were included in the modified intention-to-treat analysis. The primary end point was a composite of death, the need for dialysis, or a persistent increase of at least 50% from baseline in the serum creatinine level at 90 days. Contrast-associated acute kidney injury was a secondary end point.The sponsor stopped the trial after a prespecified interim analysis. There was no interaction between sodium bicarbonate and acetylcysteine with respect to the primary end point (P=0.33). The primary end point occurred in 110 of 2511 patients (4.4%) in the sodium bicarbonate group as compared with 116 of 2482 (4.7%) in the sodium chloride group (odds ratio, 0.93; 95% confidence interval [CI], 0.72 to 1.22; P=0.62) and in 114 of 2495 patients (4.6%) in the acetylcysteine group as compared with 112 of 2498 (4.5%) in the placebo group (odds ratio, 1.02; 95% CI, 0.78 to 1.33; P=0.88). There were no significant between-group differences in the rates of contrast-associated acute kidney injury.Among patients at high risk for renal complications who were undergoing angiography, there was no benefit of intravenous sodium bicarbonate over intravenous sodium chloride or of oral acetylcysteine over placebo for the prevention of death, need for dialysis, or persistent decline in kidney function at 90 days or for the prevention of contrast-associated acute kidney injury. (Funded by the U.S. Department of Veterans Affairs Office of Research and Development and the National Health and Medical Research Council of Australia; PRESERVE ClinicalTrials.gov number, NCT01467466 .).

  View details for PubMedID 29130810

• Antihypertensive medication withholding practices in hemodialysis: A survey study of patients and providers. Hemodialysis international. International Symposium on Home Hemodialysis Haase, S. B., Chang, S., Schiller, B., Chertow, G. M., Chang, T. I. 2018

  View details for DOI 10.1111/hdi.12640

  View details for PubMedID 29436151

• Perioperative THR-184 and AKI after Cardiac Surgery JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Himmelfarb, J., Chertow, G. M., McCullough, P. A., Mesana, T., Shaw, A. D., Sundt, T. M., Brown, C., Cortville, D., Dagenais, F., de Varennes, B., Fontes, M., Rossert, J., Tardif, J. 2018; 29 (2): 670–79

  Abstract

  AKI after cardiac surgery is associated with mortality, prolonged hospital length of stay, use of dialysis, and subsequent CKD. We evaluated the effects of THR-184, a bone morphogenetic protein-7 agonist, in patients at high risk for AKI after cardiac surgery. We conducted a randomized, double-blind, placebo-controlled, multidose comparison of the safety and efficacy of perioperative THR-184 using a two-stage seamless adaptive design in 452 patients between 18 and 85 years of age who were scheduled for nonemergent cardiac surgery requiring cardiopulmonary bypass and had recognized risk factors for AKI. The primary efficacy end point was the proportion of patients who developed AKI according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. The proportion of patients who developed AKI within 7 days of surgery was similar in THR-184 treatment groups and placebo groups (range, 74%-79%; P=0.43). Prespecified secondary end point analysis did not show significant differences in the severity of AKI stage (P=0.53) or the total duration of AKI (P=0.44). A composite of death, dialysis, or sustained impaired renal function by day 30 after surgery did not differ between groups (range, 11%-20%; P=0.46). Safety-related outcomes were similar across all treatment groups. In conclusion, compared with placebo, administration of perioperative THR-184 through a range of dose exposures failed to reduce the incidence, severity, or duration of AKI after cardiac surgery in high-risk patients.

  View details for PubMedID 29203473

• Influence of Baseline Diastolic Blood Pressure on Effects of Intensive Compared With Standard Blood Pressure Control CIRCULATION Beddhu, S., Chertow, G. M., Cheung, A. K., Cushman, W. C., Rahman, M., Greene, T., Wei, G., Campbell, R. C., Conroy, M., Freedman, B. I., Haley, W., Horwitz, E., Kitzman, D., Lash, J., Papademetriou, V., Pisoni, R., Riessen, E., Rosendorff, C., Watnick, S. G., Whittle, J., Whelton, P. K., SPRINT Res Grp 2018; 137 (2): 134–43

  Abstract

  In individuals with a low diastolic blood pressure (DBP), the potential benefits or risks of intensive systolic blood pressure (SBP) lowering are unclear.SPRINT (Systolic Blood Pressure Intervention Trial) was a randomized controlled trial that compared the effects of intensive (target <120 mm Hg) and standard (target <140 mm Hg) SBP control in 9361 older adults with high blood pressure at increased risk of cardiovascular disease. The primary outcome was a composite of cardiovascular disease events. All-cause death and incident chronic kidney disease were secondary outcomes. This post hoc analysis examined whether the effects of the SBP intervention differed by baseline DBP.Mean baseline SBP and DBP were 139.7±15.6 and 78.1±11.9 mm Hg, respectively. Regardless of the randomized treatment, baseline DBP had a U-shaped association with the hazard of the primary cardiovascular disease outcome. However, the effects of the intensive SBP intervention on the primary outcome were not influenced by baseline DBP level (P for interaction=0.83). The primary outcome hazard ratio for intensive versus standard treatment was 0.78 (95% confidence interval, 0.57-1.07) in the lowest DBP quintile (mean baseline DBP, 61±5 mm Hg) and 0.74 (95% confidence interval, 0.61-0.90) in the upper 4 DBP quintiles (mean baseline DBP, 82±9 mm Hg), with an interaction P value of 0.78. Results were similar for all-cause death and kidney events.Low baseline DBP was associated with increased risk of cardiovascular disease events, but there was no evidence that the benefit of the intensive SBP lowering differed by baseline DBP.URL: https://www.clinicaltrials.gov. Unique identifier: NCT01206062.

  View details for PubMedID 29021322

• Unplanned Emergency Department Visits and Hospital Admissions Following Ureteroscopy: Do Ureteral Stents Make a Difference? Urology Mittakanti, H. R., Conti, S. L., Pao, A. C., Chertow, G. M., Liao, J. C., Leppert, J. T., Elliott, C. S. 2018

  Abstract

  The comparative effectiveness of ureteral stents placed during ureteroscopy for urinary stone disease is widely debated. We sought to evaluate unplanned medical visits within the early post-operative period after ureteroscopy in patients with and without ureteral stent placement.We identified all ureteroscopic procedures for urinary stone disease in the California Office of Statewide Health Planning and Development (OSHPD) database from 2010-2012. The primary outcome was any emergency department visit or inpatient hospital admission in the first 7 days following ureteroscopy. Patients were sub-categorized by type of ureteroscopy (i.e. laser lithotripsy versus basket retrieval) and analyzed for significant differences between stented and unstented patients. Multivariable logistic regression was performed to determine if ureteral stent placement was independently associated with unplanned visits.Our analytic cohort included 16,060 patients undergoing 17,716 ureteroscopy procedures. A ureteral stent was placed in 86.2% of patients undergoing laser lithotripsy, and 70.5% of patients receiving basket retrieval. In the 7 days following ureteroscopy, 6.6% of patients were seen in the emergency department and 2.2% of patients were admitted to a hospital. In a fully adjusted model, the utilization of a ureteral stent was not associated with emergency department visits or inpatient admissions.Ureteral stent placement during ureteroscopy is not associated with an increased odds of emergency department visits and inpatient admissions in the early post-operative period.

  View details for PubMedID 29601836

• Would government compensation of living kidney donors exploit the poor? An empirical analysis. PloS one Held, P. J., McCormick, F., Chertow, G. M., Peters, T. G., Roberts, J. P. 2018; 13 (11): e0205655

  Abstract

  Government compensation of kidney donors would likely increase the supply of kidneys and prevent the premature deaths of tens of thousands of patients with kidney failure each year. The major argument against it is that it would exploit the poor who would be more likely to accept the offers of compensation. This overlooks the fact that many poor patients desperately need a kidney transplant and would greatly benefit from an increased supply of kidneys. The objective of this study is to empirically test the hypothesis that government compensation of kidney donors would exploit the poor. Exploitation is defined by economists and several noted ethicists as paying donors less than the fair market value of their kidney. Exploitation is expressed in monetary terms and compared with the economic benefit recipients receive from a transplant. Data are from the Scientific Registry of Transplant Recipients and the United States Renal Data System annual data reports. Educational attainment is used as a proxy for income. We estimate that if the government rewards living donors with a package of non-cash benefits worth $75,000 per kidney, donors would not be exploited. Much more important, this compensation would likely end the kidney shortage, enabling many more patients with kidney failure to obtain transplants and live longer and healthier lives. The value of kidney transplantation to a U.S. recipient is about $1,330,000, which is an order of magnitude greater than any purported exploitation of a living donor (zero to $75,000). Consequently, the aggregate net benefit to the poor alone from kidney transplantation would increase to about $12 billion per year from $1 billion per year currently. Most of the benefit would accrue to poor kidney recipients. But poor donors would receive the fair market value of their kidney, and hence would not be exploited. If the government wanted to ensure that donors also received a net benefit, it could easily do so by increasing the compensation above $75,000 per donor.

  View details for PubMedID 30485269

• Ferumoxytol for the treatment of iron deficiency anemia EXPERT REVIEW OF HEMATOLOGY Auerbach, M., Chertow, G. M., Rosner, M. 2018; 11 (10): 829–34

  Abstract

  Ferumoxytol is a superparamagnetic molecule originally developed as a contrast agent for magnetic resonance imaging. Elemental iron is contained within the carbohydrate core and is released slowly after infusion allowing a large dose of iron to be administered in a short period of time. Ferumoxytol, originally approved for iron deficiency in chronic kidney disease, received a broad label for any cause of iron deficiency after oral iron intolerance or in those circumstances when oral iron is ineffective or harmful. Areas covered: The chemistry, pharmacology and pharmacokinetics of ferumoxytol were reviewed. Retrospective, observational, and prospective phase II and III trials were reviewed. When appropriate, comparative safety and efficacy parameters were reported. Differentiation between minor infusion reactions and more severe hypersensitivity reactions that may lead to anaphylaxis is described. Expert commentary: Ferumoxytol is a safe and effective iron formulation providing a means of iron repletion in persons with iron deficiency with or without anemia. Relative to iron sucrose, ferric gluconate, and iron dextran and similar to ferric carboxymaltose and iron isomaltoside, ferumoxytol yields relatively low quantities of labile free iron. Hypersensitivity and anaphylaxis is extremely rare. Hypophosphatemia with ferumoxytol's administration is extremely rare. Optimal strategies for application of ferumoxytol-enhanced imaging and full replacement dosing in a single setting remain to be determined.

  View details for PubMedID 30188740

• Risk Factors, Incidence and Cost of Prolonged Hospitalization After Acute Respiratory Failure Marmor, M., Liu, S., Long, J., Chertow, G., Rogers, A. AMER THORACIC SOC. 2018

  View details for Web of Science ID 000449980301194

• Bardoxolone Methyl Improves Kidney Function in Patients with Chronic Kidney Disease Stage 4 and Type 2 Diabetes: Post-Hoc Analyses from Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes Study AMERICAN JOURNAL OF NEPHROLOGY Chin, M. P., Bakris, G. L., Block, G. A., Chertow, G. M., Goldsberry, A., Inker, L. A., Heerspink, H. L., O'Grady, M., Pergola, P. E., Wanner, C., Warnock, D. G., Meyer, C. J. 2018; 47 (1): 40–47

  Abstract

  Increases in measured inulin clearance, measured creatinine clearance, and estimated glomerular filtration rate (eGFR) have been observed with bardoxolone methyl in 7 studies enrolling approximately 2,600 patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). The largest of these studies was Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes (BEACON), a multinational, randomized, double-blind, placebo-controlled phase 3 trial which enrolled patients with T2D and CKD stage 4. The BEACON trial was terminated after preliminary analyses showed that patients randomized to bardoxolone methyl experienced significantly higher rates of heart failure events. We performed post-hoc analyses to characterize changes in kidney function induced by bardoxolone methyl.Patients in -BEACON (n = 2,185) were randomized 1: 1 to receive once-daily bardoxolone methyl (20 mg) or placebo. We compared the effects of bardoxolone methyl and placebo on a post-hoc composite renal endpoint consisting of ≥30% decline from baseline in eGFR, eGFR <15 mL/min/1.73 m2, and end-stage renal disease (ESRD) events (provision of dialysis or kidney transplantation).Consistent with prior studies, patients randomized to bardoxolone methyl experienced mean increases in eGFR that were sustained through study week 48. Moreover, increases in eGFR from baseline were sustained 4 weeks after cessation of treatment. Patients randomized to bardoxolone methyl were significantly less likely to experience the composite renal endpoint (hazards ratio 0.48 [95% CI 0.36-0.64]; p < 0.0001).Bardoxolone methyl preserves kidney function and may delay the onset of ESRD in patients with T2D and stage 4 CKD.

  View details for PubMedID 29402767

• Clinical Outcomes by Race and Ethnicity in the Systolic Blood Pressure Intervention Trial (SPRINT): A Randomized Clinical Trial AMERICAN JOURNAL OF HYPERTENSION Still, C. H., Rodriguez, C. J., Wright, J. T., Craven, T. E., Bress, A. P., Chertow, G. M., Whelton, P. K., Whittle, J. C., Freedman, B. I., Johnson, K. C., Foy, C. G., He, J., Kostis, J. B., Lash, J. P., Pedley, C. F., Pisoni, R., Powell, J. R., Wall, B. M., SPRINT Writing Grp 2018; 31 (1): 97–107

  Abstract

  The Systolic Blood Pressure Intervention Trial (SPRINT) showed that targeting a systolic blood pressure (SBP) of ≤ 120 mm Hg (intensive treatment) reduced cardiovascular disease (CVD) events compared to SBP of ≤ 140 mm Hg (standard treatment); however, it is unclear if this effect is similar in all racial/ethnic groups.We analyzed SPRINT data within non-Hispanic White (NHW), non-Hispanic Black (NHB), and Hispanic subgroups to address this question. High-risk nondiabetic hypertensive patients (N = 9,361; 30% NHB; 11% Hispanic) 50 years and older were randomly assigned to intensive or standard treatment. Primary outcome was a composite of the first occurrence of a myocardial infarction, acute coronary syndrome, stroke, decompensated heart failure, or CVD death.Average postbaseline SBP was similar among NHW, NHB, and Hispanics in both treatment arms. Hazard ratios (HRs) (95% confidence interval) (intensive vs. standard treatment groups) for primary outcome were 0.70 (0.57-0.86), 0.71 (0.51-0.98), 0.62 (0.33-1.15) (interaction P value = 0.85) in NHW, NHB, and Hispanics. CVD mortality HRs were 0.49 (0.29-0.81), 0.77 (0.37-1.57), and 0.17 (0.01-1.08). All-cause mortality HRs were 0.61 (0.47-0.80), 0.92 (0.63-1.35), and 1.58 (0.73-3.62), respectively. A test for differences among racial/ethnic groups in the effect of treatment assignment on all-cause mortality was not significant (Hommel-adjusted P value = 0.062) after adjustment for multiple comparisons.Targeting a SBP goal of ≤ 120 mm Hg compared to ≤ 140 mm Hg led to similar SBP control and was associated with similar benefits and risks among all racial ethnic groups, though NHBs required an average of ~0.3 more medications.Trial Number NCT01206062, ClinicalTrials.gov Identifier at https://clinicaltrials.gov/ct2/show/NCT01206062.

  View details for PubMedID 28985268

• Allogeneic Mesenchymal Stem Cells for Treatment of AKI after Cardiac Surgery JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Swaminathan, M., Stafford-Smith, M., Chertow, G. M., Warnock, D. G., Paragamian, V., Brenner, R. M., Lellouche, F., Fox-Robichaud, A., Atta, M. G., Melby, S., Mehta, R. L., Wald, R., Verma, S., Mazer, C., ACT-AKI investigators 2018; 29 (1): 260–67

  Abstract

  AKI after cardiac surgery remains strongly associated with mortality and lacks effective treatment or prevention. Preclinical studies suggest that cell-based interventions may influence functional recovery. We conducted a phase 2, randomized, double-blind, placebo-controlled trial in 27 centers across North America to determine the safety and efficacy of allogeneic human mesenchymal stem cells (MSCs) in reducing the time to recovery from AKI after cardiac surgery. We randomized 156 adult subjects undergoing cardiac surgery with evidence of early AKI to receive intra-aortic MSCs (AC607; n=67) or placebo (n=68). The primary outcome was the time to recovery of kidney function defined as return of postintervention creatinine level to baseline. The median time to recovery of kidney function was 15 days with AC607 and 12 days with placebo (25th, 75th percentile range, 10-29 versus 6-21, respectively; hazard ratio, 0.81; 95% confidence interval, 0.53 to 1.24; P=0.32). We did not detect a significant difference between groups in 30-day all-cause mortality (16.7% with AC607; 11.8% with placebo) or dialysis (10.6% with AC607; 7.4% with placebo). At follow-up, 12 patients who received AC607 and six patients who received placebo had died. Rates of other adverse events did not differ between groups. In these patients with AKI after cardiac surgery, administration of allogeneic MSCs did not decrease the time to recovery of kidney function. Our results contrast with those in preclinical studies and provide important information regarding the potential effects of MSCs in this setting.

  View details for PubMedID 29038286

  View details for PubMedCentralID PMC5748899

• Associations of Body Mass Index and Body Fat With Markers of Inflammation and Nutrition Among Patients Receiving Hemodialysis AMERICAN JOURNAL OF KIDNEY DISEASES Delgado, C., Chertow, G. M., Kaysen, G. A., Dalrymple, L. S., Kornak, J., Grimes, B., Johansen, K. L. 2017; 70 (6): 817–25

  Abstract

  Understanding the extent to which visceral and subcutaneous body fat are associated with markers of nutrition and inflammation in patients on dialysis therapy could shed light on the obesity paradox and the biology of subcutaneous fat.Cross-sectional.609 adults receiving hemodialysis who participated in the ACTIVE/ADIPOSE Study.Body mass index (BMI), waist circumference, and bioelectrical impedance spectroscopy-derived estimates of percent body fat.C-Reactive protein (CRP), interleukin 6 (IL-6), prealbumin, albumin, leptin, and adiponectin concentrations.We performed linear regression analyses to examine the extent to which proxies of visceral and subcutaneous fat were associated with inflammation, nutrition, and adiposity-related hormones.BMI was directly associated with markers of inflammation (standardized estimate for ln[CRP in mg/L]: 0.30 [95% CI, 0.22-0.38] per 10kg/m2; for ln[IL-6 in pg/mL]: 0.10 [95% CI, 0.02-0.18] per 10kg/m2), but was not associated with markers of nutrition. BMI was also inversely associated with adiponectin and directly associated with leptin. With waist circumference and percent body fat (as a proxy of visceral and subcutaneous fat, respectively) modeled together, waist circumference was associated with markers of inflammation (standardized estimate for ln[CRP in mg/L]: 0.21 [95% CI, 0.09-0.34] per 10cm; for ln[IL-6 in pg/mL]: 0.18 [95% CI, 0.07-0.29] per 10cm), whereas percent body fat was not associated with CRP (standardized estimate for ln[CRP in mg/L]: 0.03 [95% CI, -0.10 to 0.15] per 1%) and was inversely associated with IL-6 (standardized estimate for ln[IL-6 in pg/mL]: -0.15 [95% CI, -0.27 to -0.02] per 1%). In addition, waist circumference was inversely associated with prealbumin and albumin (standardized estimates of -0.12 [95% CI, -0.23 to -0.02] mg/dL per 10cm and -0.17 [95% CI, -0.28 to -0.06] g/dL per 10cm, respectively), and percent body fat was directly associated with prealbumin and albumin (0.20 [95% CI, 0.07-0.32] mg/dL and 0.15 [95% CI, 0.02-0.28] g/dL per 1%, respectively). Higher waist circumference was associated indirectly with adiponectin and directly with leptin concentrations.Although the observed associations implicate visceral fat as the cause of inflammation, it cannot be determined in this cross-sectional study.Proxies of visceral and subcutaneous fat appear to have opposing associations with biomarkers of inflammation and nutrition. Subcutaneous fat may be an indicator of nutritional status, and visceral fat, an indicator of inflammation.

  View details for PubMedID 28870376

• Do attributes of persons with chronic kidney disease differ in low-income and middle-income countries compared with high-income countries? Evidence from population-based data in six countries BMJ GLOBAL HEALTH Anand, S., Zheng, Y., Montez-Rath, M. E., Wei, W., Perico, N., Carminati, S., Narayan, K., Tandon, N., Mohan, V., Jha, V., Zhang, L., Remuzzi, G., Prabahkaran, D., Chertow, G. M. 2017; 2 (4): e000453

  Abstract

  Kidney biopsies to elucidate the cause of chronic kidney disease (CKD) are performed in a minority of persons with CKD living in high-income countries, since associated conditions-that is, diabetes mellitus, vascular disease or obesity with pre-diabetes, prehypertension or dyslipidaemia-can inform management targeted at slowing CKD progression in a majority. However, attributes of CKD may differ substantially among persons living in low-income and middle-income countries (LMICs). We used data from population or community-based studies from five LMICs (China, urban India, Moldova, Nepal and Nigeria) to determine what proportion of persons with CKD living in diverse regions fit one of the three major clinical profiles, with data from the US National Health Nutrition and Examination Survey as reference. In the USA, urban India and Moldova, 79.0%-83.9%; in China and Nepal, 62.4%-66.7% and in Nigeria, 51.6% persons with CKD fit one of three established risk profiles. Diabetes was most common in urban India and vascular disease in Moldova (50.7% and 33.2% of persons with CKD in urban India and Moldova, respectively). In Nigeria, 17.8% of persons with CKD without established risk factors had albuminuria ≥300 mg/g, the highest proportion in any country. While the majority of persons with CKD in LMICs fit into one of three established risk profiles, the proportion of persons who have CKD without established risk factors is higher than in the USA. These findings can inform tailored CKD detection and management systems and highlight the importance of studying potential causes and outcomes of CKD without established risk factors in LMICs.

  View details for PubMedID 29071132

• Safety and efficacy of ferric citrate in patients with nondialysis-dependent chronic kidney disease PLOS ONE Chertow, G. M., Block, G. A., Neylan, J. F., Pergola, P. E., Uhlig, K., Fishbane, S. 2017; 12 (11): e0188712

  Abstract

  Two randomized, placebo-controlled trials conducted in patients with nondialysis-dependent (NDD) chronic kidney disease (CKD), iron deficiency anemia, and normal or elevated serum phosphorus demonstrated that ferric citrate (FC) significantly increased hemoglobin and decreased serum phosphate concentrations. Pooling these trial results could provide a more robust evaluation of the safety and efficacy of FC in this population. We pooled results of a phase 2 (n = 149) and 3 trial (n = 233) of patients randomized and treated for up to 12 and 16 weeks, respectively. The starting dose in both trials was three 1-g (elemental iron 210 mg) tablets/day with food, up to 12 tablets/day. Doses were titrated in the phase 2 and 3 trials to lower serum phosphate concentrations to a target range (0.97-1.13 mmol/L) and to achieve a ≥10-g/L hemoglobin increase, respectively. Safety was assessed in all patients who received ≥1 dose of FC (n = 190) and placebo (n = 188). Treatment-emergent adverse events (AEs) were reported in 143 of 190 (75.3%) FC-treated and 116 of 188 (61.7%) placebo-treated patients; gastrointestinal AEs were the most frequent (94 [49.5%] vs. 52 [27.7%], respectively). Specific events reported in >5% of patients (FC vs. placebo, respectively) included discolored feces (41 [21.6%] vs. 0 [0.0%]), diarrhea (39 [20.5%] vs. 23 [12.2%]), constipation (35 [18.4%] vs. 19 [10.1%]), and nausea (18 [9.5%] vs. 8 [4.3%]). Twenty FC-treated (10.5%) and 21 placebo-treated patients (11.2%) experienced a serious AE. Two patients (1.1%) died in each group. A pooled efficacy assessment demonstrated a consistent hemoglobin rise and modest serum phosphate decline, with few excursions below the normal range. When used for treatment of patients with NDD-CKD, FC contributes to gastrointestinal AEs at higher rates than placebo, while simultaneously correcting two of the principal metabolic manifestations of CKD (iron deficiency anemia and relative hyperphosphatemia).

  View details for PubMedID 29186198

• Infrequent Provision of Palliative Care to Patients with Dialysis-Requiring AKI CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Chong, K., Silver, S. A., Long, J., Zheng, Y., Pankratz, V., Unruh, M. L., Chertow, G. M. 2017; 12 (11): 1744–52

  Abstract

  The use of palliative care in AKI is not well described. We sought to better understand palliative care practice patterns for hospitalized patients with AKI requiring dialysis in the United States.Using the 2012 National Inpatient Sample, we identified patients with AKI and palliative care encounters using validated International Classification of Diseases, Ninth Revision, Clinical Modification codes. We compared palliative care encounters in patients with AKI requiring dialysis, patients with AKI not requiring dialysis, and patients without AKI. We described the provision of palliative care in patients with AKI requiring dialysis and compared the frequency of palliative care encounters for patients with AKI requiring dialysis with that for patients with other illnesses with similarly poor prognoses. We used logistic regression to determine factors associated with the provision of palliative care, adjusting for demographics, hospital-level variables, and patient comorbidities.We identified 3,031,036 patients with AKI, of whom 91,850 (3%) received dialysis. We observed significant patient- and hospital-level differences in the provision of palliative care for patients with AKI requiring dialysis; adjusted odds were 26% (95% confidence interval, 12% to 38%) lower in blacks and 23% (95% confidence interval, 3% to 39%) lower in Hispanics relative to whites. Lower provision of palliative care was observed for rural and urban nonteaching hospitals relative to urban teaching hospitals, small and medium hospitals relative to large hospitals, and hospitals in the Northeast compared with the South. After adjusting for age and sex, there was low utilization of palliative care services for patients with AKI requiring dialysis (8%)-comparable with rates of utilization by patients with other illnesses with poor prognosis, including cardiogenic shock (9%), intracranial hemorrhage (10%), and acute respiratory distress syndrome (10%).The provision of palliative care varied widely by patient and facility characteristics. Palliative care was infrequently used in hospitalized patients with AKI requiring dialysis, despite its poor prognosis and the regular application of life-sustaining therapy.

  View details for PubMedID 29042462

  View details for PubMedCentralID PMC5672958

• Declining Rates of Hip Fracture in End-Stage Renal Disease: Analysis From the 2003-2011 Nationwide Inpatient Sample JOURNAL OF BONE AND MINERAL RESEARCH Kim, S., Liu, S., Long, J., Montez-Rath, M. E., Leonard, M. B., Chertow, G. M. 2017; 32 (11): 2297–2303

  Abstract

  The incidence of hip fracture in patients with end-stage renal disease (ESRD) is considerably higher than that in the general age- and sex-matched population. Although medical therapy for chronic kidney disease mineral bone disorder (CKD-MBD) has changed considerably over the last decade, rates of hip fracture in the entire ESRD population have not been well-characterized. Herein, we evaluated temporal trends in rates of hip fracture, in-hospital mortality, and costs of associated hospital stay in ESRD. We identified hospitalizations for hip fracture from 2003 to 2011 using the Nationwide Inpatient Sample, a representative national database inclusive of all ages and payers. We incorporated data from the United States Renal Data System and the US Census to calculate population-specific rates. Between 2003 and 2011, we identified 47,510 hip fractures in the ESRD population. The overall rate of hip fracture was 10.04/1000 person-years. The rate was 3.73/1000 person-years in patients aged less than 65 years, and 20.97/1000 person-years in patients aged 65 or older. Age- and sex-standardized rates decreased by 12.6% from 2003 (10.23/1000 person-years; 95% confidence interval [CI], 7.99/1000 to 12.47/1000) to 2011 (8.94/1000 person-years; 95% CI, 7.12/1000 to 10.75/1000). Hip fracture rates over time were virtually identical in patients aged less than 65 years; however, rates decreased by 15.3% among patients aged 65 years or older; rates declined more rapidly in older women compared with older men (p for interaction = 0.047). In-hospital mortality rate after hip fracture operation declined by 26.7% from 2003 (8.6%; 95% CI, 6.8 to 10.4) to 2011 (6.3%; 95% CI, 4.9 to 7.7). In ESRD, age- and sex-standardized hip fracture rates and associated in-hospital mortality have declined substantially over the last decade. © 2017 American Society for Bone and Mineral Research.

  View details for PubMedID 28639740

• Receipt of Nephrology Care and Clinical Outcomes Among Veterans With Advanced CKD AMERICAN JOURNAL OF KIDNEY DISEASES Fung, E., Chang, T. I., Chertow, G. M., Thomas, I., Asch, S. M., Tamura, M. 2017; 70 (5): 705–14

  Abstract

  Clinical practice guidelines recommend referral to nephrology when estimated glomerular filtration rate (eGFR) decreases to <30mL/min/1.73m2; however, evidence for benefits of nephrology care are mixed.Observational cohort using landmark analysis.A national cohort of veterans with advanced chronic kidney disease, defined as an outpatient eGFR≤30mL/min/1.73m2 for January 1, 2010, through December 31, 2010, and a prior eGFR<60mL/min/1.73m2, using administrative and laboratory data from the Department of Veterans Affairs and the US Renal Data System.Receipt and frequency of outpatient nephrology care over 12 months.Survival and progression to end-stage renal disease (ESRD; receipt of dialysis or kidney transplantation) were the primary outcomes. In addition, control of associated clinical parameters over 12 months were intermediate outcomes.Of 39,669 patients included in the cohort, 14,983 (37.8%) received nephrology care. Older age, heart failure, dementia, depression, and rapidly declining kidney function were independently associated with the absence of nephrology care. During a mean follow-up of 2.9 years, 14,719 (37.1%) patients died and 4,310 (10.9%) progressed to ESRD. In models adjusting for demographics, comorbid conditions, and trajectory of kidney function, nephrology care was associated with lower risk for death (HR, 0.88; 95% CI, 0.85-0.91), but higher risk for ESRD (HR, 1.48; 95% CI, 1.38-1.58). Among patients with clinical parameters outside guideline recommendations at cohort entry, a significantly higher adjusted proportion of patients who received nephrology care had improvement in control of hemoglobin, potassium, albumin, calcium, and phosphorus concentrations compared with those who did not receive nephrology care.May not be generalizable to nonveterans.Among patients with advanced chronic kidney disease, nephrology care was associated with lower mortality, but was not associated with lower risk for progression to ESRD.

  View details for PubMedID 28811048

• Effectiveness of Quality Improvement Strategies for the Management of CKD A Meta-Analysis CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Silver, S. A., Bell, C. M., Chertow, G. M., Shah, P. S., Shojania, K., Wald, R., Harel, Z. 2017; 12 (10): 1601–14

  Abstract

  Quality improvement interventions have enhanced care for other chronic illnesses, but their effectiveness for patients with CKD is unknown. We sought to determine the effects of quality improvement strategies on clinical outcomes in adult patients with nondialysis-requiring CKD.We conducted a systematic review of randomized trials, searching Medline and the Cochrane Effective Practice and Organization of Care database from January of 2003 to April of 2015. Eligible studies evaluated one or more of 11 prespecified quality improvement strategies, and prespecified study outcomes included at least one process of care measure, surrogate outcome, or hard clinical outcome. We used a random effects model to estimate the pooled risk ratio (RR; dichotomous data) or the mean difference (continuous data).We reviewed 15 patient-level randomized trials (n=3298 patients), and six cluster-randomized trials (n=30,042 patients). Quality improvement strategies reduced dialysis incidence (seven trials; RR, 0.85; 95% confidence interval [95% CI], 0.74 to 0.97) and LDL cholesterol concentrations (four trials; mean difference, -17.6 mg/dl; 95% CI, -28.7 to -6.5), and increased the likelihood that patients received renin-angiotensin-aldosterone system inhibitors (nine trials; RR, 1.16; 95% CI, 1.06 to 1.27). We did not observe statistically significant effects on mortality, cardiovascular events, eGFR, glycated hemoglobin, and systolic or diastolic BP.Quality improvement interventions yielded significant beneficial effects on three elements of CKD care. Estimates of the effectiveness of quality improvement strategies were limited by study number and adherence to quality improvement principles.This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2017_09_06_CJASNPodcast_17_10.mp3.

  View details for PubMedID 28877926

• Visit-to-Visit Office Blood Pressure Variability and Cardiovascular Outcomes in SPRINT (Systolic Blood Pressure Intervention Trial) HYPERTENSION Chang, T. I., Reboussin, D. M., Chertow, G. M., Cheung, A. K., Cushman, W. C., Kostis, W. J., Parati, G., Raj, D., Riessen, E., Shapiro, B., Stergiou, G. S., Townsend, R. R., Tsioufis, K., Whelton, P. K., Whittle, J., Wright, J. T., Papademetriou, V., SPRINT Res Grp 2017; 70 (4): 751-+

  Abstract

  Studies of visit-to-visit office blood pressure (BP) variability (OBPV) as a predictor of cardiovascular events and death in high-risk patients treated to lower BP targets are lacking. We conducted a post hoc analysis of SPRINT (Systolic Blood Pressure Intervention Trial), a well-characterized cohort of participants randomized to intensive (<120 mm Hg) or standard (<140 mm Hg) systolic BP targets. We defined OBPV as the coefficient of variation of the systolic BP using measurements taken during the 3-,6-, 9-, and 12-month study visits. In our cohort of 7879 participants, older age, female sex, black race, current smoking, chronic kidney disease, and coronary disease were independent determinants of higher OBPV. Use of thiazide-type diuretics or dihydropyridine calcium channel blockers was associated with lower OBPV whereas angiotensin-converting enzyme inhibitors or angiotensin receptor blocker use was associated with higher OBPV. There was no difference in OBPV in participants randomized to standard or intensive treatment groups. We found that OBPV had no significant associations with the composite end point of fatal and nonfatal cardiovascular events (n=324 primary end points; adjusted hazard ratio, 1.20; 95% confidence interval, 0.85-1.69, highest versus lowest quintile) nor with heart failure or stroke. The highest quintile of OBPV (versus lowest) was associated with all-cause mortality (adjusted hazard ratio, 1.92; confidence interval, 1.22-3.03) although the association of OBPV overall with all-cause mortality was marginal (P=0.07). Our results suggest that clinicians should continue to focus on office BP control rather than on OBPV unless definitive benefits of reducing OBPV are shown in prospective trials.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01206062.

  View details for PubMedID 28760939

• Effects of Intensive BP Control in CKD JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Cheung, A. K., Rahman, M., Reboussin, D. M., Craven, T. E., Greene, T., Kimmel, P. L., Cushman, W. C., Hawfield, A. T., Johnson, K. C., Lewis, C. E., Oparil, S., Rocco, M. V., Sink, K. M., Whelton, P. K., Wright, J. T., Basile, J., Beddhu, S., Bhatt, U., Chang, T. I., Chertow, G. M., Chonchol, M., Freedman, B. I., Haley, W., Ix, J. H., Katz, L. A., Killeen, A. A., Papademetriou, V., Ricardo, A. C., Servilla, K., Wall, B., Wolfgram, D., Yee, J., SPRINT Res Grp 2017; 28 (9): 2812–23

  Abstract

  The appropriate target for BP in patients with CKD and hypertension remains uncertain. We report prespecified subgroup analyses of outcomes in participants with baseline CKD in the Systolic Blood Pressure Intervention Trial. We randomly assigned participants to a systolic BP target of <120 mm Hg (intensive group; n=1330) or <140 mm Hg (standard group; n=1316). After a median follow-up of 3.3 years, the primary composite cardiovascular outcome occurred in 112 intensive group and 131 standard group CKD participants (hazard ratio [HR], 0.81; 95% confidence interval [95% CI], 0.63 to 1.05). The intensive group also had a lower rate of all-cause death (HR, 0.72; 95% CI, 0.53 to 0.99). Treatment effects did not differ between participants with and without CKD (P values for interactions ≥0.30). The prespecified main kidney outcome, defined as the composite of ≥50% decrease in eGFR from baseline or ESRD, occurred in 15 intensive group and 16 standard group participants (HR, 0.90; 95% CI, 0.44 to 1.83). After the initial 6 months, the intensive group had a slightly higher rate of change in eGFR (-0.47 versus -0.32 ml/min per 1.73 m2 per year; P<0.03). The overall rate of serious adverse events did not differ between treatment groups, although some specific adverse events occurred more often in the intensive group. Thus, among patients with CKD and hypertension without diabetes, targeting an SBP<120 mm Hg compared with <140 mm Hg reduced rates of major cardiovascular events and all-cause death without evidence of effect modifications by CKD or deleterious effect on the main kidney outcome.

  View details for PubMedID 28642330

• Clinical Outcomes by Race and Ethnicity in the Systolic Blood Pressure Intervention Trials (SPRINT): A Randomized Control Trial Still, C. H., Rodriguez, C. J., Wright, J. T., Craven, T. E., Bress, A. P., Chertow, G. M., Whelton, P. K., Whittle, J. C., Freeman, B., Johnson, K. C., Foy, C. G., He, J., Kostis, J. B., Lash, J. P., Pedley, C. F., Pisoni, R., Powell, J. R., Wall, B. M. LIPPINCOTT WILLIAMS & WILKINS. 2017

  View details for Web of Science ID 000523486000047

• Screening Rates for the Diagnostic Workup of Resistant Hypertension Jaffe, G. M., Krishnan, G., Stedman, M., Chertow, G. M., Leppert, J. T., Bhalla, V. LIPPINCOTT WILLIAMS & WILKINS. 2017

  View details for Web of Science ID 000523486000196

• Prehabilitation for kidney transplant candidates: Is it time? CLINICAL TRANSPLANTATION Cheng, X. S., Myers, J. N., Chertow, G. M., Rabkin, R., Chan, K. N., Chen, Y., Tan, J. C. 2017; 31 (8)

  View details for DOI 10.1111/ctr.13020

  View details for Web of Science ID 000407287900013

• Calcium-Sensing Receptor Genotype and Response to Cinacalcet in Patients Undergoing Hemodialysis CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Moe, S. M., Wetherill, L., Decker, B., Lai, D., Abdalla, S., Long, J., Vatta, M., Foroud, T. M., Chertow, G. M. 2017; 12 (7): 1128–38

  Abstract

  We tested the hypothesis that single nucleotide polymorphisms (SNPs) in the calcium-sensing receptor (CASR) alter the response to the calcimimetic cinacalcet.We analyzed DNA samples in the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) trial, a randomized trial comparing cinacalcet to placebo on a background of usual care. Of the 3883 patients randomized, 1919 (49%) consented to DNA collection, and samples from 1852 participants were genotyped for 18 CASR polymorphisms. The European ancestry (EA; n=1067) and African ancestry (AfAn; n=405) groups were assessed separately. SNPs in CASR were tested for their association with biochemical measures of mineral metabolism at baseline, percent change from baseline to 20 weeks, and risk of clinical fracture as dependent variables.There were modest associations of CASR SNPs with increased baseline serum parathyroid hormone and bone alkaline phosphatase primarily with the minor allele in the EA group (all P≤0.03), but not in the AfAn sample. In contrast, there was a modest association of decreased baseline serum calcium and FGF23 with CASR SNPs (P=0.04) primarily with the minor allele in the AfAn but not in the EA sample. The minor allele of two SNPs was associated with decreased percent reduction in parathyroid hormone from baseline to 20 weeks in the EA population (P<0.04) and this was not altered with cinacalcet. In both EA and AfAn, the same SNP (rs9740) was associated with decreased calcium with cinacalcet treatment (EA and AfAn P≤0.03). Three SNPs in high linkage disequilibrium were associated with a higher risk of clinical fracture that was attenuated by cinacalcet treatment in the EA sample (P<0.04).These modest associations, if validated, may provide explanations for differences in CKD-mineral bone disorder observed in EA and AfAn populations, and for differential biochemical responses to calcimimetics.

  View details for DOI 10.2215/CJN.11141016

  View details for Web of Science ID 000404992800014

  View details for PubMedID 28630081

  View details for PubMedCentralID PMC5498355

• Factors Associated with Frailty and Its Trajectory among Patients on Hemodialysis. Clinical journal of the American Society of Nephrology Johansen, K. L., Dalrymple, L. S., Delgado, C., Chertow, G. M., Segal, M. R., Chiang, J., Grimes, B., Kaysen, G. A. 2017

  Abstract

  Frailty is common among patients on hemodialysis and associated with adverse outcomes. However, little is known about changes in frailty over time and the factors associated with those changes.To address these questions, we examined 762 participants in the A Cohort to Investigate the Value of Exercise/Analyses Designed to Investigate the Paradox of Obesity and Survival in ESRD cohort study, among whom frailty was assessed at baseline and 12 and 24 months. We used ordinal generalized estimating equations analyses and modeled frailty (on a scale from zero to five possible components) and death during follow-up.The mean frailty score at baseline was 1.9, and the distribution of frailty scores was similar at each evaluation. However, most participants' scores changed, with patients improving almost as often as worsening (overall change, 0.2 points per year; 95% confidence interval, 0.1 to 0.3). Hispanic ethnicity (0.6 points per year; 95% confidence interval, 0.0 to 1.1) and diabetes (0.7 points per year; 95% confidence interval, 0.3 to 1.0) were associated with higher frailty scores and higher serum albumin concentration with lower frailty scores (-1.1 points per g/dl; 95% confidence interval, -1.5 to -0.7). In addition, patients whose serum albumin increased over time were less likely to become frail, with each 1-g/dl increase in albumin associated with a 0.4-point reduction in frailty score (95% confidence interval, -0.80 to -0.05). To examine the underpinnings of the association between serum albumin and frailty, we included serum IL-6, normalized protein catabolic rate, and patient self-report of hospitalization within the last year in a second model. Higher IL-6 and hospitalization were statistically significantly associated with worse frailty at any point and worsening frailty over time, whereas normalized protein catabolic rate was not independently associated with frailty.There was substantial year to year variability in frailty scores, with approximately equal numbers of patients improving and worsening. Markers of inflammation and hospitalization were independently associated with worsening frailty. Studies should examine whether interventions to address inflammation or posthospitalization rehabilitation can improve the trajectory of frailty.

  View details for DOI 10.2215/CJN.12131116

  View details for PubMedID 28576906

• Effect of Tenapanor on Serum Phosphate in Patients Receiving Hemodialysis JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Block, G. A., Rosenbaum, D. P., Leonsson-Zachrisson, M., Astrand, M., Johansson, S., Knutsson, M., Langkilde, A., Chertow, G. M. 2017; 28 (6): 1933–42

  Abstract

  Hyperphosphatemia is common among patients with CKD stage 5D and is associated with morbidity and mortality. Current guidelines recommend lowering serum phosphate concentrations toward normal. Tenapanor is a minimally absorbed small molecule inhibitor of the sodium/hydrogen exchanger isoform 3 that functions in the gut to reduce sodium and phosphate absorption. This randomized, double-blind, placebo-controlled trial assessed the effects of tenapanor on serum phosphate concentration in patients with hyperphosphatemia receiving hemodialysis. After a 1- to 3-week washout of phosphate binders, we randomly assigned 162 eligible patients (serum phosphate =6.0 to <10.0 mg/dl and a 1.5-mg/dl increase from before washout) to one of six tenapanor regimens (3 or 30 mg once daily or 1, 3, 10, or 30 mg twice daily) or placebo for 4 weeks. The primary efficacy end point was change in serum phosphate concentration from baseline (randomization) to end of treatment. In total, 115 patients (71%) completed the study. Mean serum phosphate concentrations at baseline (after washout) were 7.32-7.92 mg/dl for tenapanor groups and 7.87 mg/dl for the placebo group. Tenapanor provided dose-dependent reductions in serum phosphate level from baseline (least squares mean change: tenapanor =0.47-1.98 mg/dl; placebo =0.54 mg/dl; P=0.01). Diarrhea was the most common adverse event (tenapanor =18%-68%; placebo =12%) and frequent at the highest tenapanor doses. In conclusion, tenapanor treatment resulted in statistically significant, dose-dependent reductions in serum phosphate concentrations in patients with hyperphosphatemia receiving hemodialysis. Additional studies are required to clarify the optimal dosing of tenapanor in patients with CKD-related hyperphosphatemia.

  View details for PubMedID 28159782

  View details for PubMedCentralID PMC5461797

• Warfarin and the Risk of Stroke and Bleeding in Patients With Atrial Fibrillation Receiving Dialysis: A Systematic Review and Meta-analysis CANADIAN JOURNAL OF CARDIOLOGY Harel, Z., Chertow, G. M., Shah, P. S., Harel, S., Dorian, P., Yan, A. T., Saposnik, G., Sood, M. M., Molnar, A. O., Perl, J., Wald, R. M., Silver, S., Wald, R. 2017; 33 (6): 737–46

  Abstract

  Patients with atrial fibrillation who receive dialysis are at a high risk of ischemic stroke. The role of warfarin in mitigating this risk in patients with atrial fibrillation who receive dialysis is uncertain. Our objective was to examine the safety and efficacy of warfarin in patients who have atrial fibrillation and receive dialysis.We used MedLine, Embase, and the Cochrane Library to conduct a systematic review and meta-analysis of published and unpublished observational and interventional studies related to the use of warfarin in patients with atrial fibrillation who receive dialysis, and provided data on the risk of stroke and/or bleeding outcomes relative to placebo or no anticoagulation therapy. A random effects model was used to calculate pooled adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for these outcomes.No randomized controlled trials met the criteria for inclusion. Fourteen observational studies (20,398 participants) were included in the analysis. The use of warfarin was not associated with ischemic stroke (14 studies; 20,398 participants; aHR, 0.77; 95% CI, 0.55-1.07), intracranial hemorrhage (hemorrhagic stroke; 4 studies; 15,726 participants; aHR, 1.93; 95% CI, 0.93-4.00), gastrointestinal bleeding (3 studies; 14,693 participants; aHR, 1.19; 95% CI, 0.8-1.76), or all-cause mortality (7 studies; 16,172 participants; aHR, 0.89; 95% CI, 0.72-1.11).Observational studies suggest that warfarin was not associated with a clear benefit or harm among patients who have atrial fibrillation and receive dialysis. These estimates were limited by study heterogeneity including the inability to account for a number of important confounders such as the time in the therapeutic range. Because of the high prevalence of atrial fibrillation, stroke, and bleeding complications in this population, well designed clinical trials of warfarin and other anticoagulants are urgently needed.

  View details for PubMedID 28545622

• Effects of Ferric Citrate in Patients with Nondialysis-Dependent CKD and Iron Deficiency Anemia JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Fishbane, S., Block, G. A., Loram, L., Neylan, J., Pergola, P. E., Uhlig, K., Chertow, G. M. 2017; 28 (6): 1851–58

  Abstract

  Iron deficiency anemia is common and consequential in nondialysis-dependent CKD (NDD-CKD). Efficacy and tolerability of conventional oral iron supplements are mixed; intravenous iron administration associates with finite but important risks. We conducted a randomized double-blind clinical trial in adults with NDD-CKD and iron deficiency anemia to compare the safety and efficacy of oral ferric citrate (n=117) and placebo (n=115). The primary end point was the proportion of patients who achieved a ≥1.0 g/dl increase in hemoglobin at any time during a 16-week randomized period. Patients who completed the 16-week period could also participate in an 8-week open-label extension period. Significantly more patients randomized to ferric citrate achieved the primary end point (61 [52.1%] versus 22 [19.1%] with placebo; P<0.001). All secondary end points reached statistical significance in the ferric citrate group, including the mean relative change in hemoglobin (0.84 g/dl; 95% confidence interval, 0.58 to 1.10 g/dl; P<0.001) and the proportion of patients who achieved a sustained increase in hemoglobin (≥0.75 g/dl over any 4-week period during the randomized trial; 57 [48.7%] versus 17 [14.8%] with placebo; P<0.001). Rates of serious adverse events were similar in the ferric citrate (12.0%) and placebo groups (11.2%). Gastrointestinal disorders were the most common adverse events, with diarrhea reported in 24 (20.5%) and 19 (16.4%) and constipation in 22 (18.8%) and 15 (12.9%) patients treated with ferric citrate and placebo, respectively. Overall, in patients with NDD-CKD, we found oral ferric citrate to be a safe and efficacious treatment for iron deficiency anemia.

  View details for PubMedID 28082519

• Prehabilitation for Kidney Transplant Candidates: Is it Time? Clinical transplantation Cheng, X. S., Myers, J. N., Chertow, G. M., Rabkin, R., Chan, K. N., Chen, Y., Tan, J. C. 2017

  Abstract

  Many patients become frail with diminished cardiorespiratory fitness while awaiting kidney transplantation. Frailty and poor fitness powerfully predict mortality, transplant graft survival, and health care utilization after kidney transplantation. Efforts to intervene with post-transplant physical therapy have been met with limited success, in large part due to high study drop-out. We reviewed the literature on chronic kidney disease and exercise to propose a clinical framework for physical therapy interventions to improve fitness, scheduled for before the transplant. This framework may lead to better patient retention and compliance, and thus demonstrate better efficacy in mitigating the effects of frailty and poor fitness after kidney transplantation. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/ctr.13020

  View details for PubMedID 28564126

• Dosing of Etelcalcetide and Cinacalcet for Secondary Hyperparathyroidism Reply JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Block, G. A., Chertow, G. M. 2017; 317 (20): 2132–33

  View details for PubMedID 28535231

• Home Dialysis in the Prospective Payment System Era. Journal of the American Society of Nephrology Lin, E., Cheng, X. S., Chin, K., Zubair, T., Chertow, G. M., Bendavid, E., Bhattacharya, J. 2017

  Abstract

  The ESRD Prospective Payment System introduced two incentives to increase home dialysis use: bundling injectable medications into a single payment for treatment and paying for home dialysis training. We evaluated the effects of the ESRD Prospective Payment System on home dialysis use by patients starting dialysis in the United States from January 1, 2006 to August 31, 2013. We analyzed data on dialysis modality, insurance type, and comorbidities from the United States Renal Data System. We estimated the effect of the policy on home dialysis use with multivariable logistic regression and compared the effect on Medicare Parts A/B beneficiaries with the effect on patients with other types of insurance. The ESRD Prospective Payment System associated with a 5.0% (95% confidence interval [95% CI], 4.0% to 6.0%) increase in home dialysis use by the end of the study period. Home dialysis use increased by 5.8% (95% CI, 4.3% to 6.9%) among Medicare beneficiaries and 4.1% (95% CI, 2.3% to 5.4%) among patients covered by other forms of health insurance. The difference between these groups was not statistically significant (1.8%; 95% CI, -0.2% to 3.8%). Conversely, in both populations, the training add-on did not associate with increases in home dialysis use beyond the effect of the policy. The ESRD Prospective Payment System bundling, but not the training add-on, associated with substantial increases in home dialysis, which were identical for both Medicare and non-Medicare patients. These spill-over effects suggest that major payment changes in Medicare can affect all patients with ESRD.

  View details for DOI 10.1681/ASN.2017010041

  View details for PubMedID 28490435

• Utility in Treating Kidney Failure in End-Stage Liver Disease With Simultaneous Liver-Kidney Transplantation TRANSPLANTATION Cheng, X. S., Stedman, M. R., Chertow, G. M., Kim, W. R., Tan, J. C. 2017; 101 (5): 1111-1119

  Abstract

  Simultaneous liver-kidney (SLK) transplantation plays an important role in treating kidney failure in patients with end-stage liver disease. It used 5% of deceased donor kidney transplanted in 2015. We evaluated the utility, defined as posttransplant kidney allograft lifespan, of this practice.Using data from the Scientific Registry of Transplant Recipients, we compared outcomes for all SLK transplants between January 1, 1995, and December 3, 2014, to their donor-matched kidney used in kidney-alone (Ki) or simultaneous pancreas kidney (SPK) transplants. Primary outcome was kidney allograft lifespan, defined as the time free from death or allograft failure. Secondary outcomes included death and death-censored allograft failure. We adjusted all analyses for donor, transplant, and recipient factors.The adjusted 10-year mean kidney allograft lifespan was higher in Ki/SPK compared with SLK transplants by 0.99 years in the Model for End-stage Liver Disease era and 1.71 years in the pre-Model for End-stage Liver Disease era. Death was higher in SLK recipients relative to Ki/SPK recipients: 10-year cumulative incidences 0.36 (95% confident interval 0.33-0.38) versus 0.19 (95% confident interval 0.17-0.21).SLK transplantation exemplifies the trade-off between the principles of utility and medical urgency. With each SLK transplantation, about 1 year of allograft lifespan is traded so that sicker patients, that is, SLK transplant recipients, are afforded access to the organ. These data provide a basis against which benefits derived from urgency-based allocation can be measured.

  View details for DOI 10.1097/TP.0000000000001491

  View details for PubMedID 28437790

• Limited reduction in uremic solute concentrations with increased dialysis frequency and time in the Frequent Hemodialysis Network Daily Trial KIDNEY INTERNATIONAL Sirich, T. L., Fong, K., Larive, B., Beck, G. J., Chertow, G. M., Levin, N. W., Kliger, A. S., Plummer, N. S., Meyer, T. W., Frequent Hemodialysis Network FHN 2017; 91 (5): 1186–92

  View details for DOI 10.1016/j.kint.2016.11.002

  View details for Web of Science ID 000400541000020

• IMPACT OF ETELCALCETIDE ON FGF23 LEVELS DURING THE TREATMENT OF SECONDARY HYPERPARATHYROIDISM IN PATIENTS ON HEMODIALYSIS Wolf, M., Block, G., Chertow, G., Cooper, K., Fouqueray, B., Moe, S., Sun, Y., Tomlin, H., Vervloet, M., Oberbauer, R. OXFORD UNIV PRESS. 2017

  View details for Web of Science ID 000469797100032

• Hyperprolactinemia in end-stage renal disease and effects of frequent hemodialysis HEMODIALYSIS INTERNATIONAL Lo, J. C., Beck, G. J., Kaysen, G. A., Chan, C. T., Kliger, A. S., Rocco, M. V., Chertow, G. M. 2017; 21 (2): 190-196

  Abstract

  Introduction End-stage renal disease is associated with elevations in circulating prolactin concentrations, but the association of prolactin concentrations with intermediate health outcomes and the effects of hemodialysis frequency on changes in serum prolactin have not been examined. Methods The FHN Daily and Nocturnal Dialysis Trials compared the effects of conventional thrice weekly hemodialysis with in-center daily hemodialysis (6 days/week) and nocturnal home hemodialysis (6 nights/week) over 12 months and obtained measures of health-related quality of life, self-reported physical function, mental health and cognition. Serum prolactin concentrations were measured at baseline and 12-month follow-up in 70% of the FHN Trial cohort to examine the associations among serum prolactin concentrations and physical, mental and cognitive function and the effects of hemodialysis frequency on serum prolactin. Findings Among 177 Daily Trial and 60 Nocturnal Trial participants with baseline serum prolactin measurements, the median serum prolactin concentration was 65 ng/mL (25th-75th percentile 48-195 ng/mL) and 81% had serum prolactin concentrations >30 ng/mL. While serum prolactin was associated with sex (higher in women), we observed no association between baseline serum prolactin and age, dialysis vintage, and baseline measures of physical, mental and cognitive function. Furthermore, there was no significant effect of hemodialysis frequency on serum prolactin in either of the two trials. Discussion Serum prolactin concentrations were elevated in the large majority of patients with ESRD, but were not associated with several measures of health status. Circulating prolactin levels also do not appear to decrease in response to more frequent hemodialysis over a one-year period.

  View details for DOI 10.1111/hdi.12489

  View details for Web of Science ID 000398574500011

• ANALYSIS OF A SINGLE-ARM EXTENSION STUDY EVALUATING ETELCALETIDE STARTING DOSE FOR TREATMENT OF SECONDARY HYPERPARATHYROIDISM IN PATIENTS ON HEMODIALYSIS Cheng, S., Block, G., Dehmel, B., Deng, H., Chertow, G. W B SAUNDERS CO-ELSEVIER INC. 2017: A34

  View details for Web of Science ID 000397702100086

• FERRIC CITRATE INCREASES HEMOGLOBIN IN PATIENTS WITH NON-DIALYSIS-DEPENDENT CHRONIC KIDNEY DISEASE AND IRON DEFICIENCY ANEMIA. Pergola, P. E., Fishbane, S., Neylan, J. F., Uhlig, K., Chertow, G. M. W B SAUNDERS CO-ELSEVIER INC. 2017: A76

  View details for Web of Science ID 000397702100254

• THE INNO(2)VATE PHASE 3 PROGRAM OF VADADUSTAT FOR TREATMENT OF ANEMIA IN DIALYSIS-DEPENDENT CKD: RATIONALE AND STUDY DESIGN Winkelmayer, W., Block, G., Chertow, G., Fishbane, S., Komatsu, Y., McCullough, P., Pergola, P., Rosenberger, C., Williamson, D., Yee, J., Collins, A., Khawaja, Z., Sharma, A., Zuraw, Q., Maroni, B. W B SAUNDERS CO-ELSEVIER INC. 2017: A102

  View details for Web of Science ID 000397702100360

• Glycovariations in Key HDL-Associated Glycoproteins Differentiate Between Clinical Groups and Affect the Immunomodulatory Capacity of HDL Zivkovic, A. M., Krishnan, S., Shimoda, M., Sacchi, R., Muchena, J. K., Luxardi, G., Kaysen, G. A., Parikh, A. N., Ngassam, V., Johansen, K., Chertow, G., Grimes, B., Smilowitz, J. T., Maverakis, E., Lebrilla, C. B. FEDERATION AMER SOC EXP BIOL. 2017

  View details for Web of Science ID 000405461405436

• Thyroid function in end stage renal disease and effects of frequent hemodialysis. Hemodialysis international. International Symposium on Home Hemodialysis Lo, J. C., Beck, G. J., Kaysen, G. A., Chan, C. T., Kliger, A. S., Rocco, M. V., Li, M., Chertow, G. M. 2017

  Abstract

  End-stage renal disease (ESRD) is associated with perturbations in thyroid hormone concentrations and an increased prevalence of hypothyroidism. Few studies have examined the effects of hemodialysis dose or frequency on endogenous thyroid function.Within the Frequent Hemodialysis Network (FHN) trials, we examined the prevalence of hypothyroidism in patients with ESRD. Among those with endogenous thyroid function (without overt hyper/hypothyroidism or thyroid hormone supplementation), we examined the association of thyroid hormone concentration with multiple parameters of self-reported health status, and physical and cognitive performance, and the effects of hemodialysis frequency on serum thyroid stimulating hormone (TSH), free thyroxine (FT4), and free tri-iodothyronine (FT3) levels. Conventional thrice-weekly hemodialysis was compared to in-center (6 d/wk) hemodialysis (Daily Trial) and Nocturnal (6 nights/wk) home hemodialysis (Nocturnal Trial) over 12 months.Among 226 FHN Trial participants, the prevalence of hypothyroidism was 11% based on thyroid hormone treatment and/or serum TSH ≥8 mIU/mL. Among the remaining 195 participants (147 Daily, 48 Nocturnal) with endogenous thyroid function, TSH concentrations were modestly (directly) correlated with age (r = 0.16, P = 0.03) but not dialysis vintage. Circulating thyroid hormone levels were not associated with parameters of health status or physical and cognitive performance. Furthermore, frequent in-center and nocturnal hemodialysis did not significantly change (baseline to month 12) TSH, FT4, or FT3 concentrations in patients with endogenous thyroid function.Among patients receiving hemodialysis without overt hyper/hypothyroidism or thyroid hormone treatment, thyroid indices were not associated with multiple measures of health status and were not significantly altered with increased dialysis frequency.

  View details for DOI 10.1111/hdi.12527

  View details for PubMedID 28301073

• Sarcopenia and its individual criteria are associated, in part, with mortality among patients on hemodialysis. Kidney international Kittiskulnam, P., Chertow, G. M., Carrero, J. J., Delgado, C., Kaysen, G. A., Johansen, K. L. 2017

  Abstract

  The relative importance of sarcopenia and its individual components as independent predictors of mortality in the dialysis population has not been determined. We estimated whole-body muscle mass using pre-dialysis bioimpedance spectroscopy measurements in 645 ACTIVE/ADIPOSE-enrolled prevalent hemodialysis patients from San Francisco and Atlanta. Low muscle mass was defined as two standard deviations below sex-specific means for young adults from NHANES and indexed to height(2), body weight, body surface area, or body mass index. We evaluated the association of sarcopenia (low muscle mass) by four indexing methods, weak hand grip strength, and slow gait speed with mortality. Seventy-eight deaths were observed during a mean follow-up of 1.9 years. Sarcopenia was not significantly associated with mortality after adjusting for covariates. No muscle mass criteria were associated with death, regardless of indexing metrics. In contrast, having weak grip strength or slow walking speed was associated with mortality in the adjusted model. Only gait slowness significantly improved the predictive accuracy for death with an increase in C-statistic from 0.63 to 0.68. However, both gait slowness and hand grip weakness significantly improved the net reclassification index compared to models without performance measures (50.5% for slowness and 33.7% for weakness), whereas models with muscle size did not. Neither sarcopenia nor low muscle mass by itself was a better predictor of mortality than functional limitation alone in patients receiving hemodialysis. Thus, physical performance measures, including slow gait speed and weak hand grip strength, were associated with mortality even after adjustment for muscle size and other confounders.

  View details for DOI 10.1016/j.kint.2017.01.024

  View details for PubMedID 28318630

• Prevalence of chronic kidney disease and risk factors for its progression: A cross-sectional comparison of Indians living in Indian versus US cities PLOS ONE Anand, S., Kondal, D., Montez-Rath, M., Zheng, Y., Shivashankar, R., Singh, K., Gupta, P., Gupta, R., Ajay, V. S., Mohan, V., Pradeepa, R., Tandon, N., Ali, M. K., Narayan, K. M., Chertow, G. M., Kandula, N., Prabhakaran, D., Kanaya, A. M. 2017; 12 (3)

  Abstract

  While data from the latter part of the twentieth century consistently showed that immigrants to high-income countries faced higher cardio-metabolic risk than their counterparts in low- and middle-income countries, urbanization and associated lifestyle changes may be changing these patterns, even for conditions considered to be advanced manifestations of cardio-metabolic disease (e.g., chronic kidney disease [CKD]).Using cross-sectional data from the Center for cArdiometabolic Risk Reduction in South Asia (CARRS, n = 5294) and Mediators of Atherosclerosis in South Asians Living in America (MASALA, n = 748) studies, we investigated whether prevalence of CKD is similar among Indians living in Indian and U.S. cities. We compared crude, age-, waist-to-height ratio-, and diabetes- adjusted CKD prevalence difference. Among participants identified to have CKD, we compared management of risk factors for its progression. Overall age-adjusted prevalence of CKD was similar in MASALA (14.0% [95% CI 11.8-16.3]) compared with CARRS (10.8% [95% CI 10.0-11.6]). Among men the prevalence difference was low (prevalence difference 1.8 [95% CI -1.6,5.3]) and remained low after adjustment for age, waist-to-height ratio, and diabetes status (-0.4 [-3.2,2.5]). Adjusted prevalence difference was higher among women (prevalence difference 8.9 [4.8,12.9]), but driven entirely by a higher prevalence of albuminuria among women in MASALA. Severity of CKD--i.e., degree of albuminuria and proportion of participants with reduced glomerular filtration fraction--was higher in CARRS for both men and women. Fewer participants with CKD in CARRS were effectively treated. 4% of CARRS versus 51% of MASALA participants with CKD had A1c < 7%; and 7% of CARRS versus 59% of MASALA participants blood pressure < 140/90 mmHg. Our analysis applies only to urban populations. Demographic--particularly educational attainment--differences among participants in the two studies are a potential source of bias.Prevalence of CKD among Indians living in Indian and U.S. cities is similar. Persons with CKD living in Indian cities face higher likelihood of experiencing end-stage renal disease since they have more severe kidney disease and little evidence of risk factor management.

  View details for DOI 10.1371/journal.pone.0173554

  View details for PubMedID 28296920

• HDL Glycoprotein Composition and Site-Specific Glycosylation Differentiates Between Clinical Groups and Affects IL-6 Secretion in Lipopolysaccharide-Stimulated Monocytes SCIENTIFIC REPORTS Krishnan, S., Shimoda, M., Sacchi, R., Kailemia, M. J., Luxardi, G., Kaysen, G. A., Parikh, A. N., Ngassam, V. N., Johansen, K., Chertow, G. M., Grimes, B., Smilowitz, J. T., Maverakis, E., Lebrilla, C. B., Zivkovic, A. M. 2017; 7

  Abstract

  The goal of this pilot study was to determine whether HDL glycoprotein composition affects HDL's immunomodulatory function. HDL were purified from healthy controls (n = 13), subjects with metabolic syndrome (MetS) (n = 13), and diabetic hemodialysis (HD) patients (n = 24). Concentrations of HDL-bound serum amyloid A (SAA), lipopolysaccharide binding protein (LBP), apolipoprotein A-I (ApoA-I), apolipoprotein C-III (ApoC-III), α-1-antitrypsin (A1AT), and α-2-HS-glycoprotein (A2HSG); and the site-specific glycovariations of ApoC-III, A1AT, and A2HSG were measured. Secretion of interleukin 6 (IL-6) in lipopolysaccharide-stimulated monocytes was used as a prototypical assay of HDL's immunomodulatory capacity. HDL from HD patients were enriched in SAA, LBP, ApoC-III, di-sialylated ApoC-III (ApoC-III2) and desialylated A2HSG. HDL that increased IL-6 secretion were enriched in ApoC-III, di-sialylated glycans at multiple A1AT glycosylation sites and desialylated A2HSG, and depleted in mono-sialylated ApoC-III (ApoC-III1). Subgroup analysis on HD patients who experienced an infectious hospitalization event within 60 days (HD+) (n = 12), vs. those with no event (HD-) (n = 12) showed that HDL from HD+ patients were enriched in SAA but had lower levels of sialylation across glycoproteins. Our results demonstrate that HDL glycoprotein composition, including the site-specific glycosylation, differentiate between clinical groups, correlate with HDL's immunomodulatory capacity, and may be predictive of HDL's ability to protect from infection.

  View details for DOI 10.1038/srep43728

  View details for Web of Science ID 000396421300001

  View details for PubMedID 28287093

• Patients receiving frequent hemodialysis have better health-related quality of life compared to patients receiving conventional hemodialysis. Kidney international Garg, A. X., Suri, R. S., Eggers, P., Finkelstein, F. O., Greene, T., Kimmel, P. L., Kliger, A. S., Larive, B., Lindsay, R. M., Pierratos, A., Unruh, M., Chertow, G. M. 2017; 91 (3): 746-754

  Abstract

  Most patients with end-stage kidney disease value their health-related quality of life (HRQoL) and want to know how it will be affected by their dialysis modality. We extended the findings of two prior clinical trial reports to estimate the effects of frequent compared to conventional hemodialysis on additional measures of HRQoL. The Daily Trial randomly assigned 245 patients to receive frequent (six times per week) or conventional (three times per week) in-center hemodialysis. The Nocturnal Trial randomly assigned 87 patients to receive frequent nocturnal (six times per week) or conventional (three times per week) home hemodialysis. All patients were on conventional hemodialysis prior to randomization, with an average feeling thermometer score of 70 to 75 (a visual analog scale from 0 to 100 where 100 is perfect health), an average general health scale score of 40 to 47 (a score from 0 to 100 where 100 is perfect health), and an average dialysis session recovery time of 2 to 3 hours. Outcomes are reported as the between-treatment group differences in one-year change in HRQoL measures and analyzed using linear mixed effects models. After one year in the Daily Trial, patients assigned to frequent in-center hemodialysis reported a higher feeling thermometer score, better general health, and a shorter recovery time after a dialysis session compared to standard thrice-weekly dialysis. After one year in the Nocturnal Trial, patients assigned to frequent home hemodialysis also reported a shorter recovery time after a dialysis session, but no statistical difference in their feeling thermometer or general health scores compared to standard home dialysis schedules. Thus, patients receiving day or nocturnal hemodialysis on average recovered approximately one hour earlier from a frequent compared to conventional hemodialysis session. Patients treated in an in-center dialysis facility reported better HRQoL with frequent compared to conventional hemodialysis.

  View details for DOI 10.1016/j.kint.2016.10.033

  View details for PubMedID 28094031

• Net Budgetary Impact of Ferric Citrate as a First-Line Phosphate Binder for the Treatment of Hyperphosphatemia: A Markov Microsimulation Model DRUGS IN R&D Brunelli, S. M., Sibbel, S. P., Van Wyck, D., Sharma, A., Hsieh, A., Chertow, G. M. 2017; 17 (1): 159–66

  Abstract

  Ferric citrate (FC) has demonstrated efficacy as a phosphate binder and reduces the requirements for erythropoiesis-stimulating agents (ESAs) and intravenous (IV) iron in dialysis patients. We developed a net budgetary impact model to evaluate FC vs. other phosphate binders from the vantage of a large dialysis provider. We used a Markov microsimulation model to simulate mutually referential longitudinal effects between serum phosphate and phosphate binder dose; categories of these defined health states. Health states probabilistically determined treatment attendance and utilization of ESA and IV iron. We derived model inputs from a retrospective analysis of incident phosphate binder users from a large dialysis organization (January 2011-June 2013) and incorporated treatment effects of FC from a phase III trial. The model was run over a 1-year time horizon. We considered fixed costs of providing dialysis; costs of administering ESA and IV iron; and payment rates for dialysis, ESAs, and IV iron. In the base-case model, FC had a net budgetary impact (savings) of +US$213,223/year per 100 patients treated vs. standard of care. One-way sensitivity analyses showed a net budgetary impact of up to +US$316,296/year per 100 patients treated when higher hemoglobin levels observed with FC translated into a 30% additional ESA dose reduction, and up to +US$223,281/year per 100 patients treated when effects on missed treatment rates were varied. Two-way sensitivity analyses in which acquisition costs for ESA and IV iron were varied showed a net budgetary impact of +US$104,840 to +US$213,223/year per 100 patients treated. FC as a first-line phosphate binder would likely yield substantive savings vs. standard of care under current reimbursement.

  View details for PubMedID 28078600

  View details for PubMedCentralID PMC5318331

• Consolidation in the Dialysis Industry, Patient Choice, and Local Market Competition CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Erickson, K. F., Zheng, Y., Winkelmayer, W. C., Ho, V., Bhattacharya, J., Chertow, G. M. 2017; 12 (3): 536-545

  Abstract

  The Medicare program insures >80% of patients with ESRD in the United States. An emphasis on reducing outpatient dialysis costs has motivated consolidation among dialysis providers, with two for-profit corporations now providing dialysis for >70% of patients. It is unknown whether industry consolidation has affected patients' ability to choose among competing dialysis providers. We identified patients receiving in-center hemodialysis at the start of 2001 and 2011 from the national ESRD registry and ascertained dialysis facility ownership. For each hospital service area, we determined the maximum distance within which 90% of patients traveled to receive dialysis in 2001. We compared the numbers of competing dialysis providers within that same distance between 2001 and 2011. Additionally, we examined the Herfindahl-Hirschman Index, a metric of market concentration ranging from near zero (perfect competition) to one (monopoly) for each hospital service area. Between 2001 and 2011, the number of different uniquely owned competing providers decreased 8%. However, increased facility entry into markets to meet rising demand for care offset the effect of provider consolidation on the number of choices available to patients. The number of dialysis facilities in the United States increased by 54%, and patients experienced an average 10% increase in the number of competing proximate facilities from which they could choose to receive dialysis (P<0.001). Local markets were highly concentrated in both 2001 and 2011 (mean Herfindahl-Hirschman Index =0.46; SD=0.2 for both years), but overall market concentration did not materially change. In summary, a decade of consolidation in the United States dialysis industry did not (on average) limit patient choice or result in more concentrated local markets. However, because dialysis markets remained highly concentrated, it will be important to understand whether market competition affects prices paid by private insurers, access to dialysis care, quality of care, and associated health outcomes.

  View details for DOI 10.2215/CJN.06340616

  View details for PubMedID 27831510

• 30-Day Readmissions After an Acute Kidney Injury Hospitalization AMERICAN JOURNAL OF MEDICINE Silver, S. A., Harel, Z., McArthur, E., Nash, D. M., Acedillo, R., Kitchlu, A., Garg, A. X., Chertow, G. M., Bell, C. M., Wald, R. 2017; 130 (2): 163-?

  Abstract

  The risk of hospital readmission in acute kidney injury survivors is not well understood. We estimated the proportion of acute kidney injury patients who were rehospitalized within 30 days and identified characteristics associated with hospital readmission.We conducted a population-based study of patients who survived a hospitalization complicated by acute kidney injury from 2003-2013 in Ontario, Canada. The primary outcome was 30-day hospital readmission. We used a propensity score model to match patients with and without acute kidney injury, and a Cox proportional hazards model with death as a competing risk to identify predictors of 30-day readmission.We identified 156,690 patients who were discharged from 197 hospitals after an episode of acute kidney injury. In the subsequent 30 days, 27,457 (18%) patients were readmitted; 15,988 (10%) visited the emergency department and 7480 (5%) died. We successfully matched 111,778 patients with acute kidney injury 1:1 to patients without acute kidney injury. The likelihood of 30-day readmission was higher in acute kidney injury patients than those without acute kidney injury (hazard ratio [HR] 1.53; 95% confidence interval [CI], 1.50-1.57). Factors most strongly associated with 30-day rehospitalization were the number of hospitalizations in the preceding year (adjusted HR 1.45 for ≥2 hospitalizations; 95% CI, 1.40-1.51) and receipt of inpatient chemotherapy (adjusted HR 1.44; 95% CI, 1.32-1.58).One in 5 patients who survive a hospitalization complicated by acute kidney injury is readmitted in the next 30 days. Better strategies are needed to identify and care for acute kidney injury survivors in the community.

  View details for DOI 10.1016/j.amjmed.2016.09.016

  View details for Web of Science ID 000392623200029

• Sarcopenia among patients receiving hemodialysis: weighing the evidence. Journal of cachexia, sarcopenia and muscle Kittiskulnam, P., Carrero, J. J., Chertow, G. M., Kaysen, G. A., Delgado, C., Johansen, K. L. 2017; 8 (1): 57-68

  Abstract

  There is no consensus on how best to define low muscle mass in patients with end-stage renal disease. Use of muscle mass normalized to height-squared has been suggested by geriatric societies but may underestimate sarcopenia, particularly in the setting of excess adiposity. We compared four definitions of low muscle mass in a prevalent hemodialysis cohort.ACTIVE/ADIPOSE enrolled prevalent patients receiving hemodialysis from the San Francisco and Atlanta areas from June 2009 to August 2011. Whole-body muscle mass was estimated using bioelectrical impedance spectroscopy, performed before a midweek dialysis session (n = 645; age 56.7 ± 14.5 years, 41% women). We defined low muscle mass as muscle mass of 2SD or more below sex-specific bioelectrical impedance spectroscopy-derived means for young adults (18-49 years) from National Health and Nutrition Examination Survey and indexed to height(2) , body weight (percentage), body surface area (BSA) by the DuBois formula, or Quételet's body mass index (BMI). We compared prevalence of low muscle mass among the four methods and assessed their correlation with strength and physical performance.The prevalence of low muscle mass ranged from 8 to 32%. Muscle mass indexed to height(2) classified the smallest percentage of patients as having low muscle mass, particularly among women, whereas indexing by BSA classified the largest percentage. Low muscle mass/height(2) was present almost exclusively among normal or underweight patients, whereas indexing to body weight and BMI classified more overweight and obese patients as having low muscle mass. Handgrip strength was lower among those with low muscle mass by all methods except height(2) . Handgrip strength was directly and modestly correlated with muscle mass normalized by percentage of body weight, BSA, and BMI (ρ = 0.43, 0.56, and, 0.64, respectively) and less so with muscle/height(2) (ρ = 0.31, P < 0.001). The difference in grip strength among patients with low vs. normal muscle mass was largest according to muscle/BMI (-6.84 kg, 95% CI -8.66 to -5.02, P < 0.001). There were significant direct correlations of gait speed with muscle mass indexed to percentage of body weight, BSA, and BMI but not with muscle mass indexed to height(2) .Skeletal muscle mass normalized to height(2) may underestimate the prevalence of low muscle mass, particularly among overweight and obese patients on hemodialysis. Valid detection of sarcopenia among obese patients receiving hemodialysis requires adjustment for body size.

  View details for DOI 10.1002/jcsm.12130

  View details for PubMedID 27897415

• Cost of Acute Kidney Injury in Hospitalized Patients. Journal of hospital medicine Silver, S. A., Long, J., Zheng, Y., Chertow, G. M. 2017; 12 (2): 70-76

  Abstract

  The economic burden of acute kidney injury (AKI) is not well understood.To estimate the effects of AKI on hospitalization costs and length of stay (LOS).Using data from the 2012 National Inpatient Sample, we compared hospitalization costs and LOS with and without AKI. We used a generalized linear model with a gamma distribution and a log link fitted to AKI to adjust for demographics, hospital differences, and comorbidities.United States.29,763,649 adult hospitalizations without endstage renal disease.AKI determined using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) diagnosis codes..Hospitalization costs and LOS.AKI was associated with an increase in hospitalization costs of $7933 (95% confidence interval [CI], $7608-$8258) and an increase in LOS of 3.2 (95% CI, 3.2-3.3) days compared to patients without AKI. When adjusted for patient and hospital characteristics, the associated increase in costs was $1795 (95% CI, $1692-$1899) and in LOS, it was 1.1 (95% CI, 1.1-1.1) days. Corresponding results among patients hospitalized with AKI requiring dialysis were $42,077 (95% CI, $39,820-$44,335) and 11.5 (95% CI, 11.2-11.8) days and $11,016 (95% CI, $10,468-$11,564) and 3.9 (95% CI, 3.8-4.1) days. AKI was associated with higher hospitalization costs than myocardial infarction and gastrointestinal bleeding, and costs were comparable to those for stroke, pancreatitis, and pneumonia..In the United States, AKI is associated with excess hospitalization costs and prolonged LOS. The economic burden of AKI warrants further attention from hospitals and policymakers to enhance processes of care and develop novel treatment strategies. Journal of Hospital Medicine 2017;12:70-76.

  View details for DOI 10.12788/jhm.2683

  View details for PubMedID 28182800

• Estimating the Risk of Radiocontrast-Associated Nephropathy JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Wilhelm-Leen, E., Montez-Rath, M. E., Chertow, G. 2017; 28 (2): 653-659

  Abstract

  Estimates of the incidence of radiocontrast-associated nephropathy vary widely and suffer from misclassification of the cause of AKI and confounding. Using the Nationwide Inpatient Sample, we created multiple estimates of the risk of radiocontrast-associated nephropathy among adult patients hospitalized in the United States in 2009. First, we stratified patients according to the presence or absence of 12 relatively common diagnoses associated with AKI and evaluated the rate of AKI between strata. Next, we created a logistic regression model, controlling for comorbidity and acuity of illness, to estimate the risk of AKI associated with radiocontrast administration within each stratum. Finally, we performed an analysis stratified by the degree of preexisting comorbidity. In general, patients who received radiocontrast did not develop AKI at a clinically significant higher rate. Adjusted only for the complex survey design, patients to whom radiocontrast was and was not administered developed AKI at rates of 5.5% and 5.6%, respectively. After controlling for comorbidity and acuity of illness, radiocontrast administration associated with an odds ratio for AKI of 0.93 (95% confidence interval, 0.88 to 0.97). In conclusion, the risk of radiocontrast-associated nephropathy may be overstated in the literature and overestimated by clinicians. More accurate AKI risk estimates may improve clinical decision-making when attempting to balance the potential benefits of radiocontrast-enhanced imaging and the risk of AKI.

  View details for DOI 10.1681/ASN.2016010021

  View details for PubMedID 27688297

• Contemporary Use of Partial Nephrectomy: Are Older Patients With Impaired Kidney Function Being Left Behind? UROLOGY Leppert, J. T., Mittakanti, H. R., Thomas, I., Lamberts, R. W., Sonn, G. A., Chung, B. I., Skinner, E. C., Wagner, T. H., Chertow, G. M., Brooks, J. D. 2017; 100: 65-71

  View details for DOI 10.1016/j.urology.2016.08.044

  View details for Web of Science ID 000397168900017

• Hemodialysis Hospitalizations and Readmissions: The Effects of Payment Reform AMERICAN JOURNAL OF KIDNEY DISEASES Erickson, K. F., Winkelmayer, W. C., Chertow, G. M., Bhattacharya, J. 2017; 69 (2): 237-246

  Abstract

  In 2004, the Centers for Medicare & Medicaid Services changed reimbursement for physicians and advanced practitioners caring for patients receiving hemodialysis from a capitated to a tiered fee-for-service system, encouraging increased face-to-face visits. This early version of a pay-for-performance initiative targeted a care process: more frequent provider visits in hemodialysis. Although more frequent provider visits in hemodialysis are associated with fewer hospitalizations and rehospitalizations, it is unknown whether encouraging more frequent visits through reimbursement policy also yielded these benefits.We used a retrospective cohort interrupted time-series study design to examine whether the 2004 nephrologist reimbursement reform led to reduced hospitalizations and rehospitalizations. We also used published data to estimate a range of annual economic costs associated with more frequent visits.Medicare beneficiaries in the United States receiving hemodialysis in the 2 years prior to and following reimbursement reform.The 2 years following nephrologist reimbursement reform.Odds of hospitalization and 30-day hospital readmission for all causes and fluid overload; US dollars.We found no significant change in all-cause hospitalization or rehospitalization and slight reductions in fluid overload hospitalization and rehospitalization following reimbursement reform; the estimated economic cost associated with additional visits ranged from $13 to $87 million per year, depending on who (physicians or advanced practitioners) spent additional time visiting patients and how much additional effort was involved.Due to limited information about how much additional time providers spent seeing patients after reimbursement reform, we could only examine a range of potential economic costs associated with the reform.A Medicare reimbursement policy designed to encourage more frequent visits during outpatient hemodialysis may have been costly. The policy was associated with fewer hospitalizations and rehospitalizations for fluid overload, but had no effect on all-cause hospitalizations or rehospitalizations.

  View details for DOI 10.1053/j.ajkd.2016.08.033

  View details for PubMedID 27856087

• Blood Calcification Propensity, Cardiovascular Events, and Survival in Patients Receiving Hemodialysis in the EVOLVE Trial CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Pasch, A., Block, G. A., Bachtler, M., Smith, E. R., Jahnen-Dechent, W., Arampatzis, S., Chertow, G. M., Parfrey, P., Ma, X., Floege, J. 2017; 12 (2): 315-322

  Abstract

  Patients receiving hemodialysis are at risk of cardiovascular events. A novel blood test (T50 test) determines the individual calcification propensity of blood.T50 was determined in 2785 baseline serum samples of patients receiving hemodialysis enrolled in the Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events (EVOLVE) trial and the T50 results were related to patient outcomes.Serum albumin, bicarbonate, HDL cholesterol, and creatinine were the main factors positively/directly and phosphate was the main factor negatively/inversely associated with T50. The primary composite end point (all-cause mortality, myocardial infarction [MI], hospitalization for unstable angina, heart failure, or peripheral vascular event [PVE]) was reached in 1350 patients after a median follow-up time of 619 days. After adjustments for confounding, a lower T50 was independently associated with a higher risk of the primary composite end point as a continuous measure (hazard ratio [HR] per 1 SD lower T50, 1.15; 95% confidence interval [95% CI], 1.08 to 1.22; P<0.001). Furthermore, lower T50 was associated with a higher risk in all-cause mortality (HR per 1 SD lower T50, 1.10; 95% CI, 1.02 to 1.17; P=0.001), MI (HR per 1 SD lower T50, 1.38; 95% CI, 1.19 to 1.60; P<0.001), and PVE (HR per 1 SD lower T50, 1.22; 95% CI, 1.05 to 1.42; P=0.01). T50 improved risk prediction (integrated discrimination improvement and net reclassification improvement, P<0.001 and P=0.001) of the primary composite end point.Blood calcification propensity was independently associated with the primary composite end point, all-cause mortality, MI, and PVE in the EVOLVE study and improved risk prediction. Prospective trials should clarify whether T50-guided therapies improve outcomes.

  View details for DOI 10.2215/CJN.04720416

  View details for PubMedID 27940458

• Limited reduction in uremic solute concentrations with increased dialysis frequency and time in the Frequent Hemodialysis Network Daily Trial. Kidney international Sirich, T. L., Fong, K., Larive, B., Beck, G. J., Chertow, G. M., Levin, N. W., Kliger, A. S., Plummer, N. S., Meyer, T. W. 2017

  Abstract

  The Frequent Hemodialysis Network Daily Trial compared conventional three-times weekly treatment to more frequent treatment with a longer weekly treatment time in patients receiving in-center hemodialysis. Evaluation at one year showed favorable effects of more intensive treatment on left ventricular mass, blood pressure, and phosphate control, but modest or no effects on physical or cognitive performance. The current study compared plasma concentrations of uremic solutes in stored samples from 53 trial patients who received three-times weekly in-center hemodialysis for an average weekly time of 10.9 hours and 30 trial patients who received six-times weekly in-center hemodialysis for an average of 14.6 hours. Metabolomic analysis revealed that increased treatment frequency and time resulted in an average reduction of only 15 percent in the levels of 107 uremic solutes. Quantitative assays confirmed that increased treatment did not significantly reduce levels of the putative uremic toxins p-cresol sulfate or indoxyl sulfate. Kinetic modeling suggested that our ability to lower solute concentrations by increasing hemodialysis frequency and duration may be limited by the presence of non-dialytic solute clearances and/or changes in solute production. Thus, failure to achieve larger reductions in uremic solute concentrations may account, in part, for the limited benefits observed with increasing frequency and weekly treatment time in Frequent Hemodialysis Daily Trial participants.

  View details for DOI 10.1016/j.kint.2016.11.002

  View details for PubMedID 28089366

• Effect of Etelcalcetide vs Placebo on Serum Parathyroid Hormone in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism Two Randomized Clinical Trials JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Block, G. A., Bushinsky, D. A., Cunningham, J., Drueke, T. B., Ketteler, M., Kewalramani, R., Martin, K. J., Mix, T. C., Moe, S. M., Patel, U. D., Silver, J., Spiegel, D. M., Sterling, L., Walsh, L., Chertow, G. M. 2017; 317 (2): 146-155

  Abstract

  Secondary hyperparathyroidism contributes to extraskeletal complications in chronic kidney disease.To evaluate the effect of the intravenous calcimimetic etelcalcetide on serum parathyroid hormone (PTH) concentrations in patients receiving hemodialysis.Two parallel, phase 3, randomized, placebo-controlled treatment trials were conducted in 1023 patients receiving hemodialysis with moderate to severe secondary hyperparathyroidism. Trial A was conducted in 508 patients at 111 sites in the United States, Canada, Europe, Israel, Russia, and Australia from March 12, 2013, to June 12, 2014; trial B was conducted in 515 patients at 97 sites in the same countries from March 12, 2013, to May 12, 2014.Intravenous administration of etelcalcetide (n = 503) or placebo (n = 513) after each hemodialysis session for 26 weeks.The primary efficacy end point was the proportion of patients achieving greater than 30% reduction from baseline in mean PTH during weeks 20-27. A secondary efficacy end point was the proportion of patients achieving mean PTH of 300 pg/mL or lower.The mean age of the 1023 patients was 58.2 (SD, 14.4) years and 60.4% were men. Mean PTH concentrations at baseline and during weeks 20-27 were 849 and 384 pg/mL vs 820 and 897 pg/mL in the etelcalcetide and placebo groups, respectively, in trial A; corresponding values were 845 and 363 pg/mL vs 852 and 960 pg/mL in trial B. Patients randomized to etelcalcetide were significantly more likely to achieve the primary efficacy end point: in trial A, 188 of 254 (74.0%) vs 21 of 254 (8.3%; P < .001), for a difference in proportions of 65.7% (95% CI, 59.4%-72.1%) and in trial B, 192 of 255 (75.3%) vs 25 of 260 (9.6%; P < .001), for a difference in proportions of 65.7% (95% CI, 59.3%-72.1%). Patients randomized to etelcalcetide were significantly more likely to achieve a PTH level of 300 pg/mL or lower: in trial A, 126 of 254 (49.6%) vs 13 of 254 (5.1%; P < .001), for a difference in proportions of 44.5% (95% CI, 37.8%-51.2%) and in trial B, 136 of 255 (53.3%) vs 12 of 260 (4.6%; P < .001), for a difference in proportions of 48.7% (95% CI, 42.1%-55.4%). In trials A and B, respectively, patients receiving etelcalcetide had more muscle spasms (12.0% and 11.1% vs 7.1% and 6.2% with placebo), nausea (12.4% and 9.1% vs 5.1% and 7.3%), and vomiting (10.4% and 7.5% vs 7.1% and 3.1%).Among patients receiving hemodialysis with moderate to severe secondary hyperparathyroidism, use of etelcalcetide compared with placebo resulted in greater reduction in serum PTH over 26 weeks. Further studies are needed to assess clinical outcomes as well as longer-term efficacy and safety.clinicaltrials.gov Identifiers: NCT01788046.

  View details for DOI 10.1001/jama.2016.19456

  View details for PubMedID 28097355

• Effect of Etelcalcetide vs Cinacalcet on Serum Parathyroid Hormone in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism A Randomized Clinical Trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Block, G. A., Bushinsky, D. A., Cheng, S., Cunningham, J., Dehmel, B., Drueke, T. B., Ketteler, M., Kewalramani, R., Martin, K. J., Moe, S. M., Patel, U. D., Silver, J., Sun, Y., Wang, H., Chertow, G. M. 2017; 317 (2): 156-164

  Abstract

  Secondary hyperparathyroidism contributes to extraskeletal calcification and is associated with all-cause and cardiovascular mortality. Control is suboptimal in the majority of patients receiving hemodialysis. An intravenously (IV) administered calcimimetic could improve adherence and reduce adverse gastrointestinal effects.To evaluate the relative efficacy and safety of the IV calcimimetic etelcalcetide and the oral calcimimetic cinacalcet.A randomized, double-blind, double-dummy active clinical trial was conducted comparing IV etelcalcetide vs oral placebo and oral cinacalcet vs IV placebo in 683 patients receiving hemodialysis with serum parathyroid hormone (PTH) concentrations higher than 500 pg/mL on active therapy at 164 sites in the United States, Canada, Europe, Russia, and New Zealand. Patients were enrolled from August 2013 to May 2014, with end of follow-up in January 2015.Etelcalcetide intravenously and oral placebo (n = 340) or oral cinacalcet and IV placebo (n = 343) for 26 weeks. The IV study drug was administered 3 times weekly with hemodialysis; the oral study drug was administered daily.The primary efficacy end point was noninferiority of etelcalcetide at achieving more than a 30% reduction from baseline in mean predialysis PTH concentrations during weeks 20-27 (noninferiority margin, 12.0%). Secondary end points included superiority in achieving biochemical end points (>50% and >30% reduction in PTH) and self-reported nausea or vomiting.The mean (SD) age of the trial participants was 54.7 (14.1) years and 56.2% were men. Etelcalcetide was noninferior to cinacalcet on the primary end point. The estimated difference in proportions of patients achieving reduction in PTH concentrations of more than 30% between the 198 of 343 patients (57.7%) randomized to receive cinacalcet and the 232 of 340 patients (68.2%) randomized to receive etelcalcetide was -10.5% (95% CI, -17.5% to -3.5%, P for noninferiority, <.001; P for superiority, .004). One hundred seventy-eight patients (52.4%) randomized to etelcalcetide achieved more than 50% reduction in PTH concentrations compared with 138 patients (40.2%) randomized to cinacalcet (P = .001; difference in proportions, 12.2%; 95% CI, 4.7% to 19.5%). The most common adverse effect was decreased blood calcium (68.9% vs 59.8%).Among patients receiving hemodialysis with moderate to severe secondary hyperparathyroidism, the use of etelcalcetide was not inferior to cinacalcet in reducing serum PTH concentrations over 26 weeks; it also met superiority criteria. Further studies are needed to assess clinical outcomes as well as longer-term efficacy and safety.clinicaltrials.gov Identifier: NCT1896232.

  View details for DOI 10.1001/jama.2016.19468

  View details for PubMedID 28097356

• Predialysis volume overload and patient-reported sleep duration and quality in patients receiving hemodialysis. Hemodialysis international. International Symposium on Home Hemodialysis Abreo, A. P., Dalrymple, L. S., Chertow, G. M., Kaysen, G. A., Herzog, C. A., Johansen, K. L. 2017; 21 (1): 133-141

  Abstract

  Previous studies of patients with end-stage renal disease have examined the role of fluid shifts on apnea-hypopnea episodes, but the association between volume overload and patient-reported sleep quality or duration has not been well-established.We studied the association between predialysis bioimpedance spectroscopy-derived volume estimates and self-reported sleep quality and duration in 638 patients in the United States Renal Data System ACTIVE/ADIPOSE study receiving hemodialysis from 2009 to 2011. We used questionnaires to assess self-reported sleep duration and quality. We used relative hydration status (fluid overload/extracellular water; FO/ECW) as the primary predictor and examined associations with hours of sleep duration using linear regression. We used multivariable ordinal logistic regression to determine the association between categories of relative hydration status (normal hydration [FO/ECW < 6.8%], mild overhydration [FO/ECW 6.8%-15%], and hyperhydration [FO/ECW > 15%]) and four levels of difficulty with falling asleep, waking, and returning to sleep.Higher relative hydration status was associated with fewer hours of sleep (-0.31 hours per 10%, 95% confidence interval (CI) -0.49 to -0.13). Compared to the normal hydration group, there was a statistically significant association between higher relative hydration status category and more frequent nighttime waking (OR: mild overhydration 1.92 [95% CI 1.23-2.99], hyperhydration 1.87 [95% CI 1.16-2.99]), a trend toward more difficulty returning to sleep (OR: mild overhydration 1.46 [95% CI 0.94-2.27], hyperhydration 1.52 [95% CI 0.95-2.43]), and no association between relative hydration category and difficulty falling asleep.Hydration status was associated with self-reported sleep duration in patients on dialysis. Future studies should prospectively examine the effects of optimizing fluid status on sleep duration and quality.

  View details for DOI 10.1111/hdi.12446

  View details for PubMedID 27346666

• Donation, Not Disease! A Multiple-Hit Hypothesis on Development of Post-Donation Kidney Disease. Current transplantation reports Cheng, X. S., Glassock, R. J., Lentine, K. L., Chertow, G. M., Tan, J. C. 2017; 4 (4): 320–26

  Abstract

  The risks following living kidney donation has been the subject of rigorous investigation in the past several decades. How to utilize the burgeoning new knowledge base to better the risk assessment, education, and health maintenance of donors is unclear. We review the physiologic and epidemiologic evidences on the post-donation state and submit a multiple-hit hypothesis to reconcile the finite elevation in risk of kidney disease after donation with the benign course of most kidney donors.The risk of end-stage kidney disease is higher in kidney donors compared to similarly healthy non-kidney donors. Nonetheless, post-donation kidney disease is uncommon and arises mostly in the setting of other "hits"-either a "first hit" present at birth or a "second hit" acquired later in life.The transplant community's focus should be directed toward (1) personalized risk assessment to inform consent before donation and (2) preventing and treating development of "second hits" following kidney donation.

  View details for PubMedID 29201600

• The Economic Consequences of Acute Kidney Injury NEPHRON Silver, S. A., Chertow, G. M. 2017; 137 (4): 297–301

  Abstract

  Acute kidney injury (AKI) is an increasingly common condition associated with poor health outcomes. Combined with its rising incidence, AKI has emerged as a major public health concern with high human and financial costs. In England, the estimated inpatient costs related to AKI consume 1% of the National Health Service budget. In the United States, AKI is associated with an increase in hospitalization costs that range from $5.4 to $24.0 billion. The most expensive patients are those with AKI of sufficient severity to require dialysis, where cost increases relative to patients without AKI range from $11,016 to $42,077 per hospitalization. Even with these high costs, significant hospital-level variation still exists in the cost of AKI care. In this article, we review the economic consequences of AKI for both the general and critically ill AKI population. Our primary objective is to shed light on an opportunity for hospitals and policymakers to develop new care processes for patients with AKI that have the potential to yield substantial cost savings. By exposing the high rates of death and disability experienced by affected patients and the immense financial burden attributable to AKI, we also hope to motivate scientists and entrepreneurs to pursue a variety of innovative therapeutic strategies to combat AKI in the near term.

  View details for PubMedID 28595193

  View details for PubMedCentralID PMC5743773

• Incident CKD after Radical or Partial Nephrectomy. Journal of the American Society of Nephrology : JASN Leppert, J. T., Lamberts, R. W., Thomas, I. C., Chung, B. I., Sonn, G. A., Skinner, E. C., Wagner, T. H., Chertow, G. M., Brooks, J. D. 2017

  Abstract

  The comparative effectiveness of partial nephrectomy versus radical nephrectomy to preserve kidney function has not been well established. We determined the risk of clinically significant (stage 4 and higher) CKD after radical or partial nephrectomy among veterans treated for kidney cancer in the Veterans Health Administration (2001-2013). Among patients with preoperative eGFR≥30 ml/min per 1.73 m(2), the incidence of CKD stage 4 or higher after radical (n=9759) or partial nephrectomy (n=4370) was 7.9% overall. The median time to stage 4 or higher CKD after surgery was 5 months, after which few patients progressed. In propensity score-matched cohorts, partial nephrectomy associated with a significantly lower relative risk of incident CKD stage 4 or higher (hazard ratio, 0.34; 95% confidence interval [95% CI], 0.26 to 0.43, versus radical nephrectomy). In a parallel analysis of patients with normal or near-normal preoperative kidney function (eGFR≥60 ml/min per 1.73 m(2)), partial nephrectomy was also associated with a significantly lower relative risk of incident CKD stage 3b or higher (hazard ratio, 0.15; 95% CI, 0.11 to 0.19, versus radical nephrectomy) in propensity score-matched cohorts. Competing risk regression models produced consistent results. Finally, patients treated with a partial nephrectomy had reduced risk of mortality (hazard ratio, 0.55; 95% CI, 0.49 to 0.62). In conclusion, compared with radical nephrectomy, partial nephrectomy was associated with a marked reduction in the incidence of clinically significant CKD and with enhanced survival. Postoperative decline in kidney function occurred mainly in the first year after surgery and appeared stable over time.

  View details for PubMedID 29018140

• The Pathogenesis of Ebola Virus Disease ANNUAL REVIEW OF PATHOLOGY: MECHANISMS OF DISEASE, VOL 12 Baseler, L., Chertow, D. S., Johnson, K. M., Feldmann, H., Morens, D. M. 2017; 12: 387-418

  Abstract

  For almost 50 years, ebolaviruses and related filoviruses have been repeatedly reemerging across the vast equatorial belt of the African continent to cause epidemics of highly fatal hemorrhagic fever. The 2013-2015 West African epidemic, by far the most geographically extensive, most fatal, and longest lasting epidemic in Ebola's history, presented an enormous international public health challenge, but it also provided insights into Ebola's pathogenesis and natural history, clinical expression, treatment, prevention, and control. Growing understanding of ebolavirus pathogenetic mechanisms and important new clinical observations of the disease course provide fresh clues about prevention and treatment approaches. Although viral cytopathology and immune-mediated cell damage in ebolavirus disease often result in severe compromise of multiple organs, tissue repair and organ function recovery can be expected if patients receive supportive care with fluids and electrolytes; maintenance of oxygenation and tissue perfusion; and respiratory, renal, and cardiovascular support. Major challenges for managing future Ebola epidemics include establishment of early and aggressive epidemic control and earlier and better patient care and treatment in remote, resource-poor areas where Ebola typically reemerges. In addition, it will be important to further develop Ebola vaccines and to adopt policies for their use in epidemic and pre-epidemic situations.

  View details for DOI 10.1146/annurev-pathol-052016-100506

  View details for PubMedID 27959626

• Can twice weekly hemodialysis expand patient access under resource constraints? Hemodialysis international. International Symposium on Home Hemodialysis Savla, D., Chertow, G. M., Meyer, T., Anand, S. 2016

  Abstract

  The convention of prescribing hemodialysis on a thrice weekly schedule began empirically when it seemed that this frequency was convenient and likely to treat symptoms for a majority of patients. Later, when urea was identified as the main target and marker of clearance, studies supported the prevailing notion that thrice weekly dialysis provided appropriate clearance of urea. Today, national guidelines on hemodialysis from most countries recommend patients receive at least thrice weekly therapy. However, resource constraints in low- and middle-income countries (LMIC) have resulted in a substantial proportion of patients using less frequent hemodialysis in these settings. Observational studies of patients on twice weekly dialysis show that twice weekly therapy has noninferior survival rates compared with thrice weekly therapy. In fact, models of urea clearance also show that twice weekly therapy can meet urea clearance "targets" if patients have significant residual function or if they follow a protein-restricted diet, as may be common in LMIC. Greater reliance on twice weekly therapy, at least at the start of hemodialysis, therefore has potential to reduce health care costs and increase access to renal replacement therapy in low-resource settings; however, randomized control trials are needed to better understand long-term outcomes of twice versus thrice weekly therapy.

  View details for DOI 10.1111/hdi.12501

  View details for PubMedID 27966247

• Introduction of Biosimilar Therapeutics Into Nephrology Practice in the United States: Report of a Scientific Workshop Sponsored by the National Kidney Foundation AMERICAN JOURNAL OF KIDNEY DISEASES Wish, J. B., Charytan, C., Chertow, G. M., Kalantar-Zadeh, K., Kliger, A. S., Rubin, R. J., Yee, J., Fishbane, S. 2016; 68 (6): 843-852

  Abstract

  Biosimilars are biologic medicines highly similar to the reference product with no meaningful clinical differences in terms of safety, purity, and potency. All biologic medicines are produced by living cells, resulting in an inherent heterogeneity in their higher order structures and post-translational modifications. In 2010, the US Congress enacted legislation to streamline the approval process for biosimilars of products losing patent protection, with the goal of decreasing costs and improving patient access to therapeutically important but expensive biologic agents. In 2015, the US Food and Drug Administration approved the first biosimilar agent through this pathway. Approval of additional biosimilar agents in the United States, including those used by nephrologists, is anticipated. Given the relative lack of knowledge regarding biosimilars and their approval process and a lack of trust by the nephrology community regarding their safety and efficacy, the National Kidney Foundation conducted a symposium, Introduction of Biosimilar Therapeutics Into Nephrology Practice in the U.S., September 17 to 18, 2015. Issues related to manufacturing, the regulatory approval process, interchangeability, substitution/switching, nomenclature, and clinician and patient awareness and acceptance were examined. This report summarizes the main discussions at the symposium, highlights several controversies, and makes recommendations related to public policy, professional and patient education, and research needs.

  View details for DOI 10.1053/j.ajkd.2016.06.022

  View details for PubMedID 27599628

• Metabolic Profiling of Impaired Cognitive Function in Patients Receiving Dialysis JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Tamura, M. K., Chertow, G. M., Depner, T. A., Nissenson, A. R., Schiller, B., Mehta, R. L., Liu, S., Sirich, T. L. 2016; 27 (12): 3780-3787

  Abstract

  Retention of uremic metabolites is a proposed cause of cognitive impairment in patients with ESRD. We used metabolic profiling to identify and validate uremic metabolites associated with impairment in executive function in two cohorts of patients receiving maintenance dialysis. We performed metabolic profiling using liquid chromatography/mass spectrometry applied to predialysis plasma samples from a discovery cohort of 141 patients and an independent replication cohort of 180 patients participating in a trial of frequent hemodialysis. We assessed executive function with the Trail Making Test Part B and the Digit Symbol Substitution test. Impaired executive function was defined as a score ≥2 SDs below normative values. Four metabolites-4-hydroxyphenylacetate, phenylacetylglutamine, hippurate, and prolyl-hydroxyproline-were associated with impaired executive function at the false-detection rate significance threshold. After adjustment for demographic and clinical characteristics, the associations remained statistically significant: relative risk 1.16 (95% confidence interval [95% CI], 1.03 to 1.32), 1.39 (95% CI, 1.13 to 1.71), 1.24 (95% CI, 1.03 to 1.50), and 1.20 (95% CI, 1.05 to 1.38) for each SD increase in 4-hydroxyphenylacetate, phenylacetylglutamine, hippurate, and prolyl-hydroxyproline, respectively. The association between 4-hydroxyphenylacetate and impaired executive function was replicated in the second cohort (relative risk 1.12; 95% CI, 1.02 to 1.23), whereas the associations for phenylacetylglutamine, hippurate, and prolyl-hydroxyproline did not reach statistical significance in this cohort. In summary, four metabolites related to phenylalanine, benzoate, and glutamate metabolism may be markers of cognitive impairment in patients receiving maintenance dialysis.

  View details for DOI 10.1681/ASN.2016010039

  View details for PubMedID 27444566

• Analyzing Health-Related Quality of Life in the EVOLVE Trial: The Joint Impact of Treatment and Clinical Events. Medical decision making Briggs, A. H., Parfrey, P. S., Khan, N., Tseng, S., Dehmel, B., Kubo, Y., Chertow, G. M., Belozeroff, V. 2016; 36 (8): 965-972

  Abstract

  The Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) clinical trial evaluated the effects of cinacalcet on clinical events in patients with secondary hyperparathyroidism (sHPT) who were on hemodialysis. Health-related quality of life (HRQoL) was assessed by a generic, preference-based health outcome measure (EQ-5D) at scheduled visits and after a study event. Here, we report the HRQoL analysis from EVOLVE.We assessed changes in HRQoL from baseline to scheduled visits, and estimated the acute (3 mo) and chronic (beyond 3 mo) effects of sHPT-related events on HRQoL using generalized estimating equation analysis controlling for baseline HRQoL and randomized assignment.Data on HRQoL were available for 3547 of 3883 subjects, with 1650 events in the placebo and 1502 in the cinacalcet arm. At the study end, no difference in change from baseline HRQoL was observed in the direct comparison of EQ-5D by treatment arms. The regression analysis showed significant effects of events on HRQoL and a modest positive effect of cinacalcet. Estimated quality-adjusted life-year gains were of similar magnitude based on the observed data or the predictions from the model, with only a small gain in precision from the predicted analysis.By contrast with a conventional comparison, a regression analysis demonstrated large decrements in HRQoL after events and a modest improvement in HRQoL with cinacalcet. As randomized controlled trials are rarely powered to detect differences in HRQoL, a prespecified regression analysis may be acceptable to improve precision of the effects and understand their origin.

  View details for DOI 10.1177/0272989X16638312

  View details for PubMedID 26987347

• Hyperprolactinemia in end-stage renal disease and effects of frequent hemodialysis. Hemodialysis international. International Symposium on Home Hemodialysis Lo, J. C., Beck, G. J., Kaysen, G. A., Chan, C. T., Kliger, A. S., Rocco, M. V., Chertow, G. M. 2016

  Abstract

  Introduction End-stage renal disease is associated with elevations in circulating prolactin concentrations, but the association of prolactin concentrations with intermediate health outcomes and the effects of hemodialysis frequency on changes in serum prolactin have not been examined. Methods The FHN Daily and Nocturnal Dialysis Trials compared the effects of conventional thrice weekly hemodialysis with in-center daily hemodialysis (6 days/week) and nocturnal home hemodialysis (6 nights/week) over 12 months and obtained measures of health-related quality of life, self-reported physical function, mental health and cognition. Serum prolactin concentrations were measured at baseline and 12-month follow-up in 70% of the FHN Trial cohort to examine the associations among serum prolactin concentrations and physical, mental and cognitive function and the effects of hemodialysis frequency on serum prolactin. Findings Among 177 Daily Trial and 60 Nocturnal Trial participants with baseline serum prolactin measurements, the median serum prolactin concentration was 65 ng/mL (25th-75th percentile 48-195 ng/mL) and 81% had serum prolactin concentrations >30 ng/mL. While serum prolactin was associated with sex (higher in women), we observed no association between baseline serum prolactin and age, dialysis vintage, and baseline measures of physical, mental and cognitive function. Furthermore, there was no significant effect of hemodialysis frequency on serum prolactin in either of the two trials. Discussion Serum prolactin concentrations were elevated in the large majority of patients with ESRD, but were not associated with several measures of health status. Circulating prolactin levels also do not appear to decrease in response to more frequent hemodialysis over a one-year period.

  View details for DOI 10.1111/hdi.12489

  View details for PubMedID 27774730

• Re-evaluation of re-hospitalization and rehabilitation in renal research. Hemodialysis international. International Symposium on Home Hemodialysis Lin, E., Kurella Tamura, M., Montez-Rath, M. E., Chertow, G. M. 2016

  Abstract

  Introduction The use of administrative data to capture 30-day readmission rates in end-stage renal disease is challenging since Medicare combines claims from acute care, inpatient rehabilitation (IRF), and long-term care hospital stays into a single "Inpatient" file. For data prior to 2012, the United States Renal Data System does not contain the variables necessary to easily identify different facility types, making it likely that prior studies have inaccurately estimated 30-day readmission rates. Methods For this report, we developed two methods (a "simple method" and a "rehabilitation-adjusted method") to identify acute care, IRF, and long-term care hospital stays from United States Renal Data System claims data, and compared them to methods used in previously published reports. Findings We found that prior methods overestimated 30-day readmission rates by up to 12.3% and overestimated average 30-day readmission costs by up to 11%. In contrast, the simple and rehabilitation-adjusted methods overestimated 30-day readmission rates by 0.1% and average 30-day readmission costs by 1.8%. The rehabilitation-adjusted method also accurately identified 96.8% of IRF stays. Discussion Prior research has likely provided inaccurate estimates of 30-day readmissions in patients undergoing dialysis. In the absence of data on specific facility types particularly when using data prior to 2012, future researchers could employ our method to more accurately characterize 30-day readmission rates and associated outcomes in patients with end-stage renal disease.

  View details for DOI 10.1111/hdi.12497

  View details for PubMedID 27766736

• Waste Informatics: Establishing Characteristics of Contemporary US Landfill Quantities and Practices ENVIRONMENTAL SCIENCE & TECHNOLOGY Powell, J. T., Pons, J. C., Chertow, M. 2016; 50 (20): 10877-10884

  Abstract

  Waste generation is expected to increase in most countries for many decades with landfill disposal still the dominant solid waste management method(1-3). Yet, operational characteristics of landfills are often poorly understood with comparative statistics substantially lacking. Here, we call for a more formal waste informatics to organize and standardize waste management knowledge at multiple spatial scales through analysis of recently reported data from 1232 U.S. landfills and other high resolution data sets. We create the first known estimate of available U.S. municipal waste stocks (8.5 billion tonnes) and go on to resolve these stocks at the county level, reflecting prospective urban mining opportunities. Our analysis of disposal rates and landfill capacities reveals that more than half of U.S. states have more than 25 years of life remaining. We also estimate the gross energy potential of landfill gas in the U.S. (338 billion MJ/yr) by examining 922 operational methane collection systems and demonstrate that the greatest energy recovery opportunities lie at landfills with existing collection systems and energy conversion infrastructure. Finally, we found that the number of landfills reaching the federally defined 30-year postclosure care period will more than triple in the coming two decades, with 264 sites expected by the year 2044, highlighting the need to develop and standardize metrics carefully to define and standardize when it is appropriate to end or scale back long-term landfill monitoring.

  View details for DOI 10.1021/acs.est.6b02848

  View details for Web of Science ID 000385907200013

  View details for PubMedID 27651028

• 30-Day Readmissions after an Acute Kidney Injury Hospitalization. American journal of medicine Silver, S. A., Harel, Z., McArthur, E., Nash, D. M., Acedillo, R., Kitchlu, A., Garg, A. X., Chertow, G. M., Bell, C. M., Wald, R. 2016

  Abstract

  The risk of hospital readmission in acute kidney injury survivors is not well understood. We estimated the proportion of acute kidney injury patients who were rehospitalized within 30 days and identified characteristics associated with hospital readmission.We conducted a population-based study of patients who survived a hospitalization complicated by acute kidney injury from 2003-2013 in Ontario, Canada. The primary outcome was 30-day hospital readmission. We used a propensity score model to match patients with and without acute kidney injury, and a Cox proportional hazards model with death as a competing risk to identify predictors of 30-day readmission.We identified 156,690 patients who were discharged from 197 hospitals after an episode of acute kidney injury. In the subsequent 30 days, 27,457 (18%) patients were readmitted; 15,988 (10%) visited the emergency department and 7480 (5%) died. We successfully matched 111,778 patients with acute kidney injury 1:1 to patients without acute kidney injury. The likelihood of 30-day readmission was higher in acute kidney injury patients than those without acute kidney injury (hazard ratio [HR] 1.53; 95% confidence interval [CI], 1.50-1.57). Factors most strongly associated with 30-day rehospitalization were the number of hospitalizations in the preceding year (adjusted HR 1.45 for ≥2 hospitalizations; 95% CI, 1.40-1.51) and receipt of inpatient chemotherapy (adjusted HR 1.44; 95% CI, 1.32-1.58).One in 5 patients who survive a hospitalization complicated by acute kidney injury is readmitted in the next 30 days. Better strategies are needed to identify and care for acute kidney injury survivors in the community.

  View details for DOI 10.1016/j.amjmed.2016.09.016

  View details for PubMedID 27751901

• Results of human factors testing in a novel Hemodialysis system designed for ease of patient use HEMODIALYSIS INTERNATIONAL Wilcox, S. B., Carver, M., Yau, M., Sneeringer, P., Prichard, S., Alvarez, L., Chertow, G. M. 2016; 20 (4): 643-649

  Abstract

  Introduction Home hemodialysis has not been widely adopted despite superior outcomes relative to conventional in-center hemodialysis. Patients receiving home hemodialysis experience high rates of technique failure owing to machine complexity, training burden, and the inability to master treatments independently. Methods We conducted human factors testing on 15 health care professionals (HCPs) and 15 patients upon release of the defined training program on the Tablo™ Hemodialysis System. Each participant completed one training and one testing session conducted in a simulated clinical environment. Training sessions lasted <3 hours for HCPs and <4 hours for patients, with an hour break between sessions for knowledge decay. During the testing session, we recorded participant behavior and data according to standard performance and safety-based criteria. Findings Of 15 HCPs, 10 were registered nurses and five patient care technicians, with a broad range of dialysis work experience and no limitations other than visual correction. Of 15 patients (average age 48 years), 13 reported no limitations and two reported modest limitations-partial deafness and blindness in one eye, respectively. The average error rate was 4.4 per session for HCPs and 2.9 per session for patients out of a total possible 1,710 opportunities for errors. Despite having received minimal training, neither HCPs nor patients committed safety-related errors that required mitigation; rather, we noted only minor errors and operational difficulties. Discussion The Tablo™ Hemodialysis System is easy to use, and may help to enable self-care and home hemodialysis in settings heretofore associated with high rates of technique failure.

  View details for DOI 10.1111/hdi.12430

  View details for PubMedID 27194590

• Epoetin Alfa and Outcomes in Dialysis amid Regulatory and Payment Reform JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Chertow, G. M., Liu, J., Monde, K. L., Gilbertson, D. T., Brookhart, M. A., Beaubrun, A. C., Winkelmayer, W. C., Pollock, A., Herzog, C. A., Ashfaq, A., Sturmer, T., Rothman, K. J., Bradbury, B. D., Collins, A. J. 2016; 27 (10): 3129-3138

  Abstract

  Erythropoiesis-stimulating agents (ESAs) are commonly used to treat anemia in patients with CKD, including those receiving dialysis, although clinical trials have identified risks associated with ESA use. We evaluated the effects of changes in dialysis payment policies and product labeling instituted in 2011 on mortality and major cardiovascular events across the United States dialysis population in an open cohort study of patients on dialysis from January 1, 2005, through December 31, 2012, with Medicare as primary payer. We compared observed rates of death and major cardiovascular events in 2011 and 2012 with expected rates calculated on the basis of rates in 2005-2010, accounting for differences in patient characteristics and influenza virulence. An abrupt decline in erythropoietin dosing and hemoglobin concentration began in late 2010. Observed rates of all-cause mortality, cardiovascular mortality, and myocardial infarction in 2011 and 2012 were consistent with expected rates. During 2012, observed rates of stroke, venous thromboembolic disease (VTE), and heart failure were lower than expected (absolute deviation from trend per 100 patient-years [95% confidence interval]: -0.24 [-0.08 to -0.37] for stroke, -2.43 [-1.35 to -3.70] for VTE, and -0.77 [-0.28 to -1.27] for heart failure), although non-ESA-related changes in practice and Medicare payment penalties for rehospitalization may have confounded the results. This initial evidence suggests that action taken to mitigate risks associated with ESA use and changes in payment policy did not result in a relative increase in death or major cardiovascular events and may reflect improvements in stroke, VTE, and heart failure.

  View details for DOI 10.1681/ASN.2015111232

  View details for PubMedID 26917691

• Hip Fracture in Patients With Non-Dialysis-Requiring Chronic Kidney Disease. Journal of bone and mineral research Kim, S. M., Long, J., Montez-Rath, M., Leonard, M., Chertow, G. M. 2016; 31 (10): 1803-1809

  Abstract

  Patients with end-stage renal disease (ESRD) are at a high risk for hip fracture. Little is known about the risk for, and consequences of, hip fracture among patients with non-dialysis-requiring chronic kidney disease (CKD). We examined the incidence of hip fracture, in-hospital mortality, length of stay, and costs among patients with ESRD, non-dialysis-requiring CKD, and normal or near normal kidney function. Using the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample, a nationally representative database, we identified hospitalizations for hip fracture in 2010. We incorporated data from the United States Renal Data System (USRDS) and the US census to calculate population-specific rates. Age-standardized incidence of hip fracture was highest among patients with ESRD (3.89/1000 person-years), followed by non-dialysis-requiring CKD (1.81/1000 persons) and patients with normal or near normal kidney function (1.18/1000 persons). In-hospital mo rtality (odds ratio [OR] = 1.69, 95% confidence interval [CI] 1.46 to 1.96), lengths of stay (median [10th, 90th percentiles] 5 [3 to 11] versus 5 [3 to 10] days) and costs (median $14,807 versus $13,314) were significantly higher in patients with non-dialysis-requiring CKD relative to patients with normal or near normal kidney function. In summary, non-dialysis-requiring CKD is associated with higher age-standardized rates of hip fracture and post-hip fracture mortality and higher resource utilization. © 2016 American Society for Bone and Mineral Research.

  View details for DOI 10.1002/jbmr.2862

  View details for PubMedID 27145189

• Contemporary Use of Partial Nephrectomy: Are Older Patients With Impaired Kidney Function Being Left Behind? Urology Leppert, J. T., Mittakanti, H. R., Thomas, I., Lamberts, R. W., Sonn, G. A., Chung, B. I., Skinner, E. C., Wagner, T. H., Chertow, G. M., Brooks, J. D. 2016

  Abstract

  To assess whether patient factors, such as age and preoperative kidney function, were associated with receipt of partial nephrectomy in a national integrated healthcare system.We identified patients treated with a radical or partial nephrectomy from 2002 to 2014 in the Veterans Health Administration. We examined associations among patient age, sex, race or ethnicity, multimorbidity, baseline kidney function, tumor characteristics, and receipt of partial nephrectomy. We estimated the odds of receiving a partial nephrectomy and assessed interactions between covariates and the year of surgery to explore whether patient factors associated with partial nephrectomy changed over time.In our cohort of 14,186 patients, 4508 (31.2%) received a partial nephrectomy. Use of partial nephrectomy increased from 17% in 2002 to 32% in 2008 and to 38% in 2014. Patient race or ethnicity, age, tumor stage, and year of surgery were independently associated with receipt of partial nephrectomy. Black veterans had significantly increased odds of receipt of partial nephrectomy, whereas older patients had significantly reduced odds. Partial nephrectomy utilization increased for all groups over time, but older patients and patients with worse baseline kidney function showed the least increase in odds of partial nephrectomy.Although the utilization of partial nephrectomy increased for all groups, the greatest increase occurred in the youngest patients and those with the highest baseline kidney function. These trends warrant further investigation to ensure that patients at the highest risk of impaired kidney function are considered for partial nephrectomy whenever possible.

  View details for DOI 10.1016/j.urology.2016.08.044

  View details for PubMedID 27634733

• Clinical trials of intensive versus less intensive control of hypertension: HOPE or HYPE? KIDNEY INTERNATIONAL Wyatt, C. M., Chertow, G. M. 2016; 90 (3): 460–65

  Abstract

  The recently published Heart Outcomes Prevention Evaluation trial (HOPE-3) demonstrated no benefit of lowering blood pressure with candesartan and hydrochlorothiazide in persons at intermediate cardiovascular risk and with adequate blood pressure control as determined by the enrolling physician. The results of Systolic Blood Pressure Intervention Trial (SPRINT) and HOPE-3 highlight the importance of considering differences in study design and patient population when interpreting the results of clinical trials.

  View details for DOI 10.1016/j.kint.2016.06.021

  View details for Web of Science ID 000382415300001

  View details for PubMedID 27521103

• Overall Survival in Patients with Localized Prostate Cancer in the US Veterans Health Administration: Is PIVOT Generalizable? EUROPEAN UROLOGY Barbosa, P. V., Thomas, I., Srinivas, S., Buyyounouski, M. K., Chung, B. I., Chertow, G. M., Asch, S. M., Wagner, T. H., Brooks, J. D., Leppert, J. T. 2016; 70 (2): 227-230

  Abstract

  A better understanding of overall survival among patients with clinically localized prostate cancer (PCa) in the US Veterans Health Administration (VHA) is critical to inform PCa treatment decisions, especially in light of data from the Prostate Intervention Versus Observation Trial (PIVOT). We sought to describe patterns of survival for all patients with clinically localized PCa treated by the VHA. We created an analytic cohort of 35 954 patients with clinically localized PCa diagnosed from 1995 to 2001, approximating the PIVOT inclusion criteria (age of diagnosis ≤75 yr and clinical stage T2 or lower). Mean patient age was 65.9 yr, and median follow-up was 161 mo. Overall, 22.5% of patients were treated with surgery, 16.6% were treated with radiotherapy, and 23.1% were treated with androgen deprivation. Median survival of the entire cohort was 14 yr (25th, 75th percentiles, range: 7.9-20 yr). Among patients who received treatment with curative intent, median survival was 17.9 yr following surgery and 12.9 yr following radiotherapy. One-third of patients died within 10 yr of diagnosis compared with nearly half of the participants in PIVOT. This finding sounds a note of caution when generalizing the mortality data from PIVOT to VHA patients and those in the community.More than one-third of patients diagnosed with clinically localized prostate cancer treated through the US Veterans Health Administration from 1995 to 2001 died within 10 yr of their diagnosis. Caution should be used when generalizing the estimates of competing mortality data from PIVOT.

  View details for DOI 10.1016/j.eururo.2016.02.037

  View details for PubMedID 26948397

• New Policies, New Sources of Error: Impact of Recent Medicare Policies on Database Research Gilbertson, D. T., Liu, J., Beaubrun, A. C., Chertow, G. M., Rothman, K. J., Winkelmayer, W. C., Monda, K. L., Ashfaq, A., Brookhart, A., Collins, A. J., Bradbury, B. D. WILEY-BLACKWELL. 2016: 144

  View details for Web of Science ID 000385483501238

• Potential Effects of Medicare Payment Policy Changes on Hospitalization-Based Outcomes Research Beaubrun, A. C., Gilbertson, D. T., Chertow, G. M., Rothman, K. J., Winkelmayer, W. C., Monda, K. L., Liu, J., Ashfaq, A., Brookhart, M., Collins, A. J., Bradbury, B. D. WILEY-BLACKWELL. 2016: 143–44

  View details for Web of Science ID 000385483501237

• Sex differences in obesity, dietary habits, and physical activity among urban middle-class Bangladeshis. International journal of health sciences Saquib, J., Saquib, N., Stefanick, M. L., Khanam, M. A., Anand, S., Rahman, M., Chertow, G. M., Barry, M., Ahmed, T., Cullen, M. R. 2016; 10 (3): 363-372

  Abstract

  The sustained economic growth in Bangladesh during the previous decade has created a substantial middle-class population, who have adequate income to spend on food, clothing, and lifestyle management. Along with the improvements in living standards, has also come negative impact on health for the middle class. The study objective was to assess sex differences in obesity prevalence, diet, and physical activity among urban middle-class Bangladeshi.In this cross-sectional study, conducted in 2012, we randomly selected 402 adults from Mohammedpur, Dhaka. The sampling technique was multi-stage random sampling. We used standardized questionnaires for data collection and measured height, weight, and waist circumference.Mean age (standard deviation) was 49.4 (12.7) years. The prevalence of both generalized (79% vs. 53%) and central obesity (85% vs. 42%) were significantly higher in women than men. Women reported spending more time watching TV and spending less time walking than men (p<.05); however, men reported a higher intake of unhealthy foods such as fast food and soft drinks.We conclude that the prevalence of obesity is significantly higher in urban middle-class Bangladeshis than previous urban estimates, and the burden of obesity disproportionately affects women. Future research and public health efforts are needed to address this severe obesity problem and to promote active lifestyles.

  View details for PubMedID 27610059

• Rates and Outcomes of Parathyroidectomy for Secondary Hyperparathyroidism in the United States CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Kim, S. M., Long, J., Montez-Rath, M. E., Leonard, M. B., Norton, J. A., Chertow, G. M. 2016; 11 (7): 1260-1267

  Abstract

  Secondary hyperparathyroidism is common among patients with ESRD. Although medical therapy for secondary hyperparathyroidism has changed dramatically over the last decade, rates of parathyroidectomy for secondary hyperparathyroidism across the United States population are unknown. We examined temporal trends in rates of parathyroidectomy, in-hospital mortality, length of hospital stay, and costs of hospitalization.Using the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample, a representative national database on hospital stay regardless of age and payer in the United States, we identified parathyroidectomies for secondary hyperparathyroidism from 2002 to 2011. Data from the US Renal Data System reports were used to calculate the rate of parathyroidectomy.We identified 32,971 parathyroidectomies for secondary hyperparathyroidism between 2002 and 2011. The overall rate of parathyroidectomy was approximately 5.4/1000 patients (95% confidence interval [95% CI], 5.0/1000 to 6.0/1000). The rate decreased from 2003 (7.9/1000 patients; 95% CI, 6.2/1000 to 9.6/1000), reached a nadir in 2005 (3.3/1000 patients; 95% CI, 2.6/1000 to 4.0/1000), increased again through 2006 (5.4/1000 patients; 95% CI, 4.4/1000 to 6.4/1000), and remained stable since that time. Rates of in-hospital mortality decreased from 1.7% (95% CI, 0.8% to 2.6%) in 2002 to 0.8% (95% CI, 0.1% to 1.6%) in 2011 (P for trend <0.001). In-hospital mortality rates were significantly higher in patients with heart failure (odds ratio [OR], 4.23; 95% CI, 2.59 to 6.91) and peripheral vascular disease (OR, 4.59; 95% CI, 2.75 to 7.65) and lower among patients with prior kidney transplantation (OR, 0.20; 95% CI, 0.06 to 0.65).Despite the use of multiple medical therapies, rates of parathyroidectomy of secondary hyperparathyroidism have not declined in recent years.

  View details for DOI 10.2215/CJN.10370915

  View details for PubMedID 27269300

• Cinacalcet, dialysate calcium concentration, and cardiovascular events in the EVOLVE trial HEMODIALYSIS INTERNATIONAL Pun, P. H., Abdalla, S., Block, G. A., Chertow, G. M., Correa-Rotter, R., Dehmel, B., Drueke, T. B., Floege, J., Goodman, W. G., Herzog, C. A., London, G. M., Mahaffey, K. W., Moe, S. M., Parfrey, P. S., Wheeler, D. C., Middleton, J. P. 2016; 20 (3): 421-431

  Abstract

  Among patients receiving hemodialysis, abnormalities in calcium regulation have been linked to an increased risk of cardiovascular events. Cinacalcet lowers serum calcium concentrations through its effect on parathyroid hormone secretion and has been hypothesized to reduce the risk of cardiovascular events. In observational cohort studies, prescriptions of low dialysate calcium concentration and larger observed serum-dialysate calcium gradients have been associated with higher risks of in-dialysis facility or peri-dialytic sudden cardiac arrest. We performed this study to examine the risks associated with dialysate calcium and serum-dialysate gradients among participants in the Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events (EVOLVE) trial. In EVOLVE, 3883 hemodialysis patients were randomized 1:1 to cinacalcet or placebo. Dialysate calcium was administered at the discretion of treating physicians. We examined whether baseline dialysate calcium concentration or the serum-dialysate calcium gradient modified the effect of cinacalcet on the following adjudicated endpoints: (1) primary composite endpoint (death or first non-fatal myocardial infarction, hospitalization for unstable angina, heart failure, or peripheral vascular event); (2) cardiovascular death; and (3) sudden death. In EVOLVE, use of higher dialysate calcium concentrations was more prevalent in Europe and Latin America compared with North America. There was a significant fall in serum calcium concentration in the cinacalcet group; dialysate calcium concentrations were changed infrequently in both groups. There was no association between baseline dialysate calcium concentration or serum-dialysate calcium gradient and the endpoints examined. Neither the baseline dialysate calcium nor the serum-dialysate calcium gradient significantly modified the effects of cinacalcet on the outcomes examined. The effects of cinacalcet on cardiovascular death and major cardiovascular events are not altered by the dialysate calcium prescription and serum-dialysate calcium gradient.

  View details for DOI 10.1111/hdi.12382

  View details for PubMedID 26564024

• Intensive vs Standard Blood Pressure Control and Cardiovascular Disease Outcomes in Adults Aged >= 75 Years A Randomized Clinical Trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Williamson, J. D., Supiano, M. A., Applegate, W. B., Berlowitz, D. R., Campbell, R. C., Chertow, G. M., Fine, L. J., Haley, W. E., Hawfield, A. T., Ix, J. H., Kitzman, D., Kostis, J. B., Krousel-Wood, M. A., Launer, L. J., Oparil, S., Rodriguez, C. J., Roumie, C. L., Shorr, R. I., Sink, K. M., Wadley, V. G., Whelton, P. K., Whittle, J., Woolard, N. F., Wright, J. T., Pajewski, N. M. 2016; 315 (24): 2673-2682

  Abstract

  The appropriate treatment target for systolic blood pressure (SBP) in older patients with hypertension remains uncertain.To evaluate the effects of intensive (<120 mm Hg) compared with standard (<140 mm Hg) SBP targets in persons aged 75 years or older with hypertension but without diabetes.A multicenter, randomized clinical trial of patients aged 75 years or older who participated in the Systolic Blood Pressure Intervention Trial (SPRINT). Recruitment began on October 20, 2010, and follow-up ended on August 20, 2015.Participants were randomized to an SBP target of less than 120 mm Hg (intensive treatment group, n = 1317) or an SBP target of less than 140 mm Hg (standard treatment group, n = 1319).The primary cardiovascular disease outcome was a composite of nonfatal myocardial infarction, acute coronary syndrome not resulting in a myocardial infarction, nonfatal stroke, nonfatal acute decompensated heart failure, and death from cardiovascular causes. All-cause mortality was a secondary outcome.Among 2636 participants (mean age, 79.9 years; 37.9% women), 2510 (95.2%) provided complete follow-up data. At a median follow-up of 3.14 years, there was a significantly lower rate of the primary composite outcome (102 events in the intensive treatment group vs 148 events in the standard treatment group; hazard ratio [HR], 0.66 [95% CI, 0.51-0.85]) and all-cause mortality (73 deaths vs 107 deaths, respectively; HR, 0.67 [95% CI, 0.49-0.91]). The overall rate of serious adverse events was not different between treatment groups (48.4% in the intensive treatment group vs 48.3% in the standard treatment group; HR, 0.99 [95% CI, 0.89-1.11]). Absolute rates of hypotension were 2.4% in the intensive treatment group vs 1.4% in the standard treatment group (HR, 1.71 [95% CI, 0.97-3.09]), 3.0% vs 2.4%, respectively, for syncope (HR, 1.23 [95% CI, 0.76-2.00]), 4.0% vs 2.7% for electrolyte abnormalities (HR, 1.51 [95% CI, 0.99-2.33]), 5.5% vs 4.0% for acute kidney injury (HR, 1.41 [95% CI, 0.98-2.04]), and 4.9% vs 5.5% for injurious falls (HR, 0.91 [95% CI, 0.65-1.29]).Among ambulatory adults aged 75 years or older, treating to an SBP target of less than 120 mm Hg compared with an SBP target of less than 140 mm Hg resulted in significantly lower rates of fatal and nonfatal major cardiovascular events and death from any cause.clinicaltrials.gov Identifier: NCT01206062.

  View details for DOI 10.1001/jama.2016.7050

  View details for PubMedID 27195814

• Risk prediction to inform surveillance of chronic kidney disease in the US Healthcare Safety Net: a cohort study BMC NEPHROLOGY Xie, Y., Maziarz, M., Tuot, D. S., Chertow, G. M., Himmelfarb, J., Hall, Y. N. 2016; 17

  Abstract

  The capacity of electronic health record (EHR) data to guide targeted surveillance in chronic kidney disease (CKD) is unclear. We sought to leverage EHR data for predicting risk of progressing from CKD to end-stage renal disease (ESRD) to help inform surveillance of CKD among vulnerable patients from the healthcare safety-net.We conducted a retrospective cohort study of adults (n = 28,779) with CKD who received care within 2 regional safety-net health systems during 1996-2009 in the Western United States. The primary outcomes were progression to ESRD and death as ascertained by linkage with United States Renal Data System and Social Security Administration Death Master files, respectively, through September 29, 2011. We evaluated the performance of 3 models which included demographic, comorbidity and laboratory data to predict progression of CKD to ESRD in conditions commonly targeted for disease management (hypertension, diabetes, chronic viral diseases and severe CKD) using traditional discriminatory criteria (AUC) and recent criteria intended to guide population health management strategies.Overall, 1730 persons progressed to end-stage renal disease and 7628 died during median follow-up of 6.6 years. Performance of risk models incorporating common EHR variables was highest in hypertension, intermediate in diabetes and chronic viral diseases, and lowest in severe CKD. Surveillance of persons who were in the highest quintile of ESRD risk yielded 83-94 %, 74-95 %, and 75-82 % of cases who progressed to ESRD among patients with hypertension, diabetes and chronic viral diseases, respectively. Similar surveillance yielded 42-71 % of ESRD cases among those with severe CKD. Discrimination in all conditions was universally high (AUC ≥0.80) when evaluated using traditional criteria.Recently proposed discriminatory criteria account for varying risk distribution and when applied to common clinical conditions may help to inform surveillance of CKD in diverse populations.

  View details for DOI 10.1186/s12882-016-0272-0

  View details for PubMedID 27276913

• Antihypertensive medications and sexual function in women: baseline data from the SBP intervention trial (SPRINT) JOURNAL OF HYPERTENSION Thomas, H. N., Evans, G. W., Berlowitz, D. R., Chertow, G. M., Conroy, M. B., Foy, C. G., Glasser, S. P., Lewis, C. E., Riley, W. T., Russell, L., Williams, O., Hess, R. 2016; 34 (6): 1224-1231

  Abstract

  Hypertension is a risk factor for the development of cardiovascular and kidney disease, but treatment can substantially reduce risks. Many patients avoid antihypertensive medications because of fear of side-effects. Although associations between antihypertensives and sexual dysfunction in men have been documented, it remains unclear whether antihypertensives are associated with sexual dysfunction in women. We conducted a cross-sectional analysis of baseline data from women in the Systolic Blood Pressure Intervention Trial (SPRINT) to evaluate the relations among class of antihypertensive medication and the outcomes: sexual activity and sexual function.SPRINT enrolled individuals 50 and older with hypertension at high risk for cardiovascular disease. A subset of participants completed questionnaires regarding quality of life, including sexual function. Antihypertensive class was determined by medications taken at baseline.Of 690 women in the quality of life subset of SPRINT, 183 (26.5%) were sexually active. There were no significant differences in sexual activity among women taking one or more antihypertensives and women not taking any. Women taking an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker had higher odds of sexual activity [odds ratio 1.66 (1.12-4.27), P = 0.011]. Among sexually active women, the prevalence of sexual dysfunction was high (52.5%). No class of medication was associated with sexual dysfunction in the multivariable model.Angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use was associated with higher odds of sexual activity. Although prevalence of sexual dysfunction was high, no single class of antihypertensive medication was associated with sexual dysfunction.

  View details for DOI 10.1097/HJH.0000000000000911

  View details for Web of Science ID 000375146000029

  View details for PubMedID 27032074

  View details for PubMedCentralID PMC4859426

• ISCHEMIA in chronic kidney disease: improving the representation of patients with chronic kidney disease in cardiovascular trials KIDNEY INTERNATIONAL Wyatt, C. M., Shineski, M., Chertow, G. M., Bangalore, S. 2016; 89 (6): 1178–79

  Abstract

  Despite the high cardiovascular risk associated with chronic kidney disease, a recent systematic review confirmed that patients with kidney disease remain underrepresented in cardiovascular trials. Two ongoing trials are assessing the risk:benefit of aggressive evaluation and intervention for ischemic heart disease in patients with advanced chronic kidney disease.

  View details for DOI 10.1016/j.kint.2016.03.012

  View details for Web of Science ID 000375693100002

  View details for PubMedID 27181770

• Effects of Physician Payment Reform on Provision of Home Dialysis AMERICAN JOURNAL OF MANAGED CARE Erickson, K. F., Winkelmayer, W. C., Chertow, G. M., Bhattacharya, J. 2016; 22 (6): E215-?

  Abstract

  Patients with end-stage renal disease can receive dialysis at home or in-center. In 2004, CMS reformed physician payment for in-center hemodialysis care from a capitated to a tiered fee-for-service model, augmenting physician payment for frequent in-center visits. We evaluated whether payment reform influenced dialysis modality assignment.Cohort study of patients starting dialysis in the United States in the 3 years before and the 3 years after payment reform.We conducted difference-in-difference analyses comparing patients with traditional Medicare coverage (who were affected by the policy) to others with Medicare Advantage (who were unaffected by the policy). We also examined whether the policy had a more pronounced influence on dialysis modality assignment in areas with lower costs of traveling to dialysis facilities.Patients with traditional Medicare coverage experienced a 0.7% (95% CI, 0.2%-1.1%; P = .003) reduction in the absolute probability of home dialysis use following payment reform compared with patients with Medicare Advantage. Patients living in areas with larger dialysis facilities (where payment reform made in-center hemodialysis comparatively more lucrative for physicians) experienced a 0.9% (95% CI, 0.5%-1.4%; P < .001) reduction in home dialysis use following payment reform compared with patients living in areas with smaller facilities (where payment reform made in-center hemodialysis comparatively less lucrative for physicians).The transition from a capitated to a tiered fee-for-service payment model for in-center hemodialysis care resulted in fewer patients receiving home dialysis. This area of policy failure highlights the importance of considering unintended consequences of future physician payment reform efforts.

  View details for Web of Science ID 000380245300005

  View details for PubMedID 27355909

  View details for PubMedCentralID PMC5055389

• The effect of frequent hemodialysis on self-reported sleep quality: Frequent Hemodialysis Network Trials. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association Unruh, M. L., Larive, B., Eggers, P. W., Garg, A. X., Gassman, J. J., Finkelstein, F. O., Kimmel, P. L., Chertow, G. M. 2016; 31 (6): 984-991

  Abstract

  Many patients who receive maintenance hemodialysis experience poor sleep. Uncontrolled studies suggest frequent hemodialysis improves sleep quality, which is a strong motivation for some patients to undertake the treatment. We studied the effects of frequent in-center ('daily') and nocturnal home hemodialysis on self-reported sleep quality in two randomized trials.Participants were randomly assigned to frequent (six times per week) or conventional (three times per week) hemodialysis in the Frequent Hemodialysis Network Daily (n = 245) and Nocturnal (n = 87) Trials. We used the Medical Outcomes Study Sleep Problems Index II (SPI II), a validated and reliable instrument in patients with end-stage renal disease, to measure self-reported sleep quality. The SPI II is scored from 0-100, with a higher value indicating poorer quality of sleep. A mean relative decline in SPI II would suggest improved sleep quality. The primary sleep outcome was the change in the SPI II score over 12 months.In the Daily Trial, after adjustment for baseline SPI II, subjects randomized to frequent as compared with conventional in-center hemodialysis experienced a 4.2 [95% confidence interval (CI) 0.4-8.0] point adjusted mean relative decline in SPI II at 4 months and a 2.6 (95% CI -2.3-7.5) point adjusted mean relative decline at 12 months. In the Nocturnal Trial, subjects randomized to frequent nocturnal as compared with conventional home hemodialysis experienced 2.9 (95% CI -3.4-9.3) and 4.5 (95% CI -3.2-12.2) point mean relative declines at Months 4 and 12, respectively.Although a possible benefit of frequent in-center hemodialysis was observed at 4 months, neither frequent in-center hemodialysis nor home nocturnal hemodialysis demonstrated significant improvements in self-reported sleep quality compared with conventional hemodialysis at 12 months.

  View details for DOI 10.1093/ndt/gfw062

  View details for PubMedID 27190356

• Long-Term Effects of Frequent In-Center Hemodialysis JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Chertow, G. M., Levin, N. W., Beck, G. J., Daugirdas, J. T., Eggers, P. W., Kliger, A. S., Larive, B., Rocco, M. V., Greene, T. 2016; 27 (6): 1830-1836

  Abstract

  The Frequent Hemodialysis Network Daily Trial randomized 245 patients to receive six (frequent) or three (conventional) in-center hemodialysis sessions per week for 12 months. As reported previously, frequent in-center hemodialysis yielded favorable effects on the coprimary composite outcomes of death or change in left ventricular mass and death or change in self-reported physical health. Here, we determined the long-term effects of the 12-month frequent in-center hemodialysis intervention. We determined the vital status of patients over a median of 3.6 years (10%-90% range, 1.5-5.3 years) after randomization. Using an intention to treat analysis, we compared the mortality hazard in randomized groups. In a subset of patients from both groups, we reassessed left ventricular mass and self-reported physical health a year or more after completion of the intervention; 20 of 125 patients (16%) randomized to frequent hemodialysis died during the combined trial and post-trial observation periods in contrast to 34 of 120 patients (28%) randomized to conventional hemodialysis. The relative mortality hazard for frequent versus conventional hemodialysis was 0.54 (95% confidence interval, 0.31 to 0.93); with censoring of time after kidney transplantation, the relative hazard was 0.56 (95% confidence interval, 0.32 to 0.99). Bayesian analysis suggested a relatively high probability of clinically significant benefit and a very low probability of harm with frequent hemodialysis. In conclusion, a 12-month frequent in-center hemodialysis intervention significantly reduced long-term mortality, suggesting that frequent hemodialysis may benefit selected patients with ESRD.

  View details for DOI 10.1681/ASN.2015040426

  View details for PubMedID 26467779

• Early to Dialyze Healthy and Wise? JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Chertow, G. M., Winkelmayer, W. C. 2016; 315 (20): 2171–72

  View details for PubMedID 27209075

• How to Diagnose Solutions to a Quality of Care Problem CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Harel, Z., Silver, S. A., McQuillan, R. F., Weizman, A. V., Thomas, A., Chertow, G. M., Nesrallah, G., Chan, C. T., Bell, C. M. 2016; 11 (5): 901-907

  Abstract

  To change a particular quality of care outcome within a system, quality improvement initiatives must first understand the causes contributing to the outcome. After the causes of a particular outcome are known, changes can be made to address these causes and change the outcome. Using the example of home dialysis (home hemodialysis and peritoneal dialysis), this article within this Moving Points feature on quality improvement will provide health care professionals with the tools necessary to analyze the steps contributing to certain outcomes in health care quality and develop ideas that will ultimately lead to their resolution. The tools used to identify the main contributors to a quality of care outcome will be described, including cause and effect diagrams, Pareto analysis, and process mapping. We will also review common change concepts and brainstorming activities to identify effective change ideas. These methods will be applied to our home dialysis quality improvement project, providing a practical example that other kidney health care professionals can replicate at their local centers.

  View details for DOI 10.2215/CJN.11481015

  View details for PubMedID 27016495

• How to Use Quality Improvement Tools in Clinical Practice: A Primer for Nephrologists CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Chan, C. T., Chertow, G. M., Nesrallah, G., Bell, C. M. 2016; 11 (5): 891–92

  View details for PubMedID 27016499

  View details for PubMedCentralID PMC4858493

• How to Sustain Change and Support Continuous Quality Improvement CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Silver, S. A., McQuillan, R., Harel, Z., Weizman, A. V., Thomas, A., Nesrallah, G., Bell, C. M., Chan, C. T., Chertow, G. M. 2016; 11 (5): 916-924

  Abstract

  To achieve sustainable change, quality improvement initiatives must become the new way of working rather than something added on to routine clinical care. However, most organizational change is not maintained. In this next article in this Moving Points in Nephrology feature on quality improvement, we provide health care professionals with strategies to sustain and support quality improvement. Threats to sustainability may be identified both at the beginning of a project and when it is ready for implementation. The National Health Service Sustainability Model is reviewed as one example to help identify issues that affect long-term success of quality improvement projects. Tools to help sustain improvement include process control boards, performance boards, standard work, and improvement huddles. Process control and performance boards are methods to communicate improvement results to staff and leadership. Standard work is a written or visual outline of current best practices for a task and provides a framework to ensure that changes that have improved patient care are consistently and reliably applied to every patient encounter. Improvement huddles are short, regular meetings among staff to anticipate problems, review performance, and support a culture of improvement. Many of these tools rely on principles of visual management, which are systems transparent and simple so that every staff member can rapidly distinguish normal from abnormal working conditions. Even when quality improvement methods are properly applied, the success of a project still depends on contextual factors. Context refers to aspects of the local setting in which the project operates. Context affects resources, leadership support, data infrastructure, team motivation, and team performance. For these reasons, the same project may thrive in a supportive context and fail in a different context. To demonstrate the practical applications of these quality improvement principles, these principles are applied to a hypothetical quality improvement initiative that aims to promote home dialysis (home hemodialysis and peritoneal dialysis).

  View details for DOI 10.2215/CJN.11501015

  View details for PubMedID 27016498

• How to Measure and Interpret Quality Improvement Data CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY McQuillan, R. F., Silver, S. A., Harel, Z., Weizman, A., Thomas, A., Bell, C., Chertow, G. M., Chan, C. T., Nesrallah, G. 2016; 11 (5): 908-914

  Abstract

  This article will demonstrate how to conduct a quality improvement project using the change idea generated in "How To Use Quality Improvement Tools in Clinical Practice: How To Diagnose Solutions to a Quality of Care Problem" by Dr. Ziv Harel and colleagues in this Moving Points feature. This change idea involves the introduction of a nurse educator into a CKD clinic with a goal of increasing rates of patients performing dialysis independently at home (home hemodialysis or peritoneal dialysis). Using this example, we will illustrate a Plan-Do-Study-Act (PDSA) cycle in action and highlight the principles of rapid cycle change methodology. We will then discuss the selection of outcome, process, and balancing measures, and the practicalities of collecting these data in the clinic environment. We will also introduce the PDSA worksheet as a practical way to oversee the progress of a quality improvement project. Finally, we will demonstrate how run charts are used to visually illustrate improvement in real time, and how this information can be used to validate achievement, respond appropriately to challenges the project may encounter, and prove the significance of results. This article aims to provide readers with a clear and practical framework upon which to trial their own ideas for quality improvement in the clinical setting.

  View details for DOI 10.2215/CJN.11511015

  View details for PubMedID 27016496

• How to Begin a Quality Improvement Project CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Silver, S. A., Harel, Z., McQuillan, R., Weizman, A. V., Thomas, A., Chertow, G. M., Nesrallah, G., Bell, C. M., Chan, C. T. 2016; 11 (5): 893-900

  Abstract

  Quality improvement involves a combined effort among health care staff and stakeholders to diagnose and treat problems in the health care system. However, health care professionals often lack training in quality improvement methods, which makes it challenging to participate in improvement efforts. This article familiarizes health care professionals with how to begin a quality improvement project. The initial steps involve forming an improvement team that possesses expertise in the quality of care problem, leadership, and change management. Stakeholder mapping and analysis are useful tools at this stage, and these are reviewed to help identify individuals who might have a vested interest in the project. Physician engagement is a particularly important component of project success, and the knowledge that patients/caregivers can offer as members of a quality improvement team should not be overlooked. After a team is formed, an improvement framework helps to organize the scientific process of system change. Common quality improvement frameworks include Six Sigma, Lean, and the Model for Improvement. These models are contrasted, with a focus on the Model for Improvement, because it is widely used and applicable to a variety of quality of care problems without advanced training. It involves three steps: setting aims to focus improvement, choosing a balanced set of measures to determine if improvement occurs, and testing new ideas to change the current process. These new ideas are evaluated using Plan-Do-Study-Act cycles, where knowledge is gained by testing changes and reflecting on their effect. To show the real world utility of the quality improvement methods discussed, they are applied to a hypothetical quality improvement initiative that aims to promote home dialysis (home hemodialysis and peritoneal dialysis). This provides an example that kidney health care professionals can use to begin their own quality improvement projects.

  View details for DOI 10.2215/CJN.11491015

  View details for PubMedID 27016497

• Characterizing Frailty Status in the Systolic Blood Pressure Intervention Trial JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Pajewski, N. M., Williamson, J. D., Applegate, W. B., Berlowitz, D. R., Bolin, L. P., Chertow, G. M., Krousel-Wood, M. A., Lopez-Barrera, N., Powell, J. R., Roumie, C. L., Still, C., Sink, K. M., Tang, R., Wright, C. B., Supiano, M. A. 2016; 71 (5): 649-655

  Abstract

  The Systolic Blood Pressure Intervention Trial (SPRINT) is testing whether a lower systolic blood pressure (BP) target of 120 mm Hg leads to a reduction in cardiovascular morbidity and mortality among hypertensive, nondiabetic adults. Because there may be detrimental effects of intensive BP control, particularly in older, frail adults, we sought to characterize frailty within SPRINT to address ongoing questions about the ability of large-scale trials to enroll representative samples of noninstitutionalized, community-dwelling, older adults.We constructed a 36-item frailty index (FI) in 9,306 SPRINT participants, classifying participants as fit (FI ≤ 0.10), less fit (0.10 < FI ≤ 0.21), or frail (FI > 0.21). Recurrent event models were used to evaluate the association of the FI with the incidence of self-reported falls, injurious falls, and all-cause hospitalizations.The distribution of the FI was comparable with what has been observed in population studies, with 2,570 (27.6%) participants classified as frail. The median FI was 0.18 (interquartile range = 0.14 to 0.24) in participants aged 80 years and older (N = 1,159), similar to the median FI of 0.17 reported for participants in the Hypertension in the Very Elderly Trial. In multivariable analyses, a 1% increase in the FI was associated with increased risk for self-reported falls (hazard ratio [HR] = 1.030), injurious falls (HR = 1.035), and all-cause hospitalizations (HR = 1.038) (all p values < .0001).Large clinical trials assessing treatments to reduce cardiovascular disease risk, such as SPRINT, can enroll heterogeneous populations of older adults, including the frail elderly, comparable with general population cohorts.

  View details for DOI 10.1093/gerona/glv228

  View details for PubMedID 26755682

• ONE YEAR EFFICACY AND SAFETY OF INTRAVENOUS (IV) ETELCALCETIDE (AMG 416) IN PATIENTS ON HEMODIALYSIS (HD) WITH SECONDARY HYPERPARATHYROIDISM (SHPT) Bushinsky, D. A., Block, G. A., Cheng, S., Deng, H., Torres, P., Vervloet, M., Chertow, G. M. OXFORD UNIV PRESS. 2016: 13–14

  View details for DOI 10.1093/ndt/gfw122.03

  View details for Web of Science ID 000376653800029

• The win ratio approach to analyzing composite outcomes: An application to the EVOLVE trial CONTEMPORARY CLINICAL TRIALS Abdalla, S., Montez-Rath, M. E., Parfrey, P. S., Chertow, G. M. 2016; 48: 119-124

  Abstract

  Unlike conventional time-to-event analysis of composite endpoints in clinical trials, the "win ratio" method allows for flexibility in prioritizing their components. Here, we compare the EVOLVE trial findings using the win ratio with those from time-to-event analysis.Randomization to cinacalcet or placebo.The primary composite endpoint combining all-cause mortality and non-fatal myocardial infarction, hospitalization for unstable angina, heart failure, and peripheral vascular events.In an unadjusted analysis, we paired each participant from the cinacalcet arm with every participant from the placebo arm within randomization strata. Pairs were classified as "winners" or "losers," according to which participant died first during the shared follow-up time, or experienced the next ranked event first. We ranked non-fatal events in two ways: 1) all ranked evenly; and 2) prioritized by their effect on health-related quality of life. The win ratio equaled the total winners divided by total losers. Further analyses were conducted where the win ratio was stratified by, or adjusted for, age.The unadjusted win ratio for the primary composite endpoint was 1.09 (95% CI 0.97 to 1.21), a statistically non-significant result which supports the primary trial result - unadjusted hazard ratio 0.93 (95% CI 0.85 to 1.02). Age-stratified analyses showed a nominally significant benefit of cinacalcet (win ratio 1.14, 95% CI 1.04 to 1.26). Ranking of non-fatal outcomes by their relative effects on quality of life did not materially alter the results.The win ratio method corroborated the findings of EVOLVE based on conventional time-to-event analysis. EVOLVE ClinicalTrials.gov number: NCT00345839.

  View details for DOI 10.1016/j.cct.2016.04.001

  View details for PubMedID 27080930

• Understanding barriers to home-based and self-care in-center hemodialysis. Hemodialysis international. International Symposium on Home Hemodialysis Yau, M., Carver, M., Alvarez, L., Block, G. A., Chertow, G. M. 2016; 20 (2): 235-241

  Abstract

  Despite superior outcomes and lower associated costs, relatively few patients with end-stage renal disease undergo self-care or home hemodialysis. Few studies have examined patient- and physician-specific barriers to self-care and home hemodialysis in the modern era. The degree to which innovative technology might facilitate the adoption of these modalities is unknown. We surveyed 250 patients receiving in-center hemodialysis and 51 board-certified nephrologists to identify key barriers to adoption of self-care and home hemodialysis. Overall, 172 (69%) patients reported that they were "likely" or "very likely" to consider self-care hemodialysis if they were properly trained on a new hemodialysis system designed for self-care or home use. Nephrologists believed that patients were capable of performing many dialysis-relevant tasks, including: weighing themselves (98%), wiping down the chair and machine (84%), clearing alarms during treatment (53%), taking vital signs (46%), and cannulating vascular access (41%), but thought that patients would be willing to do the same in only 69%, 34%, 31%, 29%, and 16%, respectively. Reasons that nephrologists believe patients are hesitant to pursue self-care or home hemodialysis do not correspond in parallel or by priority to reasons reported by patients. Self-care and home hemodialysis offer several advantages to patients and dialysis providers. Overcoming real and perceived barriers with new technology, education and coordinated care will be required for these modalities to gain traction in the coming years.

  View details for DOI 10.1111/hdi.12357

  View details for PubMedID 26415746

• Misclassification of Obesity by Body Mass Index Among Patients Receiving Hemodialysis AMERICAN JOURNAL OF KIDNEY DISEASES Kittiskulnam, P., Chertow, G. M., Kaysen, G. A., Delgado, C., Dalrymple, L. S., Johansen, K. L. 2016; 67 (4): 709–11

  View details for PubMedID 26612278

  View details for PubMedCentralID PMC5657149

• Association of Performance-Based and Self-Reported Function-Based Definitions of Frailty with Mortality among Patients Receiving Hemodialysis CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Johansen, K. L., Dalrymple, L. S., Glidden, D., Delgado, C., Kaysen, G. A., Grimes, B., Chertow, G. M. 2016; 11 (4): 626-632

  Abstract

  Frailty is common among patients on dialysis and increases vulnerability to dependency and death.We examined the predictive ability of frailty on the basis of physical performance and self-reported function in participants of a US Renal Data System special study that enrolled a convenience sample of 771 prevalent patients on hemodialysis from 14 facilities in the Atlanta and northern California areas from 2009 to 2011. Performance-based frailty was assessed using direct measures of grip strength (weakness) and gait speed along with weight loss, exhaustion, and low physical activity; poor self-reported function was substituted for weakness and slow gait speed in the self-reported function-based definition. For both definitions, patients meeting three or more criteria were considered frail.The mean age of 762 patients included in analyses was 57.1±14.2 years old; 240 patients (31%) met the physical performance-based definition of frailty, and 396 (52%) met the self-reported function-based definition. There were 106 deaths during 1.7 (interquartile range, 1.4-2.4) years of follow-up. After adjusting for demographic and clinical characteristics, the hazard ratio (HR) for mortality for the performance-based definition (2.16; 95% confidence interval [95% CI], 1.41 to 3.29) was slightly higher than that of the self-reported function-based definition (HR, 1.93; 95% CI, 1.24 to 3.00). Patients who met the self-report-based definition but not the physical performance definition of frailty (n=192) were not at statistically significantly higher risk of mortality than those who were not frail by either definition (n=330; HR, 1.41; 95% CI, 0.81 to 2.45), but those who met both definitions of frailty (n=204) were at significantly higher risk (HR, 2.46; 95% CI, 1.51 to 4.01).Frailty, defined using either direct tests of physical performance or self-reported physical function, was associated with higher mortality among patients receiving hemodialysis. Future studies are needed to determine the utility of assessing frailty in clinical practice.

  View details for DOI 10.2215/CJN.03710415

  View details for PubMedID 26792529

• Chronic kidney disease, cerebral blood flow, and white matter volume in hypertensive adults NEUROLOGY Tamura, M. K., Pajewski, N. M., Bryan, R. N., Weiner, D. E., Diamond, M., Van Buren, P., Taylor, A., Beddhu, S., Rosendorff, C., Jahanian, H., Zaharchuk, G. 2016; 86 (13): 1208-1216

  Abstract

  To determine the relation between markers of kidney disease-estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR)-with cerebral blood flow (CBF) and white matter volume (WMV) in hypertensive adults.We used baseline data collected from 665 nondiabetic hypertensive adults aged ≥50 years participating in the Systolic Blood Pressure Intervention Trial (SPRINT). We used arterial spin labeling to measure CBF and structural 3T images to segment tissue into normal and abnormal WMV. We used quantile regression to estimate the association between eGFR and UACR with CBF and abnormal WMV, adjusting for sociodemographic and clinical characteristics.There were 218 participants (33%) with eGFR <60 mL/min/1.73 m(2) and 146 participants (22%) with UACR ≥30 mg/g. Reduced eGFR was independently associated with higher adjusted median CBF, but not with abnormal WMV. Conversely, in adjusted analyses, there was a linear independent association between UACR and larger abnormal WMV, but not with CBF. Compared to participants with neither marker of CKD (eGFR ≥60 mL/min/1.73 m(2) and UACR <30 mg/g), median CBF was 5.03 mL/100 g/min higher (95% confidence interval [CI] 0.78, 9.29) and abnormal WMV was 0.63 cm(3) larger (95% CI 0.08, 1.17) among participants with both markers of CKD (eGFR <60 mL/min/1.73 m(2) and UACR ≥30 mg/g).Among nondiabetic hypertensive adults, reduced eGFR was associated with higher CBF and higher UACR was associated with larger abnormal WMV.

  View details for DOI 10.1212/WNL.0000000000002527

  View details for Web of Science ID 000372853000007

  View details for PubMedCentralID PMC4818564

• Patterns and Correlates of Baseline Thiazide-Type Diuretic Prescription in the Systolic Blood Pressure Intervention Trial HYPERTENSION Chang, T. I., Evans, G., Cheung, A. K., Cushman, W. C., Diamond, M. J., Dwyer, J. P., Huan, Y., Kitzman, D., Kostis, J. B., Oparil, S., Rastogi, A., Roumie, C. L., Sahay, R., Stafford, R. S., Taylor, A. A., Wright, J. T., Chertow, G. M. 2016; 67 (3): 550-555

  Abstract

  Thiazides and thiazide-type diuretics are recommended as first-line agents for the treatment of hypertension, but contemporary information on their use in clinical practice is lacking. We examined patterns and correlates of thiazide prescription in a cross-sectional analysis of baseline data from participants enrolled in the Systolic Blood Pressure Intervention Trial (SPRINT). We examined baseline prescription of thiazides in 7582 participants receiving at least 1 antihypertensive medication by subgroup, and used log-binomial regression to calculate adjusted prevalence ratios for thiazide prescription (versus no thiazide). Forty-three percent of all participants were prescribed a thiazide at baseline, but among participants prescribed a single agent, the proportion was only 16%. The prevalence of thiazide prescription differed significantly by demographic factors, with younger participants, women, and blacks all having higher adjusted prevalence of thiazide prescription than other corresponding subgroups. Participants in the lowest category of kidney function (estimated glomerular filtration rate <30 mL/min per 1.73 m2) were half as likely to be prescribed a thiazide as participants with preserved kidney function. In conclusion, among persons with hypertension and heightened cardiovascular risk, we found that thiazide prescription varied significantly by demographics and kidney disease status, despite limited evidence about relative differences in effectiveness.

  View details for DOI 10.1161/HYPERTENSIONAHA.115.06851

  View details for PubMedID 26865200

• Validating Appetite Assessment Tools Among Patients Receiving Hemodialysis JOURNAL OF RENAL NUTRITION Molfino, A., Kaysen, G. A., Chertow, G. M., Doyle, J., Delgado, C., Dwyer, T., Laviano, A., Fanelli, F. R., Johansen, K. L. 2016; 26 (2): 103-110

  Abstract

  To test the performance of appetite assessment tools among patients receiving hemodialysis (HD).Cross-sectional.Two hundred twenty-one patients receiving HD enrolled in seven dialysis facilities in Northern California.We assessed 5 appetite assessment tools (self-assessment of appetite, subjective assessment of appetite, visual analog scale [VAS], Functional Assessment of Anorexia/Cachexia Therapy [FAACT] score, and the Anorexia Questionnaire [AQ]).Reported food intake, normalized protein catabolic rate, and change in body weight were used as criterion measures, and we assessed associations among the appetite tools and biomarkers associated with nutrition and inflammation. Patients were asked to report their appetite and the percentage of food eaten (from 0% to 100%) during the last meal compared to usual intake.Fifty-eight (26%) patients reported food intake ≤ 50% (defined as poor appetite). The prevalence of anorexia was 12% by self-assessment of appetite, 6% by subjective assessment of appetite, 24% by VAS, 17% by FAACT score, and 12% by AQ. All the tools were significantly associated with food intake ≤ 50% (P < .001), except self-assessment of appetite. The FAACT score and the VAS had the strongest association with food intake ≤ 50% (C-statistic 0.80 and 0.76). Patients with food intake ≤ 50% reported weight loss more frequently than patients without low intake (36% vs 22%) and weight gain less frequently (19% vs 35%; P = .03). Normalized protein catabolic rate was lower among anorexic patients based on the VAS (1.1 ± 0.3 vs 1.2 ± 0.3, P = .03). Ln interleukin-6 correlated inversely with food intake (P = .03), but neither interleukin-6 nor C-reactive protein correlated with any of the appetite tools. Furthermore, only the self-assessment of appetite was significantly associated with serum albumin (P = .02), prealbumin (P = .02) and adiponectin concentrations (P = .03).Alternative appetite assessment tools yielded widely different estimates of the prevalence of anorexia in HD. When considering self-reported food intake as the criterion standard for anorexia, the FAACT score and VAS discriminated patients reasonably well.

  View details for DOI 10.1053/j.jrn.2015.09.002

  View details for PubMedID 26522141

• Lessons Learned from EVOLVE for Planning of Future Randomized Trials in Patients on Dialysis CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Parfrey, P. S., Block, G. A., Correa-Rotter, R., Drueeke, T. B., Floege, J., Herzog, C. A., London, G. M., Mahaffey, K. W., Moe, S. M., Wheeler, D. C., Chertow, G. M. 2016; 11 (3): 539-546

  Abstract

  The effect of the calcimimetic cinacalcet on cardiovascular disease in patients undergoing hemodialysis with secondary hyperparathyroidism was assessed in the Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events trial. This was the largest (in size) and longest (in duration) randomized controlled clinical trial undertaken in this population. During planning, execution, analysis, and reporting of the trial, many lessons were learned, including those related to the use of a composite cardiovascular primary endpoint, definition of endpoints (particularly heart failure and severe unremitting hyperparathyroidism), importance of age for optimal stratification at randomization, use of unadjusted and adjusted intention-to-treat analysis for the primary outcome, how to respond to a lower-than-predicted event rate during the trial, development of a prespecified analytic plan that accounted for nonadherence and for cointerventions that diminished the power of the trial to observe a treatment effect, determination of the credibility of a subgroup effect, use of adverse effects database to investigate rare diseases, collection of blood for biomarker measurement not designated before trial initiation, and interpretation of the benefits-to-harms ratio for individual patients. It is likely that many of these issues will arise in the planning of future trials in CKD.

  View details for DOI 10.2215/CJN.06370615

  View details for Web of Science ID 000371453100023

  View details for PubMedID 26614406

  View details for PubMedCentralID PMC4791832

• The effects of cinacalcet on blood pressure, mortality and cardiovascular endpoints in the EVOLVE trial JOURNAL OF HUMAN HYPERTENSION Chang, T. I., AbdAlla, S., London, G. M., Block, G. A., Correa-Rotter, R., Drueeke, T. B., Floege, J., Herzog, C. A., Mahaffey, K. W., Moe, S. M., Parfrey, P. S., Wheeler, D. C., Dehmel, B., Goodman, W. G., Chertow, G. M. 2016; 30 (3): 204-209

  Abstract

  Patients with end-stage renal disease often have derangements in calcium and phosphorus homeostasis and resultant secondary hyperparathyroidism (sHPT), which may contribute to the high prevalence of arterial stiffness and hypertension. We conducted a secondary analysis of the Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events (EVOLVE) trial, in which patients receiving hemodialysis with sHPT were randomly assigned to receive cinacalcet or placebo. We sought to examine whether the effect of cinacalcet on death and major cardiovascular events was modified by baseline pulse pressure as a marker of arterial stiffness, and whether cinacalcet yielded any effects on blood pressure. As reported previously, an unadjusted intention-to-treat analysis failed to conclude that randomization to cinacalcet reduces the risk of the primary composite end point (all-cause mortality or non-fatal myocardial infarction, heart failure, hospitalization for unstable angina or peripheral vascular event). However, after prespecified adjustment for baseline characteristics, patients randomized to cinacalcet experienced a nominally significant 13% lower adjusted risk (95% confidence limit 4-20%) of the primary composite end point. The effect of cinacalcet was not modified by baseline pulse pressure (Pinteraction=0.44). In adjusted models, at 20 weeks cinacalcet resulted in a 2.2 mm Hg larger average decrease in systolic blood pressure (P=0.002) and a 1.3 mm Hg larger average decrease in diastolic blood pressure (P=0.002) compared with placebo. In summary, in the EVOLVE trial, the effect of cinacalcet on death and major cardiovascular events was independent of baseline pulse pressure.

  View details for DOI 10.1038/jhh.2015.56

  View details for PubMedID 26040438

• The Effect of Increased Frequency of Hemodialysis on Volume-Related Outcomes: A Secondary Analysis of the Frequent Hemodialysis Network Trials. Blood purification Raimann, J. G., Chan, C. T., Daugirdas, J. T., Depner, T., Gotch, F. A., Greene, T., Kaysen, G. A., Kliger, A. S., Kotanko, P., Larive, B., Lindsay, R., Rocco, M. V., Chertow, G. M., Levin, N. W. 2016; 41 (4): 277-286

  Abstract

  In previous reports of the Frequent Hemodialysis Network trials, frequent hemodialysis (HD) reduced extracellular fluid (ECF) and left ventricular mass (LVM), with more pronounced effects observed among patients with low urine volume (UVol). We analyzed the effect of frequent HD on interdialytic weight gain (IDWG) and a time-integrated estimate of ECF load (TIFL). We also explored whether volume and sodium loading contributed to the change in LVM over the study period. Treatment effects on volume parameters were analyzed for modification by UVol and the dialysate-to-serum sodium gradient. Predictors of change in LVM were determined using linear regression. Frequent HD reduced IDWG and TIFL in the Daily Trial. Among patients with UVol <100 ml/day, reduction in TIFL was associated with LVM reduction. This suggests that achievement of better volume control could attenuate changes in LVM associated with mortality and cardiovascular morbidity. TIFL may prove more useful than IDWG alone in guiding HD practice. Video Journal Club 'Cappuccino with Claudio Ronco' at http://www.karger.com/?doi=441966.

  View details for DOI 10.1159/000441966

  View details for PubMedID 26795100

• Managing Hypertension in Patients with CKD: A Marathon, Not a SPRINT. Journal of the American Society of Nephrology : JASN Chertow, G. M., Beddhu, S., Lewis, J. B., Toto, R. D., Cheung, A. K. 2016; 27 (1): 40-3

  Abstract

  In this manuscript, nephrologist-investigators from one of five Clinical Center Networks of the Systolic Blood Pressure Intervention Trial (SPRINT) provide background information and context on the intensity of anti-hypertensive therapy in conjunction with the release of detailed results from SPRINT's primary analysis. The authors highlight published evidence on the safety and efficacy of differing intensities of anti-hypertensive therapy in mild to moderate CKD, where SPRINT will help to inform practice, as well as where gaps in evidence will remain. The authors also challenge the nephrology community to renew its attention and efforts on hypertension clinical care and research.

  View details for DOI 10.1681/ASN.2015101125

  View details for PubMedID 26553785

  View details for PubMedCentralID PMC4696594

• Iron management in chronic kidney disease: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies Conference. Kidney international Macdougall, I. C., Bircher, A. J., Eckardt, K. U., Obrador, G. T., Pollock, C. A., Stenvinkel, P., Swinkels, D. W., Wanner, C., Weiss, G., Chertow, G. M. 2016; 89 (1): 28-39

  Abstract

  Before the introduction of erythropoiesis-stimulating agents (ESAs) in 1989, repeated transfusions given to patients with end-stage renal disease caused iron overload, and the need for supplemental iron was rare. However, with the widespread introduction of ESAs, it was recognized that supplemental iron was necessary to optimize hemoglobin response and allow reduction of the ESA dose for economic reasons and recent concerns about ESA safety. Iron supplementation was also found to be more efficacious via intravenous compared to oral administration, and the use of intravenous iron has escalated in recent years. The safety of various iron compounds has been of theoretical concern due to their potential to induce iron overload, oxidative stress, hypersensitivity reactions, and a permissive environment for infectious processes. Therefore, an expert group was convened to assess the benefits and risks of parenteral iron, and to provide strategies for its optimal use while mitigating the risk for acute reactions and other adverse effects.

  View details for DOI 10.1016/j.kint.2015.10.002

  View details for PubMedID 26759045

• Iron management in chronic kidney disease: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies Conference KIDNEY INTERNATIONAL Macdougall, I. C., Bircher, A. J., Eckardt, K., Obrador, G. T., Pollock, C. A., Stenvinkel, P., Swinkels, D. W., Wanner, C., Weiss, G., Chertow, G. M. 2016; 89 (1): 28-39

  Abstract

  Before the introduction of erythropoiesis-stimulating agents (ESAs) in 1989, repeated transfusions given to patients with end-stage renal disease caused iron overload, and the need for supplemental iron was rare. However, with the widespread introduction of ESAs, it was recognized that supplemental iron was necessary to optimize hemoglobin response and allow reduction of the ESA dose for economic reasons and recent concerns about ESA safety. Iron supplementation was also found to be more efficacious via intravenous compared to oral administration, and the use of intravenous iron has escalated in recent years. The safety of various iron compounds has been of theoretical concern due to their potential to induce iron overload, oxidative stress, hypersensitivity reactions, and a permissive environment for infectious processes. Therefore, an expert group was convened to assess the benefits and risks of parenteral iron, and to provide strategies for its optimal use while mitigating the risk for acute reactions and other adverse effects.

  View details for DOI 10.1016/j.kint.2015.10.002

  View details for Web of Science ID 000368321300012

• Managing Hypertension in Patients with CKD: A Marathon, Not a SPRINT JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Chertow, G. M., Beddhu, S., Lewis, J. B., Toto, R. D., Cheung, A. K. 2016; 27 (1): 40-43

  Abstract

  In this manuscript, nephrologist-investigators from one of five Clinical Center Networks of the Systolic Blood Pressure Intervention Trial (SPRINT) provide background information and context on the intensity of anti-hypertensive therapy in conjunction with the release of detailed results from SPRINT's primary analysis. The authors highlight published evidence on the safety and efficacy of differing intensities of anti-hypertensive therapy in mild to moderate CKD, where SPRINT will help to inform practice, as well as where gaps in evidence will remain. The authors also challenge the nephrology community to renew its attention and efforts on hypertension clinical care and research.

  View details for DOI 10.1681/ASN.2015101125

  View details for Web of Science ID 000367632400007

  View details for PubMedCentralID PMC4696594

• Chronic Kidney Disease Classification in Systolic Blood Pressure Intervention Trial: Comparison Using Modification of Diet in Renal Disease and CKD-Epidemiology Collaboration Definitions AMERICAN JOURNAL OF NEPHROLOGY Rocco, M. V., Chapman, A., Chertow, G. M., Cohen, D., Chen, J., Cutler, J. A., Diamond, M. J., Freedman, B. I., Hawfield, A., Judd, E., Killeen, A. A., Kirchner, K., Lewis, C. E., Pajewski, N. M., Wall, B. M., Yee, J. 2016; 44 (2): 130-140

  Abstract

  Interventional trials have used either the Modification of Diet in Renal Disease (MDRD) or chronic kidney disease (CKD)-Epidemiology Collaboration (CKD-EPI) equation for determination of estimated glomerular filtration rate (eGFR) to define whether participants have stages 3-5 CKD. The equation used to calculate eGFR may influence the number and characteristics of participants designated as having CKD.We examined the classification of CKD at baseline using both equations in the Systolic Blood Pressure Intervention Trial (SPRINT). eGFR was calculated at baseline using fasting serum creatinine values from a central laboratory.Among 9,308 participants with baseline CKD classification using the 4-variable MDRD equation specified in the SPRINT protocol, 681 (7.3%) participants were reclassified to a less advanced CKD stage (higher eGFR) and 346 (3.7%) were reclassified to a more advanced CKD stage (lower eGFR) when the CKD-EPI equation was used to calculate eGFR. For eGFRs <90 ml/min/1.73 m2, participants <75 years were more likely to be reclassified to a less advanced CKD stage; this reclassification was more likely to occur in non-blacks rather than blacks. Participants aged ≥75 years were more likely to be reclassified to a more advanced than a less advanced CKD stage, regardless of baseline CKD stage. Reclassification of baseline CKD status (eGFR <60 ml/min/1.73 m2) occurred in 3% of participants.Use of the MDRD equation led to a higher percentage of participants being classified as having CKD stages 3-4. Younger and non-black participants were more likely to be reclassified as not having CKD using the CKD-EPI equation.

  View details for DOI 10.1159/000448722

  View details for Web of Science ID 000383216200006

  View details for PubMedID 27513312

  View details for PubMedCentralID PMC5096787

• Declining Rates of Inpatient Parathyroidectomy for Primary Hyperparathyroidism in the US. PloS one Kim, S. M., Shu, A. D., Long, J., Montez-Rath, M. E., Leonard, M. B., Norton, J. A., Chertow, G. M. 2016; 11 (8)

  Abstract

  Parathyroidectomy is the only curative therapy for patients with primary hyperparathyroidism. However, the incidence, correlates and consequences of parathyroidectomy for primary hyperparathyroidism across the entire US population are unknown. We evaluated temporal trends in rates of inpatient parathyroidectomy for primary hyperparathyroidism, and associated in-hospital mortality, length of stay, and costs. We used the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (NIS) from 2002-2011. Parathyroidectomies for primary hyperparathyroidism were identified using International Classification of Diseases, Ninth Revision codes. Unadjusted and age- and sex- adjusted rates of inpatient parathyroidectomy for primary hyperparathyroidism were derived from the NIS and the annual US Census. We estimated 109,583 parathyroidectomies for primary hyperparathyroidism between 2002 and 2011. More than half (55.4%) of patients were younger than age 65, and more than three-quarters (76.8%) were female. The overall rate of inpatient parathyroidectomy was 32.3 cases per million person-years. The adjusted rate decreased from 2004 (48.3 cases/million person-years) to 2007 (31.7 cases/million person-years) and was sustained thereafter. Although inpatient parathyroidectomy rates declined over time across all geographic regions, a steeper decline was observed in the South compared to other regions. Overall in-hospital mortality rates were 0.08%: 0.02% in patients younger than 65 years and 0.14% in patients 65 years and older. Inpatient parathyroidectomy rates for primary hyperparathyroidism have declined in recent years.

  View details for DOI 10.1371/journal.pone.0161192

  View details for PubMedID 27529699

• Rehospitalizations and Emergency Department Visits after Hospital Discharge in Patients Receiving Maintenance Hemodialysis. Journal of the American Society of Nephrology Harel, Z., Wald, R., McArthur, E., Chertow, G. M., Harel, S., Gruneir, A., Fischer, H. D., Garg, A. X., Perl, J., Nash, D. M., Silver, S., Bell, C. M. 2015; 26 (12): 3141-3150

  Abstract

  Clinical outcomes after a hospital discharge are poorly defined for patients receiving maintenance in-center (outpatient) hemodialysis. To describe the proportion and characteristics of these patients who are rehospitalized, visit an emergency department, or die within 30 days after discharge from an acute hospitalization, we conducted a population-based study of all adult patients receiving maintenance in-center hemodialysis who were discharged between January 1, 2003, and December 31, 2011, from 157 acute care hospitals in Ontario, Canada. For patients with more than one hospitalization, we randomly selected a single hospitalization as the index hospitalization. Of the 11,177 patients included in the final cohort, 1926 (17%) were rehospitalized, 2971 (27%) were treated in the emergency department, and 840 (7.5%) died within 30 days of discharge. Complications of type 2 diabetes mellitus were the most common reason for rehospitalization, whereas heart failure was the most common reason for an emergency department visit. In multivariable analysis using a cause-specific Cox proportional hazards model, the following characteristics were associated with 30-day rehospitalization: older age, the number of hospital admissions in the preceding 6 months, the number of emergency department visits in the preceding 6 months, higher Charlson comorbidity index score, and the receipt of mechanical ventilation during the index hospitalization. Thus, a large proportion of patients receiving maintenance in-center hemodialysis will be readmitted or visit an emergency room within 30 days of an acute hospitalization. A focus on improving care transitions from the inpatient setting to the outpatient dialysis unit may improve outcomes and reduce healthcare costs.

  View details for DOI 10.1681/ASN.2014060614

  View details for PubMedID 25855772

• Risk Factors for Infection-Related Hospitalization in In-Center Hemodialysis CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Dalrymple, L. S., Mu, Y., Nguyen, D. V., Romano, P. S., Chertow, G. M., Grimes, B., Kaysen, G. A., Johansen, K. L. 2015; 10 (12): 2170-2180

  Abstract

  Infection-related hospitalizations have increased dramatically over the last 10 years in patients receiving in-center hemodialysis. Patient and dialysis facility characteristics associated with the rate of infection-related hospitalization were examined, with consideration of the region of care, rural-urban residence, and socioeconomic status.The US Renal Data System linked to the American Community Survey and Rural-Urban Commuting Area codes was used to examine factors associated with hospitalization for infection among Medicare beneficiaries starting in-center hemodialysis between 2005 and 2008. A Poisson mixed effects model was used to examine the associations among patient and dialysis facility characteristics and the rate of infection-related hospitalization.Among 135,545 Medicare beneficiaries, 38,475 (28%) had at least one infection-related hospitalization. The overall rate of infection-related hospitalization was 40.2 per 100 person-years. Age ≥ 85 years old, cancer, chronic obstructive pulmonary disease, inability to ambulate or transfer, drug dependence, residence in a care facility, serum albumin <3.5 g/dl at dialysis initiation, and dialysis initiation with an access other than a fistula were associated with a ≥ 20% increase in the rate of infection-related hospitalization. Patients residing in isolated small rural compared with urban areas had lower rates of hospitalization for infection (rate ratio, 0.91; 95% confidence interval, 0.86 to 0.97), and rates of hospitalization for infection varied across the ESRD networks. Measures of socioeconomic status (at the zip code level), total facility staffing, and the composition of staff (percentage of nurses) were not associated with the rate of hospitalization for infection.Patient and facility factors associated with higher rates of infection-related hospitalization were identified. The findings from this study can be used to identify patients at higher risk for infection and inform the design of infection prevention strategies.

  View details for DOI 10.2215/CJN.03050315

  View details for PubMedID 26567370

• Economic Evaluation of Cinacalcet in the United States: The EVOLVE Trial VALUE IN HEALTH Belozeroff, V., Chertow, G. M., Graham, C. N., Dehmel, B., Parfrey, P. S., Briggs, A. H. 2015; 18 (8): 1079-1087

  Abstract

  Previous economic evaluations of cinacalcet in patients with secondary hyperparathyroidism (sHPT) relied on the combination of surrogate end points in clinical trials and epidemiologic studies.The objective was to conduct an economic evaluation of cinacalcet on the basis of the EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) trial from a US payer perspective.We developed a semi-Markov model to assess the cost-effectiveness of cinacalcet in addition to conventional therapy, compared with conventional therapy alone, in patients with moderate-to-severe sHPT receiving hemodialysis. We used treatment effect estimates from the unadjusted intent-to-treat (ITT) analysis and prespecified covariate-adjusted ITT analysis as our main analyses. We assessed model sensitivity to variations in individual inputs and overall decision uncertainty through probabilistic sensitivity analyses.The incremental cost-effectiveness ratio (ICER) for cinacalcet was $61,705 per life-year and $79,562 per quality-adjusted life-year (QALY) gained using the covariate-adjusted ITT analysis. Probabilistic sensitivity analysis suggested a 73.2% chance of the ICER being below a willingness-to-pay threshold of $100,000. Treatment effects from unadjusted ITT analysis yielded an ICER of $115,876 per QALY. The model was most sensitive to the treatment effect on mortality.In the unadjusted ITT analysis, cinacalcet does not represent a cost- effective use of health care resources when applying a willingness-to-pay threshold of $100,000 per QALY. When using the covariate-adjusted ITT treatment effect, which represents the least biased estimate, however, cinacalcet is a cost-effective therapy for patients with moderate-to-severe sHPT on hemodialysis.

  View details for DOI 10.1016/j.jval.2015.08.007

  View details for PubMedID 26686794

• Risk prediction models for contrast induced nephropathy: systematic review. BMJ (Clinical research ed.) [Anonymous] 2015; 351: h5401

  View details for DOI 10.1136/bmj.h5401

  View details for PubMedID 26449860

• Effects of daily hemodialysis on heart rate variability: results from the Frequent Hemodialysis Network (FHN) Daily Trial PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES Chan, C. T., Chertow, G. M., Daugirdasl, J. T., Greene', T. H., Kotanko, P., Larive, B., Pierratosi, A., Stokes, J. B. 2015; 282 (1816)

  Abstract

  End-stage renal disease is associated with reduced heart rate variability (HRV), components of which generally are associated with advanced age, diabetes mellitus and left ventricular hypertrophy. We hypothesized that daily in-center hemodialysis (HD) would increase HRV.The Frequent Hemodialysis Network (FHN) Daily Trial randomized 245 patients to receive 12 months of six versus three times per week in-center HD. Two hundred and seven patients had baseline Holter recordings. HRV measures were calculated from 24-h Holter electrocardiograms at both baseline and 12 months in 131 patients and included low-frequency power (LF, a measure of sympathetic modulation), high-frequency power (HF, a measure of parasympathetic modulation) and standard deviation (SD) of the R-R interval (SDNN, a measure of beat-to-beat variation).Baseline to Month 12 change in LF was augmented by 50% [95% confidence interval (95% CI) 6.1-112%, P =0.022] and LF + HF was augmented by 40% (95% CI 3.3-88.4%, P = 0.03) in patients assigned to daily hemodialysis (DHD) compared with conventional HD. Changes in HF and SDNN were similar between the randomized groups. The effects of DHD on LF were attenuated by advanced age and diabetes mellitus (predefined subgroups). Changes in HF (r = -0.20, P = 0.02) and SDNN (r = -0.18, P = 0.04) were inversely associated with changes in left ventricular mass (LVM).DHD increased the LF component of HRV. Reduction of LVM by DHD was associated with increased vagal modulation of heart rate (HF) and with increased beat-to-beat heart rate variation (SDNN), suggesting an important functional correlate to the structural effects of DHD on the heart in uremia.

  View details for DOI 10.1093/ndt/gft212

  View details for Web of Science ID 000363484700016

  View details for PubMedCentralID PMC3888308

• Association of bioimpedance spectroscopy-based volume estimation with postdialysis hypotension in patients receiving hemodialysis HEMODIALYSIS INTERNATIONAL Abreo, A. P., Chertow, G. M., Dalrymple, L. S., Kaysen, G. A., Johansen, K. L. 2015; 19 (4): 536-542

  Abstract

  Clinical examination to determine the dry weight of patients on hemodialysis (HD) has been problematic, with studies showing discordance between physician assessment and objective measures of volume status.We studied the association between predialysis bioimpedance spectroscopy (BIS)-based estimates of fluid overload and postdialysis hypotension in 635 patients in the United States Renal Data System ACTIVE/ADIPOSE (A Cohort study To Investigate the Value of Exercise/Analyses Designed to Investigate the Paradox of Obesity and Survival in ESRD) study receiving HD in 2009-2011. We recorded predialysis and postdialysis weight and blood pressures over 3 consecutive HD sessions and performed BIS before a single session. Using a previously reported method of estimating normohydration weight, we estimated postdialysis fluid overload (FOpost ) in liters. We used logistic regression with extracellular water/total body water (ECW/TBW) or estimated FOpost as the primary predictor and 1 or more postdialysis systolic blood pressures less than 110 mmHg as the dependent variable. Models were adjusted for age, sex, race, ultrafiltration rate per kilogram of body weight, end-stage renal disease vintage, diabetes mellitus, heart failure, and albumin. Higher ECW/TBW was associated with lower odds of postdialysis hypotension (odds ratio [OR] 0.35, 95% confidence interval [CI] 0.15-0.84 per 0.1, P = 0.02). Every liter of FOpost was associated with lower adjusted odds of postdialysis hypotension (OR 0.86, 95% CI 0.79-0.95, P = 0.003). Prospective studies are needed to determine whether this application of BIS could improve current clinical efforts to minimize episodes of postdialysis hypotension without leading to volume overload.

  View details for DOI 10.1111/hdi.12305

  View details for PubMedID 25881673

• Cardiovascular and Renal Outcomes Trials-Is There a Difference? AMERICAN JOURNAL OF CARDIOLOGY Raggi, P., Boer, R., Goodman, W. G., Kalantar-Zadeh, K., Chertow, G. M., Belozeroff, V. 2015; 116 (6): 982-988

  Abstract

  There is a general sense that most outcomes trials in patients receiving dialysis failed to yield statistically significant benefits, in contrast to many cardiovascular (CV) trials in the general population. It is unknown whether methodologic reasons caused this discrepancy. We performed a systematic MEDLINE search for randomized trials with mortality end points of the 42 compounds most commonly used for CV indications. In total, 115 trials were selected for review. We further reviewed 9 mortality end point trials in patients receiving dialysis. The CV trials in populations not receiving dialysis enrolled from 66 to 33,357 participants with an average of 4,910; 59% of the trials showed statistically significant results. The average hazard ratio (HR) was 0.77, ranging from 0.10 to 1.65; 10 drugs had ≥5 published trials each. In the population receiving dialysis, most drugs were studied in single trials; the average number of patients was 1,500 with a range of 127 to 3,883. The average HR was 0.77 and ranged from 0.06 to 1.30. Only 22% of the trials showed statistically significant results. The limitations listed in the general population and dialysis studies were similar. In conclusion, no apparent methodologic issues were detected (other than sample size) that could justify the lower frequency of randomized trials with statistically significant results in patients receiving dialysis. The most obvious difference was the paucity of trials with each drug in the dialysis cohorts; this lowers the chances of at least 1 trial being successful.

  View details for DOI 10.1016/j.amjcard.2015.06.024

  View details for PubMedID 26198118

• Menopausal symptoms in women with chronic kidney disease. Menopause (New York, N.Y.) Cheung, K. L., Stefanick, M. L., Allison, M. A., LeBlanc, E. S., Vitolins, M. Z., Shara, N., Chertow, G. M., Winkelmayer, W. C., Kurella Tamura, M. 2015; 22 (9): 1006-1011

  Abstract

  This study aims to determine whether menopausal symptoms differed between women with chronic kidney disease (CKD) and women without CKD, and whether CKD modified associations of late vasomotor symptoms (VMS) with mortality and/or cardiovascular events.CKD, defined as estimated glomerular filtration rate lower than 60 mL/minute/1.73 m (using the Chronic Kidney Disease Epidemiology Collaboration equation), was determined in 17,891 postmenopausal women, aged 50 to 79 years at baseline, in the multiethnic Women's Health Initiative cohort. Primary outcomes were presence, severity, and timing/duration of VMS (self-reported hot flashes and night sweats) at baseline. We used polytomous logistic regression to test for associations among CKD and four VMS categories (no VMS; early VMS-present before menopause but not at study baseline; late VMS-present only at study baseline; persistent VMS-present before menopause and study baseline) and Cox regression to determine whether CKD modified associations between late VMS and mortality or cardiovascular events.Women with CKD (1,017 of 17,891; mean estimated glomerular filtration rate, 50.7 mL/min/1.73 m) were more likely to have had menopause before age 45 years (26% vs 23%, P = 0.02) but were less likely to experience VMS (38% vs 46%, P < 0.001) than women without CKD. Women with CKD were not more likely than women without CKD to experience late VMS. Late VMS (hazard ratio, 1.16; 95% CI, 1.04-1.29) and CKD (hazard ratio, 1.74; 95% CI, 1.54-1.97) were each independently associated with increased risk for mortality, but CKD did not modify the association of late VMS with mortality (Pinteraction = 0.53), coronary heart disease (Pinteraction = 0.12), or stroke (Pinteraction = 0.68).Women with mild CKD experience earlier menopause and fewer VMS than women without CKD.

  View details for DOI 10.1097/GME.0000000000000416

  View details for PubMedID 25628057

• Long-term Effects of Frequent Nocturnal Hemodialysis on Mortality: The Frequent Hemodialysis Network (FHN) Nocturnal Trial AMERICAN JOURNAL OF KIDNEY DISEASES Rocco, M. V., Daugirdas, J. T., Greene, T., Lockridge, R. S., Chan, C., Pierratos, A., Lindsay, R., Larive, B., Chertow, G. M., Beck, G. J., Eggers, P. W., Kliger, A. S. 2015; 66 (3): 459-468

  Abstract

  Few data are available regarding the long-term mortality rate for patients receiving nocturnal home hemodialysis.Posttrial observational study.Frequent Hemodialysis Network (FHN) Nocturnal Trial participants who consented to extended follow-up.The FHN Nocturnal Trial randomly assigned 87 individuals to 6-times-weekly home nocturnal hemodialysis or 3-times-weekly hemodialysis for 1 year. Patients were enrolled starting in March 2006 and follow-up was completed by May 2010. After the 1-year trial concluded, FHN Nocturnal participants were free to modify their hemodialysis prescription.We obtained dates of death and kidney transplantation through July 2011 using linkage to the US Renal Data System and queries of study centers. We used log-rank tests and Cox regression to relate mortality to the initial randomization assignment.Median follow-up for the trial and posttrial observational period was 3.7 years. In the nocturnal arm, there were 2 deaths during the 12-month trial period and an additional 12 deaths during the extended follow-up. In the conventional arm, the numbers of deaths were 1 and 4, respectively. In the nocturnal dialysis group, the overall mortality HR was 3.88 (95% CI, 1.27-11.79; P=0.01). Using as-treated analysis with a 12-month running treatment average, the HR for mortality was 3.06 (95% CI, 1.11-8.43; P=0.03). Six-month running treatment data analysis showed an HR of 1.12 (95% CI, 0.44-3.22; P=0.7).These results should be interpreted cautiously due to a surprisingly low (0.03 deaths/patient-year) mortality rate for individuals randomly assigned to conventional home hemodialysis, low statistical power for the mortality comparison due to the small sample size, and the high rate of hemodialysis prescription changes.Patients randomly assigned to nocturnal hemodialysis had a higher mortality rate than those randomly assigned to conventional dialysis. The implications of this result require further investigation.

  View details for DOI 10.1053/j.ajkd.2015.02.331

  View details for Web of Science ID 000360115400019

  View details for PubMedCentralID PMC4549208

• Long-term Effects of Frequent Nocturnal Hemodialysis on Mortality: The Frequent Hemodialysis Network (FHN) Nocturnal Trial. American journal of kidney diseases Rocco, M. V., Daugirdas, J. T., Greene, T., Lockridge, R. S., Chan, C., Pierratos, A., Lindsay, R., Larive, B., Chertow, G. M., Beck, G. J., Eggers, P. W., Kliger, A. S. 2015; 66 (3): 459-468

  Abstract

  Few data are available regarding the long-term mortality rate for patients receiving nocturnal home hemodialysis.Posttrial observational study.Frequent Hemodialysis Network (FHN) Nocturnal Trial participants who consented to extended follow-up.The FHN Nocturnal Trial randomly assigned 87 individuals to 6-times-weekly home nocturnal hemodialysis or 3-times-weekly hemodialysis for 1 year. Patients were enrolled starting in March 2006 and follow-up was completed by May 2010. After the 1-year trial concluded, FHN Nocturnal participants were free to modify their hemodialysis prescription.We obtained dates of death and kidney transplantation through July 2011 using linkage to the US Renal Data System and queries of study centers. We used log-rank tests and Cox regression to relate mortality to the initial randomization assignment.Median follow-up for the trial and posttrial observational period was 3.7 years. In the nocturnal arm, there were 2 deaths during the 12-month trial period and an additional 12 deaths during the extended follow-up. In the conventional arm, the numbers of deaths were 1 and 4, respectively. In the nocturnal dialysis group, the overall mortality HR was 3.88 (95% CI, 1.27-11.79; P=0.01). Using as-treated analysis with a 12-month running treatment average, the HR for mortality was 3.06 (95% CI, 1.11-8.43; P=0.03). Six-month running treatment data analysis showed an HR of 1.12 (95% CI, 0.44-3.22; P=0.7).These results should be interpreted cautiously due to a surprisingly low (0.03 deaths/patient-year) mortality rate for individuals randomly assigned to conventional home hemodialysis, low statistical power for the mortality comparison due to the small sample size, and the high rate of hemodialysis prescription changes.Patients randomly assigned to nocturnal hemodialysis had a higher mortality rate than those randomly assigned to conventional dialysis. The implications of this result require further investigation.

  View details for DOI 10.1053/j.ajkd.2015.02.331

  View details for PubMedID 25863828

• Risk prediction models for contrast induced nephropathy: systematic review BMJ-BRITISH MEDICAL JOURNAL Silver, S. A., Shah, P. M., Chertow, G. M., Harel, S., Wald, R., Harel, Z. 2015; 351

  Abstract

  To look at the available literature on validated prediction models for contrast induced nephropathy and describe their characteristics.Systematic review.Medline, Embase, and CINAHL (cumulative index to nursing and allied health literature) databases.Databases searched from inception to 2015, and the retrieved reference lists hand searched. Dual reviews were conducted to identify studies published in the English language of prediction models tested with patients that included derivation and validation cohorts. Data were extracted on baseline patient characteristics, procedural characteristics, modelling methods, metrics of model performance, risk of bias, and clinical usefulness. Eligible studies evaluated characteristics of predictive models that identified patients at risk of contrast induced nephropathy among adults undergoing a diagnostic or interventional procedure using conventional radiocontrast media (media used for computed tomography or angiography, and not gadolinium based contrast).16 studies were identified, describing 12 prediction models. Substantial interstudy heterogeneity was identified, as a result of different clinical settings, cointerventions, and the timing of creatinine measurement to define contrast induced nephropathy. Ten models were validated internally and six were validated externally. Discrimination varied in studies that were validated internally (C statistic 0.61-0.95) and externally (0.57-0.86). Only one study presented reclassification indices. The majority of higher performing models included measures of pre-existing chronic kidney disease, age, diabetes, heart failure or impaired ejection fraction, and hypotension or shock. No prediction model evaluated its effect on clinical decision making or patient outcomes.Most predictive models for contrast induced nephropathy in clinical use have modest ability, and are only relevant to patients receiving contrast for coronary angiography. Further research is needed to develop models that can better inform patient centred decision making, as well as improve the use of prevention strategies for contrast induced nephropathy.

  View details for DOI 10.1136/bmj.h4395

  View details for Web of Science ID 000360438200001

  View details for PubMedCentralID PMC4784870

• Risk prediction models for contrast induced nephropathy: systematic review. BMJ (Clinical research ed.) Silver, S. A., Shah, P. M., Chertow, G. M., Harel, S., Wald, R., Harel, Z. 2015; 351: h4395

  Abstract

  To look at the available literature on validated prediction models for contrast induced nephropathy and describe their characteristics.Systematic review.Medline, Embase, and CINAHL (cumulative index to nursing and allied health literature) databases.Databases searched from inception to 2015, and the retrieved reference lists hand searched. Dual reviews were conducted to identify studies published in the English language of prediction models tested with patients that included derivation and validation cohorts. Data were extracted on baseline patient characteristics, procedural characteristics, modelling methods, metrics of model performance, risk of bias, and clinical usefulness. Eligible studies evaluated characteristics of predictive models that identified patients at risk of contrast induced nephropathy among adults undergoing a diagnostic or interventional procedure using conventional radiocontrast media (media used for computed tomography or angiography, and not gadolinium based contrast).16 studies were identified, describing 12 prediction models. Substantial interstudy heterogeneity was identified, as a result of different clinical settings, cointerventions, and the timing of creatinine measurement to define contrast induced nephropathy. Ten models were validated internally and six were validated externally. Discrimination varied in studies that were validated internally (C statistic 0.61-0.95) and externally (0.57-0.86). Only one study presented reclassification indices. The majority of higher performing models included measures of pre-existing chronic kidney disease, age, diabetes, heart failure or impaired ejection fraction, and hypotension or shock. No prediction model evaluated its effect on clinical decision making or patient outcomes.Most predictive models for contrast induced nephropathy in clinical use have modest ability, and are only relevant to patients receiving contrast for coronary angiography. Further research is needed to develop models that can better inform patient centred decision making, as well as improve the use of prevention strategies for contrast induced nephropathy.

  View details for DOI 10.1136/bmj.h4395

  View details for PubMedID 26316642

  View details for PubMedCentralID PMC4784870

• Provider Visits and Early Vascular Access Placement in Maintenance Hemodialysis JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Erickson, K. F., Mell, M., Winkelmayer, W. C., Chertow, G. M., Bhattacharya, J. 2015; 26 (8): 1990-1997

  Abstract

  Medicare reimbursement policy encourages frequent provider visits for patients with ESRD undergoing hemodialysis. We hypothesize that patients seen more frequently by their nephrologist or advanced practitioner within the first 90 days of hemodialysis are more likely to undergo surgery to create an arteriovenous (AV) fistula or place an AV graft. We selected 35,959 patients aged ≥67 years starting hemodialysis in the United States from a national registry. We used multivariable regression to evaluate the associations between mean visit frequency and AV fistula creation or graft placement in the first 90 days of hemodialysis. We conducted an instrumental variable analysis to test the sensitivity of our findings to potential bias from unobserved characteristics. One additional visit per month in the first 90 days of hemodialysis was associated with a 21% increase in the odds of AV fistula creation or graft placement during that period (95% confidence interval, 19% to 24%), corresponding to an average 4.5% increase in absolute probability. An instrumental variable analysis demonstrated similar findings. Excluding visits in months when patients were hospitalized, one additional visit per month was associated with a 10% increase in odds of vascular access surgery (95% confidence interval, 8% to 13%). In conclusion, patients seen more frequently by care providers in the first 90 days of hemodialysis undergo earlier AV fistula creation or graft placement. Payment policies that encourage more frequent visits to patients at key clinical time points may yield more favorable health outcomes than policies that operate irrespective of patients' health status.

  View details for DOI 10.1681/ASN.2014050464

  View details for PubMedID 25452668

• Cinacalcet, Fibroblast Growth Factor-23, and Cardiovascular Disease in Hemodialysis The Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial CIRCULATION Moe, S. M., Chertow, G. M., Parfrey, P. S., Kubo, Y., Block, G. A., Correa-Rotter, R., Drueeke, T. B., Herzog, C. A., London, G. M., Mahaffey, K. W., Wheeler, D. C., Stolina, M., Dehmel, B., Goodman, W. G., Floege, J. 2015; 132 (1): 27-39

  Abstract

  Patients with kidney disease have disordered bone and mineral metabolism, including elevated serum concentrations of fibroblast growth factor-23 (FGF23). These elevated concentrations are associated with cardiovascular and all-cause mortality. The objective was to determine the effects of the calcimimetic cinacalcet (versus placebo) on reducing serum FGF23 and whether changes in FGF23 are associated with death and cardiovascular events.This was a secondary analysis of a randomized clinical trial comparing cinacalcet to placebo in addition to conventional therapy (phosphate binders/vitamin D) in patients receiving hemodialysis with secondary hyperparathyroidism (intact parathyroid hormone ≥300 pg/mL). The primary study end point was time to death or a first nonfatal cardiovascular event (myocardial infarction, hospitalization for angina, heart failure, or a peripheral vascular event). This analysis included 2985 patients (77% of randomized) with serum samples at baseline and 2602 patients (67%) with samples at both baseline and week 20. The results demonstrated that a significantly larger proportion of patients randomized to cinacalcet had ≥30% (68% versus 28%) reductions in FGF23. Among patients randomized to cinacalcet, a ≥30% reduction in FGF23 between baseline and week 20 was associated with a nominally significant reduction in the primary composite end point (relative hazard, 0.82; 95% confidence interval, 0.69-0.98), cardiovascular mortality (relative hazard, 0.66; 95% confidence interval, 0.50-0.87), sudden cardiac death (relative hazard, 0.57; 95% confidence interval, 0.37-0.86), and heart failure (relative hazard, 0.69; 95% confidence interval, 0.48-0.99).Treatment with cinacalcet significantly lowers serum FGF23. Treatment-induced reductions in serum FGF23 are associated with lower rates of cardiovascular death and major cardiovascular events.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00345839.

  View details for DOI 10.1161/CIRCULATIONAHA.114.013876

  View details for Web of Science ID 000357498100005

• Cinacalcet, Fibroblast Growth Factor-23, and Cardiovascular Disease in Hemodialysis: The Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial. Circulation Moe, S. M., Chertow, G. M., Parfrey, P. S., Kubo, Y., Block, G. A., Correa-Rotter, R., Drüeke, T. B., Herzog, C. A., London, G. M., Mahaffey, K. W., Wheeler, D. C., Stolina, M., Dehmel, B., Goodman, W. G., Floege, J. 2015; 132 (1): 27-39

  Abstract

  Patients with kidney disease have disordered bone and mineral metabolism, including elevated serum concentrations of fibroblast growth factor-23 (FGF23). These elevated concentrations are associated with cardiovascular and all-cause mortality. The objective was to determine the effects of the calcimimetic cinacalcet (versus placebo) on reducing serum FGF23 and whether changes in FGF23 are associated with death and cardiovascular events.This was a secondary analysis of a randomized clinical trial comparing cinacalcet to placebo in addition to conventional therapy (phosphate binders/vitamin D) in patients receiving hemodialysis with secondary hyperparathyroidism (intact parathyroid hormone ≥300 pg/mL). The primary study end point was time to death or a first nonfatal cardiovascular event (myocardial infarction, hospitalization for angina, heart failure, or a peripheral vascular event). This analysis included 2985 patients (77% of randomized) with serum samples at baseline and 2602 patients (67%) with samples at both baseline and week 20. The results demonstrated that a significantly larger proportion of patients randomized to cinacalcet had ≥30% (68% versus 28%) reductions in FGF23. Among patients randomized to cinacalcet, a ≥30% reduction in FGF23 between baseline and week 20 was associated with a nominally significant reduction in the primary composite end point (relative hazard, 0.82; 95% confidence interval, 0.69-0.98), cardiovascular mortality (relative hazard, 0.66; 95% confidence interval, 0.50-0.87), sudden cardiac death (relative hazard, 0.57; 95% confidence interval, 0.37-0.86), and heart failure (relative hazard, 0.69; 95% confidence interval, 0.48-0.99).Treatment with cinacalcet significantly lowers serum FGF23. Treatment-induced reductions in serum FGF23 are associated with lower rates of cardiovascular death and major cardiovascular events.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00345839.

  View details for DOI 10.1161/CIRCULATIONAHA.114.013876

  View details for PubMedID 26059012

• Prevalence of chronic kidney disease in two major Indian cities and projections for associated cardiovascular disease KIDNEY INTERNATIONAL Anand, S., Shivashankar, R., Ali, M. K., Kondal, D., Binukumar, B., Montez-Rath, M. E., Ajay, V. S., Pradeepa, R., Deepa, M., Gupta, R., Mohan, V., Narayan, K. M., Tandon, N., Chertow, G. M., Prabhakaran, D. 2015; 88 (1): 178-185

  Abstract

  India is experiencing an alarming rise in the burden of noncommunicable diseases, but data on the incidence of chronic kidney disease (CKD) are sparse. Using the Center for Cardiometabolic Risk Reduction in South Asia surveillance study (a population-based survey of Delhi and Chennai, India) we estimated overall, and age-, sex-, city-, and diabetes-specific prevalence of CKD, and defined the distribution of the study population by the Kidney Disease Improving Global Outcomes (KDIGO) classification scheme. The likelihood of cardiovascular events in participants with and without CKD was estimated by the Framingham and Interheart Modifiable Risk Scores. Of the 12,271 participants, 80% had complete data on serum creatinine and albuminuria. The prevalence of CKD and albuminuria, age standardized to the World Bank 2010 world population, was 8.7% (95% confidence interval: 7.9-9.4%) and 7.1% (6.4-7.7%), respectively. Nearly 80% of patients with CKD had an abnormally high hemoglobin A1c (5.7 and above). Based on KDIGO guidelines, 6.0, 1.0, and 0.5% of study participants are at moderate, high, or very high risk for experiencing CKD-associated adverse outcomes. The cardiovascular risk scores placed a greater proportion of patients with CKD in the high-risk categories for experiencing cardiovascular events when compared with participants without CKD. Thus, 1 in 12 individuals living in two of India's largest cities have evidence of CKD, with features that put them at high risk for adverse outcomes.

  View details for DOI 10.1038/ki.2015.58

  View details for PubMedID 25786102

• Associations of Trimethylamine N-Oxide With Nutritional and Inflammatory Biomarkers and Cardiovascular Outcomes in Patients New to Dialysis JOURNAL OF RENAL NUTRITION Kaysen, G. A., Johansen, K. L., Chertow, G. M., Dalrymple, L. S., Kornak, J., Grimes, B., Dwyer, T., Chassy, A. W., Fiehn, O. 2015; 25 (4): 351-356

  Abstract

  Trimethylamine N-oxide (TMAO) is a product of metabolism of phosphatidylcholine (lecithin) and carnitine by the intestinal microbiome. Elevated serum concentrations of TMAO have been linked to adverse cardiovascular outcomes in the general population. We examined correlates of serum TMAO and the relations among serum TMAO concentrations, all-cause mortality, and cardiovascular mortality and hospitalizations in a nationally derived cohort of patients new to hemodialysis (HD).We quantified serum TMAO by liquid chromatography and online tandem mass spectrometry and assessed nutritional and cardiovascular risk factors in 235 patients receiving HD and measured TMAO in pooled serum from healthy controls. We analyzed time to death and time to cardiovascular death or hospitalization using Cox proportional hazards regression.Serum TMAO concentrations of patients undergoing HD (median, 43 μM/L; 25th-75th percentile, 28-67 μM/L) were elevated compared with those with normal or near-normal kidney function (1.41 ± 0.49 μM/L). TMAO was directly correlated with serum albumin (Spearman rank correlation, 0.24; 95% CI, 0.12-0.35; P <.001), prealbumin (Spearman rank correlation, 0.19; 95% CI, 0.07-0.31; P = .003), and creatinine (Spearman rank correlation, 0.21; 95% CI, 0.08-0.33; P = .002) and inversely correlated with log C-reactive protein (Spearman rank correlation, -0.18; 95% CI, -0.30 to -0.06; P = .005). Higher serum concentrations of TMAO were not significantly associated with time to death (Spearman rank correlation, 0.84; CI, 0.65-1.09; P = .19) or time to cardiovascular hospitalization or cardiovascular death (Spearman rank correlation, 0.88; CI, 0.57-1.35; P = .55).Serum TMAO concentrations were markedly elevated and correlated directly with biochemical markers of nutritional status and inversely with markers of inflammation in patients receiving HD. There was no significant association between serum TMAO concentrations and all-cause mortality, cardiovascular death, or hospitalizations. In patients receiving dialysis-in contrast with the general population-adverse vascular effects of TMAO may be counterbalanced by associations with nutritional or inflammatory status.

  View details for DOI 10.1053/j.jrn.2015.02.006

  View details for Web of Science ID 000360282800006

  View details for PubMedCentralID PMC4469547

• Associations of Trimethylamine N-Oxide With Nutritional and Inflammatory Biomarkers and Cardiovascular Outcomes in Patients New to Dialysis. Journal of renal nutrition Kaysen, G. A., Johansen, K. L., Chertow, G. M., Dalrymple, L. S., Kornak, J., Grimes, B., Dwyer, T., Chassy, A. W., Fiehn, O. 2015; 25 (4): 351-356

  Abstract

  Trimethylamine N-oxide (TMAO) is a product of metabolism of phosphatidylcholine (lecithin) and carnitine by the intestinal microbiome. Elevated serum concentrations of TMAO have been linked to adverse cardiovascular outcomes in the general population. We examined correlates of serum TMAO and the relations among serum TMAO concentrations, all-cause mortality, and cardiovascular mortality and hospitalizations in a nationally derived cohort of patients new to hemodialysis (HD).We quantified serum TMAO by liquid chromatography and online tandem mass spectrometry and assessed nutritional and cardiovascular risk factors in 235 patients receiving HD and measured TMAO in pooled serum from healthy controls. We analyzed time to death and time to cardiovascular death or hospitalization using Cox proportional hazards regression.Serum TMAO concentrations of patients undergoing HD (median, 43 μM/L; 25th-75th percentile, 28-67 μM/L) were elevated compared with those with normal or near-normal kidney function (1.41 ± 0.49 μM/L). TMAO was directly correlated with serum albumin (Spearman rank correlation, 0.24; 95% CI, 0.12-0.35; P <.001), prealbumin (Spearman rank correlation, 0.19; 95% CI, 0.07-0.31; P = .003), and creatinine (Spearman rank correlation, 0.21; 95% CI, 0.08-0.33; P = .002) and inversely correlated with log C-reactive protein (Spearman rank correlation, -0.18; 95% CI, -0.30 to -0.06; P = .005). Higher serum concentrations of TMAO were not significantly associated with time to death (Spearman rank correlation, 0.84; CI, 0.65-1.09; P = .19) or time to cardiovascular hospitalization or cardiovascular death (Spearman rank correlation, 0.88; CI, 0.57-1.35; P = .55).Serum TMAO concentrations were markedly elevated and correlated directly with biochemical markers of nutritional status and inversely with markers of inflammation in patients receiving HD. There was no significant association between serum TMAO concentrations and all-cause mortality, cardiovascular death, or hospitalizations. In patients receiving dialysis-in contrast with the general population-adverse vascular effects of TMAO may be counterbalanced by associations with nutritional or inflammatory status.

  View details for DOI 10.1053/j.jrn.2015.02.006

  View details for PubMedID 25802017

• Longer-term Outcomes of Darbepoetin Alfa Versus Epoetin Alfa in Patients With ESRD Initiating Hemodialysis: A Quasi-experimental Cohort Study AMERICAN JOURNAL OF KIDNEY DISEASES Winkelmayer, W. C., Chang, T. I., Mitani, A. A., Wilhelm-Leen, E. R., Ding, V., Chertow, G. M., Brookhart, M. A., Goldstein, B. A. 2015; 66 (1): 106-113

  Abstract

  Adequately powered studies directly comparing hard clinical outcomes of darbepoetin alfa (DPO) versus epoetin alfa (EPO) in patients undergoing dialysis are lacking.Observational, registry-based, retrospective cohort study; we mimicked a cluster-randomized trial by comparing mortality and cardiovascular events in US patients initiating hemodialysis therapy in facilities (almost) exclusively using DPO versus EPO.Nonchain US hemodialysis facilities; each facility switching from EPO to DPO (2003-2010) was matched for location, profit status, and facility type with one EPO facility. Patients subsequently initiating hemodialysis therapy in these facilities were assigned their facility-level exposure.DPO versus EPO.All-cause mortality, cardiovascular mortality; composite of cardiovascular death, nonfatal myocardial infarction (MI), and nonfatal stroke.Unadjusted and adjusted HRs from Cox proportional hazards regression models.Of 508 dialysis facilities that switched to DPO, 492 were matched with a similar EPO facility; 19,932 (DPO: 9,465 [47.5%]; EPO: 10,467 [52.5%]) incident hemodialysis patients were followed up for 21,918 person-years during which 5,550 deaths occurred. Almost all baseline characteristics were tightly balanced. The demographics-adjusted mortality HR for DPO (vs EPO) was 1.06 (95% CI, 1.00-1.13) and was materially unchanged after adjustment for all other baseline characteristics (HR, 1.05; 95% CI, 0.99-1.12). Cardiovascular mortality did not differ between groups (HR, 1.05; 95% CI, 0.94-1.16). Nonfatal outcomes were evaluated among 9,455 patients with fee-for-service Medicare: 4,542 (48.0%) in DPO and 4,913 (52.0%) in EPO facilities. During 10,457 and 10,363 person-years, 248 and 372 events were recorded, respectively, for strokes and MIs. We found no differences in adjusted stroke or MI rates or their composite with cardiovascular death (HR, 1.10; 95% CI, 0.96-1.25).Nonrandom treatment assignment, potential residual confounding.In incident hemodialysis patients, mortality and cardiovascular event rates did not differ between patients treated at facilities predominantly using DPO versus EPO.

  View details for DOI 10.1053/j.ajkd.2015.02.339

  View details for PubMedID 25943715

• Assessing the treatment effect in a randomized controlled trial with extensive non-adherence: the EVOLVE trial. Pharmaceutical statistics Kubo, Y., Sterling, L. R., Parfrey, P. S., Gill, K., Mahaffey, K. W., Gioni, I., Trotman, M., Dehmel, B., Chertow, G. M. 2015; 14 (4): 368-?

  View details for DOI 10.1002/pst.1694

  View details for PubMedID 26096896

• Effects of Cinacalcet on Fracture Events in Patients Receiving Hemodialysis: The EVOLVE Trial. Journal of the American Society of Nephrology Moe, S. M., Abdalla, S., Chertow, G. M., Parfrey, P. S., Block, G. A., Correa-Rotter, R., Floege, J., Herzog, C. A., London, G. M., Mahaffey, K. W., Wheeler, D. C., Dehmel, B., Goodman, W. G., Drüeke, T. B. 2015; 26 (6): 1466-1475

  Abstract

  Fractures are frequent in patients receiving hemodialysis. We tested the hypothesis that cinacalcet would reduce the rate of clinical fractures in patients receiving hemodialysis using data from the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events trial, a placebo-controlled trial that randomized 3883 hemodialysis patients with secondary hyperparathyroidism to receive cinacalcet or placebo for ≤64 months. This study was a prespecified secondary analysis of the trial whose primary end point was all-cause mortality and non-fatal cardiovascular events, and one of the secondary end points was first clinical fracture event. Clinical fractures were observed in 255 of 1935 (13.2%) patients randomized to placebo and 238 of 1948 (12.2%) patients randomized to cinacalcet. In an unadjusted intention-to-treat analysis, the relative hazard for fracture (cinacalcet versus placebo) was 0.89 (95% confidence interval [95% CI], 0.75 to 1.07). After adjustment for baseline characteristics and multiple fractures, the relative hazard was 0.83 (95% CI, 0.72 to 0.98). Using a prespecified lag-censoring analysis (a measure of actual drug exposure), the relative hazard for fracture was 0.72 (95% CI, 0.58 to 0.90). When participants were censored at the time of cointerventions (parathyroidectomy, transplant, or provision of commercial cinacalcet), the relative hazard was 0.71 (95% CI, 0.58 to 0.87). Fracture rates were higher in older compared with younger patients and the effect of cinacalcet appeared more pronounced in older patients. In conclusion, using an unadjusted intention-to-treat analysis, cinacalcet did not reduce the rate of clinical fracture. However, when accounting for differences in baseline characteristics, multiple fractures, and/or events prompting discontinuation of study drug, cinacalcet reduced the rate of clinical fracture by 16%-29%.

  View details for DOI 10.1681/ASN.2014040414

  View details for PubMedID 25505257

  View details for PubMedCentralID PMC4446874

• Effects of Cinacalcet on Fracture Events in Patients Receiving Hemodialysis: The EVOLVE Trial JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Moe, S. M., Abdalla, S., Chertow, G. M., Parfrey, P. S., Block, G. A., Correa-Rotter, R., Floege, J., Herzog, C. A., London, G. M., Mahaffey, K. W., Wheeler, D. C., Dehmel, B., Goodman, W. G., Drueeke, T. B. 2015; 26 (6): 1466-1475

  Abstract

  Fractures are frequent in patients receiving hemodialysis. We tested the hypothesis that cinacalcet would reduce the rate of clinical fractures in patients receiving hemodialysis using data from the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events trial, a placebo-controlled trial that randomized 3883 hemodialysis patients with secondary hyperparathyroidism to receive cinacalcet or placebo for ≤64 months. This study was a prespecified secondary analysis of the trial whose primary end point was all-cause mortality and non-fatal cardiovascular events, and one of the secondary end points was first clinical fracture event. Clinical fractures were observed in 255 of 1935 (13.2%) patients randomized to placebo and 238 of 1948 (12.2%) patients randomized to cinacalcet. In an unadjusted intention-to-treat analysis, the relative hazard for fracture (cinacalcet versus placebo) was 0.89 (95% confidence interval [95% CI], 0.75 to 1.07). After adjustment for baseline characteristics and multiple fractures, the relative hazard was 0.83 (95% CI, 0.72 to 0.98). Using a prespecified lag-censoring analysis (a measure of actual drug exposure), the relative hazard for fracture was 0.72 (95% CI, 0.58 to 0.90). When participants were censored at the time of cointerventions (parathyroidectomy, transplant, or provision of commercial cinacalcet), the relative hazard was 0.71 (95% CI, 0.58 to 0.87). Fracture rates were higher in older compared with younger patients and the effect of cinacalcet appeared more pronounced in older patients. In conclusion, using an unadjusted intention-to-treat analysis, cinacalcet did not reduce the rate of clinical fracture. However, when accounting for differences in baseline characteristics, multiple fractures, and/or events prompting discontinuation of study drug, cinacalcet reduced the rate of clinical fracture by 16%-29%.

  View details for DOI 10.1681/ASN.2014040414

  View details for Web of Science ID 000355386100024

  View details for PubMedCentralID PMC4446874

• Dialysis plus do not resuscitate--not a contradiction. JAMA internal medicine Wilhelm-Leen, E. R., Chertow, G. M. 2015; 175 (6): 1035-1036

  View details for DOI 10.1001/jamainternmed.2015.0413

  View details for PubMedID 25915153

• Evaluating Risk of ESRD in the Urban Poor JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Maziarz, M., Black, R. A., Fong, C. T., Himmelfarb, J., Chertow, G. M., Hall, Y. N. 2015; 26 (6): 1434-1442

  Abstract

  The capacity of risk prediction to guide management of CKD in underserved health settings is unknown. We conducted a retrospective cohort study of 28,779 adults with nondialysis-requiring CKD who received health care in two large safety net health systems during 1996-2009 and were followed for ESRD through September of 2011. We developed and evaluated the performance of ESRD risk prediction models using recently proposed criteria designed to inform population health approaches to disease management: proportion of cases followed and proportion that needs to be followed. Overall, 1730 persons progressed to ESRD during follow-up (median follow-up=6.6 years). ESRD risk for time frames up to 5 years was highly concentrated among relatively few individuals. A predictive model using five common variables (age, sex, race, eGFR, and dipstick proteinuria) performed similarly to more complex models incorporating extensive sociodemographic and clinical data. Using this model, 80% of individuals who eventually developed ESRD were among the 5% of cohort members at the highest estimated risk for ESRD at 1 year. Similarly, a program that followed 8% and 13% of individuals at the highest ESRD risk would have included 80% of those who eventually progressed to ESRD at 3 and 5 years, respectively. In this underserved health setting, a simple five-variable model accurately predicts most cases of ESRD that develop within 5 years. Applying risk prediction using a population health approach may improve CKD surveillance and management of vulnerable groups by directing resources to a small subpopulation at highest risk for progressing to ESRD.

  View details for DOI 10.1681/ASN.2014060546

  View details for PubMedID 25475746

• Red blood cell transfusion, hyperkalemia, and heart failure in advanced chronic kidney disease PHARMACOEPIDEMIOLOGY AND DRUG SAFETY Gill, K., Fink, J. C., Gilbertson, D. T., Monda, K. L., Muntner, P., Lafayette, R. A., Petersen, J., Chertow, G. M., Bradbury, B. D. 2015; 24 (6): 654-662

  Abstract

  In recent years, the use of red blood cell (RBC) transfusion for the treatment of chronic kidney disease (CKD)-related anemia has increased. We used the OptumInsight medical claims database to study the association between receiving a transfusion and hyperkalemia and heart failure events.Persons 18-64 years of age with diagnosed stage 4 or 5 CKD (not requiring dialysis) between 2006 and 2010 were followed until their first hospitalization or emergency room visit with a diagnosis of hyperkalemia or heart failure, termination of insurance coverage, or death. We used a case-only design and conditional logistic regression to estimate rate ratios (RR) and 95% confidence intervals (CIs) describing associations between RBC transfusion and the risks of hyperkalemia or heart failure. We used single (1:1) and variable (1:m) self-control matching intervals, with adjustment for time-varying confounders.Seven thousand eight hundred twenty-nine individuals met our inclusion criteria; two-thirds were age 50 years or older; 43% were women and 51% had diabetes. Rates of hyperkalemia and heart failure were 7.9/100 person-years (95%CI: 7.3, 8.5) and 16.3/100 person-years (95%CI: 15.5, 17.2), respectively. RBC transfusion was associated with an increased risk of both hyperkalemia (single interval matched RR = 12.0, 95%CI: 1.3, 109; multiple interval matched RR = 6.1, 95%CI: 2.5, 15.1) and heart failure (single interval matched RR = 1.7, 95%CI: 0.3, 9.2; multiple interval matched RR = 3.8, 95%CI: 1.4, 10.3).In patients with advanced CKD, RBC transfusion appears to be associated with an elevated risk of hyperkalemia and heart failure; further investigation into these risks is warranted. Copyright © 2015 John Wiley & Sons, Ltd.

  View details for DOI 10.1002/pds.3779

  View details for PubMedID 25903095

• The Effects of Cinacalcet in Older and Younger Patients on Hemodialysis: The Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial. Clinical journal of the American Society of Nephrology Parfrey, P. S., Drüeke, T. B., Block, G. A., Correa-Rotter, R., Floege, J., Herzog, C. A., London, G. M., Mahaffey, K. W., Moe, S. M., Wheeler, D. C., Kubo, Y., Dehmel, B., Goodman, W. G., Chertow, G. M. 2015; 10 (5): 791-799

  Abstract

  The calcimimetic cinacalcet reduced the risk of death or cardiovascular (CV) events in older, but not younger, patients with moderate to severe secondary hyperparathyroidism (HPT) who were receiving hemodialysis. To determine whether the lower risk in younger patients might be due to lower baseline CV risk and more frequent use of cointerventions that reduce parathyroid hormone (kidney transplantation, parathyroidectomy, and commercial cinacalcet use), this study examined the effects of cinacalcet in older (≥65 years, n=1005) and younger (<65 years, n=2878) patients.Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) was a global, multicenter, randomized placebo-controlled trial in 3883 prevalent patients on hemodialysis, whose outcomes included death, major CV events, and development of severe unremitting HPT. The age subgroup analysis was prespecified.Older patients had higher baseline prevalence of diabetes mellitus and CV comorbidity. Annualized rates of kidney transplantation and parathyroidectomy were >3-fold higher in younger relative to older patients and were more frequent in patients randomized to placebo. In older patients, the adjusted relative hazard (95% confidence interval) for the primary composite (CV) end point (cinacalcet versus placebo) was 0.70 (0.60 to 0.81); in younger patients, the relative hazard was 0.97 (0.86 to 1.09). Corresponding adjusted relative hazards for mortality were 0.68 (0.51 to 0.81) and 0.99 (0.86 to 1.13). Reduction in the risk of severe unremitting HPT was similar in both groups.In the EVOLVE trial, cinacalcet decreased the risk of death and of major CV events in older, but not younger, patients with moderate to severe HPT who were receiving hemodialysis. Effect modification by age may be partly explained by differences in underlying CV risk and differential application of cointerventions that reduce parathyroid hormone.

  View details for DOI 10.2215/CJN.07730814

  View details for PubMedID 25710802

• Outcomes of Infection-Related Hospitalization in Medicare Beneficiaries Receiving In-Center Hemodialysis AMERICAN JOURNAL OF KIDNEY DISEASES Dalrymple, L. S., Mu, Y., Romano, P. S., Nguyen, D. V., Chertow, G. M., Delgado, C., Grimes, B., Kaysen, G. A., Johansen, K. L. 2015; 65 (5): 754-762

  Abstract

  Infection is a common cause of hospitalization in adults receiving hemodialysis. Limited data are available about downstream events resulting from or following these hospitalizations.Retrospective cohort study using the US Renal Data System.Medicare beneficiaries initiating in-center hemodialysis therapy in 2005 to 2008.Demographics, dual Medicare/Medicaid eligibility, body mass index, comorbid conditions, initial vascular access type, nephrology care prior to dialysis therapy initiation, residence in a care facility, tobacco use, biochemical measures, and type of infection.30-day hospital readmission or death following first infection-related hospitalization.60,270 Medicare beneficiaries had at least one hospitalization for infection. Of those who survived the initial hospitalization, 15,113 (27%) were readmitted and survived the 30 days following hospital discharge, 1,624 (3%) were readmitted to the hospital and then died within 30 days of discharge, and 2,425 (4%) died without hospital readmission. Complications related to dialysis access, sepsis, and heart failure accounted for 12%, 9%, and 7% of hospital readmissions, respectively. Factors associated with higher odds of 30-day readmission or death without readmission included non-Hispanic ethnicity, lower serum albumin level, inability to ambulate or transfer, limited nephrology care prior to dialysis therapy, and specific types of infection. In comparison, older age, select comorbid conditions, and institutionalization had stronger associations with death without readmission than with readmission.Findings limited to Medicare beneficiaries receiving in-center hemodialysis.Hospitalizations for infection among patients receiving in-center hemodialysis are associated with exceptionally high rates of 30-day hospital readmission and death without readmission.

  View details for DOI 10.1053/j.ajkd.2014.11.030

  View details for PubMedID 25641061

• Assessing the treatment effect in a randomized controlled trial with extensive non-adherence: the EVOLVE trial PHARMACEUTICAL STATISTICS Kubo, Y., Sterling, L. R., Parfrey, P. S., Gill, K., Mahaffey, K. W., Gioni, I., Trotman, M., Dehmel, B., Chertow, G. M. 2015; 14 (3): 242-251

  Abstract

  Intention-to-treat (ITT) analysis is widely used to establish efficacy in randomized clinical trials. However, in a long-term outcomes study where non-adherence to study drug is substantial, the on-treatment effect of the study drug may be underestimated using the ITT analysis. The analyses presented herein are from the EVOLVE trial, a double-blind, placebo-controlled, event-driven cardiovascular outcomes study conducted to assess whether a treatment regimen including cinacalcet compared with placebo in addition to other conventional therapies reduces the risk of mortality and major cardiovascular events in patients receiving hemodialysis with secondary hyperparathyroidism. Pre-specified sensitivity analyses were performed to assess the impact of non-adherence on the estimated effect of cinacalcet. These analyses included lag-censoring, inverse probability of censoring weights (IPCW), rank preserving structural failure time model (RPSFTM) and iterative parameter estimation (IPE). The relative hazard (cinacalcet versus placebo) of mortality and major cardiovascular events was 0.93 (95% confidence interval 0.85, 1.02) using the ITT analysis; 0.85 (0.76, 0.95) using lag-censoring analysis; 0.81 (0.70, 0.92) using IPCW; 0.85 (0.66, 1.04) using RPSFTM and 0.85 (0.75, 0.96) using IPE. These analyses, while not providing definitive evidence, suggest that the intervention may have an effect while subjects are receiving treatment. The ITT method remains the established method to evaluate efficacy of a new treatment; however, additional analyses should be considered to assess the on-treatment effect when substantial non-adherence to study drug is expected or observed.

  View details for DOI 10.1002/pst.1680

  View details for PubMedID 25851955

• The Effects of Cinacalcet in Older and Younger Patients on Hemodialysis: The Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Parfrey, P. S., Drueeke, T. B., Block, G. A., Correa-Rotter, R., Floege, J., Herzog, C. A., London, G. M., Mahaffey, K. W., Moe, S. M., Wheeler, D. C., Kubo, Y., Dehmel, B., Goodman, W. G., Chertow, G. M. 2015; 10 (5): 791-799

  Abstract

  The calcimimetic cinacalcet reduced the risk of death or cardiovascular (CV) events in older, but not younger, patients with moderate to severe secondary hyperparathyroidism (HPT) who were receiving hemodialysis. To determine whether the lower risk in younger patients might be due to lower baseline CV risk and more frequent use of cointerventions that reduce parathyroid hormone (kidney transplantation, parathyroidectomy, and commercial cinacalcet use), this study examined the effects of cinacalcet in older (≥65 years, n=1005) and younger (<65 years, n=2878) patients.Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) was a global, multicenter, randomized placebo-controlled trial in 3883 prevalent patients on hemodialysis, whose outcomes included death, major CV events, and development of severe unremitting HPT. The age subgroup analysis was prespecified.Older patients had higher baseline prevalence of diabetes mellitus and CV comorbidity. Annualized rates of kidney transplantation and parathyroidectomy were >3-fold higher in younger relative to older patients and were more frequent in patients randomized to placebo. In older patients, the adjusted relative hazard (95% confidence interval) for the primary composite (CV) end point (cinacalcet versus placebo) was 0.70 (0.60 to 0.81); in younger patients, the relative hazard was 0.97 (0.86 to 1.09). Corresponding adjusted relative hazards for mortality were 0.68 (0.51 to 0.81) and 0.99 (0.86 to 1.13). Reduction in the risk of severe unremitting HPT was similar in both groups.In the EVOLVE trial, cinacalcet decreased the risk of death and of major CV events in older, but not younger, patients with moderate to severe HPT who were receiving hemodialysis. Effect modification by age may be partly explained by differences in underlying CV risk and differential application of cointerventions that reduce parathyroid hormone.

  View details for DOI 10.2215/CJN.07730814

  View details for Web of Science ID 000354144900011

  View details for PubMedCentralID PMC4422239

• A 12-Week, Double-Blind, Placebo-Controlled Trial of Ferric Citrate for the Treatment of Iron Deficiency Anemia and Reduction of Serum Phosphate in Patients With CKD Stages 3-5 AMERICAN JOURNAL OF KIDNEY DISEASES Block, G. A., Fishbane, S., Rodriguez, M., Smits, G., Shemesh, S., Pergola, P. E., Wolf, M., Chertow, G. M. 2015; 65 (5): 728-736

  Abstract

  Iron deficiency anemia and serum phosphate levels > 4.0mg/dL are relatively common in chronic kidney disease stages 3 to 5 and are associated with higher risks of progressive loss of kidney function, cardiovascular events, and mortality.Double-blind, placebo-controlled, randomized trial.149 patients with estimated glomerular filtration rates < 60 mL/min/1.73 m(2), iron deficiency anemia (hemoglobin, 9.0-12.0 g/dL; transferrin saturation [TSAT]≤ 30%, serum ferritin ≤ 300 ng/mL), and serum phosphate levels ≥ 4.0 to 6.0mg/dL. Use of intravenous iron or erythropoiesis-stimulating agents was prohibited.Randomization to treatment for 12 weeks with ferric citrate coordination complex (ferric citrate) or placebo.Coprimary end points were change in TSAT and serum phosphate level from baseline to end of study. Secondary outcomes included change from baseline to end of treatment in values for ferritin, hemoglobin, intact fibroblast growth factor 23 (FGF-23), urinary phosphate excretion, and estimated glomerular filtration rate.Ferric citrate treatment increased mean TSAT from 22% ± 7% (SD) to 32% ± 14% and reduced serum phosphate levels from 4.5 ± 0.6 to 3.9 ± 0.6 mg/dL, while placebo exerted no effect on TSAT (21% ± 8% to 20% ± 8%) and less effect on serum phosphate level (4.7 ± 0.6 to 4.4 ± 0.8 mg/dL; between-group P<0.001 for each). Ferric citrate increased hemoglobin levels (from 10.5 ± 0.8 to 11.0 ± 1.0 g/dL; P<0.001 vs placebo), reduced urinary phosphate excretion 39% (P<0.001 vs placebo), and reduced serum intact FGF-23 levels from a median of 159 (IQR, 102-289) to 105 (IQR, 65-187) pg/mL (P=0.02 vs placebo). The incidence and severity of adverse effects were similar between treatment arms.The study is limited by relatively small sample size and short duration and by having biochemical rather than clinical outcomes.Short-term use of ferric citrate repletes iron stores, increases hemoglobin levels, and reduces levels of serum phosphate, urinary phosphate excretion, and FGF-23 in patients with chronic kidney disease stages 3 to 5.

  View details for DOI 10.1053/j.ajkd.2014.10.014

  View details for PubMedID 25468387

• The Effect of Cinacalcet on Calcific Uremic Arteriolopathy Events in Patients Receiving Hemodialysis: The EVOLVE Trial CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Floege, J., Kubo, Y., Floege, A., Chertow, G. M., Parfrey, P. S. 2015; 10 (5): 800-807

  Abstract

  Uncontrolled secondary hyperparathyroidism (sHPT) in patients with ESRD is a risk factor for calcific uremic arteriolopathy (CUA; calciphylaxis).Adverse event reports collected during the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events trial were used to determine the frequency of CUA in patients receiving hemodialysis who had moderate to severe sHPT, as well as the effects of cinacalcet versus placebo. CUA events were collected while patients were receiving the study drug.Among the 3861 trial patients who received at least one dose of the study drug, 18 patients randomly assigned to placebo and six assigned to cinacalcet developed CUA (unadjusted relative hazard, 0.31; 95% confidence interval [95% CI], 0.13 to 0.79; P=0.014). Corresponding cumulative event rates (95% CI) at year 4 were 0.011% (0.006% to 0.018%) and 0.005% (0.002% to 0.010%). By multivariable analysis, other factors associated with CUA included female sex, higher body mass index, higher diastolic BP, and history of dyslipidemia or parathyroidectomy. Median (10%, 90% percentile) plasma parathyroid hormone concentrations proximal to the report of CUA were 796 (225, 2093) pg/ml and 410 (71, 4957) pg/ml in patients randomly assigned to placebo and cinacalcet, respectively. Active use of vitamin K antagonists was recorded in 11 of 24 patients with CUA, nine randomly assigned to placebo, and two to cinacalcet, in contrast to 5%-7% at any one time point in patients in whom CUA was not reported.Cinacalcet appeared to reduce the incidence of CUA in hemodialysis recipients who have moderate to severe sHPT.

  View details for DOI 10.2215/CJN.10221014

  View details for PubMedID 25887067

• AURYXIA (FERRIC CITRATE), AN ORAL IRON-BASED PHOSPHATE BINDER SIGNIFICANTLY IMPROVES SERUM IRON MEASURES IN PATIENTS WITH STAGE 3, 4 AND 5 CHRONIC KIDNEY DISEASE (CKD) Fishbane, S., Block, G. A., Loram, L. C., Chertow, G. M. W B SAUNDERS CO-ELSEVIER INC. 2015: A35

  View details for Web of Science ID 000355796500086

• AURYXIA (FERRIC CITRATE) EFFECTIVELY REDUCES SERUM PHOSPHATE AND FIBROBLAST GROWTH FACTOR 23 (FGF23) LEVELS IN PATIENTS WITH STAGES 3-5 CHRONIC KIDNEY DISEASE (CKD) Block, G. A., Chertow, G. M., Fishbane, S., Loram, L. C., Wolf, M. W B SAUNDERS CO-ELSEVIER INC. 2015: A23

  View details for Web of Science ID 000355796500038

• Navigating toward research success in times of uncertainty: funding opportunities for early career investigators in nephrology. American journal of kidney diseases Ikizler, T. A., Lovett, D. H., Chertow, G. M., Mitch, W. E., Schiller, B. 2015; 65 (3): 381-383

  Abstract

  There is considerable concern within the nephrology community about recent federal budget cuts and the decreasing availability of funds for research. This is especially difficult for junior investigators who are about to start a career as physician-scientists. Accordingly, it is imperative that resources other than federal funds be made available to these individuals during this most delicate yet crucial transition period. This commentary aims to provide an overview of nonfederal funding resources, focusing on the Norman S. Coplon Extramural Grant Program. This program emphasizes support of investigators at the most fragile period in their development of an academic career; it has provided >$11 million of research funds to more than 80 individuals since 2000. The outcome has been stellar, with more than 130 publications originating from these projects and >90% of awardees staying in academia. We hope these accomplishments will encourage similar activities by other entities and scientific programs in addition to ones that are ongoing. Ultimately, these collective efforts will inspire young researchers to use their knowledge, passion, and dedication to advance research into kidney diseases.

  View details for DOI 10.1053/j.ajkd.2014.11.008

  View details for PubMedID 25542413

• Time-Updated Systolic Blood Pressure and the Progression of Chronic Kidney Disease A Cohort Study ANNALS OF INTERNAL MEDICINE Anderson, A. H., Yang, W., Townsend, R. R., Pan, Q., Chertow, G. M., Kusek, J. W., Charleston, J., He, J., Kallem, R., Lash, J. P., Miller, E. R., Rahman, M., Steigerwalt, S., Weir, M., Wright, J. T., Feldman, H. I. 2015; 162 (4): 258-?

  Abstract

  Previous reports of the longitudinal association between achieved blood pressure (BP) and end-stage renal disease (ESRD) among patients with chronic kidney disease (CKD) have not incorporated time-updated BP with appropriate covariate adjustment.To assess the association between baseline and time-updated systolic blood pressure (SBP) with CKD progression.Observational, prospective cohort study. (ClinicalTrials.gov: NCT00304148).7 U.S. clinical centers.Patients in the Chronic Renal Insufficiency Cohort Study (n = 3708) followed for a median of 5.7 years (25th to 75th percentile, 4.6 to 6.7 years).The mean of 3 seated SBP measurements made up the visit-specific SBP. Time-updated SBP was the mean of that and all previous visits. Outcomes were ESRD and the composite end point of ESRD or halving of the estimated glomerular filtration rate. Analyses investigating baseline and time-updated SBP used Cox proportional hazards models and marginal structural models, respectively.Systolic blood pressure was 130 mm Hg or greater at all visits in 19.2% of patients. The hazard ratio for ESRD among patients with SBP of 130 to 139 mm Hg, compared with SBP less than 120 mm Hg, was 1.46 (95% CI, 1.13 to 1.88) using only baseline data and 2.37 (CI, 1.48 to 3.80) using time-updated data. Among patients with SBP of 140 mm Hg or greater, corresponding hazard ratios were 1.46 (CI, 1.18 to 1.88) and 3.37 (CI, 2.26 to 5.03) for models using only baseline data and those using time-updated data, respectively.Blood pressure was measured once annually, and the cohort was not a random sample.Time-updated SBP greater than 130 mm Hg was more strongly associated with CKD progression than analyses based on baseline SBP.National Institute of Diabetes and Digestive and Kidney Diseases.

  View details for DOI 10.7326/M14-0488

  View details for Web of Science ID 000350232500015

  View details for PubMedID 25686166

  View details for PubMedCentralID PMC4404622

• Provider visit frequency and vascular access interventions in hemodialysis. Clinical journal of the American Society of Nephrology Erickson, K. F., Mell, M. W., Winkelmayer, W. C., Chertow, G. M., Bhattacharya, J. 2015; 10 (2): 269-277

  Abstract

  Medicare reimbursement policy encourages frequent provider visits to patients with ESRD undergoing hemodialysis. This study sought to determine whether more frequent face-to-face provider (physician and advanced practitioner) visits lead to more procedures and therapeutic interventions aimed at preserving arteriovenous fistulas and grafts, improved vascular access outcomes, and fewer related hospitalizations.Multivariable regression was used to evaluate the association between provider (physician and advanced practitioner) visit frequency and interventions aimed at preserving vascular access, vascular access survival, hospitalization for vascular access infection, and outpatient antibiotic use in a cohort of 63,488 Medicare beneficiaries receiving hemodialysis in the United States. Medicare claims were used to identify the type of vascular access used, access-related events, and vascular access failure.One additional provider (physician and advanced practitioner) visit per month was associated with a 13% higher odds of receiving an intervention to preserve vascular access (95% confidence interval [95% CI], 12% to 14%) but was not associated with vascular access survival (hazard ratio, 1.01; 95% CI, 0.99 to 1.03). One additional provider visit was associated with a 9% (95% CI, 5% to 14%) lower odds of hospitalization for vascular access infection and a corresponding 9% (95% CI, 5% to 14%) higher odds of outpatient intravenous antibiotic administration. However, the associated changes in absolute probabilities of hospitalization and antibiotic administration were small.More frequent face-to-face provider (physician and advanced practitioner) visits were associated with more procedures and therapeutic interventions aimed at preserving vascular accesses, but not with prolonged vascular access survival and only a small decrease in hospitalization for vascular access.

  View details for DOI 10.2215/CJN.05540614

  View details for PubMedID 25587105

• Effects of Cinacalcet on Atherosclerotic and Nonatherosclerotic Cardiovascular Events in Patients Receiving Hemodialysis: The EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) Trial JOURNAL OF THE AMERICAN HEART ASSOCIATION Wheeler, D. C., London, G. M., Parfrey, P. S., Block, G. A., Correa-Rotter, R., Dehmel, B., Drueeke, T. B., Floege, J., Kubo, Y., Mahaffey, K. W., Goodman, W. G., Moe, S. M., Trotman, M., Abdalla, S., Chertow, G. M., Herzog, C. A. 2015; 4 (1)

  View details for DOI 10.1161/JAHA.114.001363

  View details for Web of Science ID 000348597500041

• Use of novel oral anticoagulants in patients with end-stage renal disease HEMODIALYSIS INTERNATIONAL Winkelmayer, W. C., Herzog, C. A., Montez-Rath, M. E., Chang, T. I., Chertow, G. M. 2015; 19 (1): 150–53

  View details for PubMedID 25495752

• Ambulatory care after acute kidney injury: an opportunity to improve patient outcomes. Canadian journal of kidney health and disease Silver, S. A., Goldstein, S. L., Harel, Z., Harvey, A., Rompies, E. J., Adhikari, N. K., Acedillo, R., Jain, A. K., Richardson, R., Chan, C. T., Chertow, G. M., Bell, C. M., Wald, R. 2015; 2: 36

  Abstract

  PURPOSE OF REVIEW: Acute kidney injury (AKI) is an increasingly common problem among hospitalized patients. Patients who survive an AKI-associated hospitalization are at higher risk of de novo and worsening chronic kidney disease, end-stage kidney disease, cardiovascular disease, and death. For hospitalized patients with dialysis-requiring AKI, outpatient follow-up with a nephrologist within 90days of hospital discharge has been associated with enhanced survival. However, most patients who survive an AKI episode do not receive any follow-up nephrology care. This narrative review describes the experience of two new clinical programs to care for AKI patients after hospital discharge: the Acute Kidney Injury Follow-up Clinic for adults (St. Michael's Hospital and University Health Network, Toronto, Canada) and the AKI Survivor Clinic for children (Cincinnati Children's Hospital, USA).SOURCES OF INFORMATION: MEDLINE, PubMed, ISI Web of Science.FINDINGS: These two ambulatory clinics have been in existence for close to two (adult) and four (pediatric) years, and were developed separately and independently in different populations and health systems. The components of both clinics are described, including the target population, referral process, medical interventions, patient education activities, and follow-up schedule. Common elements include targeting patients with KDIGO stage 2 or 3 AKI, regular audits of the inpatient nephrology census to track eligible patients, medication reconciliation, and education on the long-term consequences of AKI.LIMITATIONS: Despite the theoretical benefits of post-AKI follow-up and the clinic components described, there is no high quality evidence to prove that the interventions implemented in these clinics will reduce morbidity or mortality. Therefore, we also present a plan to evaluate the adult AKI Follow-up Clinic in order to determine if it can improve clinical outcomes compared to patients with AKI who do not receive follow-up care.IMPLICATIONS: Follow-up of AKI survivors is low, and this review describes two different clinics that care for patients who survive an AKI episode. We believe that sharing the experiences of the AKI Follow-up Clinic and AKI Survivor Clinic provide physicians with a feasible framework to implement their own clinics, which may help AKI patients receive outpatient care commensurate with their high risk status.

  View details for PubMedID 26445676

• Planning for Hemodialysis CHRONIC RENAL DISEASE Isom, R. T., Chertow, G. M., Kimmel, P. L., Rosenberg, M. E. 2015: 751–64

  View details for DOI 10.1016/B978-0-12-411602-3.00062-7

  View details for Web of Science ID 000351158600062

• Improving Care after Acute Kidney Injury: A Prospective Time Series Study NEPHRON Silver, S. A., Harel, Z., Harvey, A., Adhikari, N. K., Slack, A., Acedillo, R., Jain, A. K., Richardson, R. M., Chan, C. T., Chertow, G. M., Bell, C. M., Wald, R. 2015; 131 (1): 43-50

  Abstract

  Acute kidney injury (AKI) complicates 15-20% of hospitalizations, and AKI survivors are at increased risk of chronic kidney disease and death. However, less than 20% of patients see a nephrologist within 3 months of discharge, even though a nephrologist visit within 90 days of discharge is associated with enhanced survival. To address this, we established an AKI Follow-Up Clinic and characterized the patterns of care delivered.We conducted a prospective time series study. All hospitalized patients who developed Kidney Disease Improving Global Outcomes (KDIGO) stage 2 or 3 AKI were eligible. The pre-intervention period consisted of electronic reminders to the nephrology consults and cardiovascular surgery services to refer to the AKI Follow-Up Clinic. In the post-intervention period, eligible patients were automatically scheduled into the AKI Follow-Up Clinic at discharge. The primary outcome was the percentage of KDIGO stages 2-3 AKI survivors assessed by a nephrologist within 30 days of discharge.In the pre-intervention period, 8 of 46 patients (17%) were seen by a nephrologist within 30 days after discharge, and no additional patients were seen for 90 days. In the post-intervention period, 17 of 69 patients (25%) were seen by a nephrologist within 30 days after discharge (p = 0.36), with an additional 30 patients seen in 90 days (47 of 69, 68%, p < 0.001). The mean serum creatinine was 99 (SD 35) µmol/l prior to hospitalization and 133 (58) µmol/l at 3 months. Fifty-five of 79 patients (70%) received at least 1 medical intervention at their first AKI Follow-Up Clinic visit.An AKI Follow-Up Clinic with an automatic referral process increased the proportion of patients seen at 90 days, but not 30 days post discharge. Being seen in the AKI Follow-Up Clinic was associated with interventions in most patients. Future research is needed to evaluate the effect of the AKI Follow-Up Clinic on patient-centered outcomes, but physicians should be aware that AKI survivors may benefit from close outpatient follow-up and a multipronged approach to care similarly for other high-risk populations.

  View details for DOI 10.1159/000438871

  View details for Web of Science ID 000362148500007

  View details for PubMedID 26329832

• Association of Self-Reported Frailty with Falls and Fractures among Patients New to Dialysis AMERICAN JOURNAL OF NEPHROLOGY Delgado, C., Shieh, S., Grimes, B., Chertow, G. M., Dalrymple, L. S., Kaysen, G. A., Kornak, J., Johansen, K. L. 2015; 42 (2): 134-140

  Abstract

  Although frailty has been linked to higher risk of falls and fracture in the general population, only few studies have examined the extent to which frailty is associated with these outcomes among patients with end-stage renal disease, who are at particularly high risk for these events.A total of 1,646 patients who were beginning maintenance hemodialysis in 297 dialysis units throughout the United States from September 2005 to June 2007 were enrolled in the Comprehensive Dialysis Study, and 1,053 Medicare beneficiaries were included in this study. Self-reported frailty was defined by the patients endorsing 2 or more of the following: poor physical functioning, exhaustion or low physical activity. Falls and fractures requiring medical attention were identified through Medicare claims data. We examined the association between frailty and the time to first fall or fracture using the Fine-Gray modification of Cox proportional hazards regression, adjusted for demographics, Quételet's body mass index, diabetes mellitus, heart failure and atherosclerosis.Seventy-seven percent of patients were frail by self-report. The median length of follow-up was 2.5 (1.0-3.9) years. Crude rates of first medically urgent falls or fractures were 66 and 126 per 1,000 person-years in non-frail and self-reported frail participants, respectively. After accounting for demographic factors, comorbidities and the competing risk of death, self-reported frailty was associated with a higher risk of falls or fractures requiring medical attention (hazards ratio 1.60, 95% CI 1.16-2.20).Participants reporting frailty experienced nearly twice the risk of medically urgent falls or fractures compared to those who did not report frailty.

  View details for DOI 10.1159/000439000

  View details for Web of Science ID 000363937800007

  View details for PubMedID 26381744

  View details for PubMedCentralID PMC4596065

• Design of a Phase 2 Clinical Trial of an ASK1 Inhibitor, GS-4997, in Patients with Diabetic Kidney Disease NEPHRON Lin, J. H., Zhang, J. J., Lin, S., Chertow, G. M. 2015; 129 (1): 29-33

  Abstract

  Most patients with diabetic kidney disease (DKD) experience disease progression despite receiving standard care therapy. Oxidative stress is associated with DKD severity and risk of progression, but currently approved therapies do not directly attenuate the pathologic consequences of oxidative stress. GS-4997 is a once daily, oral molecule that inhibits Apoptosis Signal-regulating Kinase 1 (ASK1), which is a key mediator of the deleterious effects of oxidative stress.We describe the rationale and design of a Phase 2 placebo-controlled clinical trial investigating the effects of GS-4997 in patients with T2DM and stage 3/4 DKD receiving standard of care therapy. Approximately, 300 subjects will be randomized in a stratified manner, based on the estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio, to one of four arms in this dose-ranging study. The primary endpoint is change in eGFR at 48 weeks, and the key secondary endpoint is change in albuminuria.Guided by the biology of oxidative stress signaling through ASK1, the biology of DKD pathogenesis, and solid statistical methods, the decisions made for this Phase 2 study regarding delineating study population, efficacy outcomes, treatment period and statistical methods represent innovative attempts to resolve challenges specific to DKD study design.

  View details for DOI 10.1159/000369152

  View details for Web of Science ID 000350758500006

  View details for PubMedID 25531162

• Effects of Cinacalcet on Atherosclerotic and Nonatherosclerotic Cardiovascular Events in Patients Receiving Hemodialysis: The EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) Trial JOURNAL OF THE AMERICAN HEART ASSOCIATION Wheeler, D. C., London, G. M., Parfrey, P. S., Block, G. A., Correa-Rotter, R., Dehmel, B., Drueeke, T. B., Floege, J., Kubo, Y., Mahaffey, K. W., Goodman, W. G., Moe, S. M., Trotman, M., Abdalla, S., Chertow, G. M., Herzog, C. A. 2014; 3 (6)

  Abstract

  Premature cardiovascular disease limits the duration and quality of life on long-term hemodialysis. The objective of this study was to define the frequency of fatal and nonfatal cardiovascular events attributable to atherosclerotic and nonatherosclerotic mechanisms, risk factors for these events, and the effects of cinacalcet, using adjudicated data collected during the EValuation of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) Trial.EVOLVE was a randomized, double-blind, placebo-controlled clinical trial that randomized 3883 hemodialysis patients with moderate to severe secondary hyperparathyroidism to cinacalcet or matched placebo for up to 64 months. For this post hoc analysis, the outcome measure was fatal and nonfatal cardiovascular events reflecting atherosclerotic and nonatherosclerotic cardiovascular diseases. During the trial, 1518 patients experienced an adjudicated cardiovascular event, including 958 attributable to nonatherosclerotic disease. Of 1421 deaths during the trial, 768 (54%) were due to cardiovascular disease. Sudden death was the most frequent fatal cardiovascular event, accounting for 24.5% of overall mortality. Combining fatal and nonfatal cardiovascular events, randomization to cinacalcet reduced the rates of sudden death and heart failure. Patients randomized to cinacalcet experienced fewer nonatherosclerotic cardiovascular events (adjusted relative hazard 0.84, 95% CI 0.74 to 0.96), while the effect of cinacalcet on atherosclerotic events did not reach statistical significance.Accepting the limitations of post hoc analysis, any benefits of cinacalcet on cardiovascular disease in the context of hemodialysis may result from attenuation of nonatherosclerotic processes.Unique identifier: NCT00345839. URL: ClinicalTrials.gov.

  View details for DOI 10.1161/JAHA.114.001363

  View details for Web of Science ID 000345067600025

• Reforming Medicare's Dialysis Payment Policies: Implications for Patients with Secondary Hyperparathyroidism HEALTH SERVICES RESEARCH Gupta, C., Chertow, G. M., Linthicum, M. T., Van Nuys, K., Belozeroff, V., Quarles, D., Lakdawalla, D. N. 2014; 49 (6): 1925-1943

  Abstract

  To demonstrate how expanding services covered by a "bundled payment" can also expand variation in the costs of treating patients under the bundle, using the Medicare dialysis program as an example.Observational claims-based study of 197,332 Medicare hemodialysis beneficiaries enrolled for at least one quarter during 2006-2008.We estimated how resource utilization (all health services, dialysis-related services, and medications) changes with intensity of secondary hyperparathyroidism (sHPT) treatment.Using Medicare claims, a patient-quarter level dataset was constructed, including a measure of sHPT treatment intensity.Under the existing, narrow dialysis bundle, utilization of covered services is relatively constant across treatment intensity groups; under a broader bundle, it rises more rapidly with treatment intensity.The broader Medicare dialysis bundle reimburses providers uniformly, even though patients treated more intensively for sHPT cost more to treat. Absent any payment adjustments or efforts to ensure quality, this flat payment schedule may encourage providers to avoid high-intensity patients or reduce their treatment intensity. The first incentive harms efficiency. The second may improve or worsen efficiency, depending on whether it reduces appropriate or inappropriate treatment.

  View details for DOI 10.1111/1475-6773.12202

  View details for Web of Science ID 000345346300013

  View details for PubMedID 25040130

  View details for PubMedCentralID PMC4254132

• Risk Factors for Heart Failure in Patients With Type 2 Diabetes Mellitus and Stage 4 Chronic Kidney Disease Treated With Bardoxolone Methyl JOURNAL OF CARDIAC FAILURE Chin, M. P., Wrolstad, D., Bakris, G. L., Chertow, G. M., de Zeeuw, D., Goldsberry, A., Linde, P. G., McCullough, P. A., McMurray, J. J., Wittes, J., Meyer, C. J. 2014; 20 (12): 953-958

  Abstract

  A phase 3 randomized clinical trial was designed to test whether bardoxolone methyl, a nuclear factor erythroid-2-related factor 2 (Nrf2) activator, slows progression to end-stage renal disease in patients with stage 4 chronic kidney disease and type 2 diabetes mellitus. The trial was terminated because of an increase in heart failure in the bardoxolone methyl group; many of the events were clinically associated with fluid retention.We randomized 2,185 patients with type 2 diabetes mellitus (T2DM) and stage 4 chronic kidney disease (CKD) (estimated glomerular filtration rate 15 to <30 mL min(-1) 1.73 m(-2)) to once-daily bardoxolone methyl (20 mg) or placebo. We used classification and regression tree analysis to identify baseline factors predictive of heart failure or fluid overload events. Elevated baseline B-type natriuretic peptide and previous hospitalization for heart failure were identified as predictors of heart failure events; bardoxolone methyl increased the risk of heart failure by 60% in patients with these risk factors. For patients without these baseline characteristics, the risk for heart failure events among bardoxolone methyl- and placebo-treated patients was similar (2%). The same risk factors were also identified as predictors of fluid overload and appeared to be related to other serious adverse events.Bardoxolone methyl contributed to events related to heart failure and/or fluid overload in a subpopulation of susceptible patients with an increased risk for heart failure at baseline. Careful selection of participants and vigilant monitoring of the study drug will be required in any future trials of bardoxolone methyl to mitigate the risk of heart failure and other serious adverse events.

  View details for DOI 10.1016/j.cardfail.2014.10.001

  View details for PubMedID 25307295

• Effects of cinacalcet on atherosclerotic and nonatherosclerotic cardiovascular events in patients receiving hemodialysis: the EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) trial. Journal of the American Heart Association Wheeler, D. C., London, G. M., Parfrey, P. S., Block, G. A., Correa-Rotter, R., Dehmel, B., Drüeke, T. B., Floege, J., Kubo, Y., Mahaffey, K. W., Goodman, W. G., Moe, S. M., Trotman, M., Abdalla, S., Chertow, G. M., Herzog, C. A. 2014; 3 (6)

  Abstract

  Premature cardiovascular disease limits the duration and quality of life on long-term hemodialysis. The objective of this study was to define the frequency of fatal and nonfatal cardiovascular events attributable to atherosclerotic and nonatherosclerotic mechanisms, risk factors for these events, and the effects of cinacalcet, using adjudicated data collected during the EValuation of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) Trial.EVOLVE was a randomized, double-blind, placebo-controlled clinical trial that randomized 3883 hemodialysis patients with moderate to severe secondary hyperparathyroidism to cinacalcet or matched placebo for up to 64 months. For this post hoc analysis, the outcome measure was fatal and nonfatal cardiovascular events reflecting atherosclerotic and nonatherosclerotic cardiovascular diseases. During the trial, 1518 patients experienced an adjudicated cardiovascular event, including 958 attributable to nonatherosclerotic disease. Of 1421 deaths during the trial, 768 (54%) were due to cardiovascular disease. Sudden death was the most frequent fatal cardiovascular event, accounting for 24.5% of overall mortality. Combining fatal and nonfatal cardiovascular events, randomization to cinacalcet reduced the rates of sudden death and heart failure. Patients randomized to cinacalcet experienced fewer nonatherosclerotic cardiovascular events (adjusted relative hazard 0.84, 95% CI 0.74 to 0.96), while the effect of cinacalcet on atherosclerotic events did not reach statistical significance.Accepting the limitations of post hoc analysis, any benefits of cinacalcet on cardiovascular disease in the context of hemodialysis may result from attenuation of nonatherosclerotic processes.Unique identifier: NCT00345839. URL: ClinicalTrials.gov.

  View details for DOI 10.1161/JAHA.114.001363

  View details for PubMedID 25404192

• Comparison of Self-report-Based and Physical Performance-Based Frailty Definitions Among Patients Receiving Maintenance Hemodialysis AMERICAN JOURNAL OF KIDNEY DISEASES Johansen, K. L., Dalrymple, L. S., Delgado, C., Kaysen, G. A., Kornak, J., Grimes, B., Chertow, G. M. 2014; 64 (4): 600-607

  Abstract

  A well-accepted definition of frailty includes measurements of physical performance, which may limit its clinical utility.In a cross-sectional study, we compared prevalence and patient characteristics based on a frailty definition that uses self-reported function to the classic performance-based definition and developed a modified self-report-based definition.Prevalent adult patients receiving hemodialysis in 14 centers around San Francisco and Atlanta in 2009-2011.Self-report-based frailty definition in which a score lower than 75 on the Physical Function scale of the 36-Item Short Form Health Survey (SF-36) was substituted for gait speed and grip strength in the classic definition; modified self-report definition with optimized Physical Function score cutoff points derived in a development (one-half) cohort and validated in the other half.Performance-based frailty defined as 3 of the following: weight loss, weakness, exhaustion, low physical activity, and slow gait speed.387 (53%) patients were frail based on self-reported function, of whom 209 (29% of the cohort) met the performance-based definition. Only 23 (3%) met the performance-based definition of frailty only. The self-report definition had 90% sensitivity, 64% specificity, 54% positive predictive value, 93% negative predictive value, and 72.5% overall accuracy. Intracellular water per kilogram of body weight and serum albumin, prealbumin, and creatinine levels were highest among nonfrail individuals, intermediate among those who were frail by self-report, and lowest among those who also were frail by performance. Age, percentage of body fat, and C-reactive protein level followed an opposite pattern. The modified self-report definition had better accuracy (84%; 95% CI, 79%-89%) and superior specificity (88%) and positive predictive value (67%).Our study did not address prediction of outcomes.Patients who meet the self-report-based but not the performance-based definition of frailty may represent an intermediate phenotype. A modified self-report definition can improve the accuracy of a questionnaire-based method of defining frailty.

  View details for DOI 10.1053/j.ajkd.2014.03.016

  View details for Web of Science ID 000342739900020

  View details for PubMedCentralID PMC4177262

• Thienopyridine use after coronary stenting in low income patients enrolled in medicare part D receiving maintenance dialysis. Journal of the American Heart Association Chang, T. I., Montez-Rath, M. E., Shen, J. I., Solomon, M. D., Chertow, G. M., Winkelmayer, W. C. 2014; 3 (5)

  View details for DOI 10.1161/JAHA.114.001356

  View details for PubMedID 25336465

• Comparison of self-report-based and physical performance-based frailty definitions among patients receiving maintenance hemodialysis. American journal of kidney diseases Johansen, K. L., Dalrymple, L. S., Delgado, C., Kaysen, G. A., Kornak, J., Grimes, B., Chertow, G. M. 2014; 64 (4): 600-607

  Abstract

  A well-accepted definition of frailty includes measurements of physical performance, which may limit its clinical utility.In a cross-sectional study, we compared prevalence and patient characteristics based on a frailty definition that uses self-reported function to the classic performance-based definition and developed a modified self-report-based definition.Prevalent adult patients receiving hemodialysis in 14 centers around San Francisco and Atlanta in 2009-2011.Self-report-based frailty definition in which a score lower than 75 on the Physical Function scale of the 36-Item Short Form Health Survey (SF-36) was substituted for gait speed and grip strength in the classic definition; modified self-report definition with optimized Physical Function score cutoff points derived in a development (one-half) cohort and validated in the other half.Performance-based frailty defined as 3 of the following: weight loss, weakness, exhaustion, low physical activity, and slow gait speed.387 (53%) patients were frail based on self-reported function, of whom 209 (29% of the cohort) met the performance-based definition. Only 23 (3%) met the performance-based definition of frailty only. The self-report definition had 90% sensitivity, 64% specificity, 54% positive predictive value, 93% negative predictive value, and 72.5% overall accuracy. Intracellular water per kilogram of body weight and serum albumin, prealbumin, and creatinine levels were highest among nonfrail individuals, intermediate among those who were frail by self-report, and lowest among those who also were frail by performance. Age, percentage of body fat, and C-reactive protein level followed an opposite pattern. The modified self-report definition had better accuracy (84%; 95% CI, 79%-89%) and superior specificity (88%) and positive predictive value (67%).Our study did not address prediction of outcomes.Patients who meet the self-report-based but not the performance-based definition of frailty may represent an intermediate phenotype. A modified self-report definition can improve the accuracy of a questionnaire-based method of defining frailty.

  View details for DOI 10.1053/j.ajkd.2014.03.016

  View details for PubMedID 24793033

• Thienopyridine use after coronary stenting in low income patients enrolled in medicare part D receiving maintenance dialysis. Journal of the American Heart Association Chang, T. I., Montez-Rath, M. E., Shen, J. I., Solomon, M. D., Chertow, G. M., Winkelmayer, W. C. 2014; 3 (5)

  Abstract

  Coronary stenting in patients on dialysis has increased by nearly 50% over the past decade, despite heightened risks of associated stent thrombosis and bleeding relative to the general population. We examined clopidogrel, prasugrel or ticlopidine use after percutaneous coronary intervention (PCI) with stenting in patients on dialysis. We conducted 3-, 6-, and 12-month landmark analyses to test the hypothesis that thienopyridine discontinuation prior to those time points would be associated with higher risks of death, myocardial infarction, or repeat revascularization, and a lower risk of major bleeding episodes compared with continued thienopyridine use.Using the US Renal Data System, we identified 8458 patients on dialysis with Medicare Parts A+B+D undergoing PCI with stenting between July 2007 and December 2010. Ninety-nine percent of all thienopyridine prescriptions were for clopidogrel. At 3 months, 82% of patients who received drug-eluting stents (DES) had evidence of thienopyridine use. These proportions fell to 62% and 40% at 6 and 12 months, respectively. In patients who received a bare-metal stent (BMS), 70%, 34%, and 26% of patients had evidence of thienopyridine use at 3, 6, and 12 months, respectively. In patients who received a DES, there was a suggestion of higher risks of death or myocardial infarction associated with thienopyridine discontinuation in the 3-, 6-, and 12-months landmark analyses, but no higher risk of major bleeding episodes. In patients who received a BMS, there were no differences in death or cardiovascular events, and possibly lower risk of major bleeding with thienopyridine discontinuation in the 3- and 6-month landmark analyses.The majority of patients on dialysis who undergo PCI discontinue thienopyridines before 1 year regardless of stent type. While not definitive, these data suggest that longer-term thienopyridine use may be of benefit to patients on dialysis who undergo PCI with DES.

  View details for DOI 10.1161/JAHA.114.001356

  View details for PubMedID 25336465

• Physician visits and 30-day hospital readmissions in patients receiving hemodialysis. Journal of the American Society of Nephrology Erickson, K. F., Winkelmayer, W. C., Chertow, G. M., Bhattacharya, J. 2014; 25 (9): 2079-2087

  Abstract

  A focus of health care reform has been on reducing 30-day hospital readmissions. Patients with ESRD are at high risk for hospital readmission. It is unknown whether more monitoring by outpatient providers can reduce hospital readmissions in patients receiving hemodialysis. In nationally representative cohorts of patients in the United States receiving in-center hemodialysis between 2004 and 2009, we used a quasi-experimental (instrumental variable) approach to assess the relationship between frequency of visits to patients receiving hemodialysis following hospital discharge and the probability of rehospitalization. We then used a multivariable regression model and published hospitalization data to estimate the cost savings and number of hospitalizations that could be prevented annually with additional provider visits to patients in the month following hospitalization. In the main cohort (n=26,613), one additional provider visit in the month following hospital discharge was estimated to reduce the absolute probability of 30-day hospital readmission by 3.5% (95% confidence interval, 1.6% to 5.3%). The reduction in 30-day hospital readmission ranged from 0.5% to 4.9% in an additional four cohorts tested, depending on population density around facilities, facility profit status, and patient Medicaid eligibility. At current Medicare reimbursement rates, the effort to visit patients one additional time in the month following hospital discharge could lead to 31,370 fewer hospitalizations per year, and $240 million per year saved. In conclusion, more frequent physician visits following hospital discharge are estimated to reduce rehospitalizations in patients undergoing hemodialysis. Incentives for closer outpatient monitoring following hospital discharge could lead to substantial cost savings.

  View details for DOI 10.1681/ASN.2013080879

  View details for PubMedID 24812168

• Urine electrolyte composition and diuretic therapy in heart failure: back to the future? Circulation. Heart failure Pao, A. C., Chertow, G. M. 2014; 7 (5): 697-698

  View details for DOI 10.1161/CIRCHEARTFAILURE.114.001659

  View details for PubMedID 25228317

• Prognostic stratification in older adults commencing dialysis. journals of gerontology. Series A, Biological sciences and medical sciences Cheung, K. L., Montez-Rath, M. E., Chertow, G. M., Winkelmayer, W. C., Periyakoil, V. S., Kurella Tamura, M. 2014; 69 (8): 1033-1039

  Abstract

  Accurate prognostic models could inform treatment decisions for older adults with end-stage renal disease who are considering dialysis and might identify patients more appropriate for conservative care or hospice.In a cohort of patients aged ≥67 years commencing dialysis in the United States between January 1, 2008 and June 30, 2009, we compared the discrimination of three existing instruments (the Liu index; the French Renal Epidemiology and Information Network score; and hospice eligibility criteria) for the prediction of 6-month mortality. We estimated the odds of death associated with each prognostic index using logistic regression with and without adjustment for age. Predictive indices were compared using the concordance ("c")-statistic.Of 44,109 eligible patients, 10,289 (23.3%) died within 6 months of dialysis initiation. The c-statistic for the Liu, Renal Epidemiology and Information Network, hospice eligibility criteria, and combined Liu/hospice eligibility criteria scores without and with age were 0.62/0.65, 0.63/0.66, 0.65/0.68, and 0.68/0.70, respectively. Discrimination was poorer at older ages, especially for the Liu and Renal Epidemiology and Information Network scores. Although sensitivity was poor, a Renal Epidemiology and Information Network score ≥9 or an hospice eligibility criteria ≥3 had relatively high specificity.Existing prognostic indices based on administrative data perform poorly with respect to prediction of 6-month mortality in older patients with end-stage renal disease commencing dialysis.

  View details for DOI 10.1093/gerona/glt289

  View details for PubMedID 24482541

• Homelessness and Risk of End-stage Renal Disease JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED Maziarz, M., Chertow, G. M., Himmeffarb, J., Hall, Y. N. 2014; 25 (3): 1231-1244

  Abstract

  To identify homeless people with chronic kidney disease (CKD) who were at highest risk for end-stage renal disease (ESRD), we studied 982 homeless and 15,674 domiciled people with CKD receiving public health care. We developed four risk prediction models for the primary outcome of ESRD. Overall, 71 homeless and 888 domiciled people progressed to ESRD during follow-up (median: 6.6 years). Homeless people with CKD experienced significantly higher incidence rates of ESRD than poor but domiciled peers. Most homeless people who developed progressive CKD were readily identifiable well before ESRD using a prediction model with five common variables. We estimated that program following homeless people in the highest decile of ESRD risk would have captured 64-85% of those who eventually progressed to ESRD within five years. Thus, an approach targeting homeless people at high risk for ESRD appears feasible and could reduce substantial morbidity and costs incurred by this highly vulnerable group.

  View details for Web of Science ID 000340306300021

  View details for PubMedID 25130236

  View details for PubMedCentralID PMC4285149

• Anticoagulation, delivered dose and outcomes in CRRT: The program to improve care in acute renal disease (PICARD). Hemodialysis international. International Symposium on Home Hemodialysis Claure-Del Granado, R., Macedo, E., Soroko, S., Kim, Y., Chertow, G. M., Himmelfarb, J., Ikizler, T. A., Paganini, E. P., Mehta, R. L. 2014; 18 (3): 641-649

  Abstract

  Delivered dialysis dose by continuous renal replacement therapies (CRRT) depends on circuit efficacy, which is influenced in part by the anticoagulation strategy. We evaluated the association of anticoagulation strategy used on solute clearance efficacy, circuit longevity, bleeding complications, and mortality. We analyzed data from 1740 sessions 24 h in length among 244 critically ill patients, with at least 48 h on CRRT. Regional citrate, heparin, or saline flushes was variably used to prevent or attenuate filter clotting. We calculated delivered dose using the standardized Kt/Vurea . We monitored filter efficacy by calculating effluent urea nitrogen/blood urea nitrogen ratios. Filter longevity was significantly higher with citrate (median 48, interquartile range [IQR] 20.3-75.0 hours) than with heparin (5.9, IQR 8.5-27.0 hours) or no anticoagulation (17.5, IQR 9.5-32 hours, P < 0.0001). Delivered dose was highest in treatments where citrate was employed. Bleeding complications were similar across the three groups (P = 0.25). Compared with no anticoagulation, odds of death was higher with the heparin use (odds ratio [OR] 1.82, 95% confidence interval [CI] 1.02-3.32; P = 0.033), but not with citrate (OR 1.02 95% CI 0.54-1.96; P = 0.53). Relative to heparin or no anticoagulation, the use of regional citrate for anticoagulation in CRRT was associated with significantly prolonged filter life and increased filter efficacy with respect to delivered dialysis dose. Rates of bleeding complications, transfusions, and mortality were similar across the three groups. While these and other data suggest that citrate anticoagulation may offer superior technical performance than heparin or no anticoagulation, adequately powered clinical trials comparing alternative anticoagulation strategies should be performed to evaluate overall safety and efficacy.

  View details for DOI 10.1111/hdi.12157

  View details for PubMedID 24620987

• Long-Term Safety and Efficacy of a Novel Iron-Containing Phosphate Binder, JTT-751, in Patients Receiving Hemodialysis JOURNAL OF RENAL NUTRITION Yokoyama, K., Akiba, T., Fukagawa, M., Nakayama, M., Sawada, K., Kumagai, Y., Chertow, G. M., Hirakata, H. 2014; 24 (4): 261–67

  Abstract

  JTT-751 is a novel phosphate binder containing ferric citrate as the active ingredient. This study investigated long-term safety and efficacy of JTT-751 for hyperphosphatemia in patients receiving hemodialysis.This was 52-week, phase 3, multicenter, open-label, dose titration, long-term study. All patients were receiving thrice-weekly hemodialysis for ≥3 months before the initiation of the study. JTT-751 was given at titrated doses between 1.5 and 6.0 g/day.Safety endpoints were adverse events and adverse drug reactions. Efficacy outcomes were the change in serum phosphate, corrected serum calcium, and intact parathyroid hormone. Changes in ferritin, transferrin saturation, and doses of erythropoiesis-stimulating agents (ESAs) and intravenous iron formulations were additional outcomes.One hundred and eighty patients were included in the trial. Dose-titrated JTT-751 decreased mean serum phosphate after administration and satisfactorily maintained serum phosphate concentrations throughout the entire duration of the 52-week trial. Mean serum phosphate concentrations were kept lower than 5.5 mg/dL from weeks 5 to 52. The most common adverse events were gastrointestinal disorders, which were mild to moderate in intensity. Serum ferritin concentrations rose to a peak around week 28 and stabilized thereafter. The mean intravenous iron dose decreased from 57.3 mg/4 weeks (weeks 0-12) to 3.6 mg/4 weeks (weeks 28-52); weekly ESA dose declined by 25% over the same time frame, while mean hemoglobin concentrations remained stable.JTT-751 1.5-6.0 g/day controls serum phosphorus concentrations and reduces the need for ESAs and intravenous iron in patients receiving hemodialysis.

  View details for PubMedID 24836401

• Characteristics and performance of minority-serving dialysis facilities. Health services research Hall, Y. N., Xu, P., Chertow, G. M., Himmelfarb, J. 2014; 49 (3): 971-991

  Abstract

  To examine the structure, processes, and outcomes of American dialysis facilities that predominantly treat racial-ethnic minority patients.Secondary analysis of data from all patients who initiated dialysis during 2005-2008 in the United States.In this retrospective cohort study, we examined the associations of the racial-ethnic composition of the dialysis facility with facility-level survival and achievement of performance targets for anemia and dialysis adequacy.We obtained dialysis facility- and patient-level data from the national data registry of patients with end-stage renal disease. We linked these data with clinical performance measures from the Centers for Medicare and Medicaid Services.Overall, minority-serving facilities were markedly larger, more often community based, and less likely to offer home dialysis than facilities serving predominantly white patients. A significantly higher proportion of minority-serving dialysis facilities exhibited worse than expected survival as compared with facilities serving predominantly white patients (p < .001 for each). However, clinical performance measures for anemia and dialysis adequacy were similar across minority-serving status.While minority-serving facilities generally met dialysis performance targets mandated by Medicare, they exhibited worse than expected patient survival.

  View details for DOI 10.1111/1475-6773.12144

  View details for PubMedID 24354718

• Lowering Blood Pressure to Lower the Risk of Cardiovascular Events in CKD AMERICAN JOURNAL OF KIDNEY DISEASES Chang, T. I., Owens, D. K., Chertow, G. M. 2014; 63 (6): 900–902

  View details for PubMedID 24685064

• Characteristics and Performance of Minority-Serving Dialysis Facilities HEALTH SERVICES RESEARCH Hall, Y. N., Xu, P., Chertow, G. M., Himmelfarb, J. 2014; 49 (3): 971-991

  Abstract

  To examine the structure, processes, and outcomes of American dialysis facilities that predominantly treat racial-ethnic minority patients.Secondary analysis of data from all patients who initiated dialysis during 2005-2008 in the United States.In this retrospective cohort study, we examined the associations of the racial-ethnic composition of the dialysis facility with facility-level survival and achievement of performance targets for anemia and dialysis adequacy.We obtained dialysis facility- and patient-level data from the national data registry of patients with end-stage renal disease. We linked these data with clinical performance measures from the Centers for Medicare and Medicaid Services.Overall, minority-serving facilities were markedly larger, more often community based, and less likely to offer home dialysis than facilities serving predominantly white patients. A significantly higher proportion of minority-serving dialysis facilities exhibited worse than expected survival as compared with facilities serving predominantly white patients (p < .001 for each). However, clinical performance measures for anemia and dialysis adequacy were similar across minority-serving status.While minority-serving facilities generally met dialysis performance targets mandated by Medicare, they exhibited worse than expected patient survival.

  View details for DOI 10.1111/1475-6773.12144

  View details for Web of Science ID 000335975000012

  View details for PubMedCentralID PMC4024357

• Effects of Frequent Hemodialysis on Perceived Caregiver Burden in the Frequent Hemodialysis Network Trials CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Suri, R. S., Larive, B., Hall, Y., Kimmel, P. L., Kliger, A. S., Levin, N., Tamura, M. K., Chertow, G. M. 2014; 9 (5): 936-942

  Abstract

  Patients receiving hemodialysis often perceive their caregivers are overburdened. We hypothesize that increasing hemodialysis frequency would result in higher patient perceptions of burden on their unpaid caregivers.In two separate trials, 245 patients were randomized to receive in-center daily hemodialysis (6 days/week) or conventional hemodialysis (3 days/week) while 87 patients were randomized to receive home nocturnal hemodialysis (6 nights/week) or home conventional hemodialysis for 12 months. Changes in overall mean scores over time in the 10-question Cousineau perceived burden scale were compared.In total, 173 of 245 (70%) and 80 of 87 (92%) randomized patients in the Daily and Nocturnal Trials, respectively, reported having an unpaid caregiver at baseline or during follow-up. Relative to in-center conventional dialysis, the 12-month change in mean perceived burden score with in-center daily hemodialysis was -2.1 (95% confidence interval, -9.4 to +5.3; P=0.58). Relative to home conventional dialysis, the 12-month change in mean perceived burden score with home nocturnal dialysis was +6.1 (95% confidence interval, -0.8 to +13.1; P=0.08). After multiple imputation for missing data in the Nocturnal Trial, the relative difference between home nocturnal and home conventional hemodialysis was +9.4 (95% confidence interval, +0.55 to +18.3; P=0.04). In the Nocturnal Trial, changes in perceived burden were inversely correlated with adherence to dialysis treatments (Pearson r=-0.35; P=0.02).Relative to conventional hemodialysis, in-center daily hemodialysis did not result in higher perceptions of caregiver burden. There was a trend to higher perceived caregiver burden among patients randomized to home nocturnal hemodialysis. These findings may have implications for the adoption of and adherence to frequent nocturnal hemodialysis.

  View details for DOI 10.2215/CJN.07170713

  View details for Web of Science ID 000335519300017

  View details for PubMedID 24721892

  View details for PubMedCentralID PMC4011443

• Utilization of cytoreductive nephrectomy and patient survival in the targeted therapy era. International journal of cancer. Journal international du cancer Conti, S. L., Thomas, I., Hagedorn, J. C., Chung, B. I., Chertow, G. M., Wagner, T. H., Brooks, J. D., Srinivas, S., Leppert, J. T. 2014; 134 (9): 2245-2252

  Abstract

  We sought to analyze utilization and survival outcomes of cytoreductive nephrectomy in patients with metastatic renal cell carcinoma (RCC) before and after introduction of targeted therapy. We identified patients with metastatic RCC between 1993 and 2010 in the SEER registry and examined temporal trends in utilization. We performed a joinpoint regression to determine when changes in utilization of cytoreductive nephrectomy occurred. We fitted multivariable proportional hazard models in full and propensity score-matched cohorts. We performed a difference-in-difference analysis to compare survival outcomes before and after introduction of targeted therapy. The proportion of patients undergoing cytoreductive nephrectomy increased from 1993 to 2004, from 29% to 39%. We identified a primary joinpoint of 2004, just prior to the introduction of targeted therapy. Beginning in 2005, there was a modest decrease in utilization of cytoreductive nephrectomy. Cytoreductive nephrectomy was associated with a lower adjusted relative hazard (0.41, 95% confidence interval 0.34 to 0.43). Median survival among patients receiving cytoreductive nephrectomy increased in the targeted therapy era (19 versus 13 months), while median survival among patients not receiving cytoreductive nephrectomy increased only slightly (4 versus 3 months). Difference-in-difference analysis showed a significant decrease in hazard of death among patients who received cytoreductive nephrectomy in the targeted therapy era. Despite decreased utilization in the targeted therapy era, cytoreductive nephrectomy remains associated with improved survival. Prospective randomized trials are needed to confirm the benefit of cytoreductive nephrectomy among patients with metastatic RCC treated with novel targeted therapies. © 2013 Wiley Periodicals, Inc.

  View details for PubMedID 24135850

• Bardoxolone Methyl in Type 2 Diabetes and Advanced Chronic Kidney Disease NEW ENGLAND JOURNAL OF MEDICINE Chartoumpekis, D. V., Sykiotis, G. P. 2014; 370 (18): 1767

  View details for Web of Science ID 000335405200027

• FERRIC CITRATE REDUCES FIBROBLAST GROWTH FACTOR 23 LEVELS IN PATIENTS WITH MODERATE CHRONIC KIDNEY DISEASE Block, G., Chertow, G., Fishbane, S., Rodriguez, M., Chen, M., Shemesh, S., Sharma, A., Wolf, M. OXFORD UNIV PRESS. 2014: 156

  View details for Web of Science ID 000338013500415

• Bardoxolone Methyl in Type 2 Diabetes and Advanced Chronic Kidney Disease REPLY NEW ENGLAND JOURNAL OF MEDICINE Chertow, G. M., de Zeeuw, D., BEACON Steering Comm 2014; 370 (18): 1768

  View details for Web of Science ID 000335405200030

  View details for PubMedID 24785223

• A randomized trial of JTT-751 versus sevelamer hydrochloride in patients on hemodialysis NEPHROLOGY DIALYSIS TRANSPLANTATION Yokoyama, K., Akiba, T., Fukagawa, M., Nakayama, M., Sawada, K., Kumagai, Y., Chertow, G. M., Hirakata, H. 2014; 29 (5): 1053–60

  Abstract

  JTT-751 is a novel phosphate binder containing ferric citrate as the active ingredient.In this Phase 3, multicenter, randomized, open-label, parallel-group study, we compared the efficacy and safety of JTT-751 and sevelamer hydrochloride in patients undergoing hemodialysis. A total of 230 patients with a serum phosphate ≥1.97 and <3.23 mmol/L were randomized to JTT-751 (dose adjusted between 1.5 and 6.0 g/day) or sevelamer hydrochloride (dose adjusted between 3.0 and 9.0 g/day) for 12 weeks. The primary outcome was change in serum phosphate from baseline to end of treatment. Secondary outcomes included the changes in corrected serum calcium and intact parathyroid hormone (PTH). The changes in ferritin, transferrin saturation and erythropoiesis-stimulating agent dose were additional outcomes.Changes in serum phosphate at the end of treatment were -0.82 mmol/L in the JTT-751 group and -0.78 mmol/L in the sevelamer group, establishing non-inferiority of JTT-751 compared with sevelamer (least squares mean, -0.03 mmol/L; 95% confidence interval, -0.13 to 0.07 mmol/L). Corrected serum calcium increased and PTH decreased from baseline within both groups; changes between groups were similar. Gastrointestinal disorders were the most common adverse events in both groups; the incidence of diarrhea was higher in the JTT-751 group, while constipation occurred frequently in the sevelamer group. Treatment with JTT-751 resulted in significant relative increases in serum ferritin and transferrin saturation.Efficacy and safety of JTT-751 was comparable to sevelamer in patients on hemodialysis with hyperphosphatemia. Differential adverse effects were observed; biochemical markers of iron status increased in patients treated with JTT-751.CTI-111433 (The Japan Pharmaceutical Information Center at: http//www.clinicaltrials.jp). Date of registration: 7 March 2011.

  View details for DOI 10.1093/ndt/gft483

  View details for Web of Science ID 000336093900019

  View details for PubMedID 24376274

• ZERENEX (TM) (FERRIC CITRATE) FOR THE TREATMENT OF IRON-DEFICIENCY ANEMIA AND REDUCTION OF SERUM PHOSHATE IN NON-DIALYSIS DEPENDENT CKD Block, G. A., Fishbane, S., Shemesh, S., Sharma, A., Chertow, G. M. W B SAUNDERS CO-ELSEVIER INC. 2014: A118

  View details for Web of Science ID 000335456600402

• MORTALITY DURING EXTENDED FOLLOW-UP IN THE FREQUENT HEMODIALYSIS NETWORK NOCTURNAL TRIAL Rocco, M., Daugirdas, J., Greene, T., Lockridge, R., Chan, C., Pierratos, A., Lindsay, R., Larive, B., Chertow, G., Beck, G., Eggers, P., Kliger, A., Grp, F. OXFORD UNIV PRESS. 2014: 37

  View details for Web of Science ID 000338013500087

• LONG-TERM EFFECTS OF FREQUENT IN-CENTER HEMODIALYSIS: FHN DAILY TRIAL Kliger, A. S., Chertow, G. M., Levin, N. W., Beck, G. J., Daugirdas, J. T., Eggers, P. W., Larive, B., Rocco, M. V., Greene, T. OXFORD UNIV PRESS. 2014: 37–38

  View details for Web of Science ID 000338013500089

• EFFECTS OF CINACALCET ON FRACTURE EVENTS IN PATIENTS RECEIVING HEMODIALYSIS: THE EVOLVE TRIAL Drueke, T. B., Moe, S. M., Abdalla, S., Parfrey, P. S., Chertow, G. M. OXFORD UNIV PRESS. 2014: 41

  View details for Web of Science ID 000338013500098

• THE EFFECTS OF CINACALCET IN OLDER AND YOUNGER PATIENTS ON HEMODIALYSIS: THE EVOLVE TRIAL Parfrey, P. S., Drueke, T., Block, G. A., Kubo, Y., Chertow, G. M. OXFORD UNIV PRESS. 2014: 47

  View details for Web of Science ID 000338013500111

• A DOUBLE-BLIND PLACEBO CONTROLLED RANDOMIZED TRIAL OF FERRIC CITRATE COORDINATION COMPLEX FOR THE TREATMENT OF IRON-DEFICIENCY ANEMIA AND REDUCTION OF SERUM PHOSPHATE IN PATIENTS WITH NON-DIALYSIS DEPENDENT CHRONIC KIDNEY DISEASE Block, G., Fishbane, S., Shemesh, S., Sharma, A., Wolf, M., Chertow, G. OXFORD UNIV PRESS. 2014: 151

  View details for Web of Science ID 000338013500400

• THE EFFECT OF CINACALCET ON ATHEROSCLEROTIC AND NON-ATHEROSCLEROTIC EVENTS IN HAEMODIALYSIS PATIENTS IN THE EVOLVE CLINICAL TRIAL Wheeler, D. C., Abdalla, S., Chertow, G., Parfrey, P., Herzog, C. OXFORD UNIV PRESS. 2014: 233

  View details for Web of Science ID 000338013500642

• Bardoxolone Methyl in Type 2 Diabetes and Advanced Chronic Kidney Disease REPLY NEW ENGLAND JOURNAL OF MEDICINE Himmelfarb, J., Tuttle, K. R. 2014; 370 (18): 1768–69

  View details for Web of Science ID 000335405200031

  View details for PubMedID 24785221

• Calibration of the Brief Food Frequency Questionnaire Among Patients on Dialysis JOURNAL OF RENAL NUTRITION Delgado, C., Ward, P., Chertow, G. M., Storer, L., Dalrymple, L., Block, T., Kaysen, G. A., Kornak, J., Grimes, B., Kutner, N. G., Johansen, K. L. 2014; 24 (3): 151-U30

  Abstract

  Estimating dietary intake is challenging in patients with chronic diseases. The aim of this study was to calibrate the Block Brief 2000 food frequency questionnaire (BFFQ) using 3-day food diary records among patients on dialysis.Data from 3-day food diary records from 146 patients new to dialysis were reviewed and entered into National Cancer Institute self-administered 24-hour dietary recall (ASA24), a web-based dietary interview system. The information was then re-entered omitting foods reported in the diaries that were not in the BFFQ to generate a "BFFQ-restricted" set of intakes. We modeled each major dietary component (i.e., energy [total calories], protein, carbohydrate, fat) separately using linear regression. The main independent variables were BFFQ-restricted food diary estimates computed as the average of the 3 days of diaries, restricted to items included in the BFFQ, with the unrestricted 3-day food diary averages as dependent variables.The BFFQ-restricted diary energy estimate of 1,325 ± 545 kcal was 87% of the energy intake in the full food diary (1,510.3 ± 510.4, P < .0001). The BFFQ-restricted diary carbohydrate intake was 83% of the full food diary (156.7 ± 78.7 g vs. 190.4 ± 72.7, P < .0001). The BFFQ-restricted fat intake was 90% of the full-diary-reported fat intake (50.1 ± 24.1 g vs. 56.4 ± 21.6 g, P < .0001). Daily protein intake assessments were not statistically different by BFFQ-restricted diary and full diary assessment (63.1 ± 28.5 vs. 64.1 ± 21.4 g, P = .60). The associations between BFFQ-restricted diary intake and unrestricted intake were linear. Three-day diary-reported intake could be estimated from BFFQ-restricted intake with r2 ranging from 0.36 to 0.56 (P < .0001 for energy [total calories], protein, carbohydrate, and fat). Final equations did not include adjustments for age, sex, or race because the patterns of associations were not significantly different.Energy and macronutrient estimates by BFFQ are lower than estimates from 3-day food diaries, but simple calibration equations can be used to approximate total intake from BFFQ responses.

  View details for DOI 10.1053/j.jrn.2013.12.004

  View details for Web of Science ID 000335313500004

• Estimation of 24-hour urine phosphate excretion from spot urine collection: development of a predictive equation. Journal of renal nutrition Robinson-Cohen, C., Ix, J. H., Smits, G., Persky, M., Chertow, G. M., Block, G. A., Kestenbaum, B. R. 2014; 24 (3): 194-199

  Abstract

  The management of hyperphosphatemia in patients with moderate to severe chronic kidney disease (CKD) includes dietary phosphate restriction and/or prescription of phosphate binders. Measuring phosphate intake in CKD is important for monitoring dietary adherence and for the effectiveness of therapeutic interventions. The 24-hour urine collection is the gold standard method for determining phosphate intake; however, timed urine collections are cumbersome and prone to error. We investigated the precision and accuracy of spot urine phosphate measurements, compared to 24-hour urine phosphate (24hUrP) collection.We evaluated simultaneous spot and 24hUrP measurements, collected on multiple occasions, from 143 participants in the Phosphate Normalization Trial, a randomized trial of phosphate binders versus placebo among persons with an estimated glomerular filtration rate between 20-45 mL/minute per 1.73 m2. We used residual analyses and graphical methods to model the functional relationship of spot urine phosphate and creatinine measurements with 24hUrP. We used multiple linear regression to test whether additional covariates improved model prediction, including treatment assignment, age, sex, height, weight, urine collection time, and last meal time. We internally validated results using leave-one-out cross-validation, and externally validated in an independent replication cohort.A log-log relation between the spot urine phosphate-to-creatinine ratio and 24hUrP excretion yielded the best model fit. In addition to spot urine phosphate and creatinine concentrations, inclusion of age, sex, and weight significantly improved prediction of 24hUrP. Compared with a spot urine phosphate-to-creatinine ratio alone (r2 = 0.12, P < .001), the new equation more accurately predicted 24hUrP (leave-one-out validation r2 = 0.43, P < .001, independent validation r2 = 0.39, P < .001).We describe a novel equation to predict 24hUrP excretion using spot urine phosphate and creatinine, age, sex, and weight. The equation is more accurate and precise than the urine phosphate-to-creatinine ratio alone, and it provides a simple method for estimating 24hUrP excretion in patients with nondialysis-requiring CKD.

  View details for DOI 10.1053/j.jrn.2014.02.001

  View details for PubMedID 24759300

• KRAS mutation confers resistance to antibody-dependent cellular cytotoxicity of cetuximab against human colorectal cancer cells INTERNATIONAL JOURNAL OF CANCER Conti, S. L., Thomas, I., Hagedorn, J. C., Chung, B. I., Chertow, G. M., Wagner, T. H., Brooks, J. D., Srinivas, S., Leppert, J. T. 2014; 134 (9): 2245-2252

  Abstract

  We sought to analyze utilization and survival outcomes of cytoreductive nephrectomy in patients with metastatic renal cell carcinoma (RCC) before and after introduction of targeted therapy. We identified patients with metastatic RCC between 1993 and 2010 in the SEER registry and examined temporal trends in utilization. We performed a joinpoint regression to determine when changes in utilization of cytoreductive nephrectomy occurred. We fitted multivariable proportional hazard models in full and propensity score-matched cohorts. We performed a difference-in-difference analysis to compare survival outcomes before and after introduction of targeted therapy. The proportion of patients undergoing cytoreductive nephrectomy increased from 1993 to 2004, from 29% to 39%. We identified a primary joinpoint of 2004, just prior to the introduction of targeted therapy. Beginning in 2005, there was a modest decrease in utilization of cytoreductive nephrectomy. Cytoreductive nephrectomy was associated with a lower adjusted relative hazard (0.41, 95% confidence interval 0.34 to 0.43). Median survival among patients receiving cytoreductive nephrectomy increased in the targeted therapy era (19 versus 13 months), while median survival among patients not receiving cytoreductive nephrectomy increased only slightly (4 versus 3 months). Difference-in-difference analysis showed a significant decrease in hazard of death among patients who received cytoreductive nephrectomy in the targeted therapy era. Despite decreased utilization in the targeted therapy era, cytoreductive nephrectomy remains associated with improved survival. Prospective randomized trials are needed to confirm the benefit of cytoreductive nephrectomy among patients with metastatic RCC treated with novel targeted therapies. © 2013 Wiley Periodicals, Inc.

  View details for DOI 10.1002/ijc.28550

  View details for Web of Science ID 000331006600013

• Trends in anemia care in older patients approaching end-stage renal disease in the United States (1995-2010). JAMA internal medicine Winkelmayer, W. C., Mitani, A. A., Goldstein, B. A., Brookhart, M. A., Chertow, G. M. 2014; 174 (5): 699-707

  Abstract

  IMPORTANCE Anemia is common in patients with advanced chronic kidney disease. Whereas the treatment of anemia in patients with end-stage renal disease (ESRD) has attracted considerable attention, relatively little is known about patterns and trends in the anemia care received by patients before they start maintenance dialysis or undergo preemptive kidney transplantation. OBJECTIVE To determine the trends in anemia treatment received by Medicare beneficiaries approaching ESRD. DESIGN, SETTING, AND PARTICIPANTS Closed cohort study in the United States using national ESRD registry data (US Renal Data System) of patients 67 years or older who initiated maintenance dialysis or underwent preemptive kidney transplantation between 1995 and 2010. All eligible patients had uninterrupted Medicare (A+B) coverage for at least 2 years before ESRD. EXPOSURE Time, defined as calendar year of incident ESRD. MAIN OUTCOMES AND MEASURES Use of erythropoiesis-stimulating agents (ESA), intravenous iron supplements, and blood transfusions in the 2 years prior to ESRD; hemoglobin concentration at the time of ESRD. We used multivariable modified Poisson regression to estimate utilization prevalence ratios (PRs). RESULTS Records of 466 803 patients were analyzed. The proportion of patients with incident ESRD receiving any ESA in the 2 years before increased from 3.2% in 1995 to a peak of 40.8% in 2007; thereafter, ESA use decreased modestly to 35.0% in 2010 (compared with 1995; PR, 9.85 [95% CI, 9.04-10.74]). Among patients who received an ESA, median time from first recorded ESA use to ESRD increased from 120 days in 1995 to 337 days in 2010. Intravenous iron administration increased from 1.2% (1995) to 12.3% (2010; PR, 9.20 [95% CI, 7.97-10.61]). The proportion of patients receiving any blood transfusions increased monotonically from 20.6% (1995) to 40.3% (2010; PR, 1.88 [95% CI, 1.82-1.95]). Mean hemoglobin concentrations were 9.5 g/dL in 1995, increased to a peak of 10.3 g/dL in 2006, and then decreased moderately to 9.9 g/dL in 2010. CONCLUSIONS AND RELEVANCE Between 1995 and 2010, older adults approaching ESRD were increasingly more likely to be treated with ESAs and to receive intravenous iron supplementation, but also more likely to receive blood transfusions.

  View details for PubMedID 24589911

• Bardoxolone methyl in type 2 diabetes and advanced chronic kidney disease. New England journal of medicine Chertow, G. M., de Zeeuw, D. 2014; 370 (18): 1768-?

  View details for DOI 10.1056/NEJMc1400872

  View details for PubMedID 24785220

• Calibration of the brief food frequency questionnaire among patients on dialysis. Journal of renal nutrition Delgado, C., Ward, P., Chertow, G. M., Storer, L., Dalrymple, L., Block, T., Kaysen, G. A., Kornak, J., Grimes, B., Kutner, N. G., Johansen, K. L. 2014; 24 (3): 151-156 e1

  Abstract

  Estimating dietary intake is challenging in patients with chronic diseases. The aim of this study was to calibrate the Block Brief 2000 food frequency questionnaire (BFFQ) using 3-day food diary records among patients on dialysis.Data from 3-day food diary records from 146 patients new to dialysis were reviewed and entered into National Cancer Institute self-administered 24-hour dietary recall (ASA24), a web-based dietary interview system. The information was then re-entered omitting foods reported in the diaries that were not in the BFFQ to generate a "BFFQ-restricted" set of intakes. We modeled each major dietary component (i.e., energy [total calories], protein, carbohydrate, fat) separately using linear regression. The main independent variables were BFFQ-restricted food diary estimates computed as the average of the 3 days of diaries, restricted to items included in the BFFQ, with the unrestricted 3-day food diary averages as dependent variables.The BFFQ-restricted diary energy estimate of 1,325 ± 545 kcal was 87% of the energy intake in the full food diary (1,510.3 ± 510.4, P < .0001). The BFFQ-restricted diary carbohydrate intake was 83% of the full food diary (156.7 ± 78.7 g vs. 190.4 ± 72.7, P < .0001). The BFFQ-restricted fat intake was 90% of the full-diary-reported fat intake (50.1 ± 24.1 g vs. 56.4 ± 21.6 g, P < .0001). Daily protein intake assessments were not statistically different by BFFQ-restricted diary and full diary assessment (63.1 ± 28.5 vs. 64.1 ± 21.4 g, P = .60). The associations between BFFQ-restricted diary intake and unrestricted intake were linear. Three-day diary-reported intake could be estimated from BFFQ-restricted intake with r2 ranging from 0.36 to 0.56 (P < .0001 for energy [total calories], protein, carbohydrate, and fat). Final equations did not include adjustments for age, sex, or race because the patterns of associations were not significantly different.Energy and macronutrient estimates by BFFQ are lower than estimates from 3-day food diaries, but simple calibration equations can be used to approximate total intake from BFFQ responses.

  View details for DOI 10.1053/j.jrn.2013.12.004

  View details for PubMedID 24613023

• Estimation of 24-Hour Urine Phosphate Excretion From Spot Urine Collection: Development of a Predictive Equation JOURNAL OF RENAL NUTRITION Robinson-Cohen, C., Ix, J. H., Smits, G., Persky, M., Chertow, G. M., Block, G. A., Kestenbaum, B. R. 2014; 24 (3): 194-199

  Abstract

  The management of hyperphosphatemia in patients with moderate to severe chronic kidney disease (CKD) includes dietary phosphate restriction and/or prescription of phosphate binders. Measuring phosphate intake in CKD is important for monitoring dietary adherence and for the effectiveness of therapeutic interventions. The 24-hour urine collection is the gold standard method for determining phosphate intake; however, timed urine collections are cumbersome and prone to error. We investigated the precision and accuracy of spot urine phosphate measurements, compared to 24-hour urine phosphate (24hUrP) collection.We evaluated simultaneous spot and 24hUrP measurements, collected on multiple occasions, from 143 participants in the Phosphate Normalization Trial, a randomized trial of phosphate binders versus placebo among persons with an estimated glomerular filtration rate between 20-45 mL/minute per 1.73 m2. We used residual analyses and graphical methods to model the functional relationship of spot urine phosphate and creatinine measurements with 24hUrP. We used multiple linear regression to test whether additional covariates improved model prediction, including treatment assignment, age, sex, height, weight, urine collection time, and last meal time. We internally validated results using leave-one-out cross-validation, and externally validated in an independent replication cohort.A log-log relation between the spot urine phosphate-to-creatinine ratio and 24hUrP excretion yielded the best model fit. In addition to spot urine phosphate and creatinine concentrations, inclusion of age, sex, and weight significantly improved prediction of 24hUrP. Compared with a spot urine phosphate-to-creatinine ratio alone (r2 = 0.12, P < .001), the new equation more accurately predicted 24hUrP (leave-one-out validation r2 = 0.43, P < .001, independent validation r2 = 0.39, P < .001).We describe a novel equation to predict 24hUrP excretion using spot urine phosphate and creatinine, age, sex, and weight. The equation is more accurate and precise than the urine phosphate-to-creatinine ratio alone, and it provides a simple method for estimating 24hUrP excretion in patients with nondialysis-requiring CKD.

  View details for DOI 10.1053/j.jrn.2014.02.001

  View details for Web of Science ID 000335313500010

• Temporal trends in the incidence, treatment and outcomes of hip fracture after first kidney transplantation in the United States. American journal of transplantation Sukumaran Nair, S., Lenihan, C. R., Montez-Rath, M. E., Lowenberg, D. W., Chertow, G. M., Winkelmayer, W. C. 2014; 14 (4): 943-951

  Abstract

  It is currently unknown whether any secular trends exist in the incidence and outcomes of hip fracture in kidney transplant recipients (KTR). We identified first-time KTR (1997-2010) who had >1 year of Medicare coverage and no recorded history of hip fracture. New hip fractures were identified from corresponding diagnosis and surgical procedure codes. Outcomes studied included time to hip fracture, type of surgery received and 30-day mortality. Of 69 740 KTR transplanted in 1997-2010, 597 experienced a hip fracture event during 155 341 person-years of follow-up for an incidence rate of 3.8 per 1000 person-years. While unadjusted hip fracture incidence did not change, strong confounding by case mix was present. Using year of transplantation as a continuous variable, the hazard ratio (HR) for hip fracture in 2010 compared with 1997, adjusted for demographic, dialysis, comorbid and most transplant-related factors, was 0.56 (95% confidence interval [CI]: 0.41-0.77). Adjusting for baseline immunosuppression modestly attenuated the HR (0.68; 95% CI: 0.47-0.99). The 30-day mortality was 2.2 (95% CI: 1.3-3.7) per 100 events. In summary, hip fractures remain an important complication after kidney transplantation. Since 1997, case-mix adjusted posttransplant hip fracture rates have declined substantially. Changes in immunosuppressive therapy appear to be partly responsible for these favorable findings.

  View details for DOI 10.1111/ajt.12652

  View details for PubMedID 24712332

• Utilization of Renal Mass Biopsy in Patients With Renal Cell Carcinoma Reply UROLOGY Leppert, J. T., Hanley, J., Wagner, T. H., Chung, B. I., Brooks, J. D., Srinivas, S., Chertow, G. M., Saigal, C. S. 2014; 83 (4): 779-780

  View details for DOI 10.1016/j.urology.2013.10.077

  View details for Web of Science ID 000333984000027

• THE RELATION BETWEEN ANTIHYPERTENSIVE MEDICATION AND SEXUAL FUNCTION IN WOMEN: BASELINE DATA FROM THE SPRINT STUDY Thomas, H. N., Evans, G. W., Berlowitz, D., Bonds, D. E., Chertow, G. M., Conroy, M. B., Foy, C., Glasser, S., Lewis, C. E., Riley, W. T., Russell, L., Williams, O., Hess, R. SPRINGER. 2014: S231

  View details for Web of Science ID 000340996201177

• Utilization of renal mass biopsy in patients with renal cell carcinoma. Urology Leppert, J. T., Hanley, J., Wagner, T. H., Chung, B. I., Srinivas, S., Chertow, G. M., Brooks, J. D., Saigal, C. S. 2014; 83 (4): 774-780

  Abstract

  To examine the patient, tumor, and temporal factors associated with receipt of renal mass biopsy (RMB) in a contemporary nationally representative sample.We queried the Surveillance, Epidemiology, and End Results-Medicare data set for incident cases of renal cell carcinoma diagnosed between 1992 and 2007. We tested for associations among receipt of RMB and patient and tumor characteristics, type of therapy, and procedure type. Temporal trends in receipt of RMB were characterized over the study period.Approximately 1 in 5 (20.7%) patients diagnosed with renal cell carcinoma (n = 24,702) underwent RMB before instituting therapy. There was a steady and modest increase in RMB utilization, with the highest utilization (30%) occurring in the final study year. Of patients who underwent radical (n = 15,666) or partial (n = 2211) nephrectomy, 17% and 20%, respectively, underwent RMB in advance of surgery. Sixty-five percent of patients who underwent ablation (n = 314) underwent RMB before or in conjunction with the procedure. Roughly half of patients (50.4%) treated with systemic therapy alone underwent RMB. Factors independently associated with use of RMB included younger age, black race, Hispanic ethnicity, tumor size <7 cm, and metastatic disease at presentation.At present, most patients who eventually undergo radical or partial nephrectomy do not undergo RMB, whereas most patients who eventually undergo ablation or systemic therapy do. The optimal use of RMB in the evaluation of kidney tumors has yet to be determined.

  View details for DOI 10.1016/j.urology.2013.10.073

  View details for PubMedID 24529579

• Reply. Urology Leppert, J. T., Hanley, J., Wagner, T. H., Chung, B. I., Brooks, J. D., Srinivas, S., Chertow, G. M., Saigal, C. S. 2014; 83 (4): 779-780

  View details for DOI 10.1016/j.urology.2013.10.077

  View details for PubMedID 24529590

• A Pint of Sweat Will Save a Gallon of Blood A Call for Randomized Trials of Anticoagulation in End- Stage Renal Disease CIRCULATION Granger, C. B., Chertow, G. M. 2014; 129 (11): 1190–92

  View details for PubMedID 24452751

• Association between body composition and frailty among prevalent hemodialysis patients: a US Renal Data System special study. Journal of the American Society of Nephrology Johansen, K. L., Dalrymple, L. S., Delgado, C., Kaysen, G. A., Kornak, J., Grimes, B., Chertow, G. M. 2014; 25 (2): 381-389

  Abstract

  Studies of frailty among patients on hemodialysis have relied on definitions that substitute self-reported functioning for measures of physical performance and omit weight loss or substitute alternate criteria. We examined the association between body composition and a definition of frailty that includes measured physical performance and weight loss in a cross-sectional analysis of 638 adult patients receiving maintenance hemodialysis at 14 centers. Frailty was defined as having three of following characteristics: weight loss, weakness, exhaustion, low physical activity, and slow gait speed. We performed logistic regression with body mass index (BMI) and bioelectrical impedance spectroscopy (BIS)-derived estimates of intracellular water (ICW), fat mass, and extracellular water (ECW) as the main predictors, and age, sex, race, and comorbidity as covariates. Overall, 30% of participants were frail. Older age (odds ratio [OR], 1.31 per 10 years; 95% confidence interval [95% CI], 1.14 to 1.50), diabetes (OR, 1.65; 95% CI, 1.13 to 2.40), higher fat mass (OR, 1.18; 95% CI, 1.02 to 1.37), and higher ECW (OR, 1.33; 95% CI, 1.20 to 1.47) associated with higher odds of frailty. Higher ICW associated with lower odds of frailty (OR, 0.80 per kg; 95% CI, 0.73 to 0.87). The addition of BMI data did not change the area under the receiver operating characteristics curve (AUC; AUC=0.66 versus 0.66; P=0.71), but the addition of BIS data did change the AUC (AUC=0.72; P<0.001). Thus, individual components of body composition but not BMI associate strongly with frailty in this cohort of patients receiving hemodialysis.

  View details for DOI 10.1681/ASN.2013040431

  View details for PubMedID 24158987

• Changes in serum inflammatory markers are associated with changes in apolipoprotein A1 but not B after the initiation of dialysis. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association Kaysen, G. A., Dalrymple, L. S., Grimes, B., Chertow, G. M., Kornak, J., Johansen, K. L. 2014; 29 (2): 430-437

  Abstract

  Few studies have examined the changes in lipoproteins over time and how inflammation is associated with lipoprotein concentrations among patients with end-stage renal disease on dialysis. One possible explanation for the association of low LDL cholesterol concentration and adverse outcomes is that inflammation reduces selected apolipoprotein concentrations.Serum samples were collected from a subsample of patients enrolled into the Comprehensive Dialysis Study every 3 months for up to 1 year. We examined the relation between temporal patterns in levels of inflammatory markers and changes in apolipoproteins (apo) A1 and B and the apo B/A1 ratio using linear mixed effects modeling and adjusting for potential confounders.We enrolled 266 participants from 56 dialysis facilities. The mean age was 62 years, 45% were women and 26% were black. Apo A1 was lower among patients with higher Quetelet's (body mass) index (BMI), diabetes mellitus and atherosclerosis. Apo B was lower among older patients, patients with higher serum creatinine and patients with lower BMI. Over the course of a year, apo A1 changed inversely with serum concentrations of the acute phase proteins C-reactive protein (CRP) and α1 acid glycoprotein (α1AG), while apo B did not. Changes in α1AG were more strongly associated with changes in apolipoprotein concentrations than were changes in CRP; increases in α1AG were associated with decreases in apo A1 and increases in the apo B/A1 ratio.Changes in inflammatory markers were associated with changes in apo A1, but not apo B over 1 year, suggesting that reductions in high-density lipoprotein cholesterol are associated with inflammation, either of which could mediate cardiovascular risk, but not supporting a hypothesis linking increased risk of low levels of apo B containing lipoproteins to the risk associated with inflammation.

  View details for DOI 10.1093/ndt/gft370

  View details for PubMedID 24009290

• Changes in serum inflammatory markers are associated with changes in apolipoprotein A1 but not B after the initiation of dialysis NEPHROLOGY DIALYSIS TRANSPLANTATION Kaysen, G. A., Dalrymple, L. S., Grimes, B., Chertow, G. M., Kornak, J., Johansen, K. L. 2014; 29 (2): 430-437

  Abstract

  Few studies have examined the changes in lipoproteins over time and how inflammation is associated with lipoprotein concentrations among patients with end-stage renal disease on dialysis. One possible explanation for the association of low LDL cholesterol concentration and adverse outcomes is that inflammation reduces selected apolipoprotein concentrations.Serum samples were collected from a subsample of patients enrolled into the Comprehensive Dialysis Study every 3 months for up to 1 year. We examined the relation between temporal patterns in levels of inflammatory markers and changes in apolipoproteins (apo) A1 and B and the apo B/A1 ratio using linear mixed effects modeling and adjusting for potential confounders.We enrolled 266 participants from 56 dialysis facilities. The mean age was 62 years, 45% were women and 26% were black. Apo A1 was lower among patients with higher Quetelet's (body mass) index (BMI), diabetes mellitus and atherosclerosis. Apo B was lower among older patients, patients with higher serum creatinine and patients with lower BMI. Over the course of a year, apo A1 changed inversely with serum concentrations of the acute phase proteins C-reactive protein (CRP) and α1 acid glycoprotein (α1AG), while apo B did not. Changes in α1AG were more strongly associated with changes in apolipoprotein concentrations than were changes in CRP; increases in α1AG were associated with decreases in apo A1 and increases in the apo B/A1 ratio.Changes in inflammatory markers were associated with changes in apo A1, but not apo B over 1 year, suggesting that reductions in high-density lipoprotein cholesterol are associated with inflammation, either of which could mediate cardiovascular risk, but not supporting a hypothesis linking increased risk of low levels of apo B containing lipoproteins to the risk associated with inflammation.

  View details for DOI 10.1093/ndt/gft370

  View details for Web of Science ID 000331404100028

  View details for PubMedCentralID PMC3910339

• Association between Body Composition and Frailty among Prevalent Hemodialysis Patients: A US Renal Data System Special Study JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Johansen, K. L., Dalrymple, L. S., Delgado, C., Kaysen, G. A., Kornak, J., Grimes, B., Chertow, G. M. 2014; 25 (2): 381-389

  Abstract

  Studies of frailty among patients on hemodialysis have relied on definitions that substitute self-reported functioning for measures of physical performance and omit weight loss or substitute alternate criteria. We examined the association between body composition and a definition of frailty that includes measured physical performance and weight loss in a cross-sectional analysis of 638 adult patients receiving maintenance hemodialysis at 14 centers. Frailty was defined as having three of following characteristics: weight loss, weakness, exhaustion, low physical activity, and slow gait speed. We performed logistic regression with body mass index (BMI) and bioelectrical impedance spectroscopy (BIS)-derived estimates of intracellular water (ICW), fat mass, and extracellular water (ECW) as the main predictors, and age, sex, race, and comorbidity as covariates. Overall, 30% of participants were frail. Older age (odds ratio [OR], 1.31 per 10 years; 95% confidence interval [95% CI], 1.14 to 1.50), diabetes (OR, 1.65; 95% CI, 1.13 to 2.40), higher fat mass (OR, 1.18; 95% CI, 1.02 to 1.37), and higher ECW (OR, 1.33; 95% CI, 1.20 to 1.47) associated with higher odds of frailty. Higher ICW associated with lower odds of frailty (OR, 0.80 per kg; 95% CI, 0.73 to 0.87). The addition of BMI data did not change the area under the receiver operating characteristics curve (AUC; AUC=0.66 versus 0.66; P=0.71), but the addition of BIS data did change the AUC (AUC=0.72; P<0.001). Thus, individual components of body composition but not BMI associate strongly with frailty in this cohort of patients receiving hemodialysis.

  View details for DOI 10.1681/ASN.2013040431

  View details for Web of Science ID 000337971700020

  View details for PubMedCentralID PMC3904567

• Cost-effectiveness of tolvaptan in autosomal dominant polycystic kidney disease. Annals of internal medicine Erickson, K. F., Chertow, G. M., Goldhaber-Fiebert, J. D. 2014; 160 (2): 143-?

  View details for DOI 10.7326/L14-5001-7

  View details for PubMedID 24445704

  View details for PubMedCentralID PMC4096316

• Comparison of Hospitalization Rates among For-Profit and Nonprofit Dialysis Facilities CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Dalrymple, L. S., Johansen, K. L., Romano, P. S., Chertow, G. M., Mu, Y., Ishida, J. H., Grimes, B., Kaysen, G. A., Nguyen, D. V. 2014; 9 (1): 73-81

  Abstract

  The vast majority of US dialysis facilities are for-profit and profit status has been associated with processes of care and outcomes in patients on dialysis. This study examined whether dialysis facility profit status was associated with the rate of hospitalization in patients starting dialysis.This was a retrospective cohort study of Medicare beneficiaries starting dialysis between 2005 and 2008 using data from the US Renal Data System. All-cause hospitalization was examined and compared between for-profit and nonprofit dialysis facilities through 2009 using Poisson regression. Companion analyses of cause-specific hospitalization that are likely to be influenced by dialysis facility practices including hospitalizations for heart failure and volume overload, access complications, or hyperkalemia were conducted.The cohort included 150,642 patients. Of these, 12,985 (9%) were receiving care in nonprofit dialysis facilities. In adjusted models, patients receiving hemodialysis in for-profit facilities had a 15% (95% confidence interval [95% CI], 13% to 18%) higher relative rate of hospitalization compared with those in nonprofit facilities. Among patients receiving peritoneal dialysis, the rate of hospitalization in for-profit versus nonprofit facilities was not significantly different (relative rate, 1.07; 95% CI, 0.97 to 1.17). Patients on hemodialysis receiving care in for-profit dialysis facilities had a 37% (95% CI, 31% to 44%) higher rate of hospitalization for heart failure or volume overload and a 15% (95% CI, 11% to 20%) higher rate of hospitalization for vascular access complications.Hospitalization rates were significantly higher for patients receiving hemodialysis in for-profit compared with nonprofit dialysis facilities.

  View details for DOI 10.2215/CJN.04200413

  View details for Web of Science ID 000329364700012

  View details for PubMedCentralID PMC3878699

• Visit-to-visit systolic blood pressure variability and outcomes in hemodialysis JOURNAL OF HUMAN HYPERTENSION Chang, T. I., Flythe, J. E., Brunelli, S. M., Muntner, P., Greene, T., Cheung, A. K., Chertow, G. M. 2014; 28 (1): 18-24

  Abstract

  Visit-to-visit blood pressure variability (VTV-BPV) is an independent risk factor for cardiovascular events and death in the general population. We sought to determine the association of VTV-BPV with outcomes in patients on hemodialysis, using data from a National Institutes of Health-sponsored randomized trial (the HEMO study). We used the coefficient of variation (CV) and the average real variability in systolic blood pressure (SBP) as metrics of VTV-BPV. In all, 1844 out of 1846 randomized subjects had at least three visits with SBP measurements and were included in the analysis. Median follow-up was 2.5 years (interquartile range 1.3-4.3 years), during which time there were 869 deaths from any cause and 408 (adjudicated) cardiovascular deaths. The mean pre-dialysis SBP CV was 9.9±4.6%. In unadjusted models, we found a 31% higher risk of death from any cause per 10% increase in VTV-BPV. This association was attenuated after multivariable adjustment but remained statistically significant. Similarly, we found a 28% higher risk of cardiovascular death per 10% increase in VTV-BPV, which was attenuated and no longer statistically significant in fully adjusted models. The associations among VTV-BPV, death and cardiovascular death were modified by baseline SBP. In a diverse, well-dialyzed cohort of patients on maintenance hemodialysis, VTV-BPV, assessed using metrics of variability in pre-dialysis SBP, was associated with a higher risk of all-cause mortality and a trend toward higher risk of cardiovascular mortality, particularly in patients with a lower baseline SBP.Journal of Human Hypertension advance online publication, 27 June 2013; doi:10.1038/jhh.2013.49.

  View details for DOI 10.1038/jhh.2013.49

  View details for Web of Science ID 000327940600005

• Nutrition in Kidney Disease Preface NUTRITION IN KIDNEY DISEASE, 2ND EDITION Byham-Gray, L. D., Burrowes, J. D., Chertow, G. M., ByhamGray, L. D., Burrowes, J. D., Chertow, G. M. 2014: IX-X

  View details for Web of Science ID 000344931000002

• Medicare Reimbursement Reform for Provider Visits and Health Outcomes in Patients on Hemodialysis. Forum for health economics & policy Erickson, K. F., Winkelmayer, W. C., Chertow, G. M., Bhattacharya, J. 2014; 17 (1): 53-77

  Abstract

  The relation between the quantity of many healthcare services delivered and health outcomes is uncertain. In January 2004, the Centers for Medicare and Medicaid Services introduced a tiered fee-for-service system for patients on hemodialysis, creating an incentive for providers to see patients more frequently. We analyzed the effect of this change on patient mortality, transplant wait-listing, and costs. While mortality rates for Medicare beneficiaries on hemodialysis declined after reimbursement reform, mortality declined more - or was no different - among patients whose providers were not affected by the economic incentive. Similarly, improved placement of patients on the kidney transplant waitlist was no different among patients whose providers were not affected by the economic incentive; payments for dialysis visits increased 13.7% in the year following reform. The payment system designed to increase provider visits to hemodialysis patients increased Medicare costs with no evidence of a benefit on survival or kidney transplant listing.

  View details for PubMedID 26180520

• High prevalence of chronic kidney disease in a community survey of urban Bangladeshis: a cross-sectional study. Globalization and health Anand, S., Khanam, M. A., Saquib, J., Saquib, N., Ahmed, T., Alam, D. S., Cullen, M. R., Barry, M., Chertow, G. M. 2014; 10 (1): 9-?

  Abstract

  The burden of chronic kidney disease (CKD) will rise in parallel with the growing prevalence of type two diabetes mellitus in South Asia but is understudied. Using a cross-sectional survey of adults living in a middle-income neighborhood of Dhaka, Bangladesh, we tested the hypothesis that the prevalence of CKD in this group would approach that of the U.S. and would be strongly associated with insulin resistance.We enrolled 402 eligible adults (>30 years old) after performing a multi-stage random selection procedure. We administered a questionnaire, and collected fasting serum samples and urine samples. We used the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation to estimate glomerular filtration rate, and sex-specific cut offs for albuminuria: > 1.9 mg/mmol (17 mg/g) for men, and >2.8 mg/mmol (25 mg/g) for women. We assessed health-related quality of life using the Medical Outcomes Study Short Form-12 (SF-12).A total of 357 (89%) participants with serum samples comprised the analytic cohort. Mean age of was 49.5 (± 12.7) years. Chronic kidney disease was evident in 94 (26%). Of the participants with CKD, 58 (62%) had albuminuria only. A participant with insulin resistance had a 3.6-fold increase in odds of CKD (95% confidence interval 2.1 to 6.4). Participants with stage three or more advanced CKD reported a decrement in the Physical Health Composite score of the SF-12, compared with participants without CKD.We found an alarmingly high prevalence of CKD-particularly CKD associated with insulin resistance-in middle-income, urban Bangladeshis.

  View details for DOI 10.1186/1744-8603-10-9

  View details for PubMedID 24555767

  View details for PubMedCentralID PMC3944963

• Phase Angle, Frailty and Mortality in Older Adults JOURNAL OF GENERAL INTERNAL MEDICINE Wilhelm-Leen, E. R., Hall, Y. N., Horwitz, R. I., Chertow, G. M. 2014; 29 (1): 147-154

  Abstract

  Frailty is a multidimensional phenotype that describes declining physical function and a vulnerability to adverse outcomes in the setting of physical stress such as illness or hospitalization. Phase angle is a composite measure of tissue resistance and reactance measured via bioelectrical impedance analysis (BIA). Whether phase angle is associated with frailty and mortality in the general population is unknown.To evaluate associations among phase angle, frailty and mortality.Population-based survey.Third National Health and Nutritional Examination Survey (1988-1994).In all, 4,667 persons aged 60 and older.Frailty was defined according to a set of criteria derived from a definition previously described and validated.Narrow phase angle (the lowest quintile) was associated with a four-fold higher odds of frailty among women and a three-fold higher odds of frailty among men, adjusted for age, sex, race-ethnicity and comorbidity. Over a 12-year follow-up period, the adjusted relative hazard for mortality associated with narrow phase angle was 2.4 (95 % confidence interval [95 % CI] 1.8 to 3.1) in women and 2.2 (95 % CI 1.7 to 2.9) in men. Narrow phase angle was significantly associated with mortality even among participants with little or no comorbidity.Analyses of BIA and frailty were cross-sectional; BIA was not measured serially and incident frailty during follow-up was not assessed. Participants examined at home were excluded from analysis because they did not undergo BIA.Narrow phase angle is associated with frailty and mortality independent of age and comorbidity.

  View details for DOI 10.1007/s11606-013-2585-z

  View details for PubMedID 24002625

• High prevalence of chronic kidney disease in a community survey of urban Bangladeshis: a cross-sectional study. Globalization and health Anand, S., Khanam, M. A., Saquib, J., Saquib, N., Ahmed, T., Alam, D. S., Cullen, M. R., Barry, M., Chertow, G. M. 2014; 10: 9-?

  Abstract

  The burden of chronic kidney disease (CKD) will rise in parallel with the growing prevalence of type two diabetes mellitus in South Asia but is understudied. Using a cross-sectional survey of adults living in a middle-income neighborhood of Dhaka, Bangladesh, we tested the hypothesis that the prevalence of CKD in this group would approach that of the U.S. and would be strongly associated with insulin resistance.We enrolled 402 eligible adults (>30 years old) after performing a multi-stage random selection procedure. We administered a questionnaire, and collected fasting serum samples and urine samples. We used the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation to estimate glomerular filtration rate, and sex-specific cut offs for albuminuria: > 1.9 mg/mmol (17 mg/g) for men, and >2.8 mg/mmol (25 mg/g) for women. We assessed health-related quality of life using the Medical Outcomes Study Short Form-12 (SF-12).A total of 357 (89%) participants with serum samples comprised the analytic cohort. Mean age of was 49.5 (± 12.7) years. Chronic kidney disease was evident in 94 (26%). Of the participants with CKD, 58 (62%) had albuminuria only. A participant with insulin resistance had a 3.6-fold increase in odds of CKD (95% confidence interval 2.1 to 6.4). Participants with stage three or more advanced CKD reported a decrement in the Physical Health Composite score of the SF-12, compared with participants without CKD.We found an alarmingly high prevalence of CKD-particularly CKD associated with insulin resistance-in middle-income, urban Bangladeshis.

  View details for DOI 10.1186/1744-8603-10-9

  View details for PubMedID 24555767

  View details for PubMedCentralID PMC3944963

• Comparison of hospitalization rates among for-profit and nonprofit dialysis facilities. Clinical journal of the American Society of Nephrology Dalrymple, L. S., Johansen, K. L., Romano, P. S., Chertow, G. M., Mu, Y., Ishida, J. H., Grimes, B., Kaysen, G. A., Nguyen, D. V. 2014; 9 (1): 73-81

  Abstract

  The vast majority of US dialysis facilities are for-profit and profit status has been associated with processes of care and outcomes in patients on dialysis. This study examined whether dialysis facility profit status was associated with the rate of hospitalization in patients starting dialysis.This was a retrospective cohort study of Medicare beneficiaries starting dialysis between 2005 and 2008 using data from the US Renal Data System. All-cause hospitalization was examined and compared between for-profit and nonprofit dialysis facilities through 2009 using Poisson regression. Companion analyses of cause-specific hospitalization that are likely to be influenced by dialysis facility practices including hospitalizations for heart failure and volume overload, access complications, or hyperkalemia were conducted.The cohort included 150,642 patients. Of these, 12,985 (9%) were receiving care in nonprofit dialysis facilities. In adjusted models, patients receiving hemodialysis in for-profit facilities had a 15% (95% confidence interval [95% CI], 13% to 18%) higher relative rate of hospitalization compared with those in nonprofit facilities. Among patients receiving peritoneal dialysis, the rate of hospitalization in for-profit versus nonprofit facilities was not significantly different (relative rate, 1.07; 95% CI, 0.97 to 1.17). Patients on hemodialysis receiving care in for-profit dialysis facilities had a 37% (95% CI, 31% to 44%) higher rate of hospitalization for heart failure or volume overload and a 15% (95% CI, 11% to 20%) higher rate of hospitalization for vascular access complications.Hospitalization rates were significantly higher for patients receiving hemodialysis in for-profit compared with nonprofit dialysis facilities.

  View details for DOI 10.2215/CJN.04200413

  View details for PubMedID 24370770

• Effects of daily hemodialysis on heart rate variability: results from the Frequent Hemodialysis Network (FHN) Daily Trial. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association Chan, C. T., Chertow, G. M., Daugirdas, J. T., Greene, T. H., Kotanko, P., Larive, B., Pierratos, A., Stokes, J. B. 2014; 29 (1): 168-178

  Abstract

  End-stage renal disease is associated with reduced heart rate variability (HRV), components of which generally are associated with advanced age, diabetes mellitus and left ventricular hypertrophy. We hypothesized that daily in-center hemodialysis (HD) would increase HRV.The Frequent Hemodialysis Network (FHN) Daily Trial randomized 245 patients to receive 12 months of six versus three times per week in-center HD. Two hundred and seven patients had baseline Holter recordings. HRV measures were calculated from 24-h Holter electrocardiograms at both baseline and 12 months in 131 patients and included low-frequency power (LF, a measure of sympathetic modulation), high-frequency power (HF, a measure of parasympathetic modulation) and standard deviation (SD) of the R-R interval (SDNN, a measure of beat-to-beat variation).Baseline to Month 12 change in LF was augmented by 50% [95% confidence interval (95% CI) 6.1-112%, P =0.022] and LF + HF was augmented by 40% (95% CI 3.3-88.4%, P = 0.03) in patients assigned to daily hemodialysis (DHD) compared with conventional HD. Changes in HF and SDNN were similar between the randomized groups. The effects of DHD on LF were attenuated by advanced age and diabetes mellitus (predefined subgroups). Changes in HF (r = -0.20, P = 0.02) and SDNN (r = -0.18, P = 0.04) were inversely associated with changes in left ventricular mass (LVM).DHD increased the LF component of HRV. Reduction of LVM by DHD was associated with increased vagal modulation of heart rate (HF) and with increased beat-to-beat heart rate variation (SDNN), suggesting an important functional correlate to the structural effects of DHD on the heart in uremia.

  View details for DOI 10.1093/ndt/gft212

  View details for PubMedID 24078335

• Diabetic Severity and Risk of Kidney Stone Disease EUROPEAN UROLOGY Weinberg, A. E., Patel, C. J., Chertow, G. M., Leppert, J. T. 2014; 65 (1): 242-247

  Abstract

  BACKGROUND: The prevalence of kidney stone disease is rising along with increasing rates of obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome. OBJECTIVE: To investigate the associations among the presence and severity of T2DM, glycemic control, and insulin resistance with kidney stone disease. DESIGN, SETTING, AND PARTICIPANTS: We performed a cross-sectional analysis of all adult participants in the 2007-2010 National Health and Nutrition Examination Survey (NHANES). A history of kidney stone disease was obtained by self-report. T2DM was defined by self-reported history, T2DM-related medication usage, and reported diabetic comorbidity. Insulin resistance was estimated using fasting plasma insulin (FPI) levels and the homeostasis model assessment of insulin resistance (HOMA-IR) definition. We classified glycemic control using glycosylated hemoglobin A1c (HbA1c) and fasting plasma-glucose levels (FPG). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Odds ratios (OR) for having kidney stone disease were calculated for each individual measure of T2DM severity. Logistic regression models were fitted adjusting for age, sex, race/ethnicity, smoking history, and the Quételet index (body mass index), as well as laboratory values and components of metabolic syndrome. RESULTS AND LIMITATIONS: Correlates of kidney stone disease included a self-reported history of T2DM (OR: 2.44; 95% confidence interval [CI], 1.84-3.25) and history of insulin use (OR: 3.31; 95% CI, 2.02-5.45). Persons with FPG levels 100-126mg/dl and >126mg/dl had increased odds of having kidney stone disease (OR 1.28; 95% CI, 0.95-1.72; and OR 2.29; 95% CI, 1.68-3.12, respectively). Corresponding results for persons with HbA1c 5.7-6.4% and =6.5% were OR 1.68 (95% CI, 1.17-2.42) and OR 2.82 (95% CI, 1.98-4.02), respectively. When adjusting for patient factors, a history of T2DM, the use of insulin, FPI, and HbA1c remained significantly associated with kidney stone disease. The cross-sectional design limits causal inference. CONCLUSIONS: Among persons with T2DM, more-severe disease is associated with a heightened risk of kidney stones.

  View details for DOI 10.1016/j.eururo.2013.03.026

  View details for PubMedID 23523538

• Bardoxolone Methyl in Type 2 Diabetes and Stage 4 Chronic Kidney Disease NEW ENGLAND JOURNAL OF MEDICINE de Zeeuw, D., Akizawa, T., Audhya, P., Bakris, G. L., Chin, M., Christ-Schmidt, H., Goldsberry, A., Houser, M., Krauth, M., Heerspink, H. J., McMurray, J. J., Meyer, C. J., Parving, H., Remuzzi, G., Toto, R. D., Vaziri, N. D., Wanner, C., Wittes, J., Wrolstad, D., Chertow, G. M. 2013; 369 (26): 2492-2503

  Abstract

  Although inhibitors of the renin-angiotensin-aldosterone system can slow the progression of diabetic kidney disease, the residual risk is high. Whether nuclear 1 factor (erythroid-derived 2)-related factor 2 activators further reduce this risk is unknown.We randomly assigned 2185 patients with type 2 diabetes mellitus and stage 4 chronic kidney disease (estimated glomerular filtration rate [GFR], 15 to <30 ml per minute per 1.73 m(2) of body-surface area) to bardoxolone methyl, at a daily dose of 20 mg, or placebo. The primary composite outcome was end-stage renal disease (ESRD) or death from cardiovascular causes.The sponsor and the steering committee terminated the trial on the recommendation of the independent data and safety monitoring committee; the median follow-up was 9 months. A total of 69 of 1088 patients (6%) randomly assigned to bardoxolone methyl and 69 of 1097 (6%) randomly assigned to placebo had a primary composite outcome (hazard ratio in the bardoxolone methyl group vs. the placebo group, 0.98; 95% confidence interval [CI], 0.70 to 1.37; P=0.92). In the bardoxolone methyl group, ESRD developed in 43 patients, and 27 patients died from cardiovascular causes; in the placebo group, ESRD developed in 51 patients, and 19 patients died from cardiovascular causes. A total of 96 patients in the bardoxolone methyl group were hospitalized for heart failure or died from heart failure, as compared with 55 in the placebo group (hazard ratio, 1.83; 95% CI, 1.32 to 2.55; P<0.001). Estimated GFR, blood pressure, and the urinary albumin-to-creatinine ratio increased significantly and body weight decreased significantly in the bardoxolone methyl group, as compared with the placebo group.Among patients with type 2 diabetes mellitus and stage 4 chronic kidney disease, bardoxolone methyl did not reduce the risk of ESRD or death from cardiovascular causes. A higher rate of cardiovascular events with bardoxolone methyl than with placebo prompted termination of the trial. (Funded by Reata Pharmaceuticals; BEACON ClinicalTrials.gov number, NCT01351675.).

  View details for DOI 10.1056/NEJMoa1306033

  View details for PubMedID 24206459

• Effects of Frequent Hemodialysis on Ventricular Volumes and Left Ventricular Remodeling CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Chan, C. T., Greene, T., Chertow, G. M., Kliger, A. S., Stokes, J. B., Beck, G. J., Daugirdas, J. T., Kotanko, P., Larive, B., Levin, N. W., Mehta, R. L., Rocco, M., Sanz, J., Yang, P. C., Rajagopalan, S. 2013; 8 (12): 2106-2116

  Abstract

  Higher left ventricular volume is associated with death in patients with ESRD. This work investigated the effects of frequent hemodialysis on ventricular volumes and left ventricular remodeling.The Frequent Hemodialysis Network daily trial randomized 245 patients to 12 months of six times per week versus three times per week in-center hemodialysis; the Frequent Hemodialysis Network nocturnal trial randomized 87 patients to 12 months of six times per week nocturnal hemodialysis versus three times per week predominantly home-based hemodialysis. Left and right ventricular end systolic and diastolic volumes, left ventricular mass, and ejection fraction at baseline and end of the study were ascertained by cardiac magnetic resonance imaging. The ratio of left ventricular mass/left ventricular end diastolic volume was used as a surrogate marker of left ventricular remodeling. In each trial, the effect of frequent dialysis on left or right ventricular end diastolic volume was tested between predefined subgroups.In the daily trial, frequent hemodialysis resulted in significant reductions in left ventricular end diastolic volume (-11.0% [95% confidence interval, -16.1% to -5.5%]), left ventricular end systolic volume (-14.8% [-22.7% to -6.2%]), right ventricular end diastolic volume (-11.6% [-19.0% to -3.6%]), and a trend for right ventricular end systolic volume (-11.3% [-21.4% to 0.1%]) compared with conventional therapy. The magnitude of reduction in left and right ventricular end diastolic volumes with frequent hemodialysis was accentuated among patients with residual urine output<100 ml/d (P value [interaction]=0.02). In the nocturnal trial, there were no significant changes in left or right ventricular volumes. The frequent dialysis interventions had no substantial effect on the ratio of left ventricular mass/left ventricular end diastolic volume in either trial.Frequent in-center hemodialysis reduces left and right ventricular end systolic and diastolic ventricular volumes as well as left ventricular mass, but it does not affect left ventricular remodeling.

  View details for DOI 10.2215/CJN.03280313

  View details for Web of Science ID 000327951100012

  View details for PubMedID 23970131

  View details for PubMedCentralID PMC3848394

• The Clinical Course of Treated Hyperparathyroidism Among Patients Receiving Hemodialysis and the Effect of Cinacalcet: The EVOLVE Trial JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Parfrey, P. S., Chertow, G. M., Block, G. A., Correa-Rotter, R., Drueeke, T. B., Floege, J., Herzog, C. A., London, G. M., Mahaffey, K. W., Moe, S. M., Wheeler, D. C., Dehmel, B., Trotman, M., Modafferi, D. M., Goodman, W. G. 2013; 98 (12): 4834-4844

  Abstract

  The clinical course of secondary hyperparathyroidism (sHPT) in patients on hemodialysis is not well described, and the effect of the calcimimetic cinacalcet on disease progression is uncertain.Our objective was to describe 1) the clinical course of sHPT in patients treated with phosphate binders and/or vitamin D sterols and 2) the impact of cinacalcet on the occurrence of severe unremitting HPT, defined by the persistence of markedly elevated PTH concentrations together with hypercalcemia or parathyroidectomy (PTX).This was a randomized, double-blind, placebo-controlled, global, multicenter clinical trial.Of 5755 patients screened with moderate to severe sHPT, 3883 patients on hemodialysis were included in the trial.Outcomes included PTX; severe, unremitting HPT; and use of commercial cinacalcet (a protocol violation). Intervention: Intervention was cinacalcet (30-180 mg daily) or placebo for up to 64 months.In the 1935 patients randomized to placebo, 278 patients (14%) underwent PTX (median PTH 1872 pg/mL within the previous 12 weeks from surgery). Age, sex, geographic region, co-morbidity, calcium-containing phosphate binder use, and baseline serum calcium, phosphorus, and PTH concentrations were associated with PTX. Commercial cinacalcet was started in 443 (23%) patients (median PTH 1108 pg/mL before treatment began). Severe unremitting HPT developed in 470 patients (24%). In a multivariable Cox model, the relative hazard (comparing patients randomized to cinacalcet versus placebo) of severe unremitting HPT was 0.31 (95% confidence interval = 0.26-0.37). The relative hazard differed little when adjusted by baseline clinical characteristics.Severe unremitting HPT develops frequently in patients on hemodialysis despite conventional therapy, and cinacalcet substantially reduces its occurrence.

  View details for DOI 10.1210/jc.2013-2975

  View details for Web of Science ID 000328477200057

  View details for PubMedID 24108314

• Diabetes Severity, Metabolic Syndrome, and the Risk of Erectile Dysfunction JOURNAL OF SEXUAL MEDICINE Weinberg, A. E., Eisenberg, M., Patel, C. J., Chertow, G. M., Leppert, J. T. 2013; 10 (12): 3102-3109

  Abstract

  Erectile dysfunction (ED) is more common in men with type 2 diabetes mellitus (T2DM), obesity, and/or the metabolic syndrome (MetS).The aim of this study is to investigate the associations among proxy measures of diabetic severity and the presence of MetS with ED in a nationally representative U.S. data sample.We performed a cross-sectional analysis of adult participants in the 2001-2004 National Health and Nutrition Examination Survey.ED was ascertained by self-report. T2DM severity was defined by calculated measures of glycemic control and insulin resistance (IR). IR was estimated using fasting plasma insulin (FPI) levels and the homeostasis model assessment of IR (HOMA-IR) definition. We classified glycemic control using hemoglobin-A1c (HbA1c) and fasting plasma glucose (FPG) levels. MetS was defined by the American Heart Association and National Heart, Lung, and Blood Institute criteria. Logistic regression models, adjusted for sociodemographics, risk factors, and comorbidities, were fitted for each measure of T2DM severity, MetS, and the presence of ED.Proxy measures of glycemic control and IR were associated with ED. Participants with FPG between 100-126 mg/dL (5.6-7 mmol/L) and ≥ 126 mg/dL (>7 mmol/L) had higher odds of ED, odds ratio (OR) 1.22 (confidence interval or CI, 0.83-1.80), and OR 2.68 (CI, 1.48-4.86), respectively. Participants with HbA1c 5.7-6.4% (38.8-46.4 mmol/mol) and ≥ 6.5% (47.5 mmol/mol) had higher odds of ED (OR 1.73 [CI, 1.08-2.76] and 3.70 [CI, 2.19-6.27], respectively). When FPI and HOMA-IR were evaluated by tertiles, there was a graded relation among participants in the top tertile. In multivariable models, a strong association remained between HbA1c and ED (OR 3.19 [CI,1.13-9.01]). MetS was associated with >2.5-fold increased odds of self reported ED (OR 2.55 [CI, 1.85-3.52]).Poor glycemic control, impaired insulin sensitivity, and the MetS are associated with a heightened risk of ED.

  View details for DOI 10.1111/jsm.12318

  View details for PubMedID 24010555

• Systematic evaluation of environmental and behavioural factors associated with all-cause mortality in the United States National Health and Nutrition Examination Survey. International journal of epidemiology Patel, C. J., Rehkopf, D. H., Leppert, J. T., Bortz, W. M., Cullen, M. R., Chertow, G. M., Ioannidis, J. P. 2013; 42 (6): 1795-1810

  Abstract

  Environmental and behavioural factors are thought to contribute to all-cause mortality. Here, we develop a method to systematically screen and validate the potential independent contributions to all-cause mortality of 249 environmental and behavioural factors in the National Health and Nutrition Examination Survey (NHANES).We used Cox proportional hazards regression to associate 249 factors with all-cause mortality while adjusting for sociodemographic factors on data in the 1999-2000 and 2001-02 surveys (median 5.5 follow-up years). We controlled for multiple comparisons with the false discovery rate (FDR) and validated significant findings in the 2003-04 survey (median 2.8 follow-up years). We selected 249 factors from a set of all possible factors based on their presence in both the 1999-2002 and 2003-04 surveys and linkage with at least 20 deceased participants. We evaluated the correlation pattern of validated factors and built a multivariable model to identify their independent contribution to mortality.We identified seven environmental and behavioural factors associated with all-cause mortality, including serum and urinary cadmium, serum lycopene levels, smoking (3-level factor) and physical activity. In a multivariable model, only physical activity, past smoking, smoking in participant's home and lycopene were independently associated with mortality. These three factors explained 2.1% of the variance of all-cause mortality after adjusting for demographic and socio-economic factors.Our association study suggests that, of the set of 249 factors in NHANES, physical activity, smoking, serum lycopene and serum/urinary cadmium are associated with all-cause mortality as identified in previous studies and after controlling for multiple hypotheses and validation in an independent survey. Whereas other NHANES factors may be associated with mortality, they may require larger cohorts with longer time of follow-up to detect. It is possible to use a systematic association study to prioritize risk factors for further investigation.

  View details for DOI 10.1093/ije/dyt208

  View details for PubMedID 24345851

• Vitamin d deficiency and mortality in patients receiving dialysis: the comprehensive dialysis study. Journal of renal nutrition Anand, S., Chertow, G. M., Johansen, K. L., Grimes, B., Dalrymple, L. S., Kaysen, G. A., Kurella Tamura, M. 2013; 23 (6): 422-427

  Abstract

  Although several studies have shown poorer survival among individuals with 25-hydroxy (OH) vitamin D deficiency, data on patients receiving dialysis are limited. Using data from the Comprehensive Dialysis Study (CDS), we tested the hypothesis that patients new to dialysis with low serum concentrations of 25-OH vitamin D would experience higher mortality and hospitalizations.The CDS is a prospective cohort study.We recruited participants from 56 dialysis units located throughout the United States.We obtained data on demographics, comorbidites, and laboratory values from the CDS Patient Questionnaire as well as the Medical Evidence Form (CMS form 2728). Participants provided baseline serum samples for 25-OH vitamin D measurements.We ascertained time to death and first hospitalization as well as number of first-year hospitalizations via the U.S. Renal Data System standard analysis files. We used Cox proportional hazards to determine the association between 25-OH vitamin D tertiles and survival and hospitalization. For number of hospitalizations in the first year, we used negative binomial regression.The analytic cohort was composed of 256 patients with Patient Questionnaire data and 25-OH vitamin D concentrations. The mean age of participants was 62 (±14.0) years, and mean follow-up was 3.8 years. Patients with 25-OH vitamin D concentrations in the lowest tertile (<10.6 ng/mL) at the start of dialysis experienced higher mortality (adjusted hazard ratio 1.75, 95% confidence interval [CI] 1.03-2.97) as well as hospitalization (adjusted hazard ratio 1.76, 95% CI 1.24-2.49). Patients in the lower 2 tertiles (<15.5 ng/mL) experienced a higher rate of hospitalizations in the first year (incidence rate ratio 1.70 [95% CI 1.06-2.72] for middle tertile, 1.66 [95% CI 1.10-2.51] for lowest tertile).We found a sizeable increase in mortality and hospitalization for patients on dialysis with severe 25-OH vitamin D deficiency.

  View details for DOI 10.1053/j.jrn.2013.05.003

  View details for PubMedID 23876600

• Vitamin D Deficiency and Mortality in Patients Receiving Dialysis: The Comprehensive Dialysis Study JOURNAL OF RENAL NUTRITION Anand, S., Chertow, G. M., Johansen, K. L., Grimes, B., Dalrymple, L. S., Kaysen, G. A., Tamura, M. K. 2013; 23 (6): 422-427

  Abstract

  Although several studies have shown poorer survival among individuals with 25-hydroxy (OH) vitamin D deficiency, data on patients receiving dialysis are limited. Using data from the Comprehensive Dialysis Study (CDS), we tested the hypothesis that patients new to dialysis with low serum concentrations of 25-OH vitamin D would experience higher mortality and hospitalizations.The CDS is a prospective cohort study.We recruited participants from 56 dialysis units located throughout the United States.We obtained data on demographics, comorbidites, and laboratory values from the CDS Patient Questionnaire as well as the Medical Evidence Form (CMS form 2728). Participants provided baseline serum samples for 25-OH vitamin D measurements.We ascertained time to death and first hospitalization as well as number of first-year hospitalizations via the U.S. Renal Data System standard analysis files. We used Cox proportional hazards to determine the association between 25-OH vitamin D tertiles and survival and hospitalization. For number of hospitalizations in the first year, we used negative binomial regression.The analytic cohort was composed of 256 patients with Patient Questionnaire data and 25-OH vitamin D concentrations. The mean age of participants was 62 (±14.0) years, and mean follow-up was 3.8 years. Patients with 25-OH vitamin D concentrations in the lowest tertile (<10.6 ng/mL) at the start of dialysis experienced higher mortality (adjusted hazard ratio 1.75, 95% confidence interval [CI] 1.03-2.97) as well as hospitalization (adjusted hazard ratio 1.76, 95% CI 1.24-2.49). Patients in the lower 2 tertiles (<15.5 ng/mL) experienced a higher rate of hospitalizations in the first year (incidence rate ratio 1.70 [95% CI 1.06-2.72] for middle tertile, 1.66 [95% CI 1.10-2.51] for lowest tertile).We found a sizeable increase in mortality and hospitalization for patients on dialysis with severe 25-OH vitamin D deficiency.

  View details for DOI 10.1053/j.jrn.2013.05.003

  View details for Web of Science ID 000327007600007

• Sensitization from transfusion in patients awaiting primary kidney transplant. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association Yabu, J. M., Anderson, M. W., Kim, D., Bradbury, B. D., Lou, C. D., Petersen, J., Rossert, J., Chertow, G. M., Tyan, D. B. 2013; 28 (11): 2908-2918

  Abstract

  Sensitization to human leukocyte antigen (HLA) from red blood cell (RBC) transfusion is poorly quantified and is based on outdated, insensitive methods. The objective was to evaluate the effect of transfusion on the breadth, magnitude and specificity of HLA antibody formation using sensitive and specific methods.Transfusion, demographic and clinical data from the US Renal Data System were obtained for patients on dialysis awaiting primary kidney transplant who had ≥2 HLA antibody measurements using the Luminex single-antigen bead assay. One cohort included patients with a transfusion (n = 50) between two antibody measurements matched with up to four nontransfused patients (n = 155) by age, sex, race and vintage (time on dialysis). A second crossover cohort (n = 25) included patients with multiple antibody measurements before and after transfusion. We studied changes in HLA antibody mean fluorescence intensity (MFI) and calculated panel reactive antibody (cPRA).In the matched cohort, 10 of 50 (20%) transfused versus 6 of 155 (4%) nontransfused patients had a ≥10 HLA antibodies increase of >3000 MFI (P = 0.0006); 6 of 50 (12%) transfused patients had a ≥30 antibodies increase (P = 0.0007). In the crossover cohort, the number of HLA antibodies increasing >1000 and >3000 MFI was higher in the transfused versus the control period, P = 0.03 and P = 0.008, respectively. Using a ≥3000 MFI threshold, cPRA significantly increased in both matched (P = 0.01) and crossover (P = 0.002) transfused patients.Among prospective primary kidney transplant recipients, RBC transfusion results in clinically significant increases in HLA antibody strength and breadth, which adversely affect the opportunity for future transplant.

  View details for DOI 10.1093/ndt/gft362

  View details for PubMedID 24009295

• Utilization of cytoreductive nephrectomy and patient survival in the targeted therapy era 12th International Kidney Cancer Symposium Conti, S. L., Thomas, I., Hagedorn, J. C., Chung, B. I., Chertow, G. M., Wagner, T. H., Brooks, J. D., Srinivas, S., Leppert, J. T. WILEY-BLACKWELL. 2013: 14–16

  View details for Web of Science ID 000325992100026

• Utilization of renal mass biopsy in patients with renal cell carcinoma 12th International Kidney Cancer Symposium Leppert, J. T., Hanley, J., Wagner, T. H., Chung, B. I., Srinivas, S., Chertow, G. M., Brooks, J. D., Saigal, C. S. WILEY-BLACKWELL. 2013: 14–14

  View details for Web of Science ID 000325992100024

• Baseline characteristics in the Bardoxolone methyl EvAluation in patients with Chronic kidney disease and type 2 diabetes mellitus: the Occurrence of renal eveNts (BEACON) trial. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association Lambers Heerspink, H. J., Chertow, G. M., Akizawa, T., Audhya, P., Bakris, G. L., Goldsberry, A., Krauth, M., Linde, P., McMurray, J. J., Meyer, C. J., Parving, H., Remuzzi, G., Christ-Schmidt, H., Toto, R. D., Vaziri, N. D., Wanner, C., Wittes, J., Wrolstad, D., de Zeeuw, D. 2013; 28 (11): 2841-2850

  Abstract

  Type 2 diabetes mellitus (T2DM) is the most important contributing cause of end-stage renal disease (ESRD) worldwide. Bardoxolone methyl, a nuclear factor-erythroid-2-related factor 2 activator, augments estimated glomerular filtration. The Bardoxolone methyl EvAluation in patients with Chronic kidney disease and type 2 diabetes mellitus: the Occurrence of renal eveNts (BEACON) trial was designed to establish whether bardoxolone methyl slows or prevents progression to ESRD. Herein, we describe baseline characteristics of the BEACON population.BEACON is a randomized double-blind placebo-controlled clinical trial in 2185 patients with T2DM and chronic kidney disease stage 4 (eGFR between 15 and 30 mL/min/1.73 m(2)) designed to test the hypothesis that bardoxolone methyl added to guideline-recommended treatment including inhibitors of the renin-angiotensin-aldosterone system slows or prevents progression to ESRD or cardiovascular death compared with placebo.Baseline characteristics (mean or percentage) of the population include age 68.5 years, female 43%, Caucasian 78%, eGFR 22.5 mL/min/1.73 m(2) and systolic/diastolic blood pressure 140/70 mmHg. The median urinary albumin:creatinine ratio was 320 mg/g and the frequency of micro- and macroalbuminuria was 30 and 51%, respectively. Anemia, abnormalities in markers of bone metabolism and elevations in cardiovascular biomarkers were frequently observed. A history of cardiovascular disease was present in 56%, neuropathy in 47% and retinopathy in 41% of patients.The BEACON trial enrolled a population heretofore unstudied in an international randomized controlled trial. Enrolled patients suffered with numerous co-morbid conditions and exhibited multiple laboratory abnormalities, highlighting the critical need for new therapies to optimize management of these conditions.

  View details for DOI 10.1093/ndt/gft445

  View details for PubMedID 24169612

• High prevalence of type 2 diabetes among the urban middle class in Bangladesh BMC PUBLIC HEALTH Saquib, N., Khanam, M. A., Saquib, J., Anand, S., Chertow, G. M., Barry, M., Ahmed, T., Cullen, M. R. 2013; 13

  Abstract

  The prevalence of type-2 diabetes and metabolic syndrome are increasing in the developing world; we assessed their prevalence among the urban middle class in Bangladesh.In this cross-sectional survey (n = 402), we randomly selected consenting adults (≥ 30 years) from a middle-income neighborhood in Dhaka. We assessed demography, lifestyle, and health status, measured physical indices and blood pressure and obtained blood samples. We evaluated two primary outcomes: (1) type-2 diabetes (fasting blood glucose ≥ 7.0 mmol/L or hemoglobin A1C ≥ 6.5% (48 mmol/mol) or diabetes medication use) and (2) insulin resistance (type-2 diabetes or metabolic syndrome using International Diabetes Federation criteria).Mean age and Quételet's (body mass) index were 49.4 ± 12.6 years and 27.0 ± 5.1 kg/m²; 83% were married, 41% had ≥12 years of education, 47% were employed, 47% had a family history of diabetes. Thirty-five percent had type-2 diabetes and 45% had metabolic syndrome. In multivariate models older age and family history of diabetes were significantly associated with type-2 diabetes. Older age, female sex, overweight or obese, high wealth index and positive family history of diabetes were significantly associated with insulin resistance. Participants with type-2 diabetes or insulin resistance had significantly poorer physical health only if they had associated cardiovascular disease.The prevalence of type-2 diabetes and metabolic syndrome among the middle class in Dhaka is alarmingly high. Screening services should be implemented while researchers focus on strategies to lessen the incidence and morbidity associated with these conditions.

  View details for DOI 10.1186/1471-2458-13-1032

  View details for Web of Science ID 000329293000002

  View details for PubMedID 24172217

  View details for PubMedCentralID PMC3924340

• Pre-ESRD Changes in Body Weight and Survival in Nursing Home Residents Starting Dialysis CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Stack, S., Chertow, G. M., Johansen, K. L., Si, Y., Tamura, M. K. 2013; 8 (10): 1734-1740

  Abstract

  Among patients receiving maintenance dialysis, weight loss at any body mass index is associated with mortality. However, it is not known whether weight changes before dialysis initiation are associated with mortality and if so, what risks are associated with weight gain or loss.Linking data from the US Renal Data System to a national registry of nursing home residents, this study identified 11,090 patients who started dialysis between January of 2000 and December of 2006. Patients were categorized according to weight measured between 3 and 6 months before dialysis initiation and the percentage change in body weight before dialysis initiation (divided into quintiles). The outcome was mortality within 1 year of starting dialysis.There were 361 patients (3.3%) who were underweight (Quételet's [body mass] index<18.5 kg/m(2)) and 4046 patients (36.5%) who were obese (body mass index ≥ 30 kg/m(2)) before dialysis initiation. The median percentage change in body weight before dialysis initiation was -6% (interquartile range=-13% to 1%). There were 6063 deaths (54.7%) over 1 year of follow-up. Compared with patients with minimal weight changes (-3% to 3%, quintile 4), patients with weight loss ≥ 15% (quintile 1) had 35% higher risk for mortality (95% confidence interval, 1.25 to 1.47), whereas those patients with weight gain ≥ 4% (quintile 5) had a 24% higher risk for mortality (95% confidence interval, 1.14 to 1.35) adjusted for baseline body mass index and other confounders.Among nursing home residents, changes in body weight in advance of dialysis initiation are associated with significantly higher 1-year mortality.

  View details for DOI 10.2215/CJN.01410213

  View details for PubMedID 24009221

• Piecewise Analysis of Patient Survival after Onset of AKI CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Zhang, J. H., Palevsky, P. M., Chertow, G. M., Hartigan, J., O'Connor, T. Z., Guarino, P., Zhou, B. 2013; 8 (10): 1679-1684

  Abstract

  AKI affects approximately 2%-7% of hospitalized patients and >35% of critically ill patients. Survival after AKI may be described as having an acute phase (including an initial hyperacute component) followed by a convalescent phase, which may itself have early and late components.Data from the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network (ATN) study was used to model mortality risk among patients with dialysis-requiring AKI. This study assumed that the mortality hazard can be described by a piecewise log-linear function with change points. Using an average likelihood method, the authors tested for the number of change points in a piecewise log-linear hazard model. The maximum likelihood approach to locate the change point(s) was then adopted, and associated parameters and standard errors were estimated.There were 1124 ATN participants with follow-up to 1 year. The mortality hazard of AKI decreased over time with inflections in the rate of decrease at days 4, 42, and 148, with the sharpest change at day 42. The daily rate of decline in the log of the hazard for death was 0.220 over the first 4 days, 0.046 between day 4 and day 42, 0.017 between day 42 and day 148, and 0.003 between day 148 and day 365.There appear to be two major phases of mortality risk after AKI: an early phase extending over the first 6 weeks and a late phase from 6 weeks to 1 year. Within the first 42 days, this can be further divided into hyperacute (days 1-4) and acute (days 4-42) phases. After 42 days, there appear to be early (days 42-148) and late (after day 148) convalescent phases. These findings may help to inform the design of AKI clinical trials and assist critical care physicians in prognostic stratification.

  View details for DOI 10.2215/CJN.07250712

  View details for Web of Science ID 000325268200008

• Piecewise analysis of patient survival after onset of AKI. Clinical journal of the American Society of Nephrology Zhang, J. H., Palevsky, P. M., Chertow, G. M., Hartigan, J., O'Connor, T. Z., Guarino, P., Zhou, B. 2013; 8 (10): 1679-1684

  Abstract

  AKI affects approximately 2%-7% of hospitalized patients and >35% of critically ill patients. Survival after AKI may be described as having an acute phase (including an initial hyperacute component) followed by a convalescent phase, which may itself have early and late components.Data from the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network (ATN) study was used to model mortality risk among patients with dialysis-requiring AKI. This study assumed that the mortality hazard can be described by a piecewise log-linear function with change points. Using an average likelihood method, the authors tested for the number of change points in a piecewise log-linear hazard model. The maximum likelihood approach to locate the change point(s) was then adopted, and associated parameters and standard errors were estimated.There were 1124 ATN participants with follow-up to 1 year. The mortality hazard of AKI decreased over time with inflections in the rate of decrease at days 4, 42, and 148, with the sharpest change at day 42. The daily rate of decline in the log of the hazard for death was 0.220 over the first 4 days, 0.046 between day 4 and day 42, 0.017 between day 42 and day 148, and 0.003 between day 148 and day 365.There appear to be two major phases of mortality risk after AKI: an early phase extending over the first 6 weeks and a late phase from 6 weeks to 1 year. Within the first 42 days, this can be further divided into hyperacute (days 1-4) and acute (days 4-42) phases. After 42 days, there appear to be early (days 42-148) and late (after day 148) convalescent phases. These findings may help to inform the design of AKI clinical trials and assist critical care physicians in prognostic stratification.

  View details for DOI 10.2215/CJN.07250712

  View details for PubMedID 23813558

• Cost-effectiveness of tolvaptan in autosomal dominant polycystic kidney disease. Annals of internal medicine Erickson, K. F., Chertow, G. M., Goldhaber-Fiebert, J. D. 2013; 159 (6): 382-389

  Abstract

  Chinese translationIn the TEMPO (Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes) trial, tolvaptan significantly reduced expansion of kidney volume and loss of kidney function.To determine how the benefits of tolvaptan seen in TEMPO may relate to longer-term health outcomes, such as progression to end-stage renal disease (ESRD) and death, and cost-effectiveness.A decision-analytic model.Published literature from 1993 to 2012.Persons with early autosomal dominant polycystic kidney disease.Lifetime.Societal.Patients received tolvaptan therapy until death, development of ESRD, or liver complications or no tolvaptan therapy.Median age at ESRD onset, life expectancy, discounted quality-adjusted life-years and lifetime costs (in 2010 U.S. dollars), and incremental cost-effectiveness ratios.Tolvaptan prolonged the median age at ESRD onset by 6.5 years and increased life expectancy by 2.6 years. At $5760 per month, tolvaptan cost $744 100 per quality-adjusted life-year gained compared with standard care.For patients with autosomal dominant polycystic kidney disease that progressed more slowly, the cost per quality-adjusted life-year gained was even greater for tolvaptan.Although TEMPO followed patients for 3 years, the main analysis assumed that clinical benefits persisted over patients' lifetimes.Assuming that the benefits of tolvaptan persist in the longer term, the drug may slow progression to ESRD and reduce mortality rates. However, barring an approximately 95% reduction in price, cost-effectiveness does not compare favorably with many other commonly accepted medical interventions.National Institutes of Health and Agency for Healthcare Research and Quality.

  View details for DOI 10.7326/0003-4819-159-6-201309170-00004

  View details for PubMedID 24042366

• Cost-effectiveness of tolvaptan in autosomal dominant polycystic kidney disease. Annals of internal medicine Erickson, K. F., Chertow, G. M., Goldhaber-Fiebert, J. D. 2013; 159 (6): 382-389

  Abstract

  Chinese translationIn the TEMPO (Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes) trial, tolvaptan significantly reduced expansion of kidney volume and loss of kidney function.To determine how the benefits of tolvaptan seen in TEMPO may relate to longer-term health outcomes, such as progression to end-stage renal disease (ESRD) and death, and cost-effectiveness.A decision-analytic model.Published literature from 1993 to 2012.Persons with early autosomal dominant polycystic kidney disease.Lifetime.Societal.Patients received tolvaptan therapy until death, development of ESRD, or liver complications or no tolvaptan therapy.Median age at ESRD onset, life expectancy, discounted quality-adjusted life-years and lifetime costs (in 2010 U.S. dollars), and incremental cost-effectiveness ratios.Tolvaptan prolonged the median age at ESRD onset by 6.5 years and increased life expectancy by 2.6 years. At $5760 per month, tolvaptan cost $744 100 per quality-adjusted life-year gained compared with standard care.For patients with autosomal dominant polycystic kidney disease that progressed more slowly, the cost per quality-adjusted life-year gained was even greater for tolvaptan.Although TEMPO followed patients for 3 years, the main analysis assumed that clinical benefits persisted over patients' lifetimes.Assuming that the benefits of tolvaptan persist in the longer term, the drug may slow progression to ESRD and reduce mortality rates. However, barring an approximately 95% reduction in price, cost-effectiveness does not compare favorably with many other commonly accepted medical interventions.National Institutes of Health and Agency for Healthcare Research and Quality.

  View details for DOI 10.7326/0003-4819-159-6-201309170-00004

  View details for PubMedID 24042366

• Prevention of Contrast-Induced AKI: A Review of Published Trials and the Design of the Prevention of Serious Adverse Events following Angiography (PRESERVE) Trial CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Weisbord, S. D., Gallagher, M., Kaufman, J., Cass, A., Parikh, C. R., Chertow, G. M., Shunk, K. A., McCullough, P. A., Fine, M. J., Mor, M. K., Lew, R. A., Huang, G. D., Conner, T. A., Brophy, M. T., Lee, J., Soliva, S., Palevsky, P. M. 2013; 8 (9): 1618-1631

  Abstract

  Contrast-induced AKI (CI-AKI) is a common condition associated with serious, adverse outcomes. CI-AKI may be preventable because its risk factors are well characterized and the timing of renal insult is commonly known in advance. Intravenous (IV) fluids and N-acetylcysteine (NAC) are two of the most widely studied preventive measures for CI-AKI. Despite a multitude of clinical trials and meta-analyses, the most effective type of IV fluid (sodium bicarbonate versus sodium chloride) and the benefit of NAC remain unclear. Careful review of published trials of these interventions reveals design limitations that contributed to their inconclusive findings. Such design limitations include the enrollment of small numbers of patients, increasing the risk for type I and type II statistical errors; the use of surrogate primary endpoints defined by small increments in serum creatinine, which are associated with, but not necessarily causally related to serious, adverse, patient-centered outcomes; and the inclusion of low-risk patients with intact baseline kidney function, yielding low event rates and reduced generalizability to a higher-risk population. The Prevention of Serious Adverse Events following Angiography (PRESERVE) trial is a randomized, double-blind, multicenter trial that will enroll 8680 high-risk patients undergoing coronary or noncoronary angiography to compare the effectiveness of IV isotonic sodium bicarbonate versus IV isotonic sodium chloride and oral NAC versus oral placebo for the prevention of serious, adverse outcomes associated with CI-AKI. This article discusses key methodological issues of past trials investigating IV fluids and NAC and how they informed the design of the PRESERVE trial.

  View details for DOI 10.2215/CJN.11161012

  View details for Web of Science ID 000325705500024

• Prevention of contrast-induced AKI: a review of published trials and the design of the prevention of serious adverse events following angiography (PRESERVE) trial. Clinical journal of the American Society of Nephrology Weisbord, S. D., Gallagher, M., Kaufman, J., Cass, A., Parikh, C. R., Chertow, G. M., Shunk, K. A., McCullough, P. A., Fine, M. J., Mor, M. K., Lew, R. A., Huang, G. D., Conner, T. A., Brophy, M. T., Lee, J., Soliva, S., Palevsky, P. M. 2013; 8 (9): 1618-1631

  Abstract

  Contrast-induced AKI (CI-AKI) is a common condition associated with serious, adverse outcomes. CI-AKI may be preventable because its risk factors are well characterized and the timing of renal insult is commonly known in advance. Intravenous (IV) fluids and N-acetylcysteine (NAC) are two of the most widely studied preventive measures for CI-AKI. Despite a multitude of clinical trials and meta-analyses, the most effective type of IV fluid (sodium bicarbonate versus sodium chloride) and the benefit of NAC remain unclear. Careful review of published trials of these interventions reveals design limitations that contributed to their inconclusive findings. Such design limitations include the enrollment of small numbers of patients, increasing the risk for type I and type II statistical errors; the use of surrogate primary endpoints defined by small increments in serum creatinine, which are associated with, but not necessarily causally related to serious, adverse, patient-centered outcomes; and the inclusion of low-risk patients with intact baseline kidney function, yielding low event rates and reduced generalizability to a higher-risk population. The Prevention of Serious Adverse Events following Angiography (PRESERVE) trial is a randomized, double-blind, multicenter trial that will enroll 8680 high-risk patients undergoing coronary or noncoronary angiography to compare the effectiveness of IV isotonic sodium bicarbonate versus IV isotonic sodium chloride and oral NAC versus oral placebo for the prevention of serious, adverse outcomes associated with CI-AKI. This article discusses key methodological issues of past trials investigating IV fluids and NAC and how they informed the design of the PRESERVE trial.

  View details for DOI 10.2215/CJN.11161012

  View details for PubMedID 23660180

• Temporal Trends in the Incidence, Treatment, and Outcomes of Hip Fracture in Older Patients Initiating Dialysis in the United States CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Nair, S. S., Mitani, A. A., Goldstein, B. A., Chertow, G. M., Lowenberg, D. W., Winkelmayer, W. C. 2013; 8 (8): 1336-1342

  Abstract

  BACKGROUND AND OBJECTIVES: Patients with ESRD experience a fivefold higher incidence of hip fracture than the age- and sex-matched general population. Despite multiple changes in the treatment of CKD mineral bone disorder, little is known about long-term trends in hip fracture incidence, treatment patterns, and outcomes in patients on dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Fourteen annual cohorts (1996-2009) of older patients (≥67 years) initiating dialysis in the United States were studied. Eligible patients had Medicare fee-for-service coverage for ≥2 years before dialysis initiation and were followed for ≤3 years for a first hip fracture. Type of treatment (internal fixation or partial or total hip replacement) was ascertained along with 30-day mortality. Cox and modified Poisson regressions were used to describe trends in study outcomes. RESULTS: This study followed 409,040 patients over 607,059 person-years, during which time 17,887 hip fracture events were recorded (29.3 events/1000 person-years). Compared with patients incident for ESRD in 1996, adjusted hip fracture rates increased until the 2004 cohort (+41%) and declined thereafter. Surgical treatment included internal fixation in 56%, partial hip replacement in 29%, and total hip replacement in 2%, which remained essentially unchanged over time; 30-day mortality after hip fracture declined from 20% (1996) to 16% (2009). CONCLUSIONS: Hip fracture incidence rates remain higher today than in patients reaching ESRD in 1996, despite multiple purported improvements in the management of CKD mineral bone disorder. Although recent declines in incidence and steady declines in associated short-term mortality are encouraging, hip fractures remain among the most common and consequential noncardiovascular complications of ESRD.

  View details for DOI 10.2215/CJN.10901012

  View details for PubMedID 23660182

• Oh! What a tangled web we weave. Clinical journal of the American Society of Nephrology Arora, N., Chertow, G. M. 2013; 8 (7): 1066-1067

  View details for DOI 10.2215/CJN.05420513

  View details for PubMedID 23766364

• Visit-to-visit systolic blood pressure variability and outcomes in hemodialysis. Journal of human hypertension Chang, T. I., Flythe, J. E., Brunelli, S. M., Muntner, P., Greene, T., Cheung, A. K., Chertow, G. M. 2013

  Abstract

  Visit-to-visit blood pressure variability (VTV-BPV) is an independent risk factor for cardiovascular events and death in the general population. We sought to determine the association of VTV-BPV with outcomes in patients on hemodialysis, using data from a National Institutes of Health-sponsored randomized trial (the HEMO study). We used the coefficient of variation (CV) and the average real variability in systolic blood pressure (SBP) as metrics of VTV-BPV. In all, 1844 out of 1846 randomized subjects had at least three visits with SBP measurements and were included in the analysis. Median follow-up was 2.5 years (interquartile range 1.3-4.3 years), during which time there were 869 deaths from any cause and 408 (adjudicated) cardiovascular deaths. The mean pre-dialysis SBP CV was 9.9±4.6%. In unadjusted models, we found a 31% higher risk of death from any cause per 10% increase in VTV-BPV. This association was attenuated after multivariable adjustment but remained statistically significant. Similarly, we found a 28% higher risk of cardiovascular death per 10% increase in VTV-BPV, which was attenuated and no longer statistically significant in fully adjusted models. The associations among VTV-BPV, death and cardiovascular death were modified by baseline SBP. In a diverse, well-dialyzed cohort of patients on maintenance hemodialysis, VTV-BPV, assessed using metrics of variability in pre-dialysis SBP, was associated with a higher risk of all-cause mortality and a trend toward higher risk of cardiovascular mortality, particularly in patients with a lower baseline SBP.Journal of Human Hypertension advance online publication, 27 June 2013; doi:10.1038/jhh.2013.49.

  View details for DOI 10.1038/jhh.2013.49

  View details for PubMedID 23803593

• Variation in Nephrologist Visits to Patients on Hemodialysis across Dialysis Facilities and Geographic Locations. Clinical journal of the American Society of Nephrology Erickson, K. F., Tan, K. B., Winkelmayer, W. C., Chertow, G. M., Bhattacharya, J. 2013; 8 (6): 987-994

  Abstract

  BACKGROUND AND OBJECTIVES: Geographic and other variations in medical practices lead to differences in medical costs, often without a clear link to health outcomes. This work examined variation in the frequency of physician visits to patients receiving hemodialysis to measure the relative importance of provider practice patterns (including those patterns linked to geographic region) and patient health in determining visit frequency. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This work analyzed a nationally representative 2006 database of patients receiving hemodialysis in the United States. A variation decomposition analysis of the relative importance of facility, geographic region, and patient characteristics-including demographics, socioeconomic status, and indicators of health status-in explaining physician visit frequency variation was conducted. Finally, the associations between facility, geographic and patient characteristics, and provider visit frequency were measured using multivariable regression. RESULTS: Patient characteristics accounted for only 0.9% of the total visit frequency variation. Accounting for case-mix differences, patients' hemodialysis facilities explained about 24.9% of visit frequency variation, of which 9.3% was explained by geographic region. Visit frequency was more closely associated with many facility and geographic characteristics than indicators of health status. More recent dialysis initiation and recent hospitalization were associated with decreased visit frequency. CONCLUSIONS: In hemodialysis, provider visit frequency depends more on geography and facility location and characteristics than patients' health status or acuity of illness. The magnitude of variation unrelated to patient health suggests that provider visit frequency practices do not reflect optimal management of patients on dialysis.

  View details for DOI 10.2215/CJN.10171012

  View details for PubMedID 23430207

• Cinacalcet for cardiovascular disease in patients undergoing dialysis. New England journal of medicine Chertow, G. M., Parfrey, P. S. 2013; 368 (19): 1844-1845

  View details for DOI 10.1056/NEJMc1301247

  View details for PubMedID 23656653

• Cinacalcet for Cardiovascular Disease in Patients Undergoing Dialysis REPLY NEW ENGLAND JOURNAL OF MEDICINE Chertow, G. M., Parfrey, P. S. 2013; 368 (19): 1844–45

  View details for Web of Science ID 000318540000022

  View details for PubMedID 23656656

• Cinacalcet for Cardiovascular Disease in Patients Undergoing Dialysis NEW ENGLAND JOURNAL OF MEDICINE Goldsmith, D. J., Lamb, E. J. 2013; 368 (19): 1843

  View details for Web of Science ID 000318540000020

  View details for PubMedID 23656654

• Cinacalcet for Cardiovascular Disease in Patients Undergoing Dialysis NEW ENGLAND JOURNAL OF MEDICINE Locatelli, F., Pontoriero, G., Tentori, F. 2013; 368 (19): 1843

  View details for Web of Science ID 000318540000019

  View details for PubMedID 23656657

• Effect of frequent hemodialysis on residual kidney function. Kidney international Daugirdas, J. T., Greene, T., Rocco, M. V., Kaysen, G. A., Depner, T. A., Levin, N. W., Chertow, G. M., Ornt, D. B., Raimann, J. G., Larive, B., Kliger, A. S. 2013; 83 (5): 949-958

  Abstract

  Frequent hemodialysis can alter volume status, blood pressure, and the concentration of osmotically active solutes, each of which might affect residual kidney function (RKF). In the Frequent Hemodialysis Network Daily and Nocturnal Trials, we examined the effects of assignment to six compared with three-times-per-week hemodialysis on follow-up RKF. In both trials, baseline RKF was inversely correlated with number of years since onset of ESRD. In the Nocturnal Trial, 63 participants had non-zero RKF at baseline (mean urine volume 0.76 liter/day, urea clearance 2.3 ml/min, and creatinine clearance 4.7 ml/min). In those assigned to frequent nocturnal dialysis, these indices were all significantly lower at month 4 and were mostly so at month 12 compared with controls. In the frequent dialysis group, urine volume had declined to zero in 52% and 67% of patients at months 4 and 12, respectively, compared with 18% and 36% in controls. In the Daily Trial, 83 patients had non-zero RKF at baseline (mean urine volume 0.43 liter/day, urea clearance 1.2 ml/min, and creatinine clearance 2.7 ml/min). Here, treatment assignment did not significantly influence follow-up levels of the measured indices, although the range in baseline RKF was narrower, potentially limiting power to detect differences. Thus, frequent nocturnal hemodialysis appears to promote a more rapid loss of RKF, the mechanism of which remains to be determined. Whether RKF also declines with frequent daily treatment could not be determined.

  View details for DOI 10.1038/ki.2012.457

  View details for PubMedID 23344474

• Effects of 6-Times-Weekly Versus 3-Times-Weekly Hemodialysis on Depressive Symptoms and Self-reported Mental Health: Frequent Hemodialysis Network (FHN) Trials AMERICAN JOURNAL OF KIDNEY DISEASES Unruh, M. L., Larive, B., Chertow, G. M., Eggers, P. W., Garg, A. X., Gassman, J., Tarallo, M., Finkelstein, F. O., Kimmel, P. L. 2013; 61 (5): 748-758

  Abstract

  Patients undergoing maintenance hemodialysis frequently exhibit poor mental health. We studied the effects of frequent in-center and nocturnal hemodialysis on depressive symptoms and self-reported mental health.1-year randomized controlled clinical trials.Hemodialysis centers in the United States and Canada. 332 patients were randomly assigned to frequent (6-times-weekly) compared with conventional (3-times-weekly) hemodialysis in the Frequent Hemodialysis Network (FHN) Daily (n = 245) and Nocturnal (n = 87) Trials.The Daily Trial was a trial of frequent (6-times-weekly) compared with conventional (3-times-weekly) in-center hemodialysis. The Nocturnal Trial assigned patients to either frequent nocturnal (6-times-weekly) hemodialysis or conventional (3-times-weekly) hemodialysis.Self-reported depressive symptoms and mental health.Beck Depression Inventory and the mental health composite score and emotional subscale of the RAND 36-Item Health Survey at baseline and 4 and 12 months. The mental health composite score is derived by summarizing these domains of the RAND 36-Item Health Survey: emotional, role emotional, energy/fatigue, and social functioning scales.In the Daily Trial, participants randomly assigned to frequent compared with conventional in-center hemodialysis showed no significant change over 12 months in adjusted mean Beck Depression Inventory score (-1.9 ± 0.7 vs -0.6 ± 0.7; P = 0.2), but experienced clinically significant improvements in adjusted mean mental health composite (3.7 ± 0.9 vs 0.2 ± 1.0; P = 0.007) and emotional subscale (5.2 ± 1.6 vs -0.3 ± 1.7; P = 0.01) scores. In the Nocturnal Trial, there were no significant changes in the same metrics in participants randomly assigned to nocturnal compared with conventional hemodialysis.Trial interventions were not blinded.Frequent in-center hemodialysis, as compared with conventional in-center hemodialysis, improved self-reported general mental health. Changes in self-reported depressive symptoms were not statistically significant. We were unable to conclude whether nocturnal hemodialysis yielded similar effects.

  View details for DOI 10.1053/j.ajkd.2012.11.047

  View details for Web of Science ID 000317276600016

  View details for PubMedID 23332990

• TEMPORAL TRENDS IN THE INCIDENCE, TREATMENT, AND OUTCOMES OF HIP FRACTURE IN OLDER PATIENTS INITIATING DIALYSIS IN THE UNITED STATES. International Conference on Glomerular Diseases Nair, S. S., Mitani, A. A., Goldstein, B. A., Chertow, G. M., Lowenberg, D. W., Winkelmayer, W. C. W B SAUNDERS CO-ELSEVIER INC. 2013: A93–A93

  View details for Web of Science ID 000317274900313

• DIABETIC SEVERITY AND RISK OF KIDNEY STONE DISEASE Weinberg, A., Patel, C., Chertow, G., Leppert, J. ELSEVIER SCIENCE INC. 2013: E27–E28

  View details for DOI 10.1016/j.juro.2013.02.1444

  View details for Web of Science ID 000320281600067

• Cost-Effectiveness of Statins for Primary Cardiovascular Prevention in Chronic Kidney Disease JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Erickson, K. F., Japa, S., Owens, D. K., Chertow, G. M., Garber, A. M., Goldhaber-Fiebert, J. D. 2013; 61 (12): 1250-1258

  Abstract

  The authors sought to evaluate the cost-effectiveness of statins for primary prevention of myocardial infarction (MI) and stroke in patients with chronic kidney disease (CKD).Patients with CKD have an elevated risk of MI and stroke. Although HMG Co-A reductase inhibitors (“statins”) may prevent cardiovascular events in patients with non–dialysis-requiring CKD, adverse drug effects and competing risks could materially influence net effects and clinical decision-making.We developed a decision-analytic model of CKD and cardiovascular disease (CVD) to determine the cost-effectiveness of low-cost generic statins for primary CVD prevention in men and women with hypertension and mild-to-moderate CKD. Outcomes included MI and stroke rates, discounted quality-adjusted life years (QALYs) and lifetime costs (2010 USD), and incremental cost-effectiveness ratios.For 65-year-old men with moderate hypertension and mild-to-moderate CKD, statins reduced the combined rate of MI and stroke, yielded 0.10 QALYs, and increased costs by $1,800 ($18,000 per QALY gained). For patients with lower baseline cardiovascular risks, health and economic benefits were smaller; for 65-year-old women, statins yielded 0.06 QALYs and increased costs by $1,900 ($33,400 per QALY gained). Results were sensitive to rates of rhabdomyolysis and drug costs. Statins are less cost-effective when obtained at average retail prices, particularly in patients at lower CVD risk.Although statins reduce absolute CVD risk in patients with CKD, the increased risk of rhabdomyolysis, and competing risks associated with progressive CKD, partly offset these gains. Low-cost generic statins appear cost-effective for primary prevention of CVD in patients with mild-to-moderate CKD and hypertension.

  View details for DOI 10.1016/j.jacc.2012.12.034

  View details for PubMedID 23500327

• Obesity Prevalence Soars among Urban Middle-class in Bangladesh Saquib, J., Saquib, N., Anand, S., Khanam, M., Chertow, G., Cullen, M. LIPPINCOTT WILLIAMS & WILKINS. 2013

  View details for Web of Science ID 000330596100249

• Longitudinal Measures of Serum Albumin and Prealbumin Concentrations in Incident Dialysis Patients: The Comprehensive Dialysis Study JOURNAL OF RENAL NUTRITION Dalrymple, L. S., Johansen, K. L., Chertow, G. M., Grimes, B., Anand, S., McCulloch, C. E., Kaysen, G. A. 2013; 23 (2): 91-97

  Abstract

  Serum albumin and prealbumin concentrations are strongly associated with the risk of death in dialysis patients. Our study examined the association among demographic characteristics, body composition, comorbidities, dialysis modality and access, inflammation, and longitudinal measures of albumin and prealbumin concentrations in incident dialysis patients. DESIGN, SETTING, SUBJECTS, AND OUTCOME MEASURES: The Comprehensive Dialysis Study is a prospective cohort study of incident dialysis patients; in this report, we examined the data from 266 Nutrition substudy participants who donated serum. The independent variables of interest were baseline age, sex, race, Quetélet's (body mass) index, dialysis modality and access, diabetes, heart failure, atherosclerotic vascular disease, serum creatinine level, and longitudinal measures of C-reactive protein. The outcomes of interest (dependent variables) were longitudinal measures of albumin and prealbumin concentrations, recorded at study entry and thereafter every 3 months for 1 year.In multivariable mixed linear models, female sex, peritoneal dialysis, hemodialysis with a catheter, and higher C-reactive protein concentrations were associated with lower serum albumin concentrations, and serum albumin concentrations increased slightly over the year. In comparison, prealbumin concentrations did not significantly change over time; female sex, lower body mass index, diabetes, atherosclerotic vascular disease, and higher C-reactive protein concentrations were associated with lower prealbumin concentrations. Serum creatinine had a curvilinear relation with serum albumin and prealbumin.Serum albumin level increases early in the course of dialysis, whereas prealbumin level does not, and the predictors of serum concentrations differ at any given time. Further understanding of the mechanisms underlying differences between albumin and prealbumin kinetics in dialysis patients may lead to an improved approach to the management of protein-energy wasting.

  View details for DOI 10.1053/j.jrn.2012.03.001

  View details for Web of Science ID 000315198700009

  View details for PubMedID 22633987

  View details for PubMedCentralID PMC3434280

• Association of Physical Activity with Survival among Ambulatory Patients on Dialysis: The Comprehensive Dialysis Study CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Johansen, K. L., Kaysen, G. A., Dalrymple, L. S., Grimes, B. A., Glidden, D. V., Anand, S., Chertow, G. M. 2013; 8 (2): 248-253

  Abstract

  Despite high mortality and low levels of physical activity (PA) among patients starting dialysis, the link between low PA and mortality has not been carefully evaluated.The Comprehensive Dialysis Study was a prospective cohort study that enrolled patients who started dialysis between June 2005 and June 2007 in a random sample of dialysis facilities in the United States. The Human Activity Profile (HAP) was administered to estimate PA among 1554 ambulatory enrolled patients in the Comprehensive Dialysis Study. Patients were followed until death or September 30, 2009, and the major outcome was all-cause mortality.The average age was 59.8 (14.2) years; 55% of participants were male, 28% were black, and 56% had diabetes mellitus. The majority (57.3%) had low fitness estimated from the HAP score. The median follow-up was 2.6 (interquartile range, 2.2-3.1) years. The association between PA and mortality was linear across the range of scores (1-94). After multivariable adjustment, lower adjusted activity score on the HAP was associated with higher mortality (hazard ratio, 1.30; 95% confidence interval, 1.23-1.39 per 10 points). Patients in the lowest level of fitness experienced a 3.5-fold (95% confidence interval, 2.54-4.89) increase in risk of death compared with those with average or above fitness.Low levels of PA are strongly associated with mortality among patients new to dialysis. Interventions aimed to preserve or enhance PA should be prospectively tested.

  View details for DOI 10.2215/CJN.08560812

  View details for Web of Science ID 000314488800013

  View details for PubMedID 23124787

  View details for PubMedCentralID PMC3562868

• Rationale and trial design of Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes: the Occurrence of Renal Events (BEACON). American journal of nephrology de Zeeuw, D., Akizawa, T., Agarwal, R., Audhya, P., Bakris, G. L., Chin, M., Krauth, M., Lambers Heerspink, H. J., Meyer, C. J., McMurray, J. J., Parving, H., Pergola, P. E., Remuzzi, G., Toto, R. D., Vaziri, N. D., Wanner, C., Warnock, D. G., Wittes, J., Chertow, G. M. 2013; 37 (3): 212-222

  Abstract

  Chronic kidney disease (CKD) associated with type 2 diabetes mellitus constitutes a global epidemic complicated by considerable renal and cardiovascular morbidity and mortality, despite the provision of inhibitors of the renin-angiotensin-aldosterone system (RAAS). Bardoxolone methyl, a synthetic triterpenoid that reduces oxidative stress and inflammation through Nrf2 activation and inhibition of NF-κB was previously shown to increase estimated glomerular filtration rate (eGFR) in patients with CKD associated with type 2 diabetes mellitus. To date, no antioxidant or anti-inflammatory therapy has proved successful at slowing the progression of CKD.Herein, we describe the design of Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes: the Occurrence of Renal Events (BEACON) trial, a multinational, multicenter, double-blind, randomized, placebo-controlled Phase 3 trial designed to determine whether long-term administration of bardoxolone methyl (on a background of standard therapy, including RAAS inhibitors) safely reduces renal and cardiac morbidity and mortality.The primary composite endpoint is time-to-first occurrence of either end-stage renal disease or cardiovascular death. Secondary endpoints include the change in eGFR and time to occurrence of cardiovascular events.BEACON will be the first event-driven trial to evaluate the effect of an oral antioxidant and anti-inflammatory drug in advanced CKD.

  View details for DOI 10.1159/000346948

  View details for PubMedID 23467003

• High prevalence of type 2 diabetes among the urban middle class in Bangladesh. BMC public health Saquib, N., Khanam, M. A., Saquib, J., Anand, S., Chertow, G. M., Barry, M., Ahmed, T., Cullen, M. R. 2013; 13: 1032-?

  Abstract

  The prevalence of type-2 diabetes and metabolic syndrome are increasing in the developing world; we assessed their prevalence among the urban middle class in Bangladesh.In this cross-sectional survey (n = 402), we randomly selected consenting adults (≥ 30 years) from a middle-income neighborhood in Dhaka. We assessed demography, lifestyle, and health status, measured physical indices and blood pressure and obtained blood samples. We evaluated two primary outcomes: (1) type-2 diabetes (fasting blood glucose ≥ 7.0 mmol/L or hemoglobin A1C ≥ 6.5% (48 mmol/mol) or diabetes medication use) and (2) insulin resistance (type-2 diabetes or metabolic syndrome using International Diabetes Federation criteria).Mean age and Quételet's (body mass) index were 49.4 ± 12.6 years and 27.0 ± 5.1 kg/m²; 83% were married, 41% had ≥12 years of education, 47% were employed, 47% had a family history of diabetes. Thirty-five percent had type-2 diabetes and 45% had metabolic syndrome. In multivariate models older age and family history of diabetes were significantly associated with type-2 diabetes. Older age, female sex, overweight or obese, high wealth index and positive family history of diabetes were significantly associated with insulin resistance. Participants with type-2 diabetes or insulin resistance had significantly poorer physical health only if they had associated cardiovascular disease.The prevalence of type-2 diabetes and metabolic syndrome among the middle class in Dhaka is alarmingly high. Screening services should be implemented while researchers focus on strategies to lessen the incidence and morbidity associated with these conditions.

  View details for DOI 10.1186/1471-2458-13-1032

  View details for PubMedID 24172217

• Rationale and Trial Design of Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes: The Occurrence of Renal Events (BEACON) AMERICAN JOURNAL OF NEPHROLOGY de Zeeuw, D., Akizawa, T., Agarwal, R., Audhya, P., Bakrise, G. L., Chin, M., Krauth, M., Heerspink, H. J., Meyer, C. J., McMurray, J. J., Parving, H., Pergola, P. E., Remuzzi, G., Toto, R. D., Vaziri, N. D., Wanner, C., Warnock, D. G., Wittes, J., Chertow, G. M. 2013; 37 (3): 212-222

  Abstract

  Chronic kidney disease (CKD) associated with type 2 diabetes mellitus constitutes a global epidemic complicated by considerable renal and cardiovascular morbidity and mortality, despite the provision of inhibitors of the renin-angiotensin-aldosterone system (RAAS). Bardoxolone methyl, a synthetic triterpenoid that reduces oxidative stress and inflammation through Nrf2 activation and inhibition of NF-κB was previously shown to increase estimated glomerular filtration rate (eGFR) in patients with CKD associated with type 2 diabetes mellitus. To date, no antioxidant or anti-inflammatory therapy has proved successful at slowing the progression of CKD.Herein, we describe the design of Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes: the Occurrence of Renal Events (BEACON) trial, a multinational, multicenter, double-blind, randomized, placebo-controlled Phase 3 trial designed to determine whether long-term administration of bardoxolone methyl (on a background of standard therapy, including RAAS inhibitors) safely reduces renal and cardiac morbidity and mortality.The primary composite endpoint is time-to-first occurrence of either end-stage renal disease or cardiovascular death. Secondary endpoints include the change in eGFR and time to occurrence of cardiovascular events.BEACON will be the first event-driven trial to evaluate the effect of an oral antioxidant and anti-inflammatory drug in advanced CKD.

  View details for DOI 10.1159/000346948

  View details for Web of Science ID 000317540300005

• Trends in Acute Kidney Injury, Associated Use of Dialysis, and Mortality After Cardiac Surgery, 1999 to 2008 ANNALS OF THORACIC SURGERY Lenihan, C. R., Montez-Rath, M. E., Mangano, C. T., Chertow, G. M., Winkelmayer, W. C. 2013; 95 (1): 20-28

  Abstract

  The development of acute kidney injury (AKI) after cardiac surgery is associated with significant mortality, morbidity, and cost. The last decade has seen major changes in the complexity of cardiac surgical candidates and in the number and type of cardiac surgical procedures being performed.Using data from the Nationwide Inpatient Sample, we determined the annual rates of AKI, AKI requiring dialysis (AKI-D), and inpatient mortality after cardiac surgery in the United States in the years 1999 through 2008.Inpatient mortality with AKI and AKI-D decreased from 27.9% and 45.9%, respectively, in 1999 to 12.8% and 35.3%, respectively, in 2008. Compared with 1999, the odds of AKI and AKI-D in 2008, adjusted for demographic and clinical factors, were 3.30 (95% confidence interval [CI]: 2.89 to 3.77) and 2.23 (95% CI: 1.78 to 2.80), respectively. Corresponding adjusted odds of death associated with AKI and AKI-D were 0.31 (95% CI: 0.26 to 0.36) and 0.47 (95% CI: 0.34 to 0.65.) Taken together, the attributable risks for death after cardiac surgery associated with AKI and AKI-D increased from 30% and 5%, respectively, in 1999 to 47% and 14%, respectively, in 2008.In sum, despite improvements in individual patient outcomes over the decade 1999 to 2008, the population contribution of AKI and AKI-D to inpatient mortality after surgery increased over the same period.

  View details for DOI 10.1016/j.athoracsur.2012.05.131

  View details for Web of Science ID 000313343700013

• Risk factors of short-term mortality after acute nonvariceal upper gastrointestinal bleeding in patients on dialysis: a population-based study. BMC nephrology Yang, J., Lee, T., Montez-Rath, M. E., Chertow, G. M., Winkelmayer, W. C. 2013; 14: 97-?

  View details for DOI 10.1186/1471-2369-14-97

  View details for PubMedID 23621917

• Trends in acute kidney injury, associated use of dialysis, and mortality after cardiac surgery, 1999 to 2008. Annals of thoracic surgery Lenihan, C. R., Montez-Rath, M. E., Mora Mangano, C. T., Chertow, G. M., Winkelmayer, W. C. 2013; 95 (1): 20-28

  Abstract

  The development of acute kidney injury (AKI) after cardiac surgery is associated with significant mortality, morbidity, and cost. The last decade has seen major changes in the complexity of cardiac surgical candidates and in the number and type of cardiac surgical procedures being performed.Using data from the Nationwide Inpatient Sample, we determined the annual rates of AKI, AKI requiring dialysis (AKI-D), and inpatient mortality after cardiac surgery in the United States in the years 1999 through 2008.Inpatient mortality with AKI and AKI-D decreased from 27.9% and 45.9%, respectively, in 1999 to 12.8% and 35.3%, respectively, in 2008. Compared with 1999, the odds of AKI and AKI-D in 2008, adjusted for demographic and clinical factors, were 3.30 (95% confidence interval [CI]: 2.89 to 3.77) and 2.23 (95% CI: 1.78 to 2.80), respectively. Corresponding adjusted odds of death associated with AKI and AKI-D were 0.31 (95% CI: 0.26 to 0.36) and 0.47 (95% CI: 0.34 to 0.65.) Taken together, the attributable risks for death after cardiac surgery associated with AKI and AKI-D increased from 30% and 5%, respectively, in 1999 to 47% and 14%, respectively, in 2008.In sum, despite improvements in individual patient outcomes over the decade 1999 to 2008, the population contribution of AKI and AKI-D to inpatient mortality after surgery increased over the same period.

  View details for DOI 10.1016/j.athoracsur.2012.05.131

  View details for PubMedID 23272825

• Physical activity and self-reported symptoms of insomnia, restless legs syndrome, and depression: The comprehensive dialysis study HEMODIALYSIS INTERNATIONAL Anand, S., Johansen, K. L., Grimes, B., Kaysen, G. A., Dalrymple, L. S., Kutner, N. G., Chertow, G. M. 2013; 17 (1): 50-58

  Abstract

  Symptoms of sleep and mood disturbances are common among patients on dialysis and are associated with significant decrements in survival and health-related quality of life. We used data from the Comprehensive Dialysis Study (CDS) to examine the association of self-reported physical activity with self-reported symptoms of insomnia, restless legs syndrome (RLS), and depression in patients new to dialysis. The CDS collected data on physical activity, functional status, and health-related quality of life from 1678 patients on either peritoneal (n = 169) or hemodialysis (n = 1509). The Human Activity Profile was used to measure self-reported physical activity. Symptoms were elicited in the following manner: insomnia using three questions designed to capture difficulty in initiating or maintaining sleep, RLS using three questions based on the National Institutes of Health workshop, and depression using the two-item Patient Health Questionnaire. We obtained data on symptoms of insomnia and depression for 1636, and on symptoms of RLS for 1622 (>98%) patients. Of these, 863 (53%) reported one of three insomnia symptoms as occurring at a persistent frequency. Symptoms of RLS and depression occurred in 477 (29%) and 451 (28%) of patients, respectively. The Adjusted Activity Score of the Human Activity Profile was inversely correlated with all three conditions in models adjusting for demographics, comorbid conditions, and laboratory variables. Sleep and mood disturbances were commonly reported in our large, diverse cohort of patients new to dialysis. Patients who reported lower levels of physical activity were more likely to report symptoms of insomnia, RLS, and depression.

  View details for DOI 10.1111/j.1542-4758.2012.00726.x

  View details for PubMedID 22812496

• Risk factors of short-term mortality after acute nonvariceal upper gastrointestinal bleeding in patients on dialysis: a population-based study. BMC nephrology Yang, J., Lee, T., Montez-Rath, M. E., Chertow, G. M., Winkelmayer, W. C. 2013; 14: 97-?

  Abstract

  Impaired kidney function is an established predictor of mortality after acute nonvariceal upper gastrointestinal bleeding (ANVUGIB); however, which factors are associated with mortality after ANVUGIB among patients undergoing dialysis is unknown. We examined the associations among demographic characteristics, dialysis-specific features, and comorbid conditions with short-term mortality after ANVUGIB among patients on dialysis.Design: Retrospective cohort study. Setting: United States Renal Data System (USRDS), a nation-wide registry of patients with end-stage renal disease. Participants: All ANVUGIB episodes identified by validated algorithms in Medicare-covered patients between 2003 and 2007. Measurements: Demographic characteristics and comorbid conditions from 1 year of billing claims prior to each bleeding event. We used logistic regression extended with generalized estimating equations methods to model the associations among risk factors and 30-day mortality following ANVUGIB events.From 2003 to 2007, we identified 40,016 eligible patients with 50,497 episodes of ANVUGIB. Overall 30-day mortality was 10.7% (95% CI: 10.4-11.0). Older age, white race, longer dialysis vintage, peritoneal dialysis (vs. hemodialysis), and hospitalized (vs. outpatient) episodes were independently associated with a higher risk of 30-day mortality. Most but not all comorbid conditions were associated with death after ANVUGIB. The joint ability of all factors captured to discriminate mortality was modest (c=0.68).We identified a profile of risk factors for 30-day mortality after ANVUGIB among patients on dialysis that was distinct from what had been reported in non-dialysis populations. Specifically, peritoneal dialysis and more years since initiation of dialysis were independently associated with short-term death after ANVUGIB.

  View details for DOI 10.1186/1471-2369-14-97

  View details for PubMedID 23621917

• A transcriptional blueprint for human and murine diabetic kidney disease. Diabetes Bhalla, V., Velez, M., Chertow, G. M. 2013; 62 (1): 31-33

  View details for DOI 10.2337/db12-1121

  View details for PubMedID 23258910

• Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis. New England journal of medicine Chertow, G. M., Block, G. A., Correa-Rotter, R., Drüeke, T. B., Floege, J., Goodman, W. G., Herzog, C. A., Kubo, Y., London, G. M., Mahaffey, K. W., Mix, T. C., Moe, S. M., Trotman, M., Wheeler, D. C., Parfrey, P. S. 2012; 367 (26): 2482-2494

  Abstract

  Disorders of mineral metabolism, including secondary hyperparathyroidism, are thought to contribute to extraskeletal (including vascular) calcification among patients with chronic kidney disease. It has been hypothesized that treatment with the calcimimetic agent cinacalcet might reduce the risk of death or nonfatal cardiovascular events in such patients.In this clinical trial, we randomly assigned 3883 patients with moderate-to-severe secondary hyperparathyroidism (median level of intact parathyroid hormone, 693 pg per milliliter [10th to 90th percentile, 363 to 1694]) who were undergoing hemodialysis to receive either cinacalcet or placebo. All patients were eligible to receive conventional therapy, including phosphate binders, vitamin D sterols, or both. The patients were followed for up to 64 months. The primary composite end point was the time until death, myocardial infarction, hospitalization for unstable angina, heart failure, or a peripheral vascular event. The primary analysis was performed on the basis of the intention-to-treat principle.The median duration of study-drug exposure was 21.2 months in the cinacalcet group, versus 17.5 months in the placebo group. The primary composite end point was reached in 938 of 1948 patients (48.2%) in the cinacalcet group and 952 of 1935 patients (49.2%) in the placebo group (relative hazard in the cinacalcet group vs. the placebo group, 0.93; 95% confidence interval, 0.85 to 1.02; P=0.11). Hypocalcemia and gastrointestinal adverse events were significantly more frequent in patients receiving cinacalcet.In an unadjusted intention-to-treat analysis, cinacalcet did not significantly reduce the risk of death or major cardiovascular events in patients with moderate-to-severe secondary hyperparathyroidism who were undergoing dialysis. (Funded by Amgen; EVOLVE ClinicalTrials.gov number, NCT00345839.).

  View details for DOI 10.1056/NEJMoa1205624

  View details for PubMedID 23121374

• Effect of Cinacalcet on Cardiovascular Disease in Patients Undergoing Dialysis NEW ENGLAND JOURNAL OF MEDICINE Chertow, G. M., Block, G. A., Correa-Rotter, R., Drueeke, T. B., Floege, J., Goodman, W. G., Herzog, C. A., Kubo, Y., London, G. M., Mahaffey, K. W., Mix, T. C., Moe, S. M., Trotman, M., Wheeler, D. C., Parfrey, P. S. 2012; 367 (26): 2482-2494

  Abstract

  Disorders of mineral metabolism, including secondary hyperparathyroidism, are thought to contribute to extraskeletal (including vascular) calcification among patients with chronic kidney disease. It has been hypothesized that treatment with the calcimimetic agent cinacalcet might reduce the risk of death or nonfatal cardiovascular events in such patients.In this clinical trial, we randomly assigned 3883 patients with moderate-to-severe secondary hyperparathyroidism (median level of intact parathyroid hormone, 693 pg per milliliter [10th to 90th percentile, 363 to 1694]) who were undergoing hemodialysis to receive either cinacalcet or placebo. All patients were eligible to receive conventional therapy, including phosphate binders, vitamin D sterols, or both. The patients were followed for up to 64 months. The primary composite end point was the time until death, myocardial infarction, hospitalization for unstable angina, heart failure, or a peripheral vascular event. The primary analysis was performed on the basis of the intention-to-treat principle.The median duration of study-drug exposure was 21.2 months in the cinacalcet group, versus 17.5 months in the placebo group. The primary composite end point was reached in 938 of 1948 patients (48.2%) in the cinacalcet group and 952 of 1935 patients (49.2%) in the placebo group (relative hazard in the cinacalcet group vs. the placebo group, 0.93; 95% confidence interval, 0.85 to 1.02; P=0.11). Hypocalcemia and gastrointestinal adverse events were significantly more frequent in patients receiving cinacalcet.In an unadjusted intention-to-treat analysis, cinacalcet did not significantly reduce the risk of death or major cardiovascular events in patients with moderate-to-severe secondary hyperparathyroidism who were undergoing dialysis. (Funded by Amgen; EVOLVE ClinicalTrials.gov number, NCT00345839.).

  View details for DOI 10.1056/NEJMoa1205624

  View details for Web of Science ID 000312714200006

• Venous Thromboembolism Yet Another Cardiovascular Complication of Chronic Kidney Disease? CIRCULATION Chertow, G. M., Mahaffey, K. W. 2012; 126 (16): 1937-1938

  View details for DOI 10.1161/CIRCULATIONAHA.112.138057

  View details for Web of Science ID 000309973700009

  View details for PubMedID 23071175

• Bardoxolone Methyl Decreases Megalin and Activates Nrf2 in the Kidney JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Reisman, S. A., Chertow, G. M., Hebbar, S., Vaziri, N. D., Ward, K. W., Meyer, C. J. 2012; 23 (10): 1663-1673

  Abstract

  Inflammation and oxidative stress are hallmarks and mediators of the progression of CKD. Bardoxolone methyl, a potent activator of the nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant and anti-inflammatory response, increases estimated GFR and decreases BUN, serum phosphorus, and uric acid concentrations in patients with moderate to severe CKD. However, it also increases albuminuria, which is associated with inflammation and disease progression. Therefore, we investigated whether this bardoxolone methyl-induced albuminuria may result from the downregulation of megalin, a protein involved in the tubular reabsorption of albumin and lipid-bound proteins. Administration of bardoxolone methyl to cynomolgus monkeys significantly decreased the protein expression of renal tubular megalin, which inversely correlated with the urine albumin-to-creatinine ratio. Moreover, daily oral administration of bardoxolone methyl to monkeys for 1 year did not lead to any adverse effects on renal histopathologic findings but did reduce serum creatinine and BUN, as observed in patients with CKD. Finally, the bardoxolone methyl-induced decrease in megalin corresponded with pharmacologic induction of renal Nrf2 targets, including NAD(P)H:quinone oxidoreductase 1 enzyme activity and glutathione content. This result indicates that Nrf2 may have a role in megalin regulation. In conclusion, these data suggest that the increase in albuminuria that accompanies bardoxolone methyl administration may result, at least in part, from reduced expression of megalin, which seems to occur without adverse effects and with strong induction of Nrf2 targets.

  View details for DOI 10.1681/ASN.2012050457

  View details for Web of Science ID 000309736000012

  View details for PubMedID 22859857

  View details for PubMedCentralID PMC3458470

• Individualized reduction in dialysate sodium in conventional in-center hemodialysis HEMODIALYSIS INTERNATIONAL Arramreddy, R., Sun, S. J., Mendoza, J. M., Chertow, G. M., Schiller, B. 2012; 16 (4): 473-480

  Abstract

  Recent studies have focused on the association between dialysate sodium (Na(+)) prescriptions and interdialytic weight gain (IDWG). We report on a case series of 13 patients undergoing conventional, thrice-weekly in-center hemodialysis with an individualized dialysate Na(+) prescription. Individualized dialysate Na(+) was achieved in all patients through a stepwise weekly reduction of the standard dialysate Na(+) prescription (140 mEq/L) by 2-3 mEq/L until reaching a Na(+) gradient of -2 mEq/L (dialysate Na(+) minus average plasma Na(+) over the preceding 3 months). Interdialytic weight gain, with and without indexing to dry weight (IDWG%), blood pressure, and the proportion of treatments with cramps, intradialytic hypotension (drop in systolic blood pressure >30 mmHg) and intradialytic hypotension requiring an intervention were reviewed. At the beginning of the observation period, the pre-hemodialysis (HD) plasma Na(+) concentration ranged from 130 to 141 mEq/L. When switched from the standard to the individualized dialysate Na(+) concentration, IDWG% decreased from 3.4% ± 1.6% to 2.5% ± 1.0% (P = 0.003) with no change in pre- or post-HD systolic or diastolic blood pressures (all P > 0.05). We found no significant change in the proportion of treatments with cramps (6% vs. 13%), intradialytic hypotension (62% vs. 65%), or intradialytic hypotension requiring an intervention (29% vs. 33%). Individualized reduction of dialysate Na(+) reduces IDWG% without significantly increasing the frequency of cramps or hypotension.

  View details for DOI 10.1111/j.1542-4758.2012.00701.x

  View details for PubMedID 22554224

• Donor Recipient Sex Mismatch in Kidney Transplantation GENDER MEDICINE Tan, J. C., Kim, J. P., Chertow, G. M., Grumet, F. C., Desai, M. 2012; 9 (5): 335-347

  Abstract

  The lack of reliable human proxies for minor (ie, non-HLA) histocompatibility loci hampers the ability to leverage these factors toward improving transplant outcomes. Despite conflicting reports of the effect of donor-recipient sex mismatch on renal allografts, the association between acute rejection of renal allografts and the development of human alloantibodies to the male H-Y antigen suggested to us that donor-recipient sex mismatch deserved re-evaluation.To evaluate whether the relationships between donor sex and allograft failure differed by recipient sex.We studied recipients of deceased-donor (n = 125,369) and living-donor (n = 63,139) transplants in the United States Renal Data System. Using Cox proportional hazards models stratified by donor type, we estimated the association between donor-recipient sex mismatch and death-censored allograft failure with adjustment for known risk factors, with and without the use of multiple imputation methods to account for potential bias and/or loss of efficiency due to missing data.The advantage afforded by male donor kidneys was more pronounced among male than among female recipients (8% vs 2% relative risk reduction; interaction P < 0.01). This difference is of the order of magnitude of several other risk factors affecting donor selection decisions.Donor-recipient sex mismatch affects renal allograft survival in a direction consistent with immune responses to sexually determined minor histocompatibility antigens. Our study provides a paradigm for clinical detection of markers for minor histocompatibility loci.

  View details for DOI 10.1016/j.genm.2012.07.004

  View details for PubMedID 22906727

• Effects of Phosphate Binders in Moderate CKD JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Block, G. A., Wheeler, D. C., Persky, M. S., Kestenbaum, B., Ketteler, M., Spiegel, D. M., Allison, M. A., Asplin, J., Smits, G., Hoofnagle, A. N., Kooienga, L., Thadhani, R., Mannstadt, M., Wolf, M., Chertow, G. M. 2012; 23 (8): 1407-1415

  Abstract

  Some propose using phosphate binders in the CKD population given the association between higher levels of phosphorus and mortality, but their safety and efficacy in this population are not well understood. Here, we aimed to determine the effects of phosphate binders on parameters of mineral metabolism and vascular calcification among patients with moderate to advanced CKD. We randomly assigned 148 patients with estimated GFR=20-45 ml/min per 1.73 m(2) to calcium acetate, lanthanum carbonate, sevelamer carbonate, or placebo. The primary endpoint was change in mean serum phosphorus from baseline to the average of months 3, 6, and 9. Serum phosphorus decreased from a baseline mean of 4.2 mg/dl in both active and placebo arms to 3.9 mg/dl with active therapy and 4.1 mg/dl with placebo (P=0.03). Phosphate binders, but not placebo, decreased mean 24-hour urine phosphorus by 22%. Median serum intact parathyroid hormone remained stable with active therapy and increased with placebo (P=0.002). Active therapy did not significantly affect plasma C-terminal fibroblast growth factor 23 levels. Active therapy did, however, significantly increase calcification of the coronary arteries and abdominal aorta (coronary: median increases of 18.1% versus 0.6%, P=0.05; abdominal aorta: median increases of 15.4% versus 3.4%, P=0.03). In conclusion, phosphate binders significantly lower serum and urinary phosphorus and attenuate progression of secondary hyperparathyroidism among patients with CKD who have normal or near-normal levels of serum phosphorus; however, they also promote the progression of vascular calcification. The safety and efficacy of phosphate binders in CKD remain uncertain.

  View details for DOI 10.1681/ASN.2012030223

  View details for Web of Science ID 000309783500018

  View details for PubMedID 22822075

  View details for PubMedCentralID PMC3402292

• Frailty, Dialysis Initiation, and Mortality in End-Stage Renal Disease ARCHIVES OF INTERNAL MEDICINE Bao, Y., Dalrymple, L., Chertow, G. M., Kaysen, G. A., Johansen, K. L. 2012; 172 (14): 1071-1077

  Abstract

  In light of the recent trend toward earlier dialysis initiation and its association with mortality among patients with end-stage renal disease, we hypothesized that frailty is associated with higher estimated glomerular filtration rate (eGFR) at dialysis start and may confound the relation between earlier dialysis initiation and mortality.We examined frailty among participants of the Comprehensive Dialysis Study (CDS), a special study of the US Renal Data System, which enrolled incident patients from September 1, 2005, through June 1, 2007. Patients were followed for vital status through September 30, 2009, and for time to first hospitalization through December 31, 2008. We used multivariate logistic regression to model the association of frailty with eGFR at dialysis start and proportional hazards regression to assess the outcomes of death or hospitalization.Among 1576 CDS participants included, the prevalence of frailty was 73%. In multivariate analysis, higher eGFR at dialysis initiation was associated with higher odds of frailty (odds ratio [OR], 1.44 [95% CI, 1.23-1.68] per 5 mL/min/1.73 m(2); P < .001). Frailty was independently associated with mortality (hazard ratio [HR], 1.57 [95% CI, 1.25-1.97]; P < .001) and time to first hospitalization (HR, 1.26 [95% CI, 1.09-1.45]; P < .001). While higher eGFR at dialysis initiation was associated with mortality (HR, 1.12 [95% CI, 1.02-1.23] per 5 mL/min/1.73 m(2); P = .02), the association was no longer statistically significant after frailty was accounted for (HR, 1.08 [95% CI, 0.98-1.19] per 5 mL/min/1.73 m(2); P = .11).Frailty is extremely common among patients starting dialysis in the United States and is associated with higher eGFR at dialysis initiation. Recognition of signs and symptoms of frailty by clinicians may prompt earlier initiation of dialysis and may explain, at least in part, the well-described association between eGFR at dialysis initiation and mortality.

  View details for DOI 10.1001/archinternmed.2012.3020

  View details for Web of Science ID 000306582000005

  View details for PubMedID 22733312

• Baseline characteristics of subjects enrolled in the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) trial NEPHROLOGY DIALYSIS TRANSPLANTATION Chertow, G. M., Correa-Rotter, R., Block, G. A., Drueke, T. B., Floege, J., Goodman, W. G., Herzog, C. A., Kubo, Y., London, G. M., Mahaffey, K. W., Mix, T., Moe, S. M., Wheeler, D. C., Parfrey, P. S. 2012; 27 (7): 2872-2879

  Abstract

  Secondary hyperparathyroidism (sHPT) and other abnormalities associated with chronic kidney disease-mineral bone disorder can contribute to dystrophic (including vascular) calcification. Dietary modification and variety of medications can be used to attenuate the severity of sHPT. However, it is unknown whether any of these approaches can reduce the high risks of death and cardiovascular disease in patients with end-stage renal disease.The Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) trial was designed to test the hypothesis that treatment with the calcimimetic agent cinacalcet compared with placebo (on a background of conventional therapy including phosphate binders +/- vitamin D sterols) reduces time to death or non-fatal cardiovascular events (specifically myocardial infarction, unstable angina, heart failure and peripheral arterial disease events) among patients on hemodialysis with sHPT. This report describes baseline characteristics of enrolled subjects with a focus on regional variation.There were 3883 subjects randomized from 22 countries, including the USA, Canada, Australia, three Latin American nations, Russia and 15 European nations. The burden of overt cardiovascular disease at baseline was high (e.g. myocardial infarction 12.4%, heart failure 23.3%). The median plasma parathyroid hormone concentration at baseline was 692 pg/mL (10%, 90% range, 363-1694 pg/mL). At baseline, 87.2% of subjects were prescribed phosphate binders and 57.5% were prescribed activated vitamin D derivatives. Demographic data, comorbid conditions and baseline laboratory data varied significantly across regions.EVOLVE enrolled 3883 subjects on hemodialysis with moderate to severe sHPT. Inclusion of subjects from multiple global regions with varying degrees of disease severity will enhance the external validity of the trial results.

  View details for DOI 10.1093/ndt/gfr777

  View details for PubMedID 22529163

• Factors Associated With Depressive Symptoms and Use of Antidepressant Medications Among Participants in the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC Studies AMERICAN JOURNAL OF KIDNEY DISEASES Fischer, M. J., Xie, D., Jordan, N., Kop, W. J., Krousel-Wood, M., Tamura, M. K., Kusek, J. W., Ford, V., Rosen, L. K., Strauss, L., Teal, V. L., Yaffe, K., Powe, N. R., Lash, J. P. 2012; 60 (1): 27-38

  Abstract

  Depressive symptoms are correlated with poor health outcomes in adults with chronic kidney disease (CKD). The prevalence, severity, and treatment of depressive symptoms and potential risk factors, including level of kidney function, in diverse populations with CKD have not been well studied.Cross-sectional analysis.Participants at enrollment into the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC (H-CRIC) Studies. CRIC enrolled Hispanics and non-Hispanics at 7 centers in 2003-2007, and H-CRIC enrolled Hispanics at the University of Illinois in 2005-2008.Depressive symptoms measured by Beck Depression Inventory (BDI).Demographic and clinical factors.Elevated depressive symptoms (BDI score ≥11) and antidepressant medication use.Of 3,853 participants, 27.4% had evidence of elevated depressive symptoms and 18.2% were using antidepressant medications; 31.0% of persons with elevated depressive symptoms were using antidepressants. The prevalence of elevated depressive symptoms varied by level of kidney function: 23.6% for participants with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m(2) and 33.8% of those with eGFR <30 mL/min/1.73 m(2). Lower eGFR (OR per 10-mL/min/1.73 m(2) decrease, 1.10; 95% CI, 1.04-1.17), and non-Hispanic black race (OR, 1.42; 95% CI, 1.16-1.74) were each associated with increased odds of elevated depressive symptoms after controlling for other factors. In regression analyses incorporating BDI score, whereas female sex was associated with greater odds of antidepressant use, Hispanic ethnicity, non-Hispanic black race, and higher urine albumin levels were associated with decreased odds of antidepressant use (P < 0.05 for each).Absence of clinical diagnosis of depression and use of nonpharmacologic treatments.Although elevated depressive symptoms were common in individuals with CKD, use of antidepressant medications is low. Individuals of racial and ethnic minority background and with more advanced CKD had a greater burden of elevated depressive symptoms and lower use of antidepressant medications.

  View details for DOI 10.1053/j.ajkd.2011.12.033

  View details for Web of Science ID 000305406200007

  View details for PubMedID 22497791

• Homelessness and CKD: A Cohort Study CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Hall, Y. N., Choi, A. I., Himmelfarb, J., Chertow, G. M., Bindman, A. B. 2012; 7 (7): 1094-1102

  Abstract

  This study examined the associations between homelessness and clinical outcomes of CKD among adults from the urban healthcare safety net.This retrospective cohort study examined 15,343 adults with CKD stages 3-5 who received ambulatory care during 1996-2005 from the Community Health Network of San Francisco. Main outcome measures were time to ESRD or death and frequency of emergency department visits and hospitalizations.Overall, 858 persons (6%) with CKD stages 3-5 were homeless. Homeless adults were younger, were disproportionately male and uninsured, and suffered from far higher rates of depression and substance abuse compared with adults with stable housing (P<0.001 for all comparisons). Over a median follow-up of 2.8 years (interquartile range=1.4-6.1), homeless adults experienced significantly higher crude risk of ESRD or death (hazard ratio=1.82, 95% confidence interval=1.49-2.22) compared with housed adults. This elevated risk was attenuated but remained significantly higher (adjusted hazard ratio=1.28, 95% confidence interval=1.04-1.58) after controlling for differences in sociodemographics, comorbid conditions, and laboratory variables. Homeless adults were also far more likely to use acute care services (median [interquartile range] number of emergency department visits was 9 [4-20] versus 1 [0-4], P<0.001) than housed counterparts.Homeless adults with CKD suffer from increased morbidity and mortality and use costly acute care services far more frequently than peers who are stably housed. These findings warrant additional inquiry into the unmet health needs of the homeless with CKD to provide appropriate and effective care to this disadvantaged group.

  View details for DOI 10.2215/CJN.00060112

  View details for Web of Science ID 000306148500008

  View details for PubMedID 22700883

  View details for PubMedCentralID PMC3386666

• The effect of frequent hemodialysis on nutrition and body composition: Frequent Hemodialysis Network Trial KIDNEY INTERNATIONAL Kaysen, G. A., Greene, T., Larive, B., Mehta, R. L., Lindsay, R. M., Depner, T. A., Hall, Y. N., Daugirdas, J. T., Chertow, G. M. 2012; 82 (1): 90-99

  Abstract

  We investigated the effects of frequency of hemodialysis on nutritional status by analyzing the data in the Frequent Hemodialysis Network Trial. We compared changes in albumin, body weight, and composition among 245 patients randomized to six or three times per week in-center hemodialysis (Daily Trial) and 87 patients randomized to six times per week nocturnal or three times per week conventional hemodialysis, performed largely at home (Nocturnal Trial). In the Daily Trial, there were no significant differences between groups in changes in serum albumin or the equilibrated protein catabolic rate by 12 months. There was a significant relative decrease in predialysis body weight of 1.5 ± 0.2 kg in the six times per week group at 1 month, but this significantly rebounded by 1.3 ± 0.5 kg over the remaining 11 months. Extracellular water (ECW) decreased in the six times per week compared with the three per week hemodialysis group. There were no significant between-group differences in phase angle, intracellular water, or body cell mass (BCM). In the Nocturnal Trial, there were no significant between-group differences in any study parameter. Any gain in 'dry' body weight corresponded to increased adiposity rather than muscle mass but was not statistically significant. Thus, frequent in-center hemodialysis reduced ECW but did not increase serum albumin or BCM while frequent nocturnal hemodialysis yielded no net effect on parameters of nutritional status or body composition.

  View details for DOI 10.1038/ki.2012.75

  View details for Web of Science ID 000305351300012

  View details for PubMedID 22456602

  View details for PubMedCentralID PMC3328304

• Validation of Reported Predialysis Nephrology Care of Older Patients Initiating Dialysis JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Kim, J. P., Desai, M., Chertow, G. M., Winkelmayer, W. C. 2012; 23 (6): 1078-1085

  Abstract

  The Centers for Medicare and Medicaid Services (CMS) Medical Evidence Report (form CMS-2728) queries providers about the timing of the patient's first nephrologist consultation before initiation of dialysis. The monitoring of disease-specific goals in the Healthy People 2020 initiative will use information from this question, but the accuracy of the reported information is unknown. We defined a cohort of 80,509 patients aged ≥67 years who initiated dialysis between July 2005 and December 2008 with ≥2 years of uninterrupted Medicare coverage as their primary payer. The primary referent, determined from claims data, was the first observed outpatient nephrologist consultation; secondary analyses used the earliest nephrology consultation, whether inpatient or outpatient. We used linear regression models to assess the associations among the magnitude of discrepant reporting and patient characteristics and we tested for any temporal trends. When using the earliest recorded outpatient nephrology encounter, agreement between the two sources of ascertainment was 48.2%, and the κ statistic was 0.29 when we categorized the timing of the visit into four periods (never, <6, 6-12, and >12 months). When we dichotomized the timing of first predialysis nephrology care at >12 or ≤12 months, accuracy was 70% (κ=0.36), but it differed by patient characteristics and declined over time. In conclusion, we found substantial disagreement between information from the CMS Medical Evidence Report and Medicare physician claims on the timing of first predialysis nephrologist care. More-specific instructions may improve reporting and increase the utility of form CMS-2728 for research and public health surveillance.

  View details for DOI 10.1681/ASN.2011080871

  View details for PubMedID 22518002

• Toward the optimal dose metric in continuous renal replacement therapy INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS Claure-Del Granado, R., Macedo, E., Chertow, G. M., Soroko, S., Himmelfarb, J., Ikizler, T. A., Paganini, E. P., Mehta, R. L. 2012; 35 (6): 413-424

  Abstract

  There is no consensus on the optimal method to measure delivered dialysis dose in patients with acute kidney injury (AKI). The use of direct dialysate-side quantification of dose in preference to the use of formal blood-based urea kinetic modeling and simplified blood urea nitrogen (BUN) methods has been recommended for dose assessment in critically-ill patients with AKI. We evaluate six different blood-side and dialysate-side methods for dose quantification.We examined data from 52 critically-ill patients with AKI requiring dialysis. All patients were treated with pre-dilution CVVHDF and regional citrate anticoagulation. Delivered dose was calculated using blood-side and dialysis-side kinetics. Filter function was assessed during the entire course of therapy by calculating BUN to dialysis fluid urea nitrogen (FUN) ratios q/12 hours.Median daily treatment time was 1,413 min (1,260-1,440). The median observed effluent volume per treatment was 2,355 mL/h (2,060-2,863) (p<0.001). Urea mass removal rate was 13.0 ± 7.6 mg/min. Both EKR (r²=0.250; p<0.001) and KD (r²=0.409; p<0.001) showed a good correlation with actual solute removal. EKR and KD presented a decline in their values that was related to the decrease in filter function assessed by the FUN/BUN ratio.Effluent rate (mL/kg/h) can only empirically provide an estimated of dose in CRRT. For clinical practice, we recommend that the delivered dose should be measured and expressed as KD. EKR also constitutes a good method for dose comparisons over time and across modalities.

  View details for DOI 10.5301/ijao.5000041

  View details for Web of Science ID 000308904000002

  View details for PubMedID 22466995

• Design of Clinical Trials in Acute Kidney Injury: A Report from an NIDDK Workshop-Prevention Trials CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Okusa, M. D., Molitoris, B. A., Palevsky, P. M., Chinchilli, V. M., Liu, K. D., Cheung, A. K., Weisbord, S. D., Faubel, S., Kellum, J. A., Wald, R., Chertow, G. M., Levin, A., Waikar, S. S., Murray, P. T., Parikh, C. R., Shaw, A. D., Go, A. S., Chavvla, L. S., Kaufman, J. S., Devarajan, P., Toto, R. M., Hsu, C., Greene, T. H., Mehta, R. L., Stokes, J. B., Thompson, A. M., Thompson, B. T., Westenfelder, C. S., Tumlin, J. A., Warnock, D. G., Shah, S. V., Xie, Y., Duggan, E. G., Kimmel, P. L., Star, R. A. 2012; 7 (5): 851-855

  Abstract

  AKI is an important clinical problem that has become increasingly more common. Mortality rates associated with AKI remain high despite advances in supportive care. Patients surviving AKI have increased long-term mortality and appear to be at increased risk of developing CKD and progressing to ESRD. No proven effective pharmacologic therapies are currently available for the prevention or treatment of AKI. Advances in addressing this unmet need will require the development of novel therapeutic agents based on precise understanding of key pathophysiological events and the implementation of well designed clinical trials. To address this need, the National Institute of Diabetes and Digestive and Kidney Diseases sponsored the "Clinical Trials in Acute Kidney Injury: Current Opportunities and Barriers" workshop in December 2010. The event brought together representatives from academia, industry, the National Institutes of Health, and the US Food and Drug Administration. We report the discussions of workgroups that developed outlines of clinical trials for the prevention of AKI in two patient populations: patients undergoing elective surgery who are at risk for or who develop AKI, and patients who are at risk for contrast-induced AKI. In both of these populations, primary prevention or secondary therapy can be delivered at an optimal time relative to kidney injury. The workgroups detailed primary and secondary endpoints for studies in these groups, and explored the use of adaptive clinical trial designs for trials of novel preventive strategies to improve outcomes of patients with AKI.

  View details for DOI 10.2215/CJN.12811211

  View details for Web of Science ID 000303632700023

  View details for PubMedID 22442188

• Design of Clinical Trials in AKI: A Report from an NIDDK Workshop. Trials of Patients with Sepsis and in Selected Hospital Settings CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Molitoris, B. A., Okusa, M. D., Palevsky, P. M., Chawla, L. S., Kaufman, J. S., Devarajan, P., Toto, R. M., Hsu, C., Greene, T. H., Faubel, S. G., Kellum, J. A., Wald, R., Chertow, G. M., Levin, A., Waikar, S. S., Murray, P. T., Parikh, C. R., Shaw, A. D., Go, A. S., Chinchilli, V. M., Liu, K. D., Cheung, A. K., Weisbord, S. D., Mehta, R. L., Stokes, J. B., Thompson, A. M., Thompson, B. T., Westenfelder, C. S., Turnin, J. A., Warnock, D. G., Shah, S. V., Xie, Y., Duggan, E. G., Kimmel, P. L., Star, R. A. 2012; 7 (5): 856-860

  Abstract

  AKI remains an important clinical problem, with a high mortality rate, increasing incidence, and no Food and Drug Administration-approved therapeutics. Advances in addressing this clinical need require approaches for rapid diagnosis and stratification of injury, development of therapeutic agents based on precise understanding of key pathophysiological events, and implementation of well designed clinical trials. In the near future, AKI biomarkers may facilitate trial design. To address these issues, the National Institute of Diabetes and Digestive and Kidney Diseases sponsored a meeting, "Clinical Trials in Acute Kidney Injury: Current Opportunities and Barriers," in December of 2010 that brought together academic investigators, industry partners, and representatives from the National Institutes of Health and the Food and Drug Administration. Important issues in the design of clinical trials for interventions in AKI in patients with sepsis or AKI in the setting of critical illness after surgery or trauma were discussed. The sepsis working group discussed use of severity of illness scores and focus on patients with specific etiologies to enhance homogeneity of trial participants. The group also discussed endpoints congruent with those endpoints used in critical care studies. The second workgroup emphasized difficulties in obtaining consent before admission and collaboration among interdisciplinary healthcare groups. Despite the difficult trial design issues, these clinical situations represent a clinical opportunity because of the high event rates, severity of AKI, and poor outcomes. The groups considered trial design issues and discussed advantages and disadvantages of several short- and long-term primary endpoints in these patients.

  View details for DOI 10.2215/CJN.12821211

  View details for Web of Science ID 000303632700024

  View details for PubMedID 22442184

• Challenges to enrollment and randomization of the frequent hemodialysis network (FHN) daily trial JOURNAL OF NEPHROLOGY Sergeyeva, O., Gorodetskaya, I., Ramos, R., Schiller, B. M., Larive, B., Raimann, J. G., Ting, G. O., Eggers, P. W., Chertow, G. M., Levin, N. W. 2012; 25 (3): 302-309

  Abstract

  The US National Institutes of Health (NIH) and Centers for Medicare and Medicaid Services (CMS) sponsored a randomized clinical trial comparing six versus three times per week in-center hemodialysis (the Frequent Hemodialysis Network [FHN] Daily Trial), to test the effects of frequent hemodialysis on an array of intermediate outcomes. Herein we report challenges to enrollment and randomization into the trial.Screening and enrollment was tracked at all participating dialysis clinics and specific reasons for dropout after baseline assessment were recorded for all enrolled subjects. Reasons for consent refusal were recorded in a subset of (10 out of 65) sites.The trial screened 6276 hemodialysis patients on three times weekly hemodialysis in 65 hemodialysis clinics, 3481 (55%) were considered eligible for enrollment, and 3124 (90%) were approached for consent; 378 (12%) consented and 245 were randomized (65% of those enrolled). Prospective subjects chose not to participate primarily because of the anticipated time required for three extra treatments per week and the difficulties in following the protocol.Recruitment into the FHN Daily Trial proved challenging but the goal of 250 randomized subjects was almost met.

  View details for DOI 10.5301/jn.5000160

  View details for Web of Science ID 000306096600005

  View details for PubMedID 22505248

• Design of Clinical Trials in Acute Kidney Injury: Report from an NIDDK Workshop on Trial Methodology CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Palevsky, P. M., Molitoris, B. A., Okusa, M. D., Levin, A., Waikar, S. S., Wald, R., Chertow, G. M., Murray, P. T., Parikh, C. R., Shaw, A. D., Go, A. S., Faubel, S. G., Kellum, J. A., Chinchilli, V. M., Liu, K. D., Cheung, A. K., Weisbord, S. D., Chawla, L. S., Kaufman, J. S., Devarajan, P., Toto, R. M., Hsu, C., Greene, T., Mehta, R. L., Stokes, J. B., Thompson, A. M., Thompson, B. T., Westenfelder, C. S., Tumlin, J. A., Warnock, D. G., Shah, S. V., Xie, Y., Duggan, E. G., Kimmel, P. L., Star, R. A. 2012; 7 (5): 844-850

  Abstract

  Acute kidney injury (AKI) remains a complex clinical problem associated with significant short-term morbidity and mortality and lacking effective pharmacologic interventions. Patients with AKI experience longer-term risks for progressive chronic ESRD, which diminish patients' health-related quality of life and create a larger burden on the healthcare system. Although experimental models have yielded numerous promising agents, translation into clinical practice has been unsuccessful, possibly because of issues in clinical trial design, such as delayed drug administration, masking of therapeutic benefit by adverse events, and inadequate sample size. To address issues of clinical trial design, the National Institute of Diabetes and Digestive and Kidney Diseases sponsored a workshop titled "Clinical Trials in Acute Kidney Injury: Current Opportunities and Barriers" in December 2010. Workshop participants included representatives from academia, industry, and government agencies whose areas of expertise spanned basic science, clinical nephrology, critical care medicine, biostatistics, pharmacology, and drug development. This document summarizes the discussions of collaborative workgroups that addressed issues related to patient selection, study endpoints, the role of novel biomarkers, sample size and power calculations, and adverse events and pilot/feasibility studies in prevention and treatment of AKI. Companion articles outline the discussions of workgroups for model trials related to prevention or treatment of established AKI in different clinical settings, such as in patients with sepsis.

  View details for DOI 10.2215/CJN.12791211

  View details for Web of Science ID 000303632700022

  View details for PubMedID 22442182

• Ongoing Clinical Trials in AKI CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Faubel, S., Chawla, L. S., Chertow, G. M., Goldstein, S. L., Jaber, B. L., Liu, K. D. 2012; 7 (5): 861-873

  Abstract

  AKI is an important public health issue. AKI is a common hospital complication associated with increased in-hospital and long-term mortality, extensive morbidity (including prolonged hospital length of stay), and an estimated annual cost of at least $10 billion in the United States. At present, no specific therapy has been developed to prevent AKI, hasten recovery of kidney function, or abrogate the deleterious systemic effects of AKI. However, recent progress includes establishing a consensus definition of AKI and discovery of novel biomarkers that may allow early detection of AKI. Furthermore, significant insights into the pathophysiology of AKI and its deleterious systemic effects have been gleaned from animal studies. Urgently needed are large, definitive randomized clinical trials testing interventions to prevent and/or treat AKI. This review summarizes and analyzes current ongoing clinical trials registered with clinicaltrials.gov that address prevention or management of AKI. The purpose of this review is to provide a resource for people interested in potential prophylactic and therapeutic approaches to patient care and investigators hoping to plan and execute the next round of randomized clinical trials. Finally, this review discusses research needs that are not addressed by the current clinical trials portfolio and suggests key areas for future research in AKI.

  View details for DOI 10.2215/CJN.12191111

  View details for Web of Science ID 000303632700025

  View details for PubMedID 22442183

• Effects of Six versus Three Times per Week Hemodialysis on Physical Performance, Health, and Functioning: Frequent Hemodialysis Network (FHN) Randomized Trials CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Hall, Y. N., Larive, B., Painter, P., Kaysen, G. A., Lindsay, R. M., Nissenson, A. R., Unruh, M. L., Rocco, M. V., Chertow, G. M. 2012; 7 (5): 782-794

  Abstract

  Relatively little is known about the effects of hemodialysis frequency on the disability of patients with ESRD.This study examined changes in physical performance and self-reported physical health and functioning among subjects randomized to frequent (six times per week) compared with conventional (three times per week) hemodialysis in both the Frequent Hemodialysis Network daily (n=245) and nocturnal (n=87) trials. The main outcome measures were adjusted change in scores over 12 months on the short physical performance battery (SPPB), RAND 36-item health survey physical health composite (PHC), and physical functioning subscale (PF) based on the intention to treat principle.Overall scores for SPPB, PHC, and PF were poor relative to population norms and in line with other studies in ESRD. In the Daily Trial, subjects randomized to frequent compared with conventional in-center hemodialysis experienced no significant change in SPPB (adjusted mean change of -0.20±0.19 versus -0.41±0.21, P=0.45) but experienced significant improvement in PHC (3.4±0.8 versus 0.4±0.8, P=0.009) and a relatively large change in PF that did not reach statistical significance. In the Nocturnal Trial, there were no significant differences among subjects randomized to frequent compared with conventional hemodialysis in SPPB (adjusted mean change of -0.92±0.44 versus -0.41±0.43, P=0.41), PHC (2.7±1.4 versus 2.1±1.5, P=0.75), or PF (-3.1±3.5 versus 1.1±3.6, P=0.40).Frequent in-center hemodialysis compared with conventional in-center hemodialysis improved self-reported physical health and functioning but had no significant effect on objective physical performance. There were no significant effects of frequent nocturnal hemodialysis on the same physical metrics.

  View details for DOI 10.2215/CJN.10601011

  View details for Web of Science ID 000303632700014

  View details for PubMedID 22422538

  View details for PubMedCentralID PMC3338281

• Effects of Frequent Hemodialysis on Measures of CKD Mineral and Bone Disorder JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Daugirdas, J. T., Chertow, G. M., Larive, B., Pierratos, A., Greene, T., Ayus, J. C., Kendrick, C. A., James, S. H., Miller, B. W., Schulman, G., Salusky, I. B., Kliger, A. S. 2012; 23 (4): 727-738

  Abstract

  More frequent hemodialysis sessions and longer session lengths may offer improved phosphorus control. We analyzed data from the Frequent Hemodialysis Network Daily and Nocturnal Trials to examine the effects of treatment assignment on predialysis serum phosphorus and on prescribed dose of phosphorus binder, expressed relative to calcium carbonate on a weight basis. In the Daily Trial, with prescribed session lengths of 1.5-2.75 hours six times per week, assignment to frequent hemodialysis associated with both a 0.46 mg/dl decrease (95% confidence interval [95% CI], 0.13-0.78 mg/dl) in mean serum phosphorus and a 1.35 g/d reduction (95% CI, 0.20-2.50 g/d) in equivalent phosphorus binder dose at month 12 compared with assignment to conventional hemodialysis. In the Nocturnal Trial, with prescribed session lengths of 6-8 hours six times per week, assignment to frequent hemodialysis associated with a 1.24 mg/dl decrease (95% CI, 0.68-1.79 mg/dl) in mean serum phosphorus compared with assignment to conventional hemodialysis. Among patients assigned to the group receiving six sessions per week, 73% did not require phosphorus binders at month 12 compared with only 8% of patients assigned to sessions three times per week (P<0.001). At month 12, 42% of patients on nocturnal hemodialysis required the addition of phosphorus into the dialysate to prevent hypophosphatemia. Frequent hemodialysis did not have major effects on calcium or parathyroid hormone concentrations in either trial. In conclusion, frequent hemodialysis facilitates control of hyperphosphatemia and extended session lengths could allow more liberal diets and freedom from phosphorus binders.

  View details for DOI 10.1681/ASN.2011070688

  View details for Web of Science ID 000302333300020

  View details for PubMedID 22362907

  View details for PubMedCentralID PMC3312501

• Self-reported symptoms in patients on hemodialysis with moderate to severe secondary hyperparathyroidism receiving combined therapy with cinacalcet and low-dose vitamin D sterols HEMODIALYSIS INTERNATIONAL Chertow, G. M., Lu, Z. J., Xu, X., Knight, T. G., Goodman, W. G., Bushinsky, D. A., Block, G. A. 2012; 16 (2): 188-197

  Abstract

  Patients with secondary hyperparathyroidism experience a variety of clinical symptoms which may adversely affect physical and mental function. As part of a multicenter, open-label clinical trial, subjects completed a questionnaire that included the Medical Outcomes Study Short Form-36 and 14 kidney disease-related symptoms at multiple time points during the study. Out of the 567 subjects who received at least one dose of cinacalcet, 528 to 535 (93.8-94.4%) completed all or portions of the questionnaire at baseline. The median bioactive parathyroid hormone (PTH) was 294 pg/mL (10%, 90% range, 172-655 pg/mL). Following treatment with cinacalcet and low-dose vitamin D sterols, subjects reported significant improvement in the frequency of pain in muscles, joints and bones, stiff joints, dry skin, itchy skin, excessive thirst, and trouble with memory. At end of the efficacy assessment phase (Weeks 16 to 22), the magnitude of improvement was the greatest in joint pain, bone pain, dry skin, and excessive thirst (>5 on a 0-100 scale; P < 0.001). There were no clinically or statistically significant changes in any of the Short Form-36 subscales or in the physical or mental health composite scores. Among patients on hemodialysis with moderate to severe secondary hyperparathyroidism, treatment with cinacalcet and low-dose vitamin D sterols results in significant improvement in pain in the muscles, joints and bones, joint stiffness, dry and itchy skin, excessive thirst, and trouble with memory.

  View details for DOI 10.1111/j.1542-4758.2011.00642.x

  View details for PubMedID 22118402

• Trends in Acute Nonvariceal Upper Gastrointestinal Bleeding in Dialysis Patients JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Yang, J., Lee, T., Montez-Rath, M. E., Paik, J., Chertow, G. M., Desai, M., Winkelmayer, W. C. 2012; 23 (3): 495-506

  Abstract

  Impaired kidney function is a risk factor for upper gastrointestinal (GI) bleeding, an event associated with poor outcomes. The burden of upper GI bleeding and its effect on patients with ESRD are not well described. Using data from the US Renal Data System, we quantified the rates of occurrence of and associated 30-day mortality from acute, nonvariceal upper GI bleeding in patients undergoing dialysis; we used medical claims and previously validated algorithms where available. Overall, 948,345 patients contributed 2,296,323 patient-years for study. The occurrence rates for upper GI bleeding were 57 and 328 episodes per 1000 person-years according to stringent and lenient definitions of acute, nonvariceal upper GI bleeding, respectively. Unadjusted occurrence rates remained flat (stringent) or increased (lenient) from 1997 to 2008; after adjustment for sociodemographic characteristics and comorbid conditions, however, we found a significant decline for both definitions (linear approximation, 2.7% and 1.5% per year, respectively; P<0.001). In more recent years, patients had higher hematocrit levels before upper GI bleeding episodes and were more likely to receive blood transfusions during an episode. Overall 30-day mortality was 11.8%, which declined significantly over time (relative declines of 2.3% or 2.8% per year for the stringent and lenient definitions, respectively). In summary, despite declining trends worldwide, crude rates of acute, nonvariceal upper GI bleeding among patients undergoing dialysis have not decreased in the past 10 years. Although 30-day mortality related to upper GI bleeding declined, perhaps reflecting improvements in medical care, the burden on the ESRD population remains substantial.

  View details for DOI 10.1681/ASN.2011070658

  View details for PubMedID 22266666

• Determinants of Left Ventricular Mass in Patients on Hemodialysis Frequent Hemodialysis Network (FHN) Trials CIRCULATION-CARDIOVASCULAR IMAGING Chan, C. T., Greene, T., Chertow, G. M., Kliger, A. S., Stokes, J. B., Beck, G. J., Daugirdas, J. T., Kotanko, P., Larive, B., Levin, N. W., Mehta, R. L., Rocco, M., Sanz, J., Schiller, B. M., Yang, P. C., Rajagopalan, S. 2012; 5 (2): 251-261

  Abstract

  An increase in left ventricular mass (LVM) is associated with mortality and cardiovascular morbidity in patients with end-stage renal disease.The Frequent Hemodialysis Network (FHN) Daily Trial randomized 245 patients to 12 months of 6 times per week daily in-center hemodialysis or conventional hemodialysis; the FHN Nocturnal Trial randomized 87 patients to 12 months of 6 times per week nocturnal hemodialysis or conventional hemodialysis. The main cardiac secondary outcome was change in LVM. In each trial, we examined whether several predefined baseline demographic or clinical factors as well as change in volume removal, blood pressure, or solute clearance influenced the effect of frequent hemodialysis on LVM. In the Daily Trial, frequent hemodialysis resulted in a significant reduction in LVM (13.1 g; 95% CI, 5.0-21.3 g; P=0.002), LVM index (6.9 g/m(2); 95% CI, 2.4-11.3 g/m(2); P=0.003), and percent change in geometric mean of LVM (7.0%; 95% CI, 1.0%-12.6; P=0.02). Similar trends were noted in the Nocturnal Trial but did not reach statistical significance. In the Daily Trial, a more pronounced effect of frequent hemodialysis on LVM was evident among patients with left ventricular hypertrophy at baseline. Changes in LVM were associated with changes in blood pressure (conventional hemodialysis: R=0.28, P=0.01, daily hemodialysis: R=0.54, P<0.001) and were not significantly associated with changes in other parameters.Frequent in-center hemodialysis reduces LVM. The benefit of frequent hemodialysis on LVM may be mediated by salutary effects on blood pressure. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00264758.

  View details for DOI 10.1161/CIRCIMAGING.111.969923

  View details for Web of Science ID 000302122700014

  View details for PubMedID 22360996

  View details for PubMedCentralID PMC3328963

• Prospective Safety Study of Bardoxolone Methyl in Patients with Type 2 Diabetes Mellitus, End-Stage Renal Disease and Peritoneal Dialysis International Vicenza Course on Peritoneal Dialysis Warnock, D. G., Hebbar, S., Bargman, J., Burkart, J., Davies, S., Finkelstein, F. O., Mehrotra, R., Ronco, C., Teitelbaum, I., Urakpo, K., Chertow, G. M. KARGER. 2012: 157–163

  Abstract

  Patients on peritoneal dialysis experience inflammation associated with advanced chronic kidney disease and the therapy itself. An important consequence of the inflammation may be acceleration of the rate of decline in residual renal function. The decline in residual renal function has been associated with an increased mortality for patients in this population. Bardoxolone methyl is a synthetic triterpenoid. To date, the effects of bardoxolone methyl on kidney function in humans have been studied in patients with type 2 diabetes mellitus. A large-scale event-driven study of bardoxolone methyl in patients with type 2 diabetes mellitus with stage 4 chronic kidney disease is underway. The safety of bardoxolone methyl has not been evaluated in patients with more advanced (stage 5) chronic kidney disease or patients on dialysis. This report describes a proposed double blind, prospective evaluation of bardoxolone methyl in patients with type 2 diabetes mellitus receiving peritoneal dialysis. In addition to assessing the safety of bardoxolone methyl in this population, the study will evaluate the effect of bardoxolone methyl on residual renal function over 6 months as compared to placebo.

  View details for Web of Science ID 000310253200026

  View details for PubMedID 22652731

• Acute Kidney Injury and Mortality in Hospitalized Patients AMERICAN JOURNAL OF NEPHROLOGY Wang, H. E., Muntner, P., Chertow, G. M., Warnock, D. G. 2012; 35 (4): 349-355

  Abstract

  The objective of this study was to determine the incidence of acute kidney injury (AKI) and its relation with mortality among hospitalized patients.Analysis of hospital discharge and laboratory data from an urban academic medical center over a 1-year period. We included hospitalized adult patients receiving two or more serum creatinine (sCr) measurements. We excluded prisoners, psychiatry, labor and delivery, and transferred patients, 'bedded outpatients' as well as individuals with a history of kidney transplant or chronic dialysis. We defined AKI as (a) an increase in sCr of ≥0.3 mg/dl; (b) an increase in sCr to ≥150% of baseline, or (c) the initiation of dialysis in a patient with no known history of prior dialysis. We identified factors associated with AKI as well as the relationships between AKI and in-hospital mortality. RESUlTS: Among the 19,249 hospitalizations included in the analysis, the incidence of AKI was 22.7%. Older persons, Blacks, and patients with reduced baseline kidney function were more likely to develop AKI (all p < 0.001). Among AKI cases, the most common primary admitting diagnosis groups were circulatory diseases (25.4%) and infection (16.4%). After adjustment for age, sex, race, admitting sCr concentration, and the severity of illness index, AKI was independently associated with in-hospital mortality (adjusted odds ratio 4.43, 95% confidence interval 3.68-5.35).AKI occurred in over 1 of 5 hospitalizations and was associated with a more than fourfold increased likelihood of death. These observations highlight the importance of AKI recognition as well as the association of AKI with mortality in hospitalized patients.

  View details for DOI 10.1159/000337487

  View details for Web of Science ID 000302896900007

  View details for PubMedID 22473149

  View details for PubMedCentralID PMC3362180

• Validity of Surrogate Measures for Functional Nephron Mass TRANSPLANTATION Tan, J. C., Paik, J., Chertow, G. M., Grumet, F. C., Busque, S., Lapasia, J., Desai, M. 2011; 92 (12): 1335-1341

  Abstract

  Transplanted nephron mass is an important determinant of long-term allograft survival, but accurate assessment before organ retrieval is challenging. Newer radiologic imaging techniques allow for better determination of total kidney and cortical volumes.Using volume measurements reconstructed from magnetic resonance or computed tomography imaging from living donor candidates, we characterized total kidney (n=312) and cortical volumes (n=236) according to sex, age, weight, height, body mass index (BMI), and body surface area (BSA).The mean cortical volume was 204 mL (range 105-355 mL) with no significant differences between left and right cortical volumes. The degree to which existing anthropomorphic surrogates predict nephron mass was quantified, and a diligent attempt was made to derive a better surrogate model for nephron mass. Cortical volumes were strongly associated with sex and BSA, but not with weight, height, or BMI. Four prediction models for cortical volume constructed using combinations of age, sex, race, weight, and height were compared with models including either BSA or BMI.Among existing surrogate measures, BSA was superior to BMI in predicting renal cortical volume. We were able to construct a statistically superior proxy for cortical volume, but whether relevant improvements in predictive accuracy could be gained needs further evaluation in a larger population.

  View details for DOI 10.1097/TP.0b013e31823705ef

  View details for PubMedID 22011765

• Vitamin D deficiency, self-reported physical activity and health-related quality of life: the Comprehensive Dialysis Study NEPHROLOGY DIALYSIS TRANSPLANTATION Anand, S., Kaysen, G. A., Chertow, G. M., Johansen, K. L., Grimes, B., Dalrymple, L. S., Tamura, M. K. 2011; 26 (11): 3683-3688

  Abstract

  As research has identified a wide array of biological functions of vitamin D, the consequences of vitamin D deficiency in persons with chronic kidney disease has attracted increased attention. The objective of this study was to determine the extent of 25-hydroxyvitamin D (25-OH vitamin D) deficiency and its associations with self-reported physical activity and health-related quality of life (HRQoL) among participants of the Comprehensive Dialysis Study (CDS).The nutrition substudy of the CDS enrolled patients new to dialysis from 68 dialysis units throughout the USA. Baseline 25-OH vitamin D concentration was measured using the Direct Enzyme Immunoassay (Immunodiagnostic Systems Inc.). Physical activity was measured with the Human Activity Profile (HAP); the Medical Outcomes Study Short Form-12 (SF-12) was employed to measure HRQoL.Mean age of the participants (n = 192) was 62 years. There were 124 participants (65%) with 25-OH vitamin D concentrations < 15 ng/mL, indicating deficiency, and 64 (33%) with 25-OH vitamin D ≥ 15 to <30 ng/mL, indicating insufficiency. After adjusting for age, sex, race/ethnicity, diabetes, season and center, lower 25-OH vitamin D concentrations were independently associated with lower scores on the HAP and on the Mental Component Summary of the SF-12 (P < 0.05 for both), but not with the Physical Component Summary of the SF-12.In a well-characterized cohort of incident dialysis patients, lower 25-OH vitamin D concentrations were associated with lower self-reported physical activity and poorer self-reported mental health.

  View details for DOI 10.1093/ndt/gfr098

  View details for PubMedID 21430182

• Association of Self-reported Physical Activity With Laboratory Markers of Nutrition and Inflammation: The Comprehensive Dialysis Study JOURNAL OF RENAL NUTRITION Anand, S., Chertow, G. M., Johansen, K. L., Grimes, B., Tamura, M. K., Dalrymple, L. S., Kaysen, G. A. 2011; 21 (6): 429-437

  Abstract

  Patients on dialysis maintain extremely low levels of physical activity. Prior studies have demonstrated a direct correlation between nutrition and physical activity but provide conflicting data on the link between inflammation and physical activity. Using a cohort of patients new to dialysis from the Comprehensive Dialysis Study (CDS), we examined associations of self-reported physical activity with laboratory markers of nutrition and inflammation.Between June 2005 and June 2007, CDS collected data on self-reported physical activity, nutrition, and health-related quality of life from patients starting dialysis in 296 facilities located throughout the United States. Baseline serum samples were collected from participants in a nutrition sub-study of CDS.Serum albumin and prealbumin were measured as markers of nutrition, and C-reactive protein (CRP) and α-1-acid glycoprotein as markers of inflammation. Self-reported physical activity was characterized by the maximum activity score (MAS) and adjusted activity score (AAS) of the Human Activity Profile.The mean age of participants in the analytic cohort (n = 201) was 61 years. The MAS and AAS were below the 10th and first percentile, respectively, in comparison with healthy 60 year-old norms. Both activity scores were directly correlated with albumin (r(2) = 0.3, P < .0001) and prealbumin (r(2) = 0.3, P < .0001), and inversely correlated with CRP (AAS: r(2) = -0.2, P = .01; MAS: r(2) = -0.1, P = .08). In multivariate analyses adjusting for age, gender, race/ethnicity, diabetes status, and center, both activity scores were directly correlated with prealbumin and inversely correlated with CRP.Patients new to dialysis with laboratory-based evidence of malnutrition and/or inflammation are likely to report lower levels of physical activity.

  View details for DOI 10.1053/j.jrn.2010.09.007

  View details for PubMedID 21239185

• The effects of frequent nocturnal home hemodialysis: the Frequent Hemodialysis Network Nocturnal Trial KIDNEY INTERNATIONAL Rocco, M. V., Lockridge, R. S., Beck, G. J., Eggers, P. W., Gassman, J. J., Greene, T., Larive, B., Chan, C. T., Chertow, G. M., Copland, M., Hoy, C. D., Lindsay, R. M., Levin, N. W., Ornt, D. B., Pierratos, A., Pipkin, M. F., Rajagopalan, S., Stokes, J. B., Unruh, M. L., Star, R. A., Kliger, A. S. 2011; 80 (10): 1080-1091

  Abstract

  Prior small studies have shown multiple benefits of frequent nocturnal hemodialysis compared to conventional three times per week treatments. To study this further, we randomized 87 patients to three times per week conventional hemodialysis or to nocturnal hemodialysis six times per week, all with single-use high-flux dialyzers. The 45 patients in the frequent nocturnal arm had a 1.82-fold higher mean weekly stdKt/V(urea), a 1.74-fold higher average number of treatments per week, and a 2.45-fold higher average weekly treatment time than the 42 patients in the conventional arm. We did not find a significant effect of nocturnal hemodialysis for either of the two coprimary outcomes (death or left ventricular mass (measured by MRI) with a hazard ratio of 0.68, or of death or RAND Physical Health Composite with a hazard ratio of 0.91). Possible explanations for the left ventricular mass result include limited sample size and patient characteristics. Secondary outcomes included cognitive performance, self-reported depression, laboratory markers of nutrition, mineral metabolism and anemia, blood pressure and rates of hospitalization, and vascular access interventions. Patients in the nocturnal arm had improved control of hyperphosphatemia and hypertension, but no significant benefit among the other main secondary outcomes. There was a trend for increased vascular access events in the nocturnal arm. Thus, we were unable to demonstrate a definitive benefit of more frequent nocturnal hemodialysis for either coprimary outcome.

  View details for DOI 10.1038/ki.2011.213

  View details for Web of Science ID 000296609800012

  View details for PubMedCentralID PMC3569086

• Chronic Kidney Disease and Cardiovascular Therapeutics Time to Close the Evidence Gaps JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Chang, T. I., Chertow, G. M. 2011; 58 (11): 1162-1164

  View details for DOI 10.1016/j.jacc.2011.06.010

  View details for Web of Science ID 000294449200013

  View details for PubMedID 21884955

• Living donor evaluation and exclusion: the Stanford experience CLINICAL TRANSPLANTATION Lapasia, J. B., Kong, S., Busque, S., Scandling, J. D., Chertow, G. M., Tan, J. C. 2011; 25 (5): 697-704

  Abstract

  The proportion of prospective living donors disqualified for medical reasons is unknown. The objective of this study is to delineate and quantify specific reasons for exclusion of prospective living donors from kidney donation.All adult prospective kidney donors who contacted our transplant program between October 1, 2007 and April 1, 2009 were included in our analysis (n = 484). Data were collected by review of an electronic transplant database.Of the 484 prospective donors, 39 (8%) successfully donated, 229 (47%) were excluded, 104 (22%) were actively undergoing evaluation, and 112 (23%) were withdrawn before evaluation was complete. Criteria for exclusion were medical (n = 150), psychosocial (n = 22), or histocompatibility (n = 57) reasons. Of the 150 prospective donors excluded for medical reasons, 79% were excluded because of obesity, hypertension, nephrolithiasis, and/or abnormal glucose tolerance. One hundred and forty-seven (61%) intended recipients had only one prospective living donor, of whom 63 (42%) were excluded.A significant proportion of prospective living kidney donors were excluded for medical reasons such as obesity (body mass index >30), hypertension, nephrolithiasis, and abnormal glucose tolerance. Longer-term studies are needed to characterize the risks to medically complex kidney donors and the potential risks and benefits afforded to recipients.

  View details for DOI 10.1111/j.1399-0012.2010.01336.x

  View details for PubMedID 21044160

• Model to Predict Mortality in Critically Ill Adults with Acute Kidney Injury CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Demirjian, S., Chertow, G. M., Zhang, J. H., O'Connor, T. Z., Vitale, J., Paganini, E. P., Palevsky, P. M. 2011; 6 (9): 2114-2120

  Abstract

  Acute kidney injury (AKI) requiring dialysis is associated with high mortality. Most prognostic tools used to describe case complexity and to project patient outcome lack predictive accuracy when applied in patients with AKI. In this study, we developed an AKI-specific predictive model for 60-day mortality and compared the model to the performance of two generic (Sequential Organ Failure Assessment [SOFA] and Acute Physiology and Chronic Health Evaluation II [APACHE II]) scores, and a disease specific (Cleveland Clinic [CCF]) score.Data from 1122 subjects enrolled in the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network study; a multicenter randomized trial of intensive versus less intensive renal support in critically ill patients with AKI conducted between November 2003 and July 2007 at 27 VA- and university-affiliated centers.The 60-day mortality was 53%. Twenty-one independent predictors of 60-day mortality were identified. The logistic regression model exhibited good discrimination, with an area under the receiver operating characteristic (ROC) curve of 0.85 (0.83 to 0.88), and a derived integer risk score yielded a value of 0.80 (0.77 to 0.83). Existing scoring systems, including APACHE II, SOFA, and CCF, when applied to our cohort, showed relatively poor discrimination, reflected by areas under the ROC curve of 0.68 (0.64 to 0.71), 0.69 (0.66 to 0.73), and 0.65 (0.62 to 0.69), respectively.Our new risk model outperformed existing generic and disease-specific scoring systems in predicting 60-day mortality in critically ill patients with AKI. The current model requires external validation before it can be applied to other patient populations.

  View details for DOI 10.2215/CJN.02900311

  View details for Web of Science ID 000294654200005

  View details for PubMedID 21896828

  View details for PubMedCentralID PMC3359007

• Predialysis Nephrology Care of Older Patients Approaching End-stage Renal Disease ARCHIVES OF INTERNAL MEDICINE Winkelmayer, W. C., Liu, J., Chertow, G. M., Tamura, M. K. 2011; 171 (15): 1371-1378

  Abstract

  Little is known about trends in the timing of first nephrology consultation and associated outcomes among older patients initiating dialysis.Data from patients aged 67 years or older who initiated dialysis in the United States between January 1, 1996, and December 31, 2006, were stratified by timing of the earliest identifiable nephrology visit. Trends of earlier nephrology consultation were formally examined in light of concurrently changing case mix and juxtaposed with trends in 1-year mortality rates after initiation of dialysis.Among 323,977 older patients initiating dialysis, the proportion of patients receiving nephrology care less than 3 months before initiation of dialysis decreased from 49.6% (in 1996) to 34.7% (in 2006). Patients initiated dialysis with increasingly preserved kidney function, from a mean estimated glomerular filtration rate of 8 mL/min/1.73 m(2) in 1996 to 12 mL/min/1.73 m(2) in 2006. Patients were less anemic in later years, which was partly attributable to increased use of erythropoiesis-stimulating agents, and fewer used peritoneal dialysis as the initial modality. During the same period, crude 1-year mortality rates remained unchanged (annual change in mortality rate, +0.2%; 95% confidence interval, 0% to +0.4%). Adjustment for changes in demographic and comorbidity patterns yielded estimated annual reductions in 1-year mortality rates of 0.9% (95% confidence interval, 0.7% to 1.1%), which were explained only partly by concurrent trends toward earlier nephrology consultation (annual mortality reduction after accounting for timing of nephrology care was attenuated to 0.4% [0.2% to 0.6%]).Despite significant trends toward earlier use of nephrology consultation among older patients approaching maintenance dialysis, we observed no material improvement in 1-year survival rates after dialysis initiation during the same time period.

  View details for Web of Science ID 000293642800013

  View details for PubMedID 21824952

  View details for PubMedCentralID PMC4123329

• Assessment and management of vascular disease risk in patients with chronic kidney disease JOURNAL OF CLINICAL LIPIDOLOGY Brown, W. V., Bakris, G., Lerma, E., Chertow, G. 2011; 5 (4): 251-260

  View details for DOI 10.1016/j.jacl.2011.05.001

  View details for Web of Science ID 000293939300002

  View details for PubMedID 21784369

• Angiotensin Converting Enzyme Inhibitors in Hemodialysis Chang, T. I., Shilane, D., Brunelli, S. M., Cheung, A. K., Chertow, G. M., Winkelmayer, W. C. WILEY PERIODICALS, INC. 2011: S15–S15

  View details for Web of Science ID 000294946600034

• Intradialytic Hypotension and Vascular Access Thrombosis JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Chang, T. I., Paik, J., Greene, T., Desai, M., Bech, F., Cheung, A. K., Chertow, G. M. 2011; 22 (8): 1526-1533

  Abstract

  Identifying potential modifiable risk factors to reduce the incidence of vascular access thrombosis in hemodialysis could reduce considerable morbidity and health care costs. We analyzed data from a subset of 1426 HEMO study subjects to determine whether more frequent intradialytic hypotension and/or lower predialysis systolic BP were associated with higher rates of vascular access thrombosis. Our primary outcome measure was episodes of vascular access thrombosis occurring within a given 6-month period during HEMO study follow-up. There were 2005 total episodes of vascular access thrombosis during a median 3.1 years of follow-up. The relative rate of thrombosis of native arteriovenous fistulas for the highest quartile of intradialytic hypotension was approximately twice that of the lowest quartile, independent of predialysis systolic BP and other covariates. There was no significant association of intradialytic hypotension with prosthetic arteriovenous graft thrombosis after multivariable adjustment. Higher predialysis systolic BP was associated with a lower rate of fistula and graft thrombosis, independent of intradialytic hypotension and other covariates. In conclusion, more frequent episodes of intradialytic hypotension and lower predialysis systolic BP associate with increased rates of vascular access thrombosis. These results underscore the importance of including vascular access patency in future studies of BP management in hemodialysis.

  View details for DOI 10.1681/ASN.2010101119

  View details for PubMedID 21803971

• Angiotensin-converting enzyme inhibitors and cardiovascular outcomes in patients on maintenance hemodialysis AMERICAN HEART JOURNAL Chang, T. I., Shilane, D., Brunelli, S. M., Cheung, A. K., Chertow, G. M., Winkelmayer, W. C. 2011; 162 (2): 324-330

  Abstract

  Persons with end-stage renal disease (ESRD) on hemodialysis carry an exceptionally high burden of cardiovascular disease. Angiotensin-converting enzyme inhibitors (ACEIs) are recommended for patients on dialysis, but there are few data regarding their effectiveness in ESRD.We conducted a secondary analysis of results of the HEMO study, a randomized trial of dialysis dose and membrane flux in patients on maintenance hemodialysis. We focused on the nonrandomized exposure of ACEI use, using proportional hazards regression and a propensity score analysis. The primary outcome was all-cause mortality. Secondary outcomes examined in the present analysis were cardiovascular hospitalization, heart failure hospitalization, and the composite outcomes of death or cardiovascular hospitalization and death or heart failure hospitalization.In multivariable-adjusted analyses, there were no significant associations among ACEI use and mortality (hazard ratio 0.97, 95% CI 0.82-1.14), cardiovascular hospitalization, and either composite outcome. Angiotensin-converting enzyme inhibitor use was associated with a higher risk of heart failure hospitalization (hazard ratio 1.41, 95% CI 1.11-1.80). In the propensity score-matched cohort, ACEI use was not significantly associated with any outcomes, including heart failure hospitalization.In a well-characterized cohort of patients on maintenance hemodialysis, ACEI use was not significantly associated with mortality or cardiovascular morbidity. The higher risk of heart failure hospitalization associated with ACEI use may not only reflect residual confounding but also highlights gaps in evidence when applying treatments proven effective in the general population to patients with ESRD. Our results underscore the need for definitive trials in ESRD to inform the treatment of cardiovascular disease.

  View details for DOI 10.1016/j.ahj.2011.05.004

  View details for PubMedID 21835294

• Burden on caregivers as perceived by hemodialysis patients in the Frequent Hemodialysis Network (FHN) trials NEPHROLOGY DIALYSIS TRANSPLANTATION Suri, R. S., Larive, B., Garg, A. X., Hall, Y. N., Pierratos, A., Chertow, G. M., Gorodetskeya, I., Kliger, A. S. 2011; 26 (7): 2316-2322

  Abstract

  Patients with end-stage renal disease often rely on unpaid caregivers to assist them with their daily living and medical needs. We characterized the degree to which patients enrolled in the Frequent Hemodialysis Network (FHN) trials perceived burden on their unpaid caregivers.Participants completed the Cousineau Perceived Burden Scale, a 10-question scale previously developed in hemodialysis (HD) patients. Associations between baseline burden score and prespecified variables were evaluated using multivariable linear regression.Of 412 participants, 236 (57%) reported having unpaid caregivers. Compared to those without unpaid caregivers, these participants had greater comorbidity (Charlson mean 1.8 ± 1.8 versus 1.2 ± 1.7, P < 0.001), lower Short Form-36 (SF-36) Physical Health Composite (PHC) scores (median 33 versus 41, P < 0.001, higher Beck Depression scores (mean 16 ± 11 versus 12 ± 9, P < 0.001), and worse physical function. Median Cousineau score was 35 (interquartile range 20-53) (theoretical range 0-100). Over 50% felt their caregivers were overextended, yet 60% were confident that their caregivers could handle the demands of caring for them. Higher perceived burden was not associated with ability to be randomized. In adjusted analyses, Cousineau score was inversely associated with SF-36 PHC and Mental Health Composite scores and directly associated with Beck Depression score (each P < 0.001).Most HD patients in the FHN trials perceived substantial burden on their unpaid caregivers, and self-perceived burden was associated with worse depression and quality of life. Evaluation of the effects of frequent HD on perceived burden borne by caregivers in the FHN trials will help to establish the net benefits/determents of these intensive dialytic strategies.

  View details for DOI 10.1093/ndt/gfr007

  View details for Web of Science ID 000292329500040

  View details for PubMedID 21421590

• Risk of Cardiovascular Events after Infection-Related Hospitalizations in Older Patients on Dialysis CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Dalrymple, L. S., Mohammed, S. M., Mu, Y., Johansen, K. L., Chertow, G. M., Grimes, B., Kaysen, G. A., Nguyen, D. V. 2011; 6 (7): 1708-1713

  Abstract

  Infection and cardiovascular disease are leading causes of hospitalization and death in patients on dialysis. The objective of this study was to determine whether an infection-related hospitalization increased the short-term risk of a cardiovascular event in older patients on dialysis.With use of the United States Renal Data System, patients aged 65 to 100 years who started dialysis between January 1, 2000, and December 31, 2002, were examined. All hospitalizations were examined from study entry until time of transplant, death, or December 31, 2004. All discharge diagnoses were examined to determine if an infection occurred during hospitalization. Only principal discharge diagnoses were examined to ascertain cardiovascular events of interest. We used the self-controlled case-series method to estimate the relative incidence of a cardiovascular event within 90 days after an infection-related hospitalization as compared with other times not within 90 days of such a hospitalization.A total of 16,874 patients had at least one cardiovascular event and were included in the self-controlled case-series analysis. The risk of a cardiovascular event was increased by 25% in the first 30 days after an infection and was overall increased 18% in the 90 days after an infection-related hospitalization relative to control periods.The first 90 days, and in particular the first 30 days, after an infection-related hospitalization is a high-risk period for cardiovascular events and may be an important timeframe for cardiovascular risk reduction, monitoring, and intervention in older patients on dialysis.

  View details for DOI 10.2215/CJN.10151110

  View details for Web of Science ID 000292618300027

  View details for PubMedID 21566109

  View details for PubMedCentralID PMC3133476

• Incidence, Correlates, and Consequences of Acute Kidney Injury in Patients With Pulmonary Arterial Hypertension Hospitalized With Acute Right-Side Heart Failure JOURNAL OF CARDIAC FAILURE Haddad, F., Fuh, E., Peterson, T., Skhiri, M., Kudelko, K. T., Perez, V. D., Winkelmayer, W. C., Doyle, R. L., Chertow, G. M., Zamanian, R. T. 2011; 17 (7): 533-539

  Abstract

  Though much is known about the prognostic influence of acute kidney injury (AKI) in left-side heart failure, much less is known about AKI in patients with pulmonary arterial hypertension (PAH).We identified consecutive patients with PAH who were hospitalized at Stanford Hospital for acute right-side heart failure. AKI was diagnosed according to the criteria of the Acute Kidney Injury Network. From June 1999 to June 2009, 105 patients with PAH were hospitalized for acute right-side heart failure (184 hospitalizations). AKI occurred in 43 hospitalizations (23%) in 34 patients (32%). The odds of developing AKI were higher among patients with chronic kidney disease (odds ratio [OR] 3.9, 95% confidence interval [CI] 1.8-8.5), high central venous pressure (OR 1.8, 95% CI 1.1-2.4, per 5 mm Hg), and tachycardia on admission (OR 4.3, 95% CI 2.1-8.8). AKI was strongly associated with 30-day mortality after acute right-side heart failure hospitalization (OR 5.3, 95% CI 2.2-13.2).AKI is relatively common in patients with PAH and associated with a short-term risk of death.

  View details for DOI 10.1016/j.cardfail.2011.03.003

  View details for PubMedID 21703524

• Update in Nephrology: Evidence Published in 2010 ANNALS OF INTERNAL MEDICINE Arora, N., Chertow, G. M. 2011; 154 (12): 824-U79

  View details for PubMedID 21464341

• Modeled Urea Distribution Volume and Mortality in the HEMO Study CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Daugirdas, J. T., Greene, T., Depner, T. A., Levin, N. W., Chertow, G. M. 2011; 6 (5): 1129-1138

  Abstract

  In the Hemodialysis (HEMO) Study, observed small decreases in achieved equilibrated Kt/V(urea) were noncausally associated with markedly increased mortality. Here we examine the association of mortality with modeled volume (V(m)), the denominator of equilibrated Kt/V(urea).Parameters derived from modeled urea kinetics (including V(m)) and blood pressure (BP) were obtained monthly in 1846 patients. Case mix-adjusted time-dependent Cox regressions were used to relate the relative mortality hazard at each time point to V(m) and to the change in V(m) over the preceding 6 months. Mixed effects models were used to relate V(m) to changes in intradialytic systolic BP and to other factors at each follow-up visit.Mortality was associated with V(m) and change in V(m) over the preceding 6 months. The association between change in V(m) and mortality was independent of vascular access complications. In contrast, mortality was inversely associated with V calculated from anthropometric measurements (V(ant)). In case mix-adjusted analysis using V(m) as a time-dependent covariate, the association of mortality with V(m) strengthened after statistical adjustment for V(ant). After adjustment for V(ant), higher V(m) was associated with slightly smaller reductions in intradialytic systolic BP and with risk factors for mortality including recent hospitalization and reductions in serum albumin concentration and body weight.An increase in V(m) is a marker for illness and mortality risk in hemodialysis patients.

  View details for DOI 10.2215/CJN.06340710

  View details for Web of Science ID 000290372600025

  View details for PubMedID 21511841

  View details for PubMedCentralID PMC3087780

• Dialysate sodium and sodium gradient in maintenance hemodialysis: a neglected sodium restriction approach? Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association Munoz Mendoza, J., Sun, S., Chertow, G. M., Moran, J., Doss, S., Schiller, B. 2011; 26 (4): 1281-1287

  Abstract

  A higher sodium gradient (dialysate sodium minus pre-dialysis plasma sodium) during hemodialysis (HD) has been associated with sodium loading; however, its role is not well studied. We hypothesized that a sodium dialysate prescription resulting in a higher sodium gradient is associated with increases in interdialytic weight gain (IDWG), blood pressure (BP) and thirst.We conducted a cross-sectional study on 1084 clinically stable patients on HD. A descriptive analysis of the sodium prescription was performed and clinical associations with sodium gradient were analyzed.The dialysate sodium prescription varied widely across dialysis facilities, ranging from 136 to 149 mEq/L, with a median of 140 mEq/L. The mean pre-HD plasma sodium was 136.7 ± 2.9 mEq/L, resulting in the majority of subjects (n = 904, 83%) being dialyzed against a positive sodium gradient, while the mean sodium gradient was 4.6 ± 4.4 mEq/L. After HD, the plasma sodium increased in nearly all patients (91%), reaching a mean post-HD plasma sodium of 141.3 ± 2.5 mEq/L. We found a direct correlation between IDWG and sodium gradient (r = 0.21, P < 0.0001). After adjustment for confounders and clustering by facilities, the sodium gradient was independently associated with IDWG (70 g/mEq/L, P < 0.0001). There were no significant associations among sodium gradient and BP, whether measured as pre-HD systolic (r = -0.02), diastolic (r = -0.06) or mean arterial pressure (r = -0.04). Post-HD thirst was directly correlated with sodium gradient (r = 0.11, P = 0.02).Sodium gradient is associated with statistically significant and clinically meaningful differences in IDWG in stable patients on HD.

  View details for DOI 10.1093/ndt/gfq807

  View details for PubMedID 21303968

  View details for PubMedCentralID PMC3108351

• Dialysate sodium and sodium gradient in maintenance hemodialysis: a neglected sodium restriction approach? NEPHROLOGY DIALYSIS TRANSPLANTATION Mendoza, J. M., Sun, S., Chertow, G. M., Moran, J., Doss, S., Schiller, B. 2011; 26 (4): 1281-1287

  Abstract

  A higher sodium gradient (dialysate sodium minus pre-dialysis plasma sodium) during hemodialysis (HD) has been associated with sodium loading; however, its role is not well studied. We hypothesized that a sodium dialysate prescription resulting in a higher sodium gradient is associated with increases in interdialytic weight gain (IDWG), blood pressure (BP) and thirst.We conducted a cross-sectional study on 1084 clinically stable patients on HD. A descriptive analysis of the sodium prescription was performed and clinical associations with sodium gradient were analyzed.The dialysate sodium prescription varied widely across dialysis facilities, ranging from 136 to 149 mEq/L, with a median of 140 mEq/L. The mean pre-HD plasma sodium was 136.7 ± 2.9 mEq/L, resulting in the majority of subjects (n = 904, 83%) being dialyzed against a positive sodium gradient, while the mean sodium gradient was 4.6 ± 4.4 mEq/L. After HD, the plasma sodium increased in nearly all patients (91%), reaching a mean post-HD plasma sodium of 141.3 ± 2.5 mEq/L. We found a direct correlation between IDWG and sodium gradient (r = 0.21, P < 0.0001). After adjustment for confounders and clustering by facilities, the sodium gradient was independently associated with IDWG (70 g/mEq/L, P < 0.0001). There were no significant associations among sodium gradient and BP, whether measured as pre-HD systolic (r = -0.02), diastolic (r = -0.06) or mean arterial pressure (r = -0.04). Post-HD thirst was directly correlated with sodium gradient (r = 0.11, P = 0.02).Sodium gradient is associated with statistically significant and clinically meaningful differences in IDWG in stable patients on HD.

  View details for DOI 10.1093/ndt/gfq807

  View details for Web of Science ID 000289309400026

  View details for PubMedCentralID PMC3108351

• The ADVANCE study: a randomized study to evaluate the effects of cinacalcet plus low-dose vitamin D on vascular calcification in patients on hemodialysis NEPHROLOGY DIALYSIS TRANSPLANTATION Raggi, P., Chertow, G. M., Torres, P. U., Csiky, B., Naso, A., Nossuli, K., Moustafa, M., Goodman, W. G., Lopez, N., Downey, G., Dehmel, B., Floege, J. 2011; 26 (4): 1327-1339

  Abstract

  This prospective, randomized, controlled trial compared the progression of vascular and cardiac valve calcification in 360 prevalent adult hemodialysis patients with secondary hyperparathyroidism treated with either cinacalcet plus low-dose vitamin D sterols or flexible doses of vitamin D sterols alone.Eligible subjects were on hemodialysis for ≥ 3 months with parathyroid hormone (PTH) > 300 pg/mL or PTH 150-300 pg/mL with calcium-phosphorus product > 50 mg(2)/dL(2) while receiving vitamin D. All subjects received calcium-based phosphate binders. Coronary artery calcification (CAC) and aorta and cardiac valve calcium scores were determined both by Agatston and volume scoring using multi-detector computed tomography. Subjects with Agatston CAC scores ≥ 30 were randomized to cinacalcet (30- 180 mg/day) plus low-dose calcitriol or vitamin D analog (≤ 2 μg paricalcitol equivalent/dialysis), or flexible vitamin D therapy. The primary end point was percentage change in Agatston CAC score from baseline to Week 52.Median (P10, P90) Agatston CAC scores increased 24% (-22%, 119%) in the cinacalcet group and 31% (-9%, 179%) in the flexible vitamin D group (P = 0.073). Corresponding changes in volume CAC scores were 22% (-12%, 105%) and 30% (-6%, 133%; P = 0.009). Increases in calcification scores were consistently less in the aorta, aortic valve and mitral valve among subjects treated with cinacalcet plus low-dose vitamin D sterols, and the differences between groups were significant at the aortic valve.In hemodialysis patients with moderate to severe secondary hyperparathyroidism, cinacalcet plus low-dose vitamin D sterols may attenuate vascular and cardiac valve calcification.

  View details for DOI 10.1093/ndt/gfq725

  View details for Web of Science ID 000289309400032

  View details for PubMedID 21148030

• Racial Ethnic Differences in Rates and Determinants of Deceased Donor Kidney Transplantation JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Hall, Y. N., Choi, A. I., Xu, P., O'Hare, A. M., Chertow, G. M. 2011; 22 (4): 743-751

  Abstract

  Contemporary studies have not comprehensively compared waiting times and determinants of deceased donor kidney transplantation across all major racial ethnic groups in the Unites States. Here, we compared relative rates and determinants of waitlisting and deceased donor kidney transplantation among 503,090 nonelderly adults of different racial ethnic groups who initiated hemodialysis between1995 and 2006 with follow-up through 2008. Annual rates of deceased donor transplantation from the time of dialysis initiation were lowest in American Indians/Alaska Natives (2.4%) and blacks (2.8%), intermediate in Pacific Islanders (3.1%) and Hispanics (3.2%), and highest in whites (5.9%) and Asians (6.4%). Lower rates of deceased donor transplantation among most racial ethnic minority groups appeared primarily to reflect differences in time from waitlisting to transplantation, but this was not the result of higher rates of waitlist inactivity or removal from the waitlist. The fraction of the reduced transplant rates attributable to measured factors (e.g., demographic, clinical, socioeconomic, linguistic, and geographic factors) varied from 14% in blacks to 43% in American Indians/Alaska Natives compared with whites. In conclusion, adjusted rates of deceased donor kidney transplantation remain significantly lower among racial ethnic minorities compared with whites; generally, differences in time to waitlisting were not as pronounced as differences in time between waitlisting and transplantation. Determinants of delays in time to transplantation differed substantially by racial ethnic group. Area-based efforts targeted to address racial- and ethnic-specific delays in transplantation may help to reduce overall disparities in deceased donor kidney transplantation in the United States.

  View details for DOI 10.1681/ASN.2010080819

  View details for Web of Science ID 000289494600021

  View details for PubMedID 21372209

  View details for PubMedCentralID PMC3065229

• Aspirin and Arteriovenous Graft Thrombosis in Hemodialysis: Just What the Doctor Ordered? JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Bech, F. R., Chertow, G. M. 2011; 22 (4): 595-597

  View details for DOI 10.1681/ASN.2011020181

  View details for Web of Science ID 000289494600006

  View details for PubMedID 21415154

• The 2011 ESRD Prospective Payment System: An Uncontrolled Experiment AMERICAN JOURNAL OF KIDNEY DISEASES Winkelmayer, W. C., Chertow, G. M. 2011; 57 (4): 542-546

  View details for DOI 10.1053/j.ajkd.2011.01.013

  View details for Web of Science ID 000288657100373

  View details for PubMedID 21333428

• Frequent versus Standard Hemodialysis REPLY NEW ENGLAND JOURNAL OF MEDICINE Chertow, G. M., Levin, N. W., Kliger, A. S. 2011; 364 (10): 976

  View details for Web of Science ID 000288170300022

• Effluent Volume in Continuous Renal Replacement Therapy Overestimates the Delivered Dose of Dialysis CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Claure-Del Gramdo, R., Macedo, E., Chertow, G. M., Soroko, S., Himmelfarb, J., Ikizler, T. A., Paganini, E. P., Mehta, R. L. 2011; 6 (3): 467-475

  Abstract

  Studies examining dose of continuous renal replacement therapy (CRRT) and outcomes have yielded conflicting results. Most studies considered the prescribed dose as the effluent rate represented by ml/kg per hour and reported this volume as a surrogate of solute removal. Because filter fouling can reduce the efficacy of solute clearance, the actual delivered dose may be substantially lower than the observed effluent rate.Data were examined from 52 critically ill patients with acute kidney injury (AKI) requiring dialysis. All patients were treated with predilution continuous venovenous hemodiafiltration (CVVHDF) and regional citrate anticoagulation. Filter performance was monitored during the entire course of therapy by measuring blood urea nitrogen (BUN) and dialysis fluid urea nitrogen (FUN) at initiation and every 12 hours. Filter efficacy was assessed by calculating FUN/BUN ratios every 12 hours of filter use. Prescribed urea clearance (K, ml/min) was determined from the effluent rate. Actual delivered urea clearance was determined using dialysis-side measurements.Median daily treatment time was 1413 minutes (1260 to 1440) with a total effluent volume of 46.4 ± 17.4 L and urea mass removal of 13.0 ± 7.6 mg/min. Prescribed clearance overestimated the actual delivered clearance by 23.8%. This gap between prescribed and delivered clearance was related to the decrease in filter function assessed by the FUN/BUN ratio.Effluent volume significantly overestimates delivered dose of small solutes in CRRT. To assess adequacy of CRRT, solute clearance should be measured rather than estimated by the effluent volume.

  View details for DOI 10.2215/CJN.02500310

  View details for Web of Science ID 000288480100003

  View details for PubMedID 21115626

  View details for PubMedCentralID PMC3082402

• World Kidney Day 2011 JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Hostetter, T. H., Kochis, D. J., Shaffer, R. N., Chertow, G., Harmon, W. E., Klotman, P. E., Powe, N. R., Sedor, J. R., Smedberg, P. C., Watnick, S., Winkelmayer, W. C. 2011; 22 (3): 397-398

  View details for DOI 10.1681/ASN.2011020115

  View details for Web of Science ID 000288778800001

  View details for PubMedID 21355055

• Sepsis as a cause and consequence of acute kidney injury: Program to Improve Care in Acute Renal Disease INTENSIVE CARE MEDICINE Mehta, R. L., Bouchard, J., Soroko, S. B., Ikizler, T. A., Paganini, E. P., Chertow, G. M., Himmelfarb, J. 2011; 37 (2): 241-248

  Abstract

  Sepsis commonly contributes to acute kidney injury (AKI); however, the frequency with which sepsis develops as a complication of AKI and the clinical consequences of this sepsis are unknown. This study examined the incidence of, and outcomes associated with, sepsis developing after AKI.We analyzed data from 618 critically ill patients enrolled in a multicenter observational study of AKI (PICARD). Patients were stratified according to their sepsis status and timing of incident sepsis relative to AKI diagnosis.We determined the associations among sepsis, clinical characteristics, provision of dialysis, in-hospital mortality, and length of stay (LOS), comparing outcomes among patients according to their sepsis status. Among the 611 patients with data on sepsis status, 174 (28%) had sepsis before AKI, 194 (32%) remained sepsis-free, and 243 (40%) developed sepsis a median of 5 days after AKI. Mortality rates for patients with sepsis developing after AKI were higher than in sepsis-free patients (44 vs. 21%; p < 0.0001) and similar to patients with sepsis preceding AKI (48 vs. 44%; p = 0.41). Compared with sepsis-free patients, those with sepsis developing after AKI were also more likely to be dialyzed (70 vs. 50%; p < 0.001) and had longer LOS (37 vs. 27 days; p < 0.001). Oliguria, higher fluid accumulation and severity of illness scores, non-surgical procedures after AKI, and provision of dialysis were predictors of sepsis after AKI.Sepsis frequently develops after AKI and portends a poor prognosis, with high mortality rates and relatively long LOS. Future studies should evaluate techniques to monitor for and manage this complication to improve overall prognosis.

  View details for DOI 10.1007/s00134-010-2089-9

  View details for Web of Science ID 000286633500009

  View details for PubMedID 21152901

  View details for PubMedCentralID PMC3028102

• Vascular Risk Factors and Cognitive Impairment in Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort (CRIC) Study CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Tamura, M. K., Xie, D., Yaffe, K., Cohen, D. L., Teal, V., Kasner, S. E., Messe, S. R., Sehgal, A. R., Kusek, J., DeSalvo, K. B., Cornish-Zirker, D., Cohan, J., Seliger, S. L., Chertow, G. M., Go, A. S. 2011; 6 (2): 248-256

  Abstract

  Cognitive impairment is common among persons with chronic kidney disease, but the extent to which nontraditional vascular risk factors mediate this association is unclear.We conducted cross-sectional analyses of baseline data collected from adults with chronic kidney disease participating in the Chronic Renal Insufficiency Cohort study. Cognitive impairment was defined as a Modified Mini-Mental State Exam score>1 SD below the mean score.Among 3591 participants, the mean age was 58.2±11.0 years, and the mean estimated GFR (eGFR) was 43.4±13.5 ml/min per 1.73 m2. Cognitive impairment was present in 13%. After adjustment for demographic characteristics, prevalent vascular disease (stroke, coronary artery disease, and peripheral arterial disease) and traditional vascular risk factors (diabetes, hypertension, smoking, and elevated cholesterol), an eGFR<30 ml/min per 1.73 m2 was associated with a 47% increased odds of cognitive impairment (odds ratio 1.47, 95% confidence interval 1.05, 2.05) relative to those with an eGFR 45 to 59 ml/min per 1.73 m2. This association was attenuated and no longer significant after adjustment for hemoglobin concentration. While other nontraditional vascular risk factors including C-reactive protein, homocysteine, serum albumin, and albuminuria were correlated with cognitive impairment in unadjusted analyses, they were not significantly associated with cognitive impairment after adjustment for eGFR and other confounders.The prevalence of cognitive impairment was higher among those with lower eGFR, independent of traditional vascular risk factors. This association may be explained in part by anemia.

  View details for DOI 10.2215/CJN.02660310

  View details for PubMedID 20930087

• Systolic blood pressure and mortality in prevalent haemodialysis patients in the HEMO study JOURNAL OF HUMAN HYPERTENSION Chang, T. I., Friedman, G. D., Cheung, A. K., Greene, T., Desai, M., Chertow, G. M. 2011; 25 (2): 98-105

  Abstract

  Previous studies of blood pressure and mortality in haemodialysis have yielded mixed results, perhaps due to confounding by comorbid conditions. We hypothesized that after improved accounting for confounding factors, higher systolic blood pressure (SBP) would be associated with higher all-cause mortality. We conducted a secondary analysis of data from the haemodialysis study, a randomized trial in prevalent haemodialysis patients. We used three proportional hazard models to determine the relative hazard at different levels of SBP: (1) Model-BL used baseline SBP; (2) Model-TV used SBP as a time-varying variable; and (3) Model-TV-Lag added a 3-month lag to Model-TV to de-emphasize changes in SBP associated with acute illness. In all the models, pre-dialysis SBP <120 mm Hg was associated with a higher risk of mortality compared with the referent group (140-159 mm Hg); higher pre-dialysis SBP was not associated with higher risk of mortality. In conclusion, we observed a robust association between lower pre-dialysis SBP and higher risk for all-cause and cardiovascular mortality in a well-characterized cohort of prevalent haemodialysis patients. Randomized clinical trials are needed to define optimal blood pressure targets in the haemodialysis population.

  View details for DOI 10.1038/jhh.2010.42

  View details for PubMedID 20410919

• Baseline Characteristics of Participants in the Frequent Hemodialysis Network (FHN) Daily and Nocturnal Trials AMERICAN JOURNAL OF KIDNEY DISEASES Rocco, M. V., Larive, B., Eggers, P. W., Beck, G. J., Chertow, G. M., Levin, N. W., Kliger, A. S. 2011; 57 (1): 90-100

  Abstract

  The annual mortality rate for maintenance hemodialysis patients in the United States is unacceptably high at 15%-20%. In 2004, we initiated the Frequent Hemodialysis Network (FHN) clinical trials. This report presents baseline characteristics of FHN Trial participants and compares them with hemodialysis patients tracked in US Renal Data System (USRDS) data.2 separate randomized clinical trials.FHN includes 332 patients with chronic kidney disease requiring long-term dialysis therapy enrolled in 2 separate randomized clinical trials. The FHN Daily Trial (245 randomly assigned participants) was designed to compare outcomes of 6-times-weekly in-center daily hemodialysis (1.5-2.75 h/session) with conventional 3-times-weekly in-center hemodialysis. The FHN Nocturnal Trial (87 randomly assigned participants) was designed to compare outcomes of 6-times-weekly home nocturnal (6-8 h/session) with conventional 3-times-weekly hemodialysis. USRDS data include 338,109 incident and prevalent long-term hemodialysis patients from the calendar year 2007.Participants in both trials were on average younger than the average hemodialysis patient in the United States (Daily Trial, 50.4 years; P < 0.001; Nocturnal Trial, 52.8 years; P < 0.001). Compared with USRDS data, whites were under-represented in the Daily Trial (36% vs 55%; P < 0.001), whereas Hispanics were under-represented in the Nocturnal Trial and over-represented in the Daily Trial (0% vs 28%; P < 0.001). In addition, there were more fistulas and fewer catheters in the Daily Trial (61% and 20%, respectively; P < 0.001 for both) and fewer grafts and more catheters in the Nocturnal Trial (10% and 44%, respectively; P < 0.005 for both).Clinical trial exclusion criteria and patient willingness to participate limit comparisons with the USRDS.FHN participants were younger and the racial composition for each study was different from the racial composition of the aggregate US dialysis population. Catheters for vascular access were more common in FHN Nocturnal Trial participants.

  View details for DOI 10.1053/j.ajkd.2010.08.024

  View details for Web of Science ID 000285621600014

  View details for PubMedID 21122961

  View details for PubMedCentralID PMC3058226

• The Phosphate Binder Equivalent Dose SEMINARS IN DIALYSIS Daugirdas, J. T., Finn, W. F., Emmett, M., Chertow, G. M. 2011; 24 (1): 41-49

  Abstract

  Phosphate binders include calcium acetate or carbonate, sevelamer hydrochloride or carbonate, magnesium and lanthanum carbonate, and aluminum carbonate or hydroxide. Their relative phosphate-binding capacity has been assessed in human, in vivo studies that have measured phosphate recovery from stool and/or changes in urinary phosphate excretion or that have compared pairs of different binders where dose of binder in each group was titrated to a target level of serum phosphate. The relative phosphate-binding coefficient (RPBC) based on weight of each binder can be estimated relative to calcium carbonate, the latter being set to 1.0. A systematic review of these studies gave the following estimated RPBC: for elemental lanthanum, 2.0, for sevelamer hydrochloride or carbonate 0.75, for calcium acetate 1.0, for anhydrous magnesium carbonate 1.7, and for "heavy" or hydrated, magnesium carbonate 1.3. Estimated RPBC for aluminum-containing binders were 1.5 for aluminum hydroxide and 1.9 for aluminum carbonate. The phosphate-binding equivalent dose was then defined as the dose of each binder in g × its RPBC, which would be the binding ability of an equivalent weight of calcium carbonate. The phosphate-binding equivalent dose may be useful in comparing changes in phosphate binder prescription over time when multiple binders are being prescribed, when estimating an initial binder prescription, and also in phosphate kinetic modeling.

  View details for DOI 10.1111/j.1525-139X.2011.00849.x

  View details for Web of Science ID 000287579100014

  View details for PubMedID 21338393

• RELATIONSHIP OF BODY SIZE AND MORTALITY AMONG US ASIANS AND PACIFIC ISLANDERS ON DIALYSIS ETHNICITY & DISEASE Hall, Y. N., Xu, P., Chertow, G. M. 2011; 21 (1): 40-46

  Abstract

  The influence of body size on dialysis-related mortality among Asians and Pacific Islanders--heterogeneous ethnic groups with dissimilar body compositions--is poorly understood. Our study objective was to compare the relations of body size and mortality among patients with end-stage renal disease of different ethnicities.We examined data from a cohort of 21,492 adult Asians, Pacific Islanders and non-Hispanic Whites who initiated dialysis during 1995-2003 within California, Hawaii and the US Pacific Islands.Time to death through September 22, 2008.Among both men and women, Pacific Islanders were the heaviest and Whites the tallest of the ethnic groups examined. Annual mortality rates were highest among Whites (29.6%), intermediate among Pacific Islanders (18.8%) and lowest among Asians (17.3%). Larger body size was associated with lower mortality among Pacific Islanders, Whites and most Asians on dialysis after adjustment for patient-level sociodemographic and clinical factors, area-based socioeconomic status and geographic clustering. Filipinos were the exception to this rule and showed a trend towards higher mortality with increasing body size. These findings were consistent irrespective of how body size was measured.Larger body size is associated with lower mortality among Pacific Islanders, Whites and most Asians on dialysis. Use of disaggregated ethnicity data may enhance our understanding of how ethnicity- or community-specific factors influence body size, body composition and dialysis-related outcomes in these diverse populations.

  View details for Web of Science ID 000288821700007

  View details for PubMedID 21462728

• Baseline Physical Performance, Health, and Functioning of Participants in the Frequent Hemodialysis Network (FHN) Trial AMERICAN JOURNAL OF KIDNEY DISEASES Kaysen, G. A., Larive, B., Painter, P., Craig, A., Lindsay, R. M., Rocco, M. V., Daugirdas, J. T., Schulman, G., Chertow, G. M. 2011; 57 (1): 101-112

  Abstract

  Self-reported physical health and functioning and direct measures of physical performance are decreased in hemodialysis patients and are associated with mortality and hospitalization.We determined baseline cross-sectional associations of physical performance, health, and functioning with demographics, clinical characteristics, nutritional indexes, laboratory benchmarks, and measures of body composition in participants in the Frequent Hemodialysis Network (FHN) trial.375 persons enrolled in the FHN with data for physical performance, health, and functioning.Explanatory variables were categorized into fixed factors of age, race, comorbid conditions (diabetes mellitus, heart failure, and peripheral arterial disease) and potentially modifiable factors of dialysis dose, phosphorus level, hemoglobin level, equilibrated normalized protein catabolic rate (enPCR), body composition, body mass index, phase angle, and ratio of intracellular water volume to body weight (calculated from bioelectrical impedance).Scores on tests of physical performance, health, and functioning.Physical performance measured using the Short Physical Performance Battery, self-reported physical health and functioning using the 36-Item Short Form Health Survey (SF-36). Body composition (body mass index and bioimpedance analysis) and laboratory data were obtained from affiliated dialysis providers.Relative to population norms, scores for all 3 physicality metrics were low. Poorer scores on all 3 metrics were associated with diabetes mellitus and peripheral arterial disease. Poorer scores on the SF-36 Physical Functioning subscale and Short Physical Performance Battery also were associated with age, lower ratio of intracellular water volume to body weight, and lower enPCR. Black race was associated with poorer scores on the Short Physical Performance Battery.This was a cross-sectional study of individuals agreeing to participate in the FHN study and may not be generalizable to the general dialysis population.Hemodialysis patients show markedly impaired physical performance, health, and functioning relative to population norms. Although some factors associated with these impairments are not modifiable, others may change with improvement in nutritional status or body composition.

  View details for DOI 10.1053/j.ajkd.2010.08.021

  View details for Web of Science ID 000285621600015

  View details for PubMedID 21184919

  View details for PubMedCentralID PMC3073398

• End-stage Renal Disease. American family physician Abbasi, M., Chertow, G., Hall, Y. 2010; 82 (12): 1512-?

  View details for PubMedID 21166372

• In-Center Hemodialysis Six Times per Week versus Three Times per Week NEW ENGLAND JOURNAL OF MEDICINE Chertow, G. M., Levin, N. W., Beck, G. J., Depner, T. A., Eggers, P. W., Gassman, J. J., Gorodetskaya, I., Greene, T., James, S., Larive, B., Lindsay, R. M., Mehta, R. L., Miller, B., Ornt, D. B., Rajagopalan, S., Rastogi, A., Rocco, M. V., Schiller, B., Sergeyeva, O., Schulman, G., Ting, G. O., Unruh, M. L., Star, R. A., Kliger, A. S. 2010; 363 (24): 2287-2300

  Abstract

  In this randomized clinical trial, we aimed to determine whether increasing the frequency of in-center hemodialysis would result in beneficial changes in left ventricular mass, self-reported physical health, and other intermediate outcomes among patients undergoing maintenance hemodialysis.Patients were randomly assigned to undergo hemodialysis six times per week (frequent hemodialysis, 125 patients) or three times per week (conventional hemodialysis, 120 patients) for 12 months. The two coprimary composite outcomes were death or change (from baseline to 12 months) in left ventricular mass, as assessed by cardiac magnetic resonance imaging, and death or change in the physical-health composite score of the RAND 36-item health survey. Secondary outcomes included cognitive performance; self-reported depression; laboratory markers of nutrition, mineral metabolism, and anemia; blood pressure; and rates of hospitalization and of interventions related to vascular access.Patients in the frequent-hemodialysis group averaged 5.2 sessions per week; the weekly standard Kt/V(urea) (the product of the urea clearance and the duration of the dialysis session normalized to the volume of distribution of urea) was significantly higher in the frequent-hemodialysis group than in the conventional-hemodialysis group (3.54±0.56 vs. 2.49±0.27). Frequent hemodialysis was associated with significant benefits with respect to both coprimary composite outcomes (hazard ratio for death or increase in left ventricular mass, 0.61; 95% confidence interval [CI], 0.46 to 0.82; hazard ratio for death or a decrease in the physical-health composite score, 0.70; 95% CI, 0.53 to 0.92). Patients randomly assigned to frequent hemodialysis were more likely to undergo interventions related to vascular access than were patients assigned to conventional hemodialysis (hazard ratio, 1.71; 95% CI, 1.08 to 2.73). Frequent hemodialysis was associated with improved control of hypertension and hyperphosphatemia. There were no significant effects of frequent hemodialysis on cognitive performance, self-reported depression, serum albumin concentration, or use of erythropoiesis-stimulating agents.Frequent hemodialysis, as compared with conventional hemodialysis, was associated with favorable results with respect to the composite outcomes of death or change in left ventricular mass and death or change in a physical-health composite score but prompted more frequent interventions related to vascular access. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov number, NCT00264758.).

  View details for DOI 10.1056/NEJMoa1001593

  View details for Web of Science ID 000285092100004

  View details for PubMedID 21091062

  View details for PubMedCentralID PMC3042140

• Low level of self-reported physical activity in ambulatory patients new to dialysis KIDNEY INTERNATIONAL Johansen, K. L., Chertow, G. M., Kutner, N. G., Dalrymple, L. S., Grimes, B. A., Kaysen, G. A. 2010; 78 (11): 1164-1170

  Abstract

  Physical inactivity contributes to the frailty and the decline in function that develops over time among patients with end-stage renal disease. We assessed physical activity among 1547 ambulatory patients new to dialysis in the United States Renal Data System Comprehensive Dialysis Study. We used a self-reporting Human Activity Profile that included Maximal and Adjusted Activity Scores and compared results to established norms by age and gender. Physical activity was found to be extremely low with scores for all age and gender categories below the 5th percentile of healthy individuals and 95% of patients had scores consonant with low fitness. Older age, female gender, diabetes, atherosclerotic disease, and a low level of education were associated with lower activity scores assessed by univariate and multivariable linear regression analysis. Higher serum albumin, creatinine, and lower body mass index, but not hemoglobin levels, were associated with greater physical activity. By multivariable analysis, patients on hemodialysis using a catheter reported lower levels of physical activity compared to those on peritoneal dialysis, hemodialysis using an arteriovenous fistula, or with a graft. Lower Maximal and Adjusted Activity Scores were associated with poor physical function and mental health. Hence, physical activity is distressingly low among patients new to dialysis. Thus, strategies to enhance activity in these patients should be explored.

  View details for DOI 10.1038/ki.2010.312

  View details for Web of Science ID 000284173300015

  View details for PubMedID 20811334

• Blood Pressure Control in Type 2 Diabetes Mellitus AMERICAN JOURNAL OF KIDNEY DISEASES Chang, T. I., Cheung, A. K., Chertow, G. M. 2010; 56 (6): 1029-1031

  View details for DOI 10.1053/j.ajkd.2010.08.007

  View details for PubMedID 20870328

• Curbing the Use of Ultrasonography in the Diagnosis of Acute Kidney Injury Penny Wise or Pound Foolish? ARCHIVES OF INTERNAL MEDICINE Liu, K. D., Chertow, G. M. 2010; 170 (21): 1907-1908

  View details for Web of Science ID 000284480000010

  View details for PubMedID 21098349

• Off-Label Use of Phosphate Binders in Non-Dialysis-Dependent CKD AMERICAN JOURNAL OF KIDNEY DISEASES Winkelmayer, W. C., Chertow, G. M. 2010; 56 (5): 813-816

  View details for DOI 10.1053/j.ajkd.2010.09.004

  View details for Web of Science ID 000283261700006

  View details for PubMedID 20970022

• Determinants of Cardiac Autonomic Dysfunction in ESRD CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Chan, C. T., Levin, N. W., Chertow, G. M., Lariye, B., Schulman, G., Kotanko, P. 2010; 5 (10): 1821-1827

  Abstract

  Cardiovascular events are common in patients with ESRD. Whether sympathetic overactivity or vagal withdrawal contribute to cardiovascular events is unclear. We determined the general prevalence and clinical correlates of heart rate variability in patients on hemodialysis.We collected baseline information on demographics, clinical conditions, laboratory values, medications, physical performance, left ventricular mass (LVM), and 24-hour Holter monitoring on 239 subjects enrolled in the Frequent Hemodialysis Network Daily Trial.The mean R-R interval was 812 ± 217 ms. The SD of R-R intervals was 79.1 ± 40.3 ms. Spectral power analyses showed low-frequency (sympathetic modulation of heart rate) and high-frequency power (HF; vagal modulation of heart rate) to be 106.0 (interquartile range, 48.0 to 204 ms(2)) and 42.4 ms(2) (interquartile range, 29.4 to 56.3 ms(2)), respectively. LVM was inversely correlated with log HF (-0.02 [-0.0035; -0.0043]) and the R-R interval (-1.00 [-1.96; -0.032]). Physical performance was associated with mean R-R intervals (1.98 [0.09; 3.87]) and SD of R-R intervals (0.58 [0.049; 1.10]). After adjustment for age, race, ESRD vintage, diabetes, and physical performance, the relationship between log HF and LVM (per 10 g) remained significant (-0.025 [-0.042; -0.0085]).Holter findings in patients on hemodialysis are characterized by sympathetic overactivity and vagal withdrawal and are associated with higher LVM and impaired physical performance. Understanding the spectrum of autonomic heart rate modulation and its determinants could help to guide preventive and therapeutic strategies.

  View details for DOI 10.2215/CJN.03080410

  View details for Web of Science ID 000282836400017

  View details for PubMedID 20616163

  View details for PubMedCentralID PMC2974383

• Updated comorbidity assessments and outcomes in prevalent hemodialysis patients HEMODIALYSIS INTERNATIONAL Chang, T. I., Paik, J., Greene, T., Miskulin, D. C., Chertow, G. M. 2010; 14 (4): 478-485

  Abstract

  When evaluating clinical characteristics and outcomes in patients on hemodialysis, the prevalence and severity of comorbidity may change over time. Knowing whether updated assessments of comorbidity enhance predictive power will assist the design of future studies. We conducted a secondary data analysis of 1846 prevalent hemodialysis patients from 15 US clinical centers enrolled in the HEMO study. Our primary explanatory variable was the Index of Coexistent Diseases score, which aggregates comorbidities, as a time-constant and time-varying covariate. Our outcomes of interest were all-cause mortality, time to first hospitalization, and total hospitalizations. We used Cox proportional hazards regression. Accounting for an updated comorbidity assessment over time yielded a more robust association with mortality than accounting for baseline comorbidity alone. The variation explained by time-varying comorbidity assessments on time to death was greater than age, baseline serum albumin, diabetes, or any other covariates. There was a less pronounced advantage of updated comorbidity assessments on determining time to hospitalization. Updated assessments of comorbidity significantly strengthen the ability to predict death in patients on hemodialysis. Future studies in dialysis should invest the necessary resources to include repeated assessments of comorbidity.

  View details for DOI 10.1111/j.1542-4758.2010.00468.x

  View details for PubMedID 20955281

• Can Rescaling Dose of Dialysis to Body Surface Area in the HEMO Study Explain the Different Responses to Dose in Women versus Men? CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Daugirdas, J. T., Greene, T., Chertow, G. M., Depner, T. A. 2010; 5 (9): 1628-1636

  Abstract

  In the Hemodialysis (HEMO) Study, the lower death rate in women but not in men assigned to the higher dose (Kt/V) could have resulted from use of "V" as the normalizing factor, since women have a lower anthropometric V per unit of surface area (V/SA) than men.The effect of Kt/V on mortality was re-examined after normalizing for surface area and expressing dose as surface area normalized standard Kt/V (SAn-stdKt/V).Both men and women in the high-dose group received approximately 16% more dialysis (when expressed as SAn-stdKt/V) than the controls. SAn-stdKt/V clustered into three levels: 2.14/wk for conventional dose women, 2.44/wk for conventional dose men or 2.46/wk for high-dose women, and 2.80/wk for high-dose men. V/SA was associated with the effect of dose assignment on the risk of death; above 20 L/m(2), the mortality hazard ratio = 1.23 (0.99 to 1.53); below 20 L/m(2), hazard ratio = 0.78 (0.65 to 0.95), P = 0.002. Within gender, V/SA did not modify the effect of dose on mortality.When normalized to body surface area rather than V, the dose of dialysis in women in the HEMO Study was substantially lower than in men. The lowest surface-area-normalized dose was received by women randomized to the conventional dose arm, possibly explaining the sex-specific response to dialysis dose. Results are consistent with the hypothesis that when dialysis dose is expressed as Kt/V, women, due to their lower V/SA ratio, require a higher amount than men.

  View details for DOI 10.2215/CJN.02350310

  View details for Web of Science ID 000281685600015

  View details for PubMedID 20595687

  View details for PubMedCentralID PMC2974404

• On the relative safety of intravenous iron formulations: New answers, new questions AMERICAN JOURNAL OF HEMATOLOGY Chertow, G. M., Winkelmayer, W. C. 2010; 85 (9): 643-644

  View details for DOI 10.1002/ajh.21835

  View details for Web of Science ID 000281601900002

  View details for PubMedID 20687100

• Infection-Related Hospitalizations in Older Patients With ESRD AMERICAN JOURNAL OF KIDNEY DISEASES Dalrymple, L. S., Johansen, K. L., Chertow, G. M., Cheng, S., Grimes, B., Gold, E. B., Kaysen, G. A. 2010; 56 (3): 522-530

  Abstract

  Infection is an important cause of hospitalization and death in patients receiving dialysis. Few studies have examined the full range of infections experienced by dialysis patients. The purpose of this study is to examine types, rates, and risk factors for infection in older persons starting dialysis therapy.Retrospective observational cohort study.The cohort was assembled from the US Renal Data System and included patients aged 65-100 years who initiated dialysis therapy between January 1, 2000, and December 31, 2002. Exclusions included prior kidney transplant, unknown dialysis modality, or death, loss to follow-up, or transplant during the first 90 days of dialysis therapy. Patients were followed up until death, transplant, or study end on December 31, 2004.Baseline demographics, comorbid conditions, and serum albumin and hemoglobin levels.Infection-related hospitalizations were ascertained using discharge International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Hospitalization rates were calculated for each type of infection. The Wei-Lin-Weissfeld model was used to examine risk factors for up to 4 infection-related events.119,858 patients were included, 7,401 of whom were on peritoneal dialysis therapy. During a median follow-up of 1.9 years, infection-related diagnoses were observed in approximately 35% of all hospitalizations. Approximately 50% of patients had at least 1 infection-related hospitalization. Rates (per 100 person-years) of pulmonary, soft-tissue, and genitourinary infections ranged from 8.3-10.3 in patients on peritoneal dialysis therapy and 10.2-15.3 in patients on hemodialysis therapy. Risk factors for infection included older age, female sex, diabetes, heart failure, pulmonary disease, and low serum albumin level.Use of ICD-9-CM codes, reliance on Medicare claims to capture hospitalizations, use of the Medical Evidence Form to ascertain comorbid conditions, and absence of data for dialysis access.Infection-related hospitalization is frequent in older patients on dialysis therapy. A broad range of infections, many unrelated to dialysis access, result in hospitalization in this population.

  View details for DOI 10.1053/j.ajkd.2010.04.016

  View details for Web of Science ID 000281203200015

  View details for PubMedID 20619518

  View details for PubMedCentralID PMC2926212

• Prevalence and Correlates of Cognitive Impairment in Hemodialysis Patients: The Frequent Hemodialysis Network Trials CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Tamura, M. K., Larive, B., Unruh, M. L., Stokes, J. B., Nissenson, A., Mehta, R. L., Chertow, G. M. 2010; 5 (8): 1429-1438

  Abstract

  Cognitive impairment is common among persons with ESRD, but the underlying mechanisms are unknown. This study evaluated the prevalence of cognitive impairment and association with modifiable ESRD- and dialysis-associated factors in a large group of hemodialysis patients.Cross-sectional analyses were conducted on baseline data collected from 383 subjects participating in the Frequent Hemodialysis Network trials. Global cognitive impairment was defined as a score <80 on the Modified Mini-Mental State Exam, and impaired executive function was defined as a score >or=300 seconds on the Trailmaking B test. Five main categories of explanatory variables were examined: urea clearance, nutritional markers, hemodynamic measures, anemia, and central nervous system (CNS)-active medications.Subjects had a mean age of 51.6 +/- 13.3 years and a median ESRD vintage of 2.6 years. Sixty-one subjects (16%) had global cognitive impairment, and 110 subjects (29%) had impaired executive function. In addition to several nonmodifiable factors, the use of H1-receptor antagonists and opioids were associated with impaired executive function. No strong association was found between several other potentially modifiable factors associated with ESRD and dialysis therapy, such as urea clearance, proxies of dietary protein intake and other nutritional markers, hemodynamic measures, and anemia with global cognition and executive function after adjustment for case-mix factors.Cognitive impairment, especially impaired executive function, is common among hemodialysis patients, but with the exception of CNS-active medications, is not strongly associated with several ESRD- and dialysis-associated factors.

  View details for DOI 10.2215/CJN.01090210

  View details for PubMedID 20576825

• Vitamin D deficiency and frailty in older Americans JOURNAL OF INTERNAL MEDICINE Wilhelm-Leen, E. R., Hall, Y. N., DEBOER, I. H., Chertow, G. M. 2010; 268 (2): 171-180

  Abstract

  To explore the relation between 25-hydroxyvitamin D deficiency and frailty. Frailty is a multidimensional phenotype that describes declining physical function and a vulnerability to adverse outcomes in the setting of physical stress such as illness or hospitalization. Low serum concentrations of 25-hydroxyvitamin D are known to be associated with multiple chronic diseases such as cardiovascular disease and diabetes, in addition to all cause mortality.Using data from the Third National Health and Nutrition Survey (NHANES III), we evaluated the association between low serum 25-hydroxyvitamin D concentration and frailty, defined according to a set of criteria derived from a definition previously described and validated.Nationally representative survey of noninstitutionalized US residents collected between 1988 and 1994.25-Hydroxyvitamin D deficiency, defined as a serum concentration <15 ng mL(-1), was associated with a 3.7-fold increase in the odds of frailty amongst whites and a fourfold increase in the odds of frailty amongst non-whites. This association persisted after sensitivity analyses adjusting for season of the year and latitude of residence, intended to reduce misclassification of persons as 25-hydroxyvitamin D deficient or insufficient.Low serum 25-hydroxyvitamin D concentrations are associated with frailty amongst older adults.

  View details for DOI 10.1111/j.1365-2796.2010.02248.x

  View details for PubMedID 20528970

• Hyperparathyroidism with hypercalcaemia in chronic kidney disease: primary or tertiary? NDT plus Lunn, M. R., Muñoz Mendoza, J., Pasche, L. J., Norton, J. A., Ayco, A. L., Chertow, G. M. 2010; 3 (4): 366-371

  Abstract

  Objective . This study aims to highlight the challenges in the diagnosis of hyperparathyroidism (HPT) in patients with advanced chronic kidney disease (CKD). Methods . In this report, we describe a middle-aged Filipino gentleman with underlying CKD who presented with intractable nausea, vomiting, severe and medically refractory hypercalcaemia and parathyroid hormone (PTH) concentrations in excess of 2400 pg/mL. The underlying pathophysiology as well as the aetiologies and current relevant literature are discussed. We also suggest an appropriate diagnostic approach to identify and promptly treat patients with CKD, HPT and hypercalcaemia. Results . Evaluation confirmed the presence of a large parathyroid adenoma; HPT and hypercalcaemia resolved rapidly following resection. Conclusion . This case report is remarkable for its severe hypercalcaemia requiring haemodialysis, large adenoma size, acute-on-chronic kidney injury and markedly elevated PTH concentration in association with primary HPT in CKD.

  View details for DOI 10.1093/ndtplus/sfq077

  View details for PubMedID 25949433

• Projected Effect of Dietary Salt Reductions on Future Cardiovascular Disease EDITORIAL COMMENT OBSTETRICAL & GYNECOLOGICAL SURVEY Bibbins-Domingo, K., Chertow, G. M., Coxson, P. G., Moran, A., Lightwood, J. M., Pletcher, M. J., Goldman, L. 2010; 65 (7): 441–42

  View details for DOI 10.1097/OGX.0b013e3181e5f253

  View details for Web of Science ID 000281249300017

• Reexploring Differences among For-Profit and Nonprofit Dialysis Providers HEALTH SERVICES RESEARCH Lee, D. K., Chertow, G. M., Zenios, S. A. 2010; 45 (3): 633-646

  Abstract

  To determine whether profit status is associated with differences in hospital days per patient, an outcome that may also be influenced by provider financial goals.United States Renal Data System Standard Analysis Files and Centers for Medicare and Medicaid Services cost reports.We compared the number of hospital days per patient per year across for-profit and nonprofit dialysis facilities during 2003. To address possible referral bias in the assignment of patients to dialysis facilities, we used an instrumental variable regression method and adjusted for selected patient-specific factors, facility characteristics such as size and chain affiliation, as well as metrics of market competition.All patients who received in-center hemodialysis at any time in 2003 and for whom Medicare was the primary payer were included (N=170,130; roughly two-thirds of the U.S. hemodialysis population). Patients dialyzed at hospital-based facilities and patients with no dialysis facilities within 30 miles of their residence were excluded.Overall, adjusted hospital days per patient were 17+/-5 percent lower in nonprofit facilities. The difference between nonprofit and for-profit facilities persisted with the correction for referral bias. There was no association between hospital days per patient per year and chain affiliation, but larger facilities had inferior outcomes (facilities with 73 or more patients had a 14+/-1.7 percent increase in hospital days relative to facilities with 35 or fewer patients). Differences in outcomes among for-profit and nonprofit facilities translated to 1,600 patient-years in hospital that could be averted each year if the hospital utilization rates in for-profit facilities were to decrease to the level of their nonprofit counterparts.Hospital days per patient-year were statistically and clinically significantly lower among nonprofit dialysis providers. These findings suggest that the indirect incentives in Medicare's current payment system may provide insufficient incentive for for-profit providers to achieve optimal patient outcomes.

  View details for DOI 10.1111/j.1475-6773.2010.01103.x

  View details for Web of Science ID 000277291400003

  View details for PubMedID 20403066

  View details for PubMedCentralID PMC2875752

• Study design and subject baseline characteristics in the ADVANCE study: effects of cinacalcet on vascular calcification in haemodialysis patients NEPHROLOGY DIALYSIS TRANSPLANTATION Floege, J., Raggi, P., Block, G. A., Torres, P. U., Csiky, B., Naso, A., Nossuli, K., Moustafa, M., Goodman, W. G., Lopez, N., Downey, G., Dehmel, B., Chertow, G. M. 2010; 25 (6): 1916-1923

  Abstract

  The ADVANCE (A Randomized Study to Evaluate the Effects of Cinacalcet plus Low-Dose Vitamin D on Vascular Calcification in Subjects with Chronic Kidney Disease Receiving Haemodialysis) Study objective is to assess the effect of cinacalcet plus low-dose active vitamin D versus flexible dosing of active vitamin D on progression of coronary artery calcification (CAC) in haemodialysis patients. We report the ADVANCE Study design and baseline subject characteristics.ADVANCE is a multinational, multicentre, randomized, open-label study. Adult haemodialysis patients with moderate to severe secondary hyperparathyroidism (intact parathyroid hormone [iPTH] >300 pg/mL or bio-intact PTH >160 pg/mL) and baseline CAC score >or=30 were stratified by CAC score (>or=30-399, >or=400-999, >or=1000) and randomized in a 1:1 ratio to cinacalcet (30-180 mg/day) plus low-dose active vitamin D (cinacalcet group) or flexible dosing of active vitamin D alone (control). The study had three phases: screening, 20-week dose titration and 32-week follow-up. CAC scores obtained by cardiac computed tomography were determined at screening and weeks 28 and 52. The primary end point was percentage change in CAC score from baseline to Week 52.Subjects (n = 360) were randomized to cinacalcet or control. Mean age was 61.5 years, 43% were women, and median dialysis vintage was 36.7 months (range, 2.7-351.5 months). The baseline geometric mean CAC score by the Agatston method was 548.7 (95% confidence interval, 480.5-626.6). Baseline CAC score was independently associated with age, sex, dialysis vintage, diabetes and iPTH. Subjects also had extensive aortic and valvular calcification at baseline.Subjects enrolled in ADVANCE have extensive CAC at baseline. The ADVANCE Study should help determine whether cinacalcet attenuates progression of vascular calcification.

  View details for DOI 10.1093/ndt/gfp762

  View details for Web of Science ID 000280027400033

  View details for PubMedID 20110249

• Kidney Disease, Hospitalized Hypertension, and Cardiovascular Events: Cause or Consequence? CIRCULATION Chertow, G. M., Chang, T. I. 2010; 121 (20): 2160-2161

  View details for DOI 10.1161/CIRCULATIONAHA.110.956904

  View details for Web of Science ID 000278018500002

  View details for PubMedID 20458007

• Chronic Kidney Disease in the Urban Poor CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Hall, Y. N., Choi, A. I., Chertow, G. M., Bindman, A. B. 2010; 5 (5): 828-835

  Abstract

  In the United States, relatively little is known about clinical outcomes of chronic kidney disease (CKD) in vulnerable populations utilizing public health systems. The primary study objectives were to describe patient characteristics, incident ESRD, and mortality in adults with nondialysis-dependent CKD receiving care in the health care safety net.Time to ESRD and time to death were examined among a cohort of 15,353 ambulatory adults with nondialysis-dependent CKD from the Community Health Network of San Francisco.The mean age of the CKD cohort was 59.0 +/- 13.8 years; 50% of the cohort was younger than 60 years and 26% was younger than 50 years. Most (72%) were members of nonwhite racial-ethnic groups, 73% were indigent (annual income <$15,000) and 18% were uninsured. In adjusted analyses, blacks [hazard ratio (95% confidence interval), 4.00 (2.99 to 5.35)], Hispanics [2.20 (1.46 to 3.30)], and Asians/Pacific Islanders [3.84 (2.73 to 5.40)] had higher risks of progression to ESRD than non-Hispanic whites. The higher risk of progression to ESRD among nonwhite compared with white persons with CKD was not explained by lower relative mortality.Adults with CKD stages 3 to 5 cared for within an urban public health system were relatively young and predominantly nonwhite-both factors associated with a higher risk of progression to ESRD. These findings call for targeted efforts to assess the burden and progression of CKD within other public and safety-net health systems in this country.

  View details for DOI 10.2215/CJN.09011209

  View details for Web of Science ID 000277483300016

  View details for PubMedID 20200149

  View details for PubMedCentralID PMC2863975

• Weekend Hospital Admission, Acute Kidney Injury, and Mortality JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY James, M. T., Wald, R., Bell, C. M., Tonelli, M., Hemmelgarn, B. R., Waikar, S. S., Chertow, G. M. 2010; 21 (5): 845-851

  Abstract

  Admission to the hospital on weekends is associated with increased mortality for several acute illnesses. We investigated whether patients admitted on a weekend with acute kidney injury (AKI) were more likely to die than those admitted on a weekday. Using the Nationwide Inpatient Sample, a large database of admissions to acute care, nonfederal hospitals in the United States, we identified 963,730 admissions with a diagnosis of AKI between 2003 and 2006. Of these, 214,962 admissions (22%) designated AKI as the primary reason for admission (45,203 on a weekend and 169,759 on a weekday). We used logistic regression models to examine the adjusted odds of in-hospital mortality associated with weekend versus weekday admission. Compared with admission on a weekday, patients admitted with a primary diagnosis of AKI on a weekend had a higher odds of death [adjusted odds ratio (OR) 1.07, 95% confidence interval (CI) 1.02 to 1.12]. The risk for death with admission on a weekend for AKI was more pronounced in smaller hospitals (adjusted OR 1.17, 95% CI 1.03 to 1.33) compared with larger hospitals (adjusted OR 1.07, 95% CI 1.01 to 1.13). Increased mortality was also associated with weekend admission among patients with AKI as a secondary diagnosis across a spectrum of co-existing medical diagnoses. In conclusion, among patients hospitalized with AKI, weekend admission is associated with a higher risk for death compared with admission on a weekday.

  View details for DOI 10.1681/ASN.2009070682

  View details for Web of Science ID 000277600400019

  View details for PubMedID 20395373

  View details for PubMedCentralID PMC2865737

• Standard Kt/V-urea: a method of calculation that includes effects of fluid removal and residual kidney clearance KIDNEY INTERNATIONAL Daugirdas, J. T., Depner, T. A., Greene, T., Levin, N. W., Chertow, G. M., Rocco, M. V. 2010; 77 (7): 637-644

  Abstract

  Standard Kt/V(urea) (stdKt/V) is a hypothetical continuous clearance in patients treated with intermittent hemodialysis based on the generation rate of urea nitrogen and the average predialysis urea nitrogen. Previous equations to estimate stdKt/V were derived using a fixed-volume model. To determine the impact of fluid removal as well as residual urea clearance on stdKt/V, we modeled 245 hemodialysis sessions (including conventional 3/week, in-center 6/week, and at-home nocturnal 6/week) in 210 patients enrolled in the Frequent Hemodialysis Network Daily and Nocturnal clinical trials. To examine the role of fluid removal, modeled stdKt/V was compared to stdKt/V estimated from a previously published simplified equation. In a subgroup of 45 sessions with residual urea clearance over 1.5 ml/min, the contribution of residual urea clearance to stdKt/V was measured. For all dialysis schedules, the fixed-volume equation predicted stdKt/V well when both fluid removal and residual urea clearance were set to zero. When fluid removal was included, modeled stdKt/V was slightly underestimated for all three modes of hemodialysis. The shortfall correlated directly with weekly fluid removal and inversely with modeled urea volume. Modeled stdKt/V compressed residual urea clearance to about 70% of its measured value and the fractional downsizing significantly correlated inversely with treatment Kt/V. Our new equation predicted modeled stdKt/V with a high level of accuracy, even when substantial fluid removal and residual urea clearance were present.

  View details for DOI 10.1038/ki.2009.525

  View details for Web of Science ID 000275573500012

  View details for PubMedID 20107428

• GFR estimating equations, CKD prevalence and the public health JOURNAL OF INTERNAL MEDICINE Chang, T. I., Chertow, G. M. 2010; 267 (4): 354-356

  View details for DOI 10.1111/j.1365-2796.2009.02172.x

  View details for Web of Science ID 000275518600002

  View details for PubMedID 20433581

• Shorter dialysis times are associated with higher mortality among incident hemodialysis patients KIDNEY INTERNATIONAL Brunelli, S. M., Chertow, G. M., Ankers, E. D., Lowrie, E. G., Thadhani, R. 2010; 77 (7): 630-636

  Abstract

  There is an association between hemodialysis session length and mortality independent of the effects of session duration on urea clearance. However, previous studies did not consider changes in session length over time nor did they control for the influence of time-dependent confounding. Using data from a national cohort of 8552 incident patients on thrice-weekly, in-center hemodialysis, we applied marginal structural analysis to determine the association between session length and mortality. Exposure was based on prescribed session length with the outcome being death from any cause. On the 31st day after initiating dialysis, the patients were considered at-risk and remained so until death, censoring, or completion of 1 year on dialysis. On primary marginal structural analysis, session lengths <4 h were associated with a 42% increase in mortality. Sensitivity analyses showed a dose-response relationship between session duration and mortality, and a consistency of findings across prespecified subgroups. Our study suggests that shorter hemodialysis sessions are associated with higher mortality when marginal structural analysis was used to adjust for time-dependent confounding. Further studies are needed to confirm these findings and determine causality.

  View details for DOI 10.1038/ki.2009.523

  View details for Web of Science ID 000275573500011

  View details for PubMedID 20090666

  View details for PubMedCentralID PMC2864594

• The elderly patients on hemodialysis. Minerva urologica e nefrologica = The Italian journal of urology and nephrology Anand, S., Kurella Tamura, M., Chertow, G. M. 2010; 62 (1): 87-101

  Abstract

  Nephrologists care for an increasing number of elderly patients on hemodialysis. As such, an understanding of the overlap among complications of hemodialysis and geriatric syndromes is crucial. This article reviews hemodialysis management issues including vascular access, hypertension, anemia and bone and mineral disorders with an attention towards the distinct medical needs of the elderly. Key concepts of geriatrics frailty, dementia and palliative care are also discussed, as nephrologists frequently participate in decision-making directed toward balancing longevity, functional status and the burden of therapy.

  View details for PubMedID 20424572

• The elderly patients on hemodialysis MINERVA UROLOGICA E NEFROLOGICA Anand, S., Tamura, M. K., Chertow, G. M. 2010; 62 (1): 87-101

  Abstract

  Nephrologists care for an increasing number of elderly patients on hemodialysis. As such, an understanding of the overlap among complications of hemodialysis and geriatric syndromes is crucial. This article reviews hemodialysis management issues including vascular access, hypertension, anemia and bone and mineral disorders with an attention towards the distinct medical needs of the elderly. Key concepts of geriatrics frailty, dementia and palliative care are also discussed, as nephrologists frequently participate in decision-making directed toward balancing longevity, functional status and the burden of therapy.

  View details for Web of Science ID 000208661300008

• Projected Effect of Dietary Salt Reductions on Future Cardiovascular Disease NEW ENGLAND JOURNAL OF MEDICINE Bibbins-Domingo, K., Chertow, G. M., Coxson, P. G., Moran, A., Lightwood, J. M., Pletcher, M. J., Goldman, L. 2010; 362 (7): 590-599

  Abstract

  The U.S. diet is high in salt, with the majority coming from processed foods. Reducing dietary salt is a potentially important target for the improvement of public health.We used the Coronary Heart Disease (CHD) Policy Model to quantify the benefits of potentially achievable, population-wide reductions in dietary salt of up to 3 g per day (1200 mg of sodium per day). We estimated the rates and costs of cardiovascular disease in subgroups defined by age, sex, and race; compared the effects of salt reduction with those of other interventions intended to reduce the risk of cardiovascular disease; and determined the cost-effectiveness of salt reduction as compared with the treatment of hypertension with medications.Reducing dietary salt by 3 g per day is projected to reduce the annual number of new cases of CHD by 60,000 to 120,000, stroke by 32,000 to 66,000, and myocardial infarction by 54,000 to 99,000 and to reduce the annual number of deaths from any cause by 44,000 to 92,000. All segments of the population would benefit, with blacks benefiting proportionately more, women benefiting particularly from stroke reduction, older adults from reductions in CHD events, and younger adults from lower mortality rates. The cardiovascular benefits of reduced salt intake are on par with the benefits of population-wide reductions in tobacco use, obesity, and cholesterol levels. A regulatory intervention designed to achieve a reduction in salt intake of 3 g per day would save 194,000 to 392,000 quality-adjusted life-years and $10 billion to $24 billion in health care costs annually. Such an intervention would be cost-saving even if only a modest reduction of 1 g per day were achieved gradually between 2010 and 2019 and would be more cost-effective than using medications to lower blood pressure in all persons with hypertension.Modest reductions in dietary salt could substantially reduce cardiovascular events and medical costs and should be a public health target.

  View details for DOI 10.1056/NEJMoa0907355

  View details for Web of Science ID 000274571200007

  View details for PubMedID 20089957

  View details for PubMedCentralID PMC3066566

• Chronic Kidney Disease and Cognitive Function in Older Adults: Findings from the Chronic Renal Insufficiency Cohort Cognitive Study JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Yaffe, K., Ackerson, L., Tamura, M. K., Le Blanc, P., Kusek, J. W., Sehgal, A. R., Cohen, D., Anderson, C., Appel, L., DeSalvo, K., Ojo, A., Seliger, S., Robinson, N., Makos, G., Go, A. S. 2010; 58 (2): 338-345

  Abstract

  To investigate cognitive impairment in older, ethnically diverse individuals with a broad range of kidney function, to evaluate a spectrum of cognitive domains, and to determine whether the relationship between chronic kidney disease (CKD) and cognitive function is independent of demographic and clinical factors.Cross-sectional.Chronic Renal Insufficiency Cohort Study.Eight hundred twenty-five adults aged 55 and older with CKD.Estimated glomerular filtration rate (eGFR, mL/min per 1.73 m(2)) was estimated using the four-variable Modification of Diet in Renal Disease equation. Cognitive scores on six cognitive tests were compared across eGFR strata using linear regression; multivariable logistic regression was used to examine level of CKD and clinically significant cognitive impairment (score < or =1 standard deviations from the mean).Mean age of the participants was 64.9, 50.4% were male, and 44.5% were black. After multivariable adjustment, participants with lower eGFR had lower cognitive scores on most cognitive domains (P<.05). In addition, participants with advanced CKD (eGFR<30) were more likely to have clinically significant cognitive impairment on global cognition (adjusted odds ratio (AOR) 2.0, 95% CI=1.1-3.9), naming (AOR=1.9, 95% CI=1.0-3.3), attention (AOR=2.4, 95% CI=1.3-4.5), executive function (AOR=2.5, 95% CI=1.9-4.4), and delayed memory (AOR=1.5, 95% CI=0.9-2.6) but not on category fluency (AOR=1.1, 95% CI=0.6-2.0) than those with mild to moderate CKD (eGFR 45-59).In older adults with CKD, lower level of kidney function was associated with lower cognitive function on most domains. These results suggest that older patients with advanced CKD should be screened for cognitive impairment.

  View details for DOI 10.1111/j.1532-5415.2009.02670.x

  View details for Web of Science ID 000274183800017

  View details for PubMedID 20374407

  View details for PubMedCentralID PMC2852884

• Comparison of methods for estimating glomerular filtration rate in critically ill patients with acute kidney injury NEPHROLOGY DIALYSIS TRANSPLANTATION Bouchard, J., Macedo, E., Soroko, S., Chertow, G. M., Himmelfarb, J., Ikizler, T. A., Paganini, E. P., Mehta, R. L. 2010; 25 (1): 102-107

  Abstract

  In critically ill patients with acute kidney injury, estimates of kidney function are used to modify drug dosing, adjust nutritional therapy and provide dialytic support. However, estimating glomerular filtration rate is challenging due to fluctuations in kidney function, creatinine production and fluid balance. We hypothesized that commonly used glomerular filtration rate prediction equations overestimate kidney function in patients with acute kidney injury and that improved estimates could be obtained by methods incorporating changes in creatinine generation and fluid balance.We analysed data from a multicentre observational study of acute kidney injury in critically ill patients. We identified 12 non-dialysed, non-oliguric patients with consecutive increases in creatinine for at least 3 and up to 7 days who had measurements of urinary creatinine clearance. Glomerular filtration rate was estimated by Cockcroft-Gault, Modification of Diet in Renal Disease, Jelliffe equation and Jelliffe equation with creatinine adjusted for fluid balance (Modified Jelliffe) and compared to measured urinary creatinine clearance.Glomerular filtration rate estimated by Jelliffe and Modification of Diet in Renal Disease equation correlated best with urinary creatinine clearances. Estimated glomerular filtration rate by Cockcroft-Gault, Modification of Diet in Renal Disease and Jelliffe overestimated urinary creatinine clearance was 80%, 33%, 10%, respectively, and Modified Jelliffe underestimated GFR by 2%.In patients with acute kidney injury, glomerular filtration rate estimating equations can be improved by incorporating data on creatinine generation and fluid balance. A better assessment of glomerular filtration rate in acute kidney injury could improve evaluation and management and guide interventions.

  View details for DOI 10.1093/ndt/gfp392

  View details for Web of Science ID 000273113100019

  View details for PubMedID 19679558

  View details for PubMedCentralID PMC2910324

• Use of Standard Kt/V for Comparison of Efficiency Between Continuous Renal Replacement Therapies and Intermittent Hemodialysis in Acute Kidney Injury Claure-Del Granado, R., Macedo, E., Soroko, S., Chertow, G. M., Himmelfarb, J., Ikizler, A., Paganini, E. P., Mehta, R. L. KARGER. 2010: 229–30

  View details for Web of Science ID 000284644600028

• End-stage renal disease. Clinical evidence Abbasi, M. A., Chertow, G. M., Hall, Y. N. 2010; 2010

  Abstract

  End-stage renal disease (ESRD) affects more than 1500 people per million population in countries with a high prevalence, such as Japan, Taiwan, and the US. Approximately two-thirds of people with ESRD receive haemodialysis, one quarter have kidney transplants, and one tenth receive peritoneal dialysis. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of different doses for peritoneal dialysis? What are the effects of different doses and membrane fluxes for haemodialysis? What are the effects of interventions aimed at preventing secondary complications? We searched: Medline, Embase, The Cochrane Library, and other important databases up to October 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).We found 26 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.In this systematic review we present information relating to the effectiveness and safety of the following interventions: cinacalcet, darbepoetin, erythropoietin, haemodialysis (standard-dose, increased-dose), high membrane-flux haemodialysis, increased-dose peritoneal dialysis, low membrane-flux haemodialysis, mupirocin, sevelamer, standard-dose dialysis, and statins.

  View details for PubMedID 21418665

  View details for PubMedCentralID PMC3217820

• Fluid accumulation, recognition and staging of acute kidney injury in critically-ill patients CRITICAL CARE Macedo, E., Bouchard, J., Soroko, S. H., Chertow, G. M., Himmelfarb, J., Ikizler, T. A., Paganini, E. P., Mehta, R. L. 2010; 14 (3)

  Abstract

  Serum creatinine concentration (sCr) is the marker used for diagnosing and staging acute kidney injury (AKI) in the RIFLE and AKIN classification systems, but is influenced by several factors including its volume of distribution. We evaluated the effect of fluid accumulation on sCr to estimate severity of AKI.In 253 patients recruited from a prospective observational study of critically-ill patients with AKI, we calculated cumulative fluid balance and computed a fluid-adjusted sCr concentration reflecting the effect of volume of distribution during the development phase of AKI. The time to reach a relative 50% increase from the reference sCr using the crude and adjusted sCr was compared. We defined late recognition to estimate severity of AKI when this time interval to reach 50% relative increase between the crude and adjusted sCr exceeded 24 hours.The median cumulative fluid balance increased from 2.7 liters on day 2 to 6.5 liters on day 7. The difference between adjusted and crude sCr was significantly higher at each time point and progressively increased from a median difference of 0.09 mg/dL to 0.65 mg/dL after six days. Sixty-four (25%) patients met criteria for a late recognition to estimate severity progression of AKI. This group of patients had a lower urine output and a higher daily and cumulative fluid balance during the development phase of AKI. They were more likely to need dialysis but showed no difference in mortality compared to patients who did not meet the criteria for late recognition of severity progression.In critically-ill patients, the dilution of sCr by fluid accumulation may lead to underestimation of the severity of AKI and increases the time required to identify a 50% relative increase in sCr. A simple formula to correct sCr for fluid balance can improve staging of AKI and provide a better parameter for earlier recognition of severity progression.

  View details for DOI 10.1186/cc9004

  View details for Web of Science ID 000283781800028

  View details for PubMedID 20459609

  View details for PubMedCentralID PMC2911707

• Effects of Reduced Intradialytic Urea Generation Rate and Residual Renal Clearance on Modeled Urea Distribution Volume and Kt/V in Conventional, Daily, and Nocturnal Dialysis SEMINARS IN DIALYSIS Daugirdas, J. T., Depner, T. A., Greene, T., Levin, N. W., Chertow, G. M., Rocco, M. V., Stokes, J. B. 2010; 23 (1): 19-24

  Abstract

  Classic urea modeling assumes that both urea generation rate (G) and residual renal urea clearance (Kru) are constant throughout the week, but this may not be true. Reductions in intradialysis G could be caused by lower plasma amino acid levels due to predialysis/intradialysis fasting and also to losses of amino acids into the dialysate. Intradialytic reductions in Kru could be due to lower intravascular volume, blood pressure, or osmotic load. To determine the possible effects of reduced G or Kru during dialysis on the calculation of the volume of distribution (V) and Kt/Vurea, we modeled 3 and 6/week nocturnal, 6/week short daily, and 3/week conventional hemodialysis. A modified 2-pool mathematical model of urea mass balance with a constant time-averaged G was used, but the model was altered to allow adjustment of the ratio of dialytic/interdialytic G (Gd/Gid) and dialytic/total Kru (Krud/Kru) to vary from 1.0 down to near zero. In patients dialyzed six times per week for 400 minutes per session, when Gd/Gid was decreased from 1.0 to 0.05, the predicted urea reduction ratio (URR) increased from 68.9% to 80.2%. To achieve an increased URR of this magnitude under conditions of constant G (Gd/Gid=1.0) required a decrease in modeled urea volume (V) of 36%. At Gd/Gid ratios of 0.8 or 0.6 (corresponding to 20% or 40% reductions in intradialysis G), the modeled URR was increased to 71.0% or 73.3%, causing a 7% or 15% factitious decrease in V. The error was intermediate for the 3/week nocturnal schedule, and was much less pronounced for the 6/week daily and 3/week conventional treatments. Reductions in intradialytic Kru had the opposite effect, lowering the predicted URR and increasing the apparent V, but here the errors were of much lesser amplitude. The results suggest that, particularly for nocturnal dialysis, the standard "constant G" urea kinetic model may need to be modified.

  View details for DOI 10.1111/j.1525-139X.2009.00688.x

  View details for Web of Science ID 000274806000007

  View details for PubMedID 20331814

• Preexisting Chronic Kidney Disease: A Potential for Improved Outcomes from Acute Kidney Injury CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Khosla, N., Soroko, S. B., Chertow, G. M., Himmelfarb, J., Ikizler, T. A., Paganini, E., Mehta, R. L. 2009; 4 (12): 1914-1919

  Abstract

  Acute kidney injury (AKI) is associated with adverse outcomes in critically ill patients. The influence of preexisting chronic kidney disease (CKD) on AKI outcomes is unclear.We analyzed data from a prospective observational cohort study of AKI in critically ill patients who received nephrology consultation: the Program to Improve Care in Acute Renal Disease. In-hospital mortality rate, length of stay, and dialysis dependence were compared in patients with and without a prior history of CKD, defined by an elevated serum creatinine, proteinuria, and/or abnormal renal ultrasound within a year before hospitalization. We hypothesized that patients with AKI and prior history of CKD would have lower mortality rates, shorter lengths of stay, and higher rates of dialysis dependence than patients without prior history of CKD.Patients with AKI and a prior history of CKD were older and underwent nephrology consultation earlier in the course of AKI. In-hospital mortality rate was lower (31 versus 40%, P = 0.04), and median intensive care unit length of stay was 4.6 d shorter (14.7 versus 19.3 d, P = 0.001) in patients with a prior history of CKD. Among dialyzed survivors, patients with prior CKD were also more likely to be dialysis dependent at hospital discharge. Differences in outcome were most evident in patients with lower severity of illness.Among critically ill patients with AKI, those with prior CKD experience a lower mortality rate but are more likely to be dialysis dependent at hospital discharge. Future studies should determine optimal strategies for managing AKI with and without a prior history of CKD.

  View details for DOI 10.2215/CJN.01690309

  View details for Web of Science ID 000272587100005

  View details for PubMedID 19965524

  View details for PubMedCentralID PMC2798877

• Medication errors in chronic kidney disease: one piece in the patient safety puzzle KIDNEY INTERNATIONAL Fink, J. C., Chertow, G. M. 2009; 76 (11): 1123-1125

  Abstract

  Patients with chronic kidney disease (CKD) are at increased risk of harm as a consequence of errors in medical care. Hug and colleagues highlight the significance of adverse drug events in hospitalized patients with CKD. Their findings demonstrate the role adverse drug events play in the safety of patients with CKD and underscore the importance of novel strategies intended to reduce such medical errors.

  View details for DOI 10.1038/ki.2009.315

  View details for Web of Science ID 000271815900001

  View details for PubMedID 19910946

• Increased fluid intake does not augment capacity to lay down new collagen in nursing home residents at risk for pressure ulcers: A randomized, controlled clinical trial WOUND REPAIR AND REGENERATION Stotts, N. A., Hopf, H. W., Kayser-Jones, J., Chertow, G. M., Cooper, B. A., Wu, H. 2009; 17 (6): 780-788

  Abstract

  Prevention of pressure ulcers is fundamental to safe care of nursing home residents yet the role of hydration in pressure ulcer prevention has not been systematically examined. This randomized clinical trial was undertaken to determine whether administration of supplemental fluid to nursing home residents at risk for pressure ulcers would enhance collagen deposition, increase estimated total body water, augment subcutaneous tissue oxygenation, and was safe. After a baseline period, 64 subjects were randomized to receive the fluid volume prescribed or additional fluid (prescribed plus 10 mL/kg) for 5 days. Participants' potential to heal as measured with hydroxyproline was low at baseline and did not increase significantly during treatment when additional fluid was systematically provided. Fluid intake increased significantly during treatment. Estimates of total body water and subcutaneous oxygen did not increase, indicating hydration was not improved. Supplemental fluid did not result in overhydration as measured by clinical parameters. Further work is needed to examine the relationship between fluid intake and hydration in nursing home residents as well as the role of hydration in pressure ulcer prevention.

  View details for DOI 10.1111/j.1524-475X.2009.00539.x

  View details for Web of Science ID 000271314900003

  View details for PubMedID 19821962

• Fetuin-A and Change in Body Composition in Older Persons JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Ix, J. H., Wassel, C. L., Chertow, G. M., Koster, A., Johnson, K. C., Tylavsky, F. A., Cauley, J. A., Cummings, S. R., Harris, T. B., Shlipak, M. G. 2009; 94 (11): 4492-4498

  Abstract

  Fetuin-A inhibits the insulin receptor in vitro. Higher serum fetuin-A concentrations are associated with type 2 diabetes longitudinally and greater adiposity in cross-sectional analyses. Whether higher fetuin-A concentrations are associated with accumulation of adiposity over time is unknown.To determine the association of fetuin-A levels with changes in body composition over 5 yr.Observational cohort study nested in the Health Aging and Body Composition Study.Serum fetuin-A levels.Visceral adipose tissue (VAT), abdominal sc adipose tissue, and thigh muscle area by computed tomography, and waist circumference and body mass index were measured at baseline and again after 5 yr. Percent change and extreme change (>1.5 sds) in each measure were calculated.Over 5 yr, subjects lost body mass in each measure, including 6% decline in VAT. Yet each sd (0.42 g/liter) higher fetuin-A concentration was associated with a 5.5% increase in VAT over 5 yr (95% confidence interval 1.9-9.2%; P = 0.003) in models adjusted for age, sex, race, clinical site, diabetes, physical activity, triglycerides, kidney function, and the baseline VAT score. Similarly, higher fetuin-A concentrations were associated with extreme VAT gain (relative risk 1.70, 95% confidence interval 1.12-2.60, P = 0.01). Fetuin-A concentrations were not statistically significant associated with change in any other measures of body composition (P > 0.20).Higher fetuin-A concentrations are associated with the accumulation of VAT in well-functioning, community-living older persons. The mechanisms linking fetuin-A, VAT, and insulin resistance remain to be determined.

  View details for DOI 10.1210/jc.2009-0916

  View details for Web of Science ID 000271470800048

  View details for PubMedID 19820014

  View details for PubMedCentralID PMC2775641

• Functional Status of Elderly Adults before and after Initiation of Dialysis NEW ENGLAND JOURNAL OF MEDICINE Tamura, M. K., Covinsky, K. E., Chertow, G. M., Yaffe, K., Landefeld, C. S., McCulloch, C. E. 2009; 361 (16): 1539-1547

  Abstract

  It is unclear whether functional status before dialysis is maintained after the initiation of this therapy in elderly patients with end-stage renal disease (ESRD).Using a national registry of patients undergoing dialysis, which was linked to a national registry of nursing home residents, we identified all 3702 nursing home residents in the United States who were starting treatment with dialysis between June 1998 and October 2000 and for whom at least one measurement of functional status was available before the initiation of dialysis. Functional status was measured by assessing the degree of dependence in seven activities of daily living (on the Minimum Data Set-Activities of Daily Living [MDS-ADL] scale of 0 to 28 points, with higher scores indicating greater functional difficulty).The median MDS-ADL score increased from 12 during the 3 months before the initiation of dialysis to 16 during the 3 months after the initiation of dialysis. Three months after the initiation of dialysis, functional status had been maintained in 39% of nursing home residents, but by 12 months after the initiation of dialysis, 58% had died and predialysis functional status had been maintained in only 13%. In a random-effects model, the initiation of dialysis was associated with a sharp decline in functional status, indicated by an increase of 2.8 points in the MDS-ADL score (95% confidence interval [CI], 2.5 to 3.0); this decline was independent of age, sex, race, and functional-status trajectory before the initiation of dialysis. The decline in functional status associated with the initiation of dialysis remained substantial (1.7 points; 95% CI, 1.4 to 2.1), even after adjustment for the presence or absence of an accelerated functional decline during the 3-month period before the initiation of dialysis.Among nursing home residents with ESRD, the initiation of dialysis is associated with a substantial and sustained decline in functional status.

  View details for PubMedID 19828531

• Dialysis-requiring acute renal failure increases the risk of progressive chronic kidney disease KIDNEY INTERNATIONAL Lo, L. J., Go, A. S., Chertow, G. M., McCulloch, C. E., Fan, D., Ordonez, J. D., Hsu, C. 2009; 76 (8): 893-899

  Abstract

  To determine whether acute renal failure (ARF) increases the long-term risk of progressive chronic kidney disease (CKD), we studied the outcome of patients whose initial kidney function was normal or near normal but who had an episode of dialysis-requiring ARF and did not develop end-stage renal disease within 30 days following hospital discharge. The study encompassed 556,090 adult members of Kaiser Permanente of Northern California hospitalized over an 8 year period, who had pre-admission estimated glomerular filtration rates (eGFR) equivalent to or greater than 45 ml/min/1.73 m(2) and who survived hospitalization. After controlling for potential confounders such as baseline level of eGFR and diabetes status, dialysis-requiring ARF was independently associated with a 28-fold increase in the risk of developing stage 4 or 5 CKD and more than a twofold increased risk of death. Our study shows that in a large, community-based cohort of patients with pre-existing normal or near normal kidney function, an episode of dialysis-requiring ARF was a strong independent risk factor for a long-term risk of progressive CKD and mortality.

  View details for DOI 10.1038/ki.2009.289

  View details for Web of Science ID 000270354700018

  View details for PubMedID 19641480

  View details for PubMedCentralID PMC2771754

• Fluid accumulation, survival and recovery of kidney function in critically ill patients with acute kidney injury 41st Annual Meeting of the American-Society-of-Nephrology/Annual Renal Week Bouchard, J., Soroko, S. B., Chertow, G. M., Himmelfarb, J., Ikizler, T. A., Paganini, E. P., Mehta, R. L. NATURE PUBLISHING GROUP. 2009: 422–27

  Abstract

  Fluid accumulation is associated with adverse outcomes in critically ill patients. Here, we sought to determine if fluid accumulation is associated with mortality and non-recovery of kidney function in critically ill adults with acute kidney injury. Fluid overload was defined as more than a 10% increase in body weight relative to baseline, measured in 618 patients enrolled in a prospective multicenter observational study. Patients with fluid overload experienced significantly higher mortality within 60 days of enrollment. Among dialyzed patients, survivors had significantly lower fluid accumulation when dialysis was initiated compared to non-survivors after adjustments for dialysis modality and severity score. The adjusted odds ratio for death associated with fluid overload at dialysis initiation was 2.07. In non-dialyzed patients, survivors had significantly less fluid accumulation at the peak of their serum creatinine. Fluid overload at the time of diagnosis of acute kidney injury was not associated with recovery of kidney function. However, patients with fluid overload when their serum creatinine reached its peak were significantly less likely to recover kidney function. Our study shows that in patients with acute kidney injury, fluid overload was independently associated with mortality. Whether the fluid overload was the result of a more severe renal failure or it contributed to its cause will require clinical trials in which the role of fluid administration to such patients is directly tested.

  View details for DOI 10.1038/ki.2009.159

  View details for Web of Science ID 000268536800011

  View details for PubMedID 19436332

• Characteristics of Uninsured Americans with Chronic Kidney Disease JOURNAL OF GENERAL INTERNAL MEDICINE Hall, Y. N., Rodriguez, R. A., Boyko, E. J., Chertow, G. M., O'Hare, A. M. 2009; 24 (8): 917-922

  Abstract

  In the United States, public health insurance is available for nearly all persons with end-stage renal disease (ESRD). Little is known about the extent of health insurance coverage for persons with non-dialysis dependent chronic kidney disease (CKD).To describe patterns of health insurance coverage for adults with non-dialysis dependent CKD and to examine risk factors for progression of CKD to ESRD and management of hypertension among those lacking insurance.Cross-sectional analysis of data from a nationally representative sample of 16,148 US adults aged 20 years or older who participated in the National Health and Nutrition Examination Survey 1999-2006.National prevalence estimates of health insurance coverage, ESRD risk factors, and treatment of hypertension.An estimated 10.0% (95% CI, 8.3%-12.0%) of US adults with non-dialysis dependent CKD were uninsured, 60.9% (95% CI, 58.2%-63.7%) had private insurance and 28.7% (95% CI, 26.4%-31.1%) had public insurance alone. Uninsured persons with non-dialysis dependent CKD were more likely to be under the age of 50 (62.8% vs. 23.0%, P < 0.001) and nonwhite (58.7%, vs. 21.8%, P < 0.001) compared with their insured counterparts. Approximately two-thirds of uninsured adults with non-dialysis dependent CKD had at least one modifiable risk factor for CKD progression, including 57% with hypertension, 40% who were obese, 22% with diabetes, and 13% with overt albuminuria. In adjusted analyses, uninsured persons with non-dialysis dependent CKD were less likely to be treated for their hypertension (OR, 0.59; 95% CI, 0.40-0.85) and less likely to be receiving recommended therapy with angiotensin inhibitors (OR, 0.45; 95% CI, 0.26-0.77) compared with those with insurance coverage.Uninsured persons with non-dialysis dependent CKD are at higher risk for progression to ESRD than their insured counterparts but are less likely to receive recommended interventions to slow disease progression. Lack of public health insurance for patients with non-dialysis dependent CKD may result in missed opportunities to slow disease progression and thereby reduce the public burden of ESRD.

  View details for DOI 10.1007/s11606-009-1028-3

  View details for Web of Science ID 000268069500005

  View details for PubMedID 19506974

  View details for PubMedCentralID PMC2710472

• Frailty and Chronic Kidney Disease: The Third National Health and Nutrition Evaluation Survey AMERICAN JOURNAL OF MEDICINE Wilhelm-Leen, E. R., Hall, Y. N., Tamura, M. K., Chertow, G. M. 2009; 122 (7): 664-U86

  Abstract

  Frailty is common in the elderly and in persons with chronic diseases. Few studies have examined the association of frailty with chronic kidney disease.We used data from the Third National Health and Nutrition Examination Survey to estimate the prevalence of frailty among persons with chronic kidney disease. We created a definition of frailty based on established validated criteria, modified to accommodate available data. We used logistic regression to determine whether and to what degree stages of chronic kidney disease were associated with frailty. We also examined factors that might mediate the association between frailty and chronic kidney disease.The overall prevalence of frailty was 2.8%. However, among persons with moderate to severe chronic kidney disease (estimated glomerular filtration rate < 45 mL/min/1.73 m2), 20.9% were frail. The odds of frailty were significantly increased among all stages of chronic kidney disease, even after adjustment for the residual effects of age, sex, race, and prevalent chronic diseases. The odds of frailty associated with chronic kidney disease were only marginally attenuated with additional adjustment for sarcopenia, anemia, acidosis, inflammation, vitamin D deficiency, hypertension, and cardiovascular disease. Frailty and chronic kidney disease were independently associated with mortality.Frailty is significantly associated with all stages of chronic kidney disease and particularly with moderate to severe chronic kidney disease. Potential mechanisms underlying the chronic kidney disease and frailty connection remain elusive.

  View details for DOI 10.1016/j.amjmed.2009.01.026

  View details for PubMedID 19559169

• A randomized double-blind pilot study of serum phosphorus normalization in chronic kidney disease: A new paradigm for clinical outcomes studies in nephrology HEMODIALYSIS INTERNATIONAL Block, G. A., Persky, M. S., Ketteler, M., Kestenbaum, B., Thadhani, R., Kooienga, L., Spiegel, D., Asplin, J., Ehrlich, J., Dennis, V., Nissenson, A., Chertow, G. M., Wheeler, D. C. 2009; 13 (3): 360-362

  View details for DOI 10.1111/j.1542-4758.2009.00387.x

  View details for Web of Science ID 000269057200019

  View details for PubMedID 19601992

• The relationship between laboratory-based outcome measures and mortality in end-stage renal disease: A systematic review HEMODIALYSIS INTERNATIONAL Desai, A. A., Nissenson, A., Chertow, G. M., Farid, M., Singh, I., van Oijen, M. G., Esrailian, E., Solomon, M. D., Spiegel, B. M. 2009; 13 (3): 347-359

  Abstract

  Despite data that traditional laboratory-based outcome measures in dialysis are improving over time, population-based data indicate that mortality rates are not improving in parallel. With increased focus on performance measures based on laboratory-based outcomes (e.g., hematocrit, albumin, and parathyroid hormone), less emphasis has been placed on other markers, some of which may be stronger predictors of mortality. We performed a systematic review to interpret the predictive value of laboratory-based outcome measures in dialysis. We identified studies with data regarding the predictive value of laboratory-based outcomes for mortality in dialysis. We calculated the sample size-weighted pooled relative risk of death with dichotomized "high" vs. "low" levels of each measure. We rank-ordered predictors by scaling the pooled relative risk of each measure by its pooled standard deviation. There were 5171 titles, of which 128 (representing 44 laboratory-based outcomes) were selected. Nine were significantly associated with mortality, in order of decreasing scaled effect size: (1) tumor necrosis factor-alpha, (2) hematocrit, (3) interleukin-6, (4) troponin T, (5) Kt/V(urea), (6) prealbumin, (7) urea reduction ratio, (8) serum albumin, and (9) C-reactive protein. Other oft-cited measures such as calcium phosphate product and parathyroid hormone were not significantly associated with mortality in pooled analysis. Quality improvement efforts to improve traditional laboratory-based outcomes in end-stage renal disease are necessary, but likely insufficient, to improve overall mortality in dialysis. Renewed consideration of cardiovascular, inflammatory, and nutritional markers that are especially strong predictors of mortality may have important implications for risk stratification and targeted therapeutic interventions.

  View details for DOI 10.1111/j.1542-4758.2009.00377.x

  View details for Web of Science ID 000269057200018

  View details for PubMedID 19583604

• Phosphorus binders and survival: need for randomized trials NATURE REVIEWS NEPHROLOGY Ix, J. H., Chertow, G. M. 2009; 5 (7): 368-370

  Abstract

  An observational study suggests that administration of phosphorus binders dramatically improves survival rates in patients on incident hemodialysis-even in those without hyperphosphatemia. Randomized clinical trials should drive changes in the relevant clinical practice.

  View details for DOI 10.1038/nrneph.2009.78

  View details for Web of Science ID 000267342600003

  View details for PubMedID 19556991

• Melamine nephrotoxicity: an emerging epidemic in an era of globalization KIDNEY INTERNATIONAL Bhalla, V., Grimm, P. C., Chertow, G. M., Pao, A. C. 2009; 75 (8): 774-779

  Abstract

  Recent outbreaks of nephrolithiasis and acute kidney injury among children in China have been linked to ingestion of milk-based infant formula contaminated with melamine. These cases provide evidence in humans for the nephrotoxicity of melamine, which previously had been described only in animals. The consequences of this outbreak are already severe and will likely continue to worsen. Herein we summarize the global impact of the melamine milk contamination, the reemergence of melamine-tainted animal feed, and potential mechanisms of melamine nephrotoxicity. Large-scale epidemiologic studies are necessary to further characterize this disease and to assess its potential long-term sequelae. This epidemic of environmental kidney disease highlights the morbidity associated with adulterated food products available in today's global marketplace and reminds us of the unique vulnerability of the kidney to environmental insults. Melamine is the latest in a growing list of diverse potentially toxic compounds about which nephrologists and other health-care providers responsible for the diagnosis and management of kidney disease must now be aware.

  View details for DOI 10.1038/ki.2009.16

  View details for PubMedID 19212415

• IMPACT OF CINACALCET THERAPY ON PATIENT-REPORTED SYMPTOMS IN PATIENTS WITH MODERATE TO SEVERE SECONDARY HYPERPARATHYROIDISM Spring Clinical Meeting of the National-Kidney-Foundation Block, G. A., Xu, X., Lu, Z. J., Bushinsky, D. A., Goodman, W., Knight, T., Chertow, G. M. W B SAUNDERS CO-ELSEVIER INC. 2009: A29–A29

  View details for Web of Science ID 000264632400053

• Population Reductions in Coronary Heart Disease Associated with Modest Decreases in Salt Intake: Projections from the CHD Policy Model Bibbins-Domingo, K., Chertow, G., Moran, A., Coxson, P., Goldman, L. LIPPINCOTT WILLIAMS & WILKINS. 2009: E294

  View details for Web of Science ID 000264243700125

• Cautious Optimism Concerning Long-Term Safety of Kidney Donation. NEW ENGLAND JOURNAL OF MEDICINE Tan, J. C., Chertow, G. M. 2009; 360 (5): 522-523

  View details for Web of Science ID 000262812400015

  View details for PubMedID 19179321

• Choroidopathy and kidney disease: a case report and review of the literature. Cases journal Kamdar, N. V., Erko, A., Ehrlich, J. S., Kim, J. W., Kambham, N., Chertow, G. M. 2009; 2: 7425-?

  Abstract

  The patient was a 41 year-old Mexican American women who presented with a decrease in visual acuity along with periorbital and peripheral edema. She was diagnosed with bilateral serous retinal detachment and diffuse proliferative lupus nephritis. She improved considerably in hospital after treatment with corticosteroids.

  View details for DOI 10.1186/1757-1626-2-7425

  View details for PubMedID 19829960

• Intensity of renal replacement therapy in acute kidney injury: perspective from within the Acute Renal Failure Trial Network Study CRITICAL CARE Palevsky, P. M., O'Connor, T. Z., Chertow, G. M., Crowley, S. T., Zhang, J. H., Kellum, J. A. 2009; 13 (4)

  Abstract

  Determination of the optimal dose of renal replacement therapy in critically ill patients with acute kidney injury has been controversial. Questions have recently been raised regarding the design and execution of the US Department of Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network (ATN) Study, which demonstrated no improvement in 60-day all-cause mortality with more intensive management of renal replacement therapy. In the present article we present our rationale for these aspects of the design and conduct of the study, including our use of both intermittent and continuous modalities of renal support, our approach to initiation of study therapy and the volume management during study therapy. In addition, the article presents data on hypotension during therapy and recovery of kidney function in the perspective of other studies of renal support in acute kidney injury. Finally, we address the implications of the ATN Study results for clinical practice from the perspective of the study investigators.

  View details for DOI 10.1186/cc7901

  View details for Web of Science ID 000272225600066

  View details for PubMedID 19678919

  View details for PubMedCentralID PMC2750132

• An Empiric Estimate of the Value of Life: Updating the Renal Dialysis Cost-Effectiveness Standard VALUE IN HEALTH Lee, C. P., Chertow, G. M., Zenios, S. A. 2009; 12 (1): 80-87

  Abstract

  Proposals to make decisions about coverage of new technology by comparing the technology's incremental cost-effectiveness with the traditional benchmark of dialysis imply that the incremental cost-effectiveness ratio of dialysis is seen a proxy for the value of a statistical year of life. The frequently used ratio for dialysis has, however, not been updated to reflect more recently available data on dialysis.We developed a computer simulation model for the end-stage renal disease population and compared cost, life expectancy, and quality adjusted life expectancy of current dialysis practice relative to three less costly alternatives and to no dialysis. We estimated incremental cost-effectiveness ratios for these alternatives relative to the next least costly alternative and no dialysis and analyzed the population distribution of the ratios. Model parameters and costs were estimated using data from the Medicare population and a large integrated health-care delivery system between 1996 and 2003. The sensitivity of results to model assumptions was tested using 38 scenarios of one-way sensitivity analysis, where parameters informing the cost, utility, mortality and morbidity, etc. components of the model were by perturbed +/-50%.The incremental cost-effectiveness ratio of dialysis of current practice relative to the next least costly alternative is on average $129,090 per quality-adjusted life-year (QALY) ($61,294 per year), but its distribution within the population is wide; the interquartile range is $71,890 per QALY, while the 1st and 99th percentiles are $65,496 and $488,360 per QALY, respectively. Higher incremental cost-effectiveness ratios were associated with older age and more comorbid conditions. Sensitivity to model parameters was comparatively small, with most of the scenarios leading to a change of less than 10% in the ratio.The value of a statistical year of life implied by dialysis practice currently averages $129,090 per QALY ($61,294 per year), but is distributed widely within the dialysis population. The spread suggests that coverage decisions using dialysis as the benchmark may need to incorporate percentile values (which are higher than the average) to be consistent with the Rawlsian principles of justice of preserving the rights and interests of society's most vulnerable patient groups.

  View details for DOI 10.1111/j.1524-4733.2008.00401.x

  View details for Web of Science ID 000262696800012

  View details for PubMedID 19911442

• Regional Variation in Kidney Transplant Outcomes: Trends Over Time CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Chakkera, H. A., Chertow, G. M., O'Hare, A. M., Amend, W. J., Gonwa, T. A. 2009; 4 (1): 152-159

  Abstract

  Clinical outcomes after kidney transplant have improved considerably in the United States over the past several decades. However, the degree to which this has occurred uniformly across the country is unknown.Regional variations in graft failure after kidney transplant during three different time periods were examined. These time periods were chosen to coincide with major shifts in immunosuppressant usage: Era 1, cyclosporine usage, 1988 through 1989; Era 2, introduction of tacrolimus and mycophenolate mofetil, 1994 through 1995; and Era 3, widespread use of tacrolimus and mycophenolate mofetil, 1998 through 1999. Patient data were obtained from the United States Renal Data System database. For each period, regional differences in time from transplant to graft failure (organ removal, death, or return to dialysis) were examined. For each region, differences in graft failure over time were examined.One-year graft survival rates ranged from 76% to 83% between regions in Era 1 (n = 13,669), from 84% to 89% in Era 2 (n = 17,456), and from 87.5% to 92% in Era 3 (n = 20,375). Three-year graft survival ranged from 65% to 75% between regions in Era 1, from 84% to 89% in Era 2, and from 77% to 86% in Era 3. Adjusted models for donor and recipient characteristics showed improvements in graft survival over time in all United Network for Organ Sharing regions with minimal variation across regions.Regional differences in graft survival after kidney transplant are minimal, particularly when compared with the dramatic improvements in graft survival that have occurred over time.

  View details for DOI 10.2215/CJN.02050408

  View details for Web of Science ID 000262681200024

  View details for PubMedID 18922989

  View details for PubMedCentralID PMC2615693

• Neighborhood poverty and kidney transplantation among US Asians and Pacific Islanders with end-stage renal disease AMERICAN JOURNAL OF TRANSPLANTATION Halla, Y. N., O'Harea, A. M., Younga, B. A., Boyko, E. J., Chertow, G. M. 2008; 8 (11): 2402-2409

  Abstract

  The degree to which low transplant rates among Asians and Pacific Islanders in the United States are confounded by poverty and reduced access to care is unknown. We examined the relationship between neighborhood poverty and kidney transplant rates among 22 152 patients initiating dialysis during 1995-2003 within 1800 ZIP codes in California, Hawaii and the US-Pacific Islands. Asians and whites on dialysis were distributed across the spectrum of poverty, while Pacific Islanders were clustered in the poorest areas. Overall, worsening neighborhood poverty was associated with lower relative rates of transplant (adjusted HR [95% CI] for areas with > or =20% vs. <5% residents living in poverty, 0.41 [0.32-0.53], p < 0.001). At every level of poverty, Asians and Pacific Islanders experienced lower transplant rates compared with whites. The degree of disparity increased with worsening neighborhood poverty (adjusted HR [95% CI] for Asians-Pacific Islanders vs. whites, 0.64 [0.51-0.80], p < 0.001 for areas with <5% and 0.30 [0.21-0.44], p < 0.001 for areas with > or =20% residents living in poverty; race-poverty level interaction, p = 0.039). High levels of neighborhood poverty are associated with lower transplant rates among Asians and Pacific Islanders compared with whites. Our findings call for studies to identify cultural and local barriers to transplant among Asians and Pacific Islanders, particularly those residing in resource-poor neighborhoods.

  View details for DOI 10.1111/j.1600-6143.2008.02413.x

  View details for Web of Science ID 000259937000029

  View details for PubMedID 18808403

• Optimal Initiation and Management of Dialysis Therapy OPERATIONS RESEARCH Lee, C. P., Chertow, G. M., Zenios, S. A. 2008; 56 (6): 1428-1449

  View details for DOI 10.1287/opre.1080.0613

  View details for Web of Science ID 000263565300008

• Management of acute kidney injury in the intensive care unit - A cost-effectiveness analysis of daily vs alternate-day hemodialysis ARCHIVES OF INTERNAL MEDICINE Desai, A. A., Baras, J., Berk, B. B., Nakajima, A., Garber, A. M., Owens, D., Chertow, G. M. 2008; 168 (16): 1761-1767

  Abstract

  Although evidence suggests that a higher hemodialysis dose and/or frequency may be associated with improved outcomes, the cost-effectiveness of a daily hemodialysis strategy for critically ill patients with acute kidney injury (AKI) is unknown.We developed a Markov model of the cost, quality of life, survival, and incremental cost-effectiveness of daily hemodialysis, compared with alternate-day hemodialysis, for patients with AKI in the intensive care unit (ICU). We employed a societal perspective with a lifetime analytic time horizon. We modeled the efficacy of daily hemodialysis as a reduction in the relative risk of death on the basis of data reported in the 2004 clinical trial published by Schiffl et al. We performed 1- and 2-way sensitivity analyses across cost, efficacy, and utility input variables. The main outcome measure was cost per quality-adjusted life-year (QALY).In the base case for a 60-year-old man, daily hemodialysis was projected to add 2.14 QALYs and $10,924 in cost. We found that the cost-effectiveness of daily hemodialysis compared with alternate-day hemodialysis was $5084 per QALY gained. The incremental cost-effectiveness ratio became less favorable (>$50,000 per QALY gained) when the maintenance hemodialysis rate of the daily hemodialysis group was varied to more than 27% and when the difference in 14-day postdischarge mortality between the alternatives was varied to less than 0.5%.Daily hemodialysis is a cost-effective strategy compared with alternate-day hemodialysis for patients with severe AKI in the ICU.

  View details for PubMedID 18779463

• A comparison of change in measured and estimated glomerular filtration rate in patients with nondiabetic kidney disease CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Xie, D., Joffe, M. M., Brunelli, S. M., Beck, G., Chertow, G. M., Fink, J. C., Greene, T., Hsu, C., Kusek, J. W., Landis, R., Lash, J., Levey, A. S., O'Conner, A., Ojo, A., Rahman, M., Townsend, R. R., Wang, H., Feldman, H. I. 2008; 3 (5): 1332-1338

  Abstract

  All glomerular filtration rate (GFR) estimating equations have been developed from cross-sectional data. The aims of this study were to examine the concordance between use of measured GFR (mGFR) and estimated GFR (eGFR) in tracking changes in kidney function over time among patients with moderately severe chronic kidney disease.A retrospective cohort study of subjects who had been enrolled in the MDRD Study A and who had two or more contemporaneous assessments of mGFR and eGFR (n = 542; mGFR range, 25 to 55 ml/min per 1.73 m(2)) during the chronic phase (month 4 and afterwards). mGFR was based on urinary iothalamate clearance; eGFR was based on the 4-variable MDRD Study equation. Temporal changes in GFR were assessed by within-subject linear regression of time on GFR.Median follow-up time for all subjects was 2.6 yr; median number of GFR measurements was six. The eGFR slope tended to underestimate measured decrements in GFR. The absolute value of the difference in mGFR and eGFR slopes was

  View details for DOI 10.2215/CJN.05631207

  View details for Web of Science ID 000258757500020

  View details for PubMedID 18667734

  View details for PubMedCentralID PMC2518808

• Cost-effectiveness of frequent in-center hemodialysis JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Lee, C. P., Zenios, S. A., Chertow, G. M. 2008; 19 (9): 1792-1797

  Abstract

  Published evidence suggests that frequent hemodialysis (more than three times per week) for patients with ESRD may improve health-related quality of life and has the potential to increase longevity and reduce hospitalization and other complications. Here, a Monte Carlo simulation model was used to compare varying combinations of in-center hemodialysis frequency (three to six treatments per week) and session length (2 to 4.5 h per session) with regard to unadjusted and quality-adjusted life-years and total lifetime costs for a cohort of 200,000 patients, representing the prevalent ESRD population. The incremental cost-effectiveness ratio was calculated for the various regimens relative to a conventional hemodialysis regimen (three treatments per week, 3.5 h per session). Using conservative assumptions of the potential effects of more frequent hemodialysis on outcomes, most strategies achieved a cost-effectiveness ratio of <$125,000, although all had a cost-effectiveness ratio of >$75,000. The cost-effectiveness ratio increased with the frequency of hemodialysis. More frequent in-center hemodialysis strategies could become cost-neutral if the cost per hemodialysis session could be reduced by 32 to 43%. No other change in model assumptions achieved cost neutrality. In conclusion, given the extraordinarily high costs of the ESRD program, the viability of more frequent hemodialysis strategies depends on significant improvements in the economic model underlying the delivery of hemodialysis.

  View details for DOI 10.1681/ASN.2008010001

  View details for Web of Science ID 000259167000023

  View details for PubMedID 18614773

  View details for PubMedCentralID PMC2518444

• Surface-Area-Normalized Kt/V: A Method of Rescaling Dialysis Dose to Body Surface Area-Implications for Different-Size Patients by Gender SEMINARS IN DIALYSIS Daugirdas, J. T., Depner, T. A., Greene, T., Kuhlmann, M. K., Levin, N. W., Chertow, G. M., Rocco, M. V. 2008; 21 (5): 415-421

  Abstract

  Dialysis is measured as Kt/V, which scales the dose (Kt) to body water content (V). Scaling dialysis dose to body surface area (S(dub)) has been advocated, but the implications of such rescaling have not been examined. We developed a method of rescaling measured Kt/V to S(dub) and studied the effect of such alternative scaling on the minimum adequacy values that might then be applied in male and female patients of varying body size. We examined anthropometric estimates of V and S (Watson vs. Dubois estimates) in 1765 patients enrolled in the HEMO study after excluding patients with amputations. An S-normalized target stdKt/V was defined, and an adequacy ratio (R) was computed for each patient as R = D/N where D = delivered stdKt/V (calculated using the Gotch-Leypoldt equation for stdKt/V) and N = the S-normalized minimum target value. In the HEMO data set, we determined the extent to which baseline (prerandomization) stdKt/V values would have exceeded such an S-based minimum target stdKt/V. The median V(wat):S(dub) ratios were significantly higher in men (21.34) than in women (18.50). The average of these (20) was used to normalize the current suggested minimally adequate value (stdKt/V > or = 2.0/week) to the S-normalized target value (stdKt/S > or = 40 L/M(2)), assuming that average modeled V = average anthropometric V. To achieve this S-normalized target, the required single-pool (sp) Kt/V was always higher in women than in men at any level of body size. For small patients (V(wat) = 25L), required stdKt/V values were 2.05 and 2.21/week for men and women, respectively, corresponding to spKt/V values of 1.31 and 1.52/session. On the other hand, large (V(wat) = 50L) male patients would need spKt/V values of only 1.0/session. Prerandomization baseline dialysis sessions in the HEMO study were found to meet such a new S-based standard in almost all (766/773) men and in 885/992 women. An analysis of scaling dose to anthropometrically estimated liver size (L) showed similar gender ratios for V(wat):L and V(wat):S(dub), providing a potential physiologic explanation underpinning S-based scaling. S-based scaling of the dialysis dose would require considerably higher doses in small patients and in women, and would allow somewhat lower doses in larger male patients. Current dialysis practice would largely meet such an S-based adequacy standard if the dose were normalized to a V(wat):S(dub) ratio of 20.

  View details for DOI 10.1111/j.1525-139X.2008.00482.x

  View details for Web of Science ID 000260253000010

  View details for PubMedID 18945330

  View details for PubMedCentralID PMC2692381

• Comparison of Proposed Alternative Methods for Rescaling Dialysis Close: Resting Energy Expenditure, High Metabolic Rate Organ Mass, Liver Size, and Body Surface Area SEMINARS IN DIALYSIS Daugirdas, J. T., Levin, N. W., Kotanko, P., Depner, T. A., Kuhlmann, M. K., Chertow, G. M., Rocco, M. V. 2008; 21 (5): 377-384

  Abstract

  A number of denominators for scaling the dose of dialysis have been proposed as alternatives to the urea distribution volume (V). These include resting energy expenditure (REE), mass of high metabolic rate organs (HMRO), visceral mass, and body surface area. Metabolic rate is an unlikely denominator as it varies enormously among humans with different levels of activity and correlates poorly with the glomerular filtration rate. Similarly, scaling based on HMRO may not be optimal, as many organs with high metabolic rates such as spleen, brain, and heart are unlikely to generate unusually large amounts of uremic toxins. Visceral mass, in particular the liver and gut, has potential merit as a denominator for scaling; liver size is related to protein intake and the liver, along with the gut, is known to be responsible for the generation of suspected uremic toxins. Surface area is time-honored as a scaling method for glomerular filtration rate and scales similarly to liver size. How currently recommended dialysis doses might be affected by these alternative rescaling methods was modeled by applying anthropometric equations to a large group of dialysis patients who participated in the HEMO study. The data suggested that rescaling to REE would not be much different from scaling to V. Scaling to HMRO mass would mandate substantially higher dialysis doses for smaller patients of either gender. Rescaling to liver mass would require substantially more dialysis for women compared with men at all levels of body size. Rescaling to body surface area would require more dialysis for smaller patients of either gender and also more dialysis for women of any size. Of these proposed alternative rescaling measures, body surface area may be the best, because it reflects gender-based scaling of liver size and thereby the rate of generation of uremic toxins.

  View details for DOI 10.1111/j.1525-139X.2008.00483.x

  View details for Web of Science ID 000260253000001

  View details for PubMedID 18945324

  View details for PubMedCentralID PMC2692384

• Intensity of renal support in critically ill patients with acute kidney injury NEW ENGLAND JOURNAL OF MEDICINE Palevsky, P. M., Zhang, J. H., O'Connor, T. Z., Chertow, G. M., Crowley, S. T., Choudhury, D., Finkel, K., Kellum, J. A., Paganini, E., Schein, R. M., Smith, M. W., Swanson, K. M., Thompson, B. T., Vijayan, A., Watnick, S., Star, R. A., Peduzzi, P. 2008; 359 (1): 7-20

  Abstract

  The optimal intensity of renal-replacement therapy in critically ill patients with acute kidney injury is controversial.We randomly assigned critically ill patients with acute kidney injury and failure of at least one nonrenal organ or sepsis to receive intensive or less intensive renal-replacement therapy. The primary end point was death from any cause by day 60. In both study groups, hemodynamically stable patients underwent intermittent hemodialysis, and hemodynamically unstable patients underwent continuous venovenous hemodiafiltration or sustained low-efficiency dialysis. Patients receiving the intensive treatment strategy underwent intermittent hemodialysis and sustained low-efficiency dialysis six times per week and continuous venovenous hemodiafiltration at 35 ml per kilogram of body weight per hour; for patients receiving the less-intensive treatment strategy, the corresponding treatments were provided thrice weekly and at 20 ml per kilogram per hour.Baseline characteristics of the 1124 patients in the two groups were similar. The rate of death from any cause by day 60 was 53.6% with intensive therapy and 51.5% with less-intensive therapy (odds ratio, 1.09; 95% confidence interval, 0.86 to 1.40; P=0.47). There was no significant difference between the two groups in the duration of renal-replacement therapy or the rate of recovery of kidney function or nonrenal organ failure. Hypotension during intermittent dialysis occurred in more patients randomly assigned to receive intensive therapy, although the frequency of hemodialysis sessions complicated by hypotension was similar in the two groups.Intensive renal support in critically ill patients with acute kidney injury did not decrease mortality, improve recovery of kidney function, or reduce the rate of nonrenal organ failure as compared with less-intensive therapy involving a defined dose of intermittent hemodialysis three times per week and continuous renal-replacement therapy at 20 ml per kilogram per hour. (ClinicalTrials.gov number, NCT00076219.)

  View details for Web of Science ID 000257246000003

  View details for PubMedID 18492867

  View details for PubMedCentralID PMC2574780

• Combined therapy with cinacalcet and low doses of vitamin D sterols in patients with moderate to severe secondary hyperparathyroidism NEPHROLOGY DIALYSIS TRANSPLANTATION Block, G. A., Zeig, S., Sugihara, J., Chertow, G. M., Chi, E. M., Turner, S. A., Bushinsky, D. A. 2008; 23 (7): 2311-2318

  Abstract

  Adequate control of all four KDOQI biochemical targets for chronic kidney disease, bone and mineral disorder (CKD-MBD), which include parathyroid hormone (PTH), calcium (Ca), phosphorus (P) and Ca x P, remains difficult and is accomplished in <6% of patients receiving haemodialysis. The objective of the current study was to determine whether treatment with cinacalcet combined with low doses of vitamin D sterols improves control of both PTH and Ca x P among haemodialysis patients with secondary hyperparathyroidism (sHPT).This multicentre, open-label study enrolled haemodialysis subjects (N = 444) with moderate to severe sHPT (mean serum biPTH > 160-430 pg/mL) (approximately iPTH 300-800 pg/mL or ng/L). Cinacalcet was titrated sequentially (30-180 mg/day) during an 8-week dose-titration phase to achieve biPTH

  View details for DOI 10.1093/ndt/gfn026

  View details for Web of Science ID 000257413600034

  View details for PubMedID 18310602

• Higher serum creatinine concentrations in black patients with chronic kidney disease: Beyond nutritional status and body composition CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Hsu, J., Johansen, K. L., Hsu, C., Kaysen, G. A., Chertow, G. M. 2008; 3 (4): 992-997

  Abstract

  Serum creatinine concentrations tend to be higher in black than white individuals and people of other races or ethnicities. These differences have been assumed to be largely related to race-related differences in body composition, especially muscle mass.In a diverse population of hemodialysis patients, we compared mean serum creatinine concentrations in black versus nonblack patients, adjusting for case mix (age, gender, diabetes, and dialysis vintage), body size (height, weight), laboratory parameters of nutritional status (albumin, predialysis blood urea nitrogen, transferrin, phosphorus, glucose), dialysis dosage (urea reduction ratio), and parameters of bioelectrical impedance (resistance and reactance), proxies for body composition.Adjusted mean serum creatinine concentrations were significantly higher in black versus nonblack patients (11.7 versus 10.0 mg/dl; P < 0.0001). Black patients were roughly four-fold more likely to have a serum creatinine concentration >10 mg/dl and six-fold more likely to have a serum creatinine concentration >15 mg/dl. Higher serum creatinine concentrations were associated with a lower relative risk for death (0.93; 95% confidence interval 0.88 to 0.98 per mg/dl); the association was slightly more pronounced among nonblack patients.Serum creatinine concentrations are significantly higher in black compared with nonblack hemodialysis patients; these differences are not readily explained by differences in nutritional status or body composition.

  View details for DOI 10.2215/CJN.00090108

  View details for PubMedID 18417750

• The risk of acute renal failure in patients with chronic kidney disease KIDNEY INTERNATIONAL Hsu, C. Y., Ordonez, J. D., Chertow, G. M., Fan, D., McCulloch, C. E., Go, A. S. 2008; 74 (1): 101-107

  Abstract

  Few studies have defined how the risk of hospital-acquired acute renal failure varies with the level of estimated glomerular filtration rate (GFR). It is also not clear whether common factors such as diabetes mellitus, hypertension and proteinuria increase the risk of nosocomial acute renal failure independent of GFR. To determine this we compared 1,746 hospitalized adult members of Kaiser Permanente Northern California who developed dialysis-requiring acute renal failure with 600,820 hospitalized members who did not. Patient GFR was estimated from the most recent outpatient serum creatinine measurement prior to admission. The adjusted odds ratios were significantly and progressively elevated from 1.95 to 40.07 for stage 3 through stage 5 patients (not yet on maintenance dialysis) compared to patients with estimated GFR in the stage 1 and 2 range. Similar associations were seen after controlling for inpatient risk factors. Pre-admission baseline diabetes mellitus, diagnosed hypertension and known proteinuria were also independent risk factors for acute kidney failure. Our study shows that the propensity to develop in-hospital acute kidney failure is another complication of chronic kidney disease whose risk markedly increases even in the upper half of stage 3 estimated GFR. Several common risk factors for chronic kidney disease also increase the peril of nosocomial acute kidney failure.

  View details for DOI 10.1038/ki.2008.107

  View details for Web of Science ID 000256788900014

  View details for PubMedID 18385668

  View details for PubMedCentralID PMC2673528

• Lessons for successful study enrollment from the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network Study 39th Annual Meeting of the American-Society-of-Nephrology/Annual Renal Week Crowley, S. T., Chertow, G. M., Vitale, J., O'Connor, T., Zhang, J., Schein, R. M., Choudhury, D., Finkel, K., Vijayan, A., Paganini, E., Palevsky, P. M. AMER SOC NEPHROLOGY. 2008: 955–61

  Abstract

  Design elements of clinical trials can introduce recruitment bias and reduce study efficiency. Trials involving the critically ill may be particularly prone to design-related inefficiencies.Enrollment into the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network Study was systematically monitored. Reasons for nonenrollment into this study comparing strategies of renal replacement therapy in critically ill patients with acute kidney injury were categorized as modifiable or nonmodifiable.4339 patients were screened; 2744 fulfilled inclusion criteria. Of these, 1034 were ineligible by exclusion criteria. Of the remaining 1710 patients, 1124 (65.7%) enrolled. Impediments to informed consent excluded 21.4% of potentially eligible patients. Delayed identification of potential patients, physician refusal, and involvement in competing trials accounted for 4.4, 2.7, and 2.3% of exclusions. Comfort measures only status, chronic illness, chronic kidney disease, and obesity excluded 11.8, 7.8, 7.6, and 5.9% of potential patients. Modification of an enrollment window reduced the loss of patients from 6.6 to 2.3%.The Acute Renal Failure Trial Network Study's enrollment efficiency compared favorably with previous intensive care unit intervention trials and supports the representativeness of its enrolled population. Impediments to informed consent highlight the need for nontraditional acquisition methods. Restrictive enrollment windows may hamper recruitment but can be effectively modified. The low rate of physician refusal acknowledges clinical equipoise in the study design. Underlying comorbidities are important design considerations for future trials that involve the critically ill with acute kidney injury.

  View details for DOI 10.2215/CJN.05621207

  View details for Web of Science ID 000257260700006

  View details for PubMedID 18385390

  View details for PubMedCentralID PMC2440269

• Trends and outcomes associated with serum albumin concentration among incident dialysis patients in the United States JOURNAL OF RENAL NUTRITION Kaysen, G. A., Johansen, K. L., Cheng, S., Jin, C., Chertow, G. M. 2008; 18 (4): 323-331

  Abstract

  Serum albumin concentrations are associated with mortality, and respond to nutritional and inflammatory states. To explore whether changing demographics and practice patterns in dialysis have influenced serum albumin concentrations, we analyzed trends in serum albumin among incident patients on dialysis from 1995 through 2004.Mean serum albumin concentrations declined significantly over time, even after accounting for changes in age, diabetes, body size, and other factors. Although laboratory assays were not uniform within or across years, serum albumin declined over time, regardless of the reported laboratory lower limit of normal. Moreover, serum albumin retained its potent association with mortality over time. Lower serum albumin was especially hazardous among younger patients and blacks, and was less hazardous among persons with diabetes as a primary cause of kidney disease.Despite higher body weights and the initiation of dialysis earlier in the course of progressive chronic kidney disease, hypoalbuminemia remains common and hazardous to persons starting dialysis.

  View details for DOI 10.1053/j.jrn.2008.04.002

  View details for Web of Science ID 000257637800001

  View details for PubMedID 18558296

• High-molecular weight iron dextran: A wolf in sheep's clothing? JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Rodgers, G. M., Auerbach, M., Cella, D., Chertow, G. M., Coyne, D. W., Glaspy, J. A., Henry, D. H. 2008; 19 (5): 833-834

  View details for Web of Science ID 000255423300001

  View details for PubMedID 18369084

• Diagnosis, epidemiology and outcomes of acute kidney injury CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Waikar, S. S., Liu, K. D., Chertow, G. M. 2008; 3 (3): 844-861

  Abstract

  Acute kidney injury is an increasingly common and potentially catastrophic complication in hospitalized patients. Early observational studies from the 1980s and 1990s established the general epidemiologic features of acute kidney injury: the incidence, prognostic significance, and predisposing medical and surgical conditions. Recent multicenter observational cohorts and administrative databases have enhanced our understanding of the overall disease burden of acute kidney injury and trends in its epidemiology. An increasing number of clinical studies focusing on specific types of acute kidney injury (e.g., in the setting of intravenous contrast, sepsis, and major surgery) have provided further details into this heterogeneous syndrome. Despite our sophisticated understanding of the epidemiology and pathobiology of acute kidney injury, current prevention strategies are inadequate and current treatment options outside of renal replacement therapy are nonexistent. This failure to innovate may be due in part to a diagnostic approach that has stagnated for decades and continues to rely on markers of glomerular filtration (blood urea nitrogen and creatinine) that are neither sensitive nor specific. There has been increasing interest in the identification and validation of novel biomarkers of acute kidney injury that may permit earlier and more accurate diagnosis. This review summarizes the major epidemiologic studies of acute kidney injury and efforts to modernize the approach to its diagnosis.

  View details for DOI 10.2215/CJN.05191107

  View details for Web of Science ID 000255382300030

  View details for PubMedID 18337550

• Toward the promise of renal replacement therapy JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Chertow, G. M., Waikar, S. S. 2008; 19 (5): 839-840

  View details for DOI 10.1681/ASN.2008030291

  View details for Web of Science ID 000255423300004

  View details for PubMedID 18385414

• Giving supplemental fluid to older nursing home residents is safe but may not reduce under-hydration Stotts, N. A., Hopf, H. W., Kayser-Jones, J., Chertow, G., Cooper, B. A., Wu, H. S. BLACKWELL PUBLISHING. 2008: A27

  View details for Web of Science ID 000253761000084

• Increased fluid alone does not increase hydroxyproline levels in older nursing home residents at-risk for pressure ulcers Stotts, N. A., Hopf, H. W., Kayser-Jones, J., Chertow, G., Cooper, B. A., Wu, H. S. BLACKWELL PUBLISHING. 2008: A26

  View details for Web of Science ID 000253761000081

• Kidney dysfunction and fatal cardiovascular disease - an association independent of atherosclerotic events: Results from the Health, Aging, and Body Composition (Health ABC) study AMERICAN HEART JOURNAL Deo, R., Fyr, C. L., Fried, L. F., Newman, A. B., Harris, T. B., Angleman, S., Green, C., Kritchevsky, S. B., Chertow, G. M., Cummings, S. R., Shlipak, M. G. 2008; 155 (1): 62-68

  Abstract

  Impaired kidney function has been associated with increased risk for death, myocardial infarction, stroke, and heart failure in high-risk populations. We evaluated whether impaired kidney function predicted risk of fatal cardiovascular disease independent of prevalent and incident cardiovascular events.The Health, Aging, and Body Composition study is a cohort of well-functioning, elderly participants aged 70 to 79 years at entry. We measured serum cystatin C and creatinine from baseline plasma samples of 3044 participants and followed them over 6 years, examining the associations among kidney function, cardiovascular death, and incident cardiovascular events. Cystatin C was categorized as low (< 0.84 mg/L), medium (0.84-1.18 mg/L), or high (> or = 1.19 mg/L); serum creatinine (cutoff value of > or = 1.3 in women and > or = 1.5 in men) and estimated glomerular filtration rate (eGFR; greater and less than 60 mL/min per 1.73 m2) were dichotomized.During follow-up, 242 cardiovascular deaths occurred, of which 69 were in participants without prior cardiovascular events; 294 incident cardiovascular events occurred including 135 myocardial infarctions and 163 strokes. Higher cystatin C concentrations were significantly associated with cardiovascular death (adjusted hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.05-2.76 for the medium cystatin C group; and HR 2.24, 95% CI 1.30-3.86 for the high cystatin C group, relative to the low cystatin C group). The point estimate was of greater magnitude in the analysis that excluded prevalent cardiovascular disease (adjusted HR 2.68, 95% CI 0.94-7.70 for the medium cystatin C group; and HR 4.91, 95% CI, 1.55-15.54 for the high cystatin C group). Elevated creatinine levels (adjusted HR 1.54, 95% CI 1.02-2.33, and HR 2.28, 95% CI 1.10-4.73 among participants without a history of cardiovascular disease) were also associated with cardiovascular death. No significant association was found between low eGFR and cardiovascular death. In addition, cystatin C, low eGFR, or elevated creatinine levels were not associated with other cardiovascular events.Impaired kidney function is a strong predictor of cardiovascular death, particularly among participants without prior history of cardiovascular disease.

  View details for DOI 10.1016/j.ahj.2007.08.012

  View details for Web of Science ID 000251732400010

  View details for PubMedID 18082491

• Predictive and pathogenetic value of plasma biomarkers for acute kidney injury in patients with acute lung injury CRITICAL CARE MEDICINE Liu, K. D., Glidden, D. V., Eisner, M. D., Parsons, P. E., Ware, L. B., Wheeler, A., Korpak, A., Thompson, T., Chertow, G. M., Matthay, M. A. 2007; 35 (12): 2755-2761

  Abstract

  To identify biological and clinical predictors of acute kidney injury in subjects with acute lung injury.Secondary data analysis from a multicenter, randomized clinical trial.Intensive care units in ten university medical centers.A total of 876 patients enrolled in the first National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Clinical Network trial.Study subjects were randomized to receive a low tidal volume ventilation strategy and pharmacologic therapy with ketoconazole or lisofylline in a factorial design.We tested the association of baseline levels of interleukin-6, interleukin-8, interleukin-10, von Willebrand factor, tumor necrosis factor-[alpha], type I and II soluble tumor necrosis factor receptors (sTNFR-I and -II), protein C, plasminogen activator inhibitor-1 (PAI-1), surfactant protein-A, surfactant protein-D, and intracellular adhesion molecule-1 with subsequent acute kidney injury. Of 876 study participants who did not have end-stage renal disease, 209 (24%) developed acute kidney injury, defined as a rise in serum creatinine of >50% from baseline over the first four study days. The 180-day mortality rate for subjects with acute kidney injury was 58%, compared with 28% in those without acute kidney injury (p < .001). Interleukin-6, sTNFR-I, sTNFR-II, and PAI-1 levels were independently associated with acute kidney injury after adjustment for demographics, interventions, and severity of illness. A combination of clinical and biological predictors had the best area under the receiver operating characteristic curve, and the contribution of sTNFR-I and PAI-1 to this model was highly significant (p = .0003).Elevations in PAI-1, interleukin-6, and the sTNFRs in subjects with acute kidney injury suggest that disordered coagulation, inflammation, and neutrophil-endothelial interactions play important roles in the pathogenesis of acute kidney injury. The combination of these biological and clinical risk factors may have important and additive value in predictive models for acute kidney injury.

  View details for DOI 10.1097/01.CCM.0000291649.72238.6D

  View details for Web of Science ID 000251346700012

  View details for PubMedID 18074478

  View details for PubMedCentralID PMC3293249

• Significance of frailty among dialysis patients JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Johansen, K. L., Chertow, G. M., Jin, C., Kutner, N. G. 2007; 18 (11): 2960-2967

  View details for DOI 10.1681/ASN.2007020221

  View details for Web of Science ID 000250737600025

  View details for PubMedID 17942958

• Kidney function as a predictor of loss of lean mass in older adults: Health, aging and body composition study JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Fried, L. F., Boudreau, R., Lee, J. S., Chertow, G., Kurella-Tamura, M., Shlipak, M. G., Ding, J., Sellmeyer, D., Tylavsky, F. A., Simsonick, E., Kritchevsky, S. B., Harris, T. B., Newman, A. B. 2007; 55 (10): 1578-1584

  Abstract

  To assess the association between kidney function and change in body composition in older individuals.Prospective cohort study.Two sites, Pittsburgh, Pennsylvania, and Memphis, Tennessee.Three thousand twenty-six well-functioning, participants aged 70 to 79 in the Health, Aging and Body Composition Study.Body composition (bone-free lean mass and fat mass) was measured using dual x-ray absorptiometry annually for 4 years. Kidney function was measured at baseline according to serum creatinine (SCr). Comorbidity and inflammatory markers were evaluated as covariates in mixed-model, repeated-measures analysis.High SCr was associated with loss of lean mass in men but not women, with a stronger relationship in black men (P=.02 for difference between slopes for white and black men). In white men, after adjustment for age and comorbidity, higher SCr remained associated with loss of lean mass (-0.07+/-0.03 kg/y greater loss per 0.4 mg/dL (1 standard deviation (SD)), P=.009) but was attenuated after adjustment for inflammatory factors (-0.05+/-0.03 kg/y greater loss per SD, P=.10). In black men, the relationship between SCr and loss of lean mass (-0.19+/-0.04 kg/y per SD, P<.001) persisted after adjustment for inflammation and overall weight change.Impaired kidney function may contribute to loss of lean mass in older men. Inflammation appeared to mediate the relationship in white but not black men. Future studies should strive to elucidate mechanisms linking kidney disease and muscle loss and identify treatments to minimize loss of lean mass and its functional consequences.

  View details for DOI 10.1111/j.1532-5415.2007.01398.x

  View details for Web of Science ID 000249825500011

  View details for PubMedID 17908060

• Race and mortality after acute renal failure JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Waikar, S. S., Curhan, G. C., Ayanian, J. Z., Chertow, G. M. 2007; 18 (10): 2740-2748

  Abstract

  Black patients receiving dialysis for end-stage renal disease in the United States have lower mortality rates than white patients. Whether racial differences exist in mortality after acute renal failure is not known. We studied acute renal failure in patients hospitalized between 2000 and 2003 using the Nationwide Inpatient Sample and found that black patients had an 18% (95% confidence interval [CI] 16 to 21%) lower odds of death than white patients after adjusting for age, sex, comorbidity, and the need for mechanical ventilation. Similarly, among those with acute renal failure requiring dialysis, black patients had a 16% (95% CI 10 to 22%) lower odds of death than white patients. In stratified analyses of patients with acute renal failure, black patients had significantly lower adjusted odds of death than white patients in settings of coronary artery bypass grafting, cardiac catheterization, acute myocardial infarction, congestive heart failure, pneumonia, sepsis, and gastrointestinal hemorrhage. Black patients were more likely than white patients to be treated in hospitals that care for a larger number of patients with acute renal failure, and black patients had lower in-hospital mortality than white patients in all four quartiles of hospital volume. In conclusion, in-hospital mortality is lower for black patients with acute renal failure than white patients. Future studies should assess the reasons for this difference.

  View details for DOI 10.1681/ASN.2006091060

  View details for Web of Science ID 000250985900017

  View details for PubMedID 17855647

  View details for PubMedCentralID PMC3023164

• Chronic kidney disease mineral bone disorder and health-related quality of life among incident end-stage renal-disease patients JOURNAL OF RENAL NUTRITION Johansen, K. L., Chertow, G. M. 2007; 17 (5): 305-313

  Abstract

  Our objective was to determine the extent to which chronic kidney disease mineral bone disorder (CKD-MBD) is associated with health-related quality of life among incident dialysis patients.This study's design was a cross-sectional analysis.This was part of the United States Renal Data System Dialysis Morbidity and Mortality Study (DMMS), Wave 2.The patients comprised 2590 adult participants in DMMS Wave 2, for whom quality of life and laboratory data were available.We stratified patients according to their serum concentrations of phosphorus, calcium, and parathyroid hormone (PTH), and compared health-related quality of life as a function of these indicators in analyses adjusted for demographic, clinical, and other laboratory variables.Main outcome measures included Physical Component Summary (PCS) and Mental Component Summary (MCS) scores, and the Symptom score of the Kidney Disease Quality of Life.Both high and low serum phosphorus concentrations were associated with lower PCS scores (-1.25 to -1.48 points compared with the reference category), as was low PTH (-1.49 points). Low serum phosphorus was associated with more severe symptoms of kidney disease (-3.88 points), but there were no associations between high phosphorus or either extreme of PTH and the Symptom score. Serum calcium concentration and the calcium x phosphorus product were unassociated with PCS or Symptom scores. There were no associations among phosphorus, calcium, or PTH and MCS. Analyses simultaneously controlling for serum phosphorus, calcium, and PTH showed similar results.High and low serum phosphorus and low PTH are associated with slightly poorer self-reported physical functioning. Clinical trials will be necessary to determine whether and to what extent improvement in health status may occur with the correction of selected disorders of mineral metabolism.

  View details for DOI 10.1053/j.jrn.2007.06.005

  View details for Web of Science ID 000249688400003

  View details for PubMedID 17720099

  View details for PubMedCentralID PMC2737501

• Evaluation of cinacalcet therapy to lower cardiovascular events (EVOLVE): Rationale and design overview CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Chertow, G. M., Pupim, L. B., Block, G. A., Correa-Rotter, R., Drueke, T. B., Floege, J., Goodman, W. G., London, G. M., Mahaffey, K. W., Moe, S. M., Wheeler, D. C., Albizem, M., Olson, K., Klassen, P., Parfrey, P. 2007; 2 (5): 898-905

  Abstract

  The dramatically high rates of mortality and cardiovascular morbidity observed among dialysis patients highlights the importance of identifying and implementing strategies to lower cardiovascular risk in this population. Results from clinical trials undertaken thus far, including trials on lipid reduction, normalization of hematocrit, and increased dialysis dosage, have been unsuccessful. Available data indicate that abnormalities in calcium and phosphorus metabolism, as a result of either secondary hyperparathyroidism alone or the therapeutic measures used to manage secondary hyperparathyroidism, are associated with an increased risk for death and cardiovascular events. However, no prospective trials have evaluated whether interventions that modify these laboratory parameters result in a reduction in adverse cardiovascular outcomes.Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events is a global, phase 3, double-blind, randomized, placebo-controlled trial evaluating the effects of cinacalcet on mortality and cardiovascular events in hemodialysis patients with secondary hyperparathyroidism. Approximately 3800 patients from 22 countries will be randomly assigned to cinacalcet or placebo. Flexible use of traditional therapies will be permitted. The primary end point is the composite of time to all-cause mortality or first nonfatal cardiovascular event (myocardial infarction, hospitalization for unstable angina, heart failure, or peripheral vascular disease, including lower extremity revascularization and nontraumatic amputation).The study will be event driven (terminated at 1882 events) with an anticipated duration of approximately 4 yr.Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events will determine whether management of secondary hyperparathyroidism with cinacalcet reduces the risk for mortality and cardiovascular events in hemodialysis patients.

  View details for DOI 10.2215/CJN.04381206

  View details for Web of Science ID 000249039500007

  View details for PubMedID 17702710

• Rise of pay for performance: Implications for care of people with chronic kidney disease CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Desai, A. A., Garber, A. M., Chertow, G. M. 2007; 2 (5): 1087-1095

  Abstract

  Many health care providers and policy makers believe that health care financing systems fail to reward high-quality care. In recent years, federal and private payers have begun to promote pay for performance, or value-based purchasing, initiatives to raise the quality of care. This report describes conceptual issues in the design and implementation of pay for performance for chronic kidney disease and ESRD care. It also considers the implications of recent ESRD payment policy changes on the broader goals of pay for performance. Congressionally mandated bundle payment demonstration for dialysis, newly implemented case-mix adjustment of the composite rate, and G codes for the monthly capitation payment are important opportunities to understand facility and provider behavior with particular attention to patient selection and treatment practices. Well-designed payment systems will reward quality care for patients while maintaining appropriate accountability and fairness for health care providers.

  View details for DOI 10.2215/CJN.00510107

  View details for PubMedID 17702735

• Community-based incidence of acute renal failure KIDNEY INTERNATIONAL Hsu, C., McCulloch, C. E., Fan, D., Ordonez, J. D., Chertow, G. M., Go, A. S. 2007; 72 (2): 208-212

  Abstract

  There is limited information about the true incidence of acute renal failure (ARF). Most studies could not quantify disease frequency in the general population as they are hospital-based and confounded by variations in threshold and the rate of hospitalization. Earlier studies relied on diagnostic codes to identify non-dialysis requiring ARF. These underestimated disease incidence since the codes have low sensitivity. Here we quantified the incidence of non-dialysis and dialysis-requiring ARF among members of a large integrated health care delivery system - Kaiser Permanente of Northern California. Non-dialysis requiring ARF was identified using changes in inpatient serum creatinine values. Between 1996 and 2003, the incidence of non-dialysis requiring ARF increased from 322.7 to 522.4 whereas that of dialysis-requiring ARF increased from 19.5 to 29.5 per 100,000 person-years. ARF was more common in men and among the elderly, although those aged 80 years or more were less likely to receive acute dialysis treatment. We conclude that the use of serum creatinine measurements to identify cases of non-dialysis requiring ARF resulted in much higher estimates of disease incidence compared with previous studies. Both dialysis-requiring and non-dialysis requiring ARFs are becoming more common. Our data underscore the public health importance of ARF.

  View details for DOI 10.1038/sj.ki.5002297

  View details for Web of Science ID 000248220100012

  View details for PubMedID 17507907

  View details for PubMedCentralID PMC2673495

• Association of fetuin-A with mitral annular calcification and aortic stenosis among persons with coronary heart disease - Data from the heart and soul study CIRCULATION Ix, J. H., Chertow, G. M., Shlipak, M. G., Brandenburg, V. M., Ketteler, M., Whooley, M. A. 2007; 115 (19): 2533-2539

  Abstract

  Fetuin-A is a multifunctional hepatic secretory protein that inhibits dystrophic vascular and valvular calcification. Lower serum fetuin-A concentrations are associated with valvular calcification in persons with end-stage renal disease. Whether fetuin-A is associated with valvular calcification in other patient populations is unknown.We evaluated the associations among serum fetuin-A concentrations, mitral annular calcification, and aortic stenosis in 970 ambulatory persons with coronary heart disease and without severe kidney disease. The presence or absence of mitral annular calcification and aortic stenosis was determined by transthoracic echocardiography. The subjects' mean age was 66 years; 81% were men; 189 (20%) had mitral annular calcification; and 79 (8%) had aortic stenosis. Participants were categorized by tertiles of fetuin-A concentrations. Those within the highest fetuin-A tertile had significantly lower odds of mitral annular calcification compared with the lowest tertile (adjusted odds ratio, 0.47; 95% confidence interval, 0.29 to 0.77; P=0.002); this association was similar regardless of diabetes status (P for interaction=0.34). In contrast, the association of fetuin-A with aortic stenosis was modified by the presence or absence of diabetes mellitus (P for interaction=0.03). Among participants without diabetes, the highest fetuin-A tertile had a significantly lower odds of aortic stenosis compared with the lowest tertile (adjusted odds ratio, 0.37; 95% confidence interval, 0.15 to 0.92; P=0.03), whereas among participants with diabetes, no statistically significant association was observed between fetuin-A and aortic stenosis (adjusted odds ratio, 1.49; 95% confidence interval, 0.48 to 4.63; P=0.49).Among persons with coronary heart disease, we observed an inverse association of fetuin-A and mitral annular calcification. An inverse association also was observed between fetuin-A and aortic stenosis among participants without diabetes mellitus. Fetuin-A may represent an important inhibitor of dystrophic calcification in persons with coronary heart disease.

  View details for DOI 10.1161/CIRCULATIONAHA.106.682450

  View details for Web of Science ID 000246453300013

  View details for PubMedID 17485576

  View details for PubMedCentralID PMC2771196

• The incidence and prognostic significance of acute kidney injury CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION Waikar, S. S., Liu, K. D., Chertow, G. M. 2007; 16 (3): 227-236

  Abstract

  Acute kidney injury is an increasingly common and potentially catastrophic complication in hospitalized patients. This review summarizes the major epidemiologic studies that have informed our understanding of the incidence and prognostic significance of acute kidney injury.Early observational studies from the 1980s and 1990s established the general epidemiologic features of acute kidney injury, including the incidence, prognostic significance and predisposing medical and surgical conditions. Recent multicenter observational cohorts and administrative databases have enhanced our understanding of the overall disease burden of acute kidney injury and trends in its epidemiology. An increasing number of clinical studies focusing on specific types of acute kidney injury (e.g. following exposure to intravenous contrast, sepsis and major surgery) have provided further details into this heterogeneous syndrome.In light of the increasing incidence and prognostic significance of acute kidney injury, new strategies for prevention and treatment are desperately needed.

  View details for Web of Science ID 000246000600008

  View details for PubMedID 17420666

  View details for PubMedCentralID PMC3027554

• Octogenarians and nonagenarians starting dialysis in the United States ANNALS OF INTERNAL MEDICINE Kurella, M., Covinsky, K. E., Collins, A. J., Chertow, G. M. 2007; 146 (3): 177-183

  Abstract

  The elderly constitute the fastest-growing segment of the end-stage renal disease (ESRD) population, but the epidemiology and outcomes of dialysis among the very elderly, that is, those 80 years of age and older, have not been previously examined at a national level.To describe recent trends in the incidence and outcomes of octogenarians and nonagenarians starting dialysis.Observational study.U.S. Renal Data System, a comprehensive, national registry of patients with ESRD.Octogenarians and nonagenarians initiating dialysis between 1996 and 2003.Rates of dialysis initiation and survival.The number of octogenarians and nonagenarians starting dialysis increased from 7054 persons in 1996 to 13,577 persons in 2003, corresponding to an average annual increase in dialysis initiation of 9.8%. After we accounted for population growth, the rate of dialysis initiation increased by 57% (rate ratio, 1.57 [95% CI, 1.53 to 1.62]) between 1996 and 2003. One-year mortality for octogenarians and nonagenarians after dialysis initiation was 46%. Compared with octogenarians and nonagenarians initiating dialysis in 1996, those starting dialysis in 2003 had a higher glomerular filtration rate and less morbidity related to chronic kidney disease but no difference in 1-year survival. Clinical characteristics strongly associated with death were older age, nonambulatory status, and more comorbid conditions.Survival of patients with incident ESRD who did not begin dialysis could not be assessed.The number of octogenarians and nonagenarians initiating dialysis has increased considerably over the past decade, while overall survival for patients on dialysis remains modest. Estimates of prognosis based on patient characteristics, when considered in conjunction with individual values and preferences, may aid in dialysis decision making for the very elderly.

  View details for Web of Science ID 000243957400003

  View details for PubMedID 17283348

• Frequent Hemodialysis Network (FHN) randomized trials: Study design KIDNEY INTERNATIONAL Suri, R. S., Garg, A. X., Chertow, G. M., Levin, N. W., Rocco, M. V., Greene, T., Beck, G. J., Gassman, J. J., Eggers, P. W., Star, R. A., Ornt, D. B., Kliger, A. S. 2007; 71 (4): 349-359

  Abstract

  Observational studies suggest improvements with frequent hemodialysis (HD), but its true efficacy and safety remain uncertain. The Frequent Hemodialysis Network Trials Group is conducting two multicenter randomized trials of 250 subjects each, comparing conventional three times weekly HD with (1) in-center daily HD and (2) home nocturnal HD. Daily HD will be delivered for 1.5-2.75 h, 6 days/week, with target eK(t)/V(n) > or = 0.9/session, whereas nocturnal HD will be delivered for > or = 6 h, 6 nights/week, with target stdK(t)/V of > or = 4.0/week. Subjects will be followed for 1 year. The composite of mortality with the 12-month change in (i) left ventricular mass index (LVMI) by magnetic resonance imaging, and (ii) SF-36 RAND Physical Health Composite (PHC) are specified as co-primary outcomes. The seven main secondary outcomes are between group comparisons of: change in LVMI, change in PHC, change in Beck Depression Inventory score, change in Trail Making Test B score, change in pre-HD serum albumin, change in pre-HD serum phosphorus, and rates of non-access hospitalization or death. Changes in blood pressure and erythropoiesis will also be assessed. Safety outcomes will focus on vascular access complications and burden of treatment. Data will be obtained on the cost of delivering frequent HD compared to conventional HD. Efforts will be made to reduce bias, including blinding assessment of subjective outcomes. Because no large-scale randomized trials of frequent HD have been previously conducted, the first year has been designated a Vanguard Phase, during which feasibility of randomization, ability to deliver the interventions, and adherence will be evaluated.

  View details for DOI 10.1038/sj.ki.5002032

  View details for Web of Science ID 000244082200018

  View details for PubMedID 17164834

• Phosphorus balance and mineral metabolism with 3 h daily hemodialysis 39th Annual Meeting of the American-Society-of-Nephrology/Annual Renal Week Ayus, J. C., Achinger, S. G., Mizani, M. R., Chertow, G. M., Furmaga, W., Lee, S., Rodriguez, F. NATURE PUBLISHING GROUP. 2007: 336–42

  Abstract

  Poor control of mineral metabolism is independently associated with mortality in patients receiving hemodialysis. We analyzed data from a 12-month, prospective, non-randomized, controlled study of daily hemodialysis (DHD) (six sessions/week 3 h each) (n=26) vs conventional hemodialysis (CHD) (three sessions/week 4 h each) (n=51) for achievement of mineral metabolism goals and we performed a substudy of weekly dialytic phosphorus removal in DHD vs CHD. Phosphorus control was superior in the DHD group (% change from baseline to end-of-study -27+/-30% vs +7%+/-35% in the CHD group, P=0.0001). Percentage of patients using phosphate binders decreased from 77 to 40% among subjects on DHD, whereas these parameters did not change (76 vs 77%) in the CHD group (P=0.03 by Breslow-Day test for homogeneity of the odds ratios). Weekly mean phosphorus removal was higher in the DHD group (2452+/-720 mg/week vs 1572+/-366 mg/week, P=0.04). Mean normalized protein catabolic rate increased (0.90+/-0.43-1.22+/-0.26 g/kg/day, P=0.0013). DHD was also associated with an increase in the percent of subjects achieving three or more mineral metabolism goals (for phosphorus, calcium x phosphorus and parathyroid hormone) (15 vs 46%, P=0.046). In conclusion, DHD improves phosphorus control by increasing dialytic phosphorus removal while maintaining nutritional status and reducing the use of phosphate binders. The net effect allows for improved achievement of mineral metabolism goals.

  View details for DOI 10.1038/sj.ki.5002044

  View details for Web of Science ID 000244082200016

  View details for PubMedID 17191084

• Association of cystatin C with mortality, cardiovascular events, and incident heart failure among persons with coronary heart disease - Data from the Heart and Soul Study CIRCULATION Ix, J. H., Shlipak, M. G., Chertow, G. M., Whooley, M. A. 2007; 115 (2): 173-179

  Abstract

  Serum creatinine and related estimating equations predict cardiovascular events and mortality among persons with coronary heart disease (CHD). Cystatin C is a novel and sensitive endogenous marker of kidney function. Whether cystatin C concentrations are associated with adverse events among ambulatory persons with CHD is unknown.Nine hundred ninety ambulatory persons with CHD were categorized into quartiles of serum cystatin C at inception, with < or = 0.91 mg/L constituting the lowest quartile (I) and > or = 1.30 mg/L constituting the highest (IV). Cox proportional hazards models evaluated time to all-cause mortality, cardiovascular events (composite of CHD death, myocardial infarction, and stroke), and incident heart failure. After a median follow-up of 37 months, 132 participants (13%) died, 101 (10%) had cardiovascular events, and 57 (7%) had incident heart failure. Compared with participants in the lowest cystatin C quartile, those in the highest quartile were at increased risk of all-cause mortality (hazard ratio, 3.6; 95% CI, 1.8 to 7.0), cardiovascular events (hazard ratio, 2.0; 95% CI, 1.0 to 3.8), and incident heart failure (hazard ratio, 2.6; 95% CI, 1.0 to 6.9) in analyses adjusted for traditional cardiovascular risk factors. Cystatin C in the highest quartile predicted similar risk for these outcomes among participants with lower (< or = 60 mL/min per 1.73 m2) or higher estimated glomerular filtration rate and among participants with or without microalbuminuria.High cystatin C concentrations predict substantial increased risks of all-cause mortality, cardiovascular events, and incident heart failure among ambulatory persons with CHD. This risk is not completely captured by measures of kidney function routinely used in clinical practice.

  View details for DOI 10.1161/CIRCULATIONAHA.106.644286

  View details for Web of Science ID 000243523600007

  View details for PubMedID 17190862

  View details for PubMedCentralID PMC2771187

• End stage renal disease. Clinical evidence Hall, Y. N., Chertow, G. M. 2007; 2007

  Abstract

  End stage renal disease (ESRD) affects over 1500 people per million population in countries with a high prevalence, such as the USA and Japan. Approximately two thirds of people with ESRD receive haemodialysis, a quarter have kidney transplants, and a tenth receive peritoneal dialysis. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of different doses and osmotic agents for peritoneal dialysis? What are the effects of different doses and membrane fluxes for haemodialysis? What are the effects of interventions aimed at preventing secondary complications? We searched: Medline, Embase, The Cochrane Library and other important databases up to April 2007 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).We found 20 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.In this systematic review we present information relating to the effectiveness and safety of the following interventions: cinacalcet, darbepoetin, dextrose solutions, erythropoietin, haemodialysis (standard-dose, increased-dose), high-membrane-flux haemodialysis, icodextrin, increased-dose peritoneal dialysis, low-membrane-flux haemodialysis, mupirocin, sevelamer, and standard-dose dialysis.

  View details for PubMedID 19450356

  View details for PubMedCentralID PMC2943808

• Cystatin C and measures of physical function in elderly adults - The health, aging, and body composition (HABC) study AMERICAN JOURNAL OF EPIDEMIOLOGY Odden, M. C., Chertow, G. M., Fried, L. F., Newman, A. B., Connelly, S., Angleman, S., Harris, T. B., Simonsick, E. M., Shlipak, M. G. 2006; 164 (12): 1180-1189

  Abstract

  Most studies of the relation between kidney function and physical function have been conducted in persons with advanced kidney disease and have used creatinine-based measures of kidney function. Cystatin C concentration is a measure of kidney function that is independent of muscle mass, unlike creatinine. Using baseline data on 3,043 elderly adults from the Health, Aging, and Body Composition Study (Blacks and Whites recruited from Pittsburgh, Pennsylvania, and Memphis, Tennessee, in 1997-1998), the authors examined the cross-sectional association between cystatin C level and performance on several tests of physical function. After adjustment for demographic and lifestyle variables, chronic health conditions, and inflammation, each standard-deviation (0.34 mg/liter) increase in cystatin C concentration was associated with 1.32 odds (95% confidence interval (CI): 1.20, 1.46) of not completing a 400-m walk, a 10.9-second (95% CI: 8.1, 13.8) slower 400-m walk time, a 0.11-point (95% CI: 0.09, 0.13) reduction in lower extremity performance score, a 1.12-kg (95% CI: 0.83, 1.40) lower grip strength, and a 4.7-nm (95% CI: 3.5, 5.9) lower knee extension strength. In contrast, when kidney function was measured by estimated glomerular filtration rate, the association of kidney function with physical function was only evident below 60 ml/minute/1.73 m2. In these older adults, mild decrements in kidney function, as measured by cystatin C concentration, were associated with poorer physical function.

  View details for DOI 10.1093/aje/kwj333

  View details for Web of Science ID 000242714800006

  View details for PubMedID 17035344

• Less-than-subtotal parathyroidectomy increases the risk of persistent/recurrent hyperparathyroidism after parathyroidectomy in tertiary hyperparathyroidism after renal transplantation 27th Annual Meeting of the American-Association-of-Endocrine-Surgeons Triponez, F., Kebebew, E., Dosseh, D., Duh, Q., Hazzan, M., Noel, C., Chertow, G. M., Wambergue, F., Fleury, D., Lemaitre, V., Proye, C. A., Clark, O. H. MOSBY-ELSEVIER. 2006: 990–97

  Abstract

  The optimal surgical approach for tertiary hyperparathyroidism (HPT) after kidney transplantation is unknown. Existing studies are limited by small sample size, lack of adjustment for kidney function, and no long-term follow-up.We retrospectively analyzed 74 patients with tertiary HPT who underwent parathyroidectomy at two centers since 1978. Persistent HPT was defined as parathyroid hormone (PTH) concentrations in excess of the K/DOQI target range for the corresponding estimated creatinine clearance (eCrCl).Seventy-four patients had 83 operations (72 subtotal and 11 less-than-subtotal parathyroidectomies). Mean follow-up time was 5.4 +/- 4.7 years. Calcium concentrations decreased significantly after parathyroidectomy (2.83 vs 2.28 mmol/L, P < 0.001), as did eCrCl (54.5 vs 44.9 mL/min, P < 0.001) and PTH (382 vs 132 pg/mL, P < 0.001). In the multivariable regression analysis, only the type of operation and postoperative eCrCl were significantly correlated with PTH at follow-up. A limited parathyroidectomy was associated with a fivefold increase in risk of persistent or recurrent hyperparathyroidism.The use of limited parathyroidectomy for tertiary HPT after kidney transplantation has a higher risk of persistent/recurrent HPT. Subtotal parathyroidectomy is recommended for patients with tertiary HPT.

  View details for DOI 10.1016/j.surg.2006.06.039

  View details for Web of Science ID 000243335800035

  View details for PubMedID 17188148

• Survival by dialysis modality in critically ill patients with acute kidney injury JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Cho, K. C., Himmelfarb, J., Paganini, E., Ikizler, T. A., Soroko, S. H., Mehta, R. L., Chertow, G. M. 2006; 17 (11): 3132-3138

  Abstract

  Among critically ill patients, acute kidney injury (AKI) requiring dialysis is associated with mortality rates generally in excess of 50%. Continuous renal replacement therapies (CRRT) often are recommended and widely used, although data to support its superiority over intermittent hemodialysis (IHD) are lacking. Data from the Program to Improve Care in Acute Renal Disease (PICARD), a multicenter observational study of AKI, were analyzed. Among 398 patients who required dialysis, the risk for death within 60 d was examined by assigned initial dialysis modality (CRRT [n = 206] versus IHD [n = 192]) using standard Kaplan-Meier product limit estimates, proportional hazards ("Cox") regression methods, and a propensity score approach to account for selection effects. Crude survival rates were lower for patients who were treated with CRRT than IHD (survival at 30 d 45 versus 58%; P = 0.006). Adjusted for age, hepatic failure, sepsis, thrombocytopenia, blood urea nitrogen, and serum creatinine and stratified by site, the relative risk for death associated with CRRT was 1.82 (95% confidence interval 1.26 to 2.62). Further adjustment for the propensity score did not materially alter the association (relative risk 1.92; 95% confidence interval 1.28 to 2.89). Among critically ill patients with AKI, CRRT was associated with increased mortality. Although the results could reflect residual confounding by severity of illness, these data provide no evidence for a survival benefit afforded by CRRT. Larger, prospective, randomized clinical trials to compare CRRT and IHD in severe AKI are needed.

  View details for DOI 10.1681/ASN.2006030268

  View details for Web of Science ID 000241912100025

  View details for PubMedID 17021268

• Risks for end-stage renal disease, cardiovascular events, and death in Hispanic versus non-Hispanic white adults with chronic kidney disease JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Peralta, C. A., Shlipak, M. G., Fan, D., Ordonez, J., Lash, J. P., Chertow, G. M., Go, A. S. 2006; 17 (10): 2892-2899

  Abstract

  Rates of ESRD are rising faster in Hispanic than non-Hispanic white individuals, but reasons for this are unclear. Whether rates of cardiovascular events and mortality differ among Hispanic and non-Hispanic white patients with chronic kidney disease (CKD) also is not well understood. Therefore, this study examined the associations between Hispanic ethnicity and risks for ESRD, cardiovascular events, and death in patients with CKD. A total of 39,550 patients with stages 3 to 4 CKD from Kaiser Permanente of Northern California were included. Hispanic ethnicity was obtained from self-report supplemented by surname matching. GFR was estimated from the abbreviated Modification of Diet in Renal Disease equation, and clinical outcomes, patient characteristics, and longitudinal medication use were ascertained from health plan databases and state mortality files. After adjustment for sociodemographic characteristics, Hispanic ethnicity was associated with an increased risk for ESRD (hazard ratio [HR] 1.93; 95% confidence interval [CI] 1.72 to 2.17) when compared with non-Hispanic white patients, which was attenuated after controlling for diabetes and insulin use (HR 1.50; 95% CI 1.33 to 1.69). After further adjustment for potential confounders, Hispanic ethnicity remained independently associated with an increased risk for ESRD (HR 1.33; 95% CI 1.17 to 1.52) as well as a lower risk for cardiovascular events (HR 0.82; 95% CI 0.76 to 0.88) and death (HR 0.72; 95% CI 0.66 to 0.79). Among a large cohort of patients with CKD, Hispanic ethnicity was associated with lower rates of death and cardiovascular events and a higher rate of progression to ESRD. The higher prevalence of diabetes among Hispanic patients only partially explained the increased risk for ESRD. Further studies are required to elucidate the cause(s) of ethnic disparities in CKD-associated outcomes.

  View details for DOI 10.1681/ASN.2005101122

  View details for Web of Science ID 000240926500029

  View details for PubMedID 16959827

• Tesio catheter access for long-term maintenance hemodialysis RADIOLOGY Wang, J., LaBerge, J. M., Chertow, G. M., Kerlan, R. K., Wilson, M. W., Gordon, R. L. 2006; 241 (1): 284-290

  Abstract

  To retrospectively determine the long-term outcome (>6 months) of placement of tunneled hemodialysis catheters.The HIPAA-compliant study protocol was approved by the Committee on Human Research, which waived the requirement for informed consent. The records of patients who underwent hemodialysis with the Tesio system (Medcomp, Harleysville, Pa) at a single outpatient dialysis unit between March 1994 and March 2004 were reviewed. The length of catheter access and the requirements for percutaneous revision were recorded, and unassisted- and assisted-access survival times were computed by using the Kaplan-Meier method.Three hundred three primary Tesio accesses were created in 200 patients (mean age, 62.3 years +/- 16.3 [standard deviation]; 102 women [51.0%]). Fifty-nine of 303 accesses (19.5%) were percutaneously revised with catheter exchange. During follow-up, 200 of 303 accesses (66.0%) were terminated (117 because they were no longer needed and 83 because of catheter malfunction), and 103 (34.0%) accesses were functioning at the time of last follow-up. The mean duration of catheter access was 247 days (range, 3-2016 days). One hundred twenty-six (41.6%) accesses remained in use for more than 6 months; 50 (16.5%), for more than 1 year; 20 (6.6%), for more than 2 years; 14 (4.6%), for more than 3 years; and five (1.7%), for more than 4 years. Assisted-access survival was 78.1%, 60.0%, 51.5%, 51.5%, and 46.8% at 6 months and 1, 2, 3, and 4 years, respectively.Tesio catheters frequently function for periods longer than 6 months and, when necessary, they can function for many years.

  View details for DOI 10.1148/radiol.2411050349

  View details for Web of Science ID 000240765100035

  View details for PubMedID 16990680

• Cystatin C, left ventricular hypertrophy, and diastolic dysfunction: Data from The Heart and Soul Study 46th Annual Meeting of the Council-on-Epidemiology-and-Prevention Ix, J. H., Shlipak, M. G., Chertow, G. M., Ali, S., Schiller, N. B., Whooley, M. A. CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS. 2006: 601–7

  Abstract

  Impaired kidney function, as measured by serum cystatin C, is associated with risk of incident heart failure. Whether cystatin C is associated with preclinical cardiac structural abnormalities is unknown. We evaluate whether cystatin C is associated with left ventricular hypertrophy, diastolic dysfunction, and systolic dysfunction among 818 outpatients with coronary artery disease who were free of clinical heart failure.The 818 study participants were categorized into quartiles based on serum cystatin C concentrations, with < or =0.91 mg/L constituting the lowest quartile (I) and > or =1.28 mg/L constituting the highest (IV). Left ventricular hypertrophy (left ventricular mass index >90 g/m(2) by truncated ellipsoid method), diastolic dysfunction (impaired relaxation, pseudo-normal, or restrictive filling patterns) and systolic dysfunction (left ventricular ejection fraction < or =50%) were determined by echocardiography. Left ventricular hypertrophy was present in 68% of participants in quartile IV, compared with 44% of those in quartile I (adjusted odds ratio [OR] 2.17; 95% confidence interval [CI] 1.34 to 3.52; P = .002). Diastolic dysfunction was present in 52% of participants in quartile IV, compared with 24% of those in quartile I (adjusted OR 1.79; 95% CI 1.04 to 3.11; P = .04). Systolic dysfunction was present in 12% of those in quartile IV, compared with 6% of those in quartile I (adjusted OR 1.83; 95% CI 0.75 to 4.46; P = .15).Higher cystatin C concentrations are strongly associated with left ventricular hypertrophy and diastolic dysfunction in outpatients with coronary artery disease and without heart failure.

  View details for DOI 10.1016/j.cardfail.2006.07.005

  View details for Web of Science ID 000241534400003

  View details for PubMedID 17045178

  View details for PubMedCentralID PMC2799994

• Studying the prevention of acute kidney injury: Lessons from an 18th-century mathematician 38th Annual Meeting of the American-Society-of-Nephrology/Annual Renal Week Chertow, G. M., Palevsky, P. M., Greene, T. AMER SOC NEPHROLOGY. 2006: 1124–27

  View details for DOI 10.2215/CJN.01200406

  View details for Web of Science ID 000242173000033

  View details for PubMedID 17699335

• A simulation model to estimate the cost and effectiveness of alternative dialysis initiation strategies MEDICAL DECISION MAKING Lee, C. P., Chertow, G. M., Zenios, S. A. 2006; 26 (5): 535-549

  Abstract

  Patients with end-stage renal disease (ESRD) require dialysis to maintain survival. The optimal timing of dialysis initiation in terms of cost-effectiveness has not been established.We developed a simulation model of individuals progressing towards ESRD and requiring dialysis. It can be used to analyze dialysis strategies and scenarios. It was embedded in an optimization frame worked to derive improved strategies.Actual (historical) and simulated survival curves and hospitalization rates were virtually indistinguishable. The model overestimated transplantation costs (10%) but it was related to confounding by Medicare coverage. To assess the model's robustness, we examined several dialysis strategies while input parameters were perturbed. Under all 38 scenarios, relative rankings remained unchanged. An improved policy for a hypothetical patient was derived using an optimization algorithm.The model produces reliable results and is robust. It enables the cost-effectiveness analysis of dialysis strategies.

  View details for DOI 10.1177/0272989X06290488

  View details for Web of Science ID 000240896700009

  View details for PubMedID 16997929

• Timing of initiation of dialysis in critically ill patients with acute kidney injury CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Liu, K. D., Himmelfarb, J., Paganini, E., Ikizler, T. A., Soroko, S. H., Mehta, R. L., Chertow, G. M. 2006; 1 (5): 915-919

  Abstract

  Among critically ill patients, acute kidney injury (AKI) is a relatively common complication that is associated with an increased risk for death and other complications. To date, no treatment has been developed to prevent or attenuate established AKI. Dialysis often is required, but the optimal timing of initiation of dialysis is unknown. Data from the Program to Improve Care in Acute Renal Disease (PICARD), a multicenter observational study of AKI, were analyzed. Among 243 patients who did not have chronic kidney disease and who required dialysis for severe AKI, we examined the risk for death within 60 d from the diagnosis of AKI by the blood urea nitrogen (BUN) concentration at the start of dialysis (BUN < or = 76 mg/dl in the low degree of azotemia group [n = 122] versus BUN > 76 mg/dl in the high degree of azotemia group [n = 121]). Standard Kaplan-Meier product limit estimates, proportional hazards (Cox) regression methods, and a propensity score approach were used to account for selection effects. Crude survival rates were slightly lower for patients who started dialysis at higher BUN concentrations, despite a lesser burden of organ system failure. Adjusted for age, hepatic failure, sepsis, thrombocytopenia, and serum creatinine and stratified by site and initial dialysis modality, the relative risk for death that was associated with initiation of dialysis at a higher BUN was 1.85 (95% confidence interval 1.16 to 2.96). Further adjustment for the propensity score did not materially alter the association (relative risk 1.97; 95% confidence interval 1.21 to 3.20). Among critically ill patients with AKI, initiation of dialysis at higher BUN concentrations was associated with an increased risk for death. Although the results could reflect residual confounding by severity of illness, they provide a rationale for prospective testing of alternative dialysis initiation strategies in critically ill patients with severe AKI.

  View details for DOI 10.2215/CJN.01430406

  View details for Web of Science ID 000242173000005

  View details for PubMedID 17699307

• Mortality after acute renal failure: Models for prognostic stratification and risk adjustment KIDNEY INTERNATIONAL Chertow, G. M., Soroko, S. H., Paganini, E. P., Cho, K. C., Himmelfarb, J., Ikizler, T. A., Mehta, R. L. 2006; 70 (6): 1120-1126

  Abstract

  To adjust adequately for comorbidity and severity of illness in quality improvement efforts and prospective clinical trials, predictors of death after acute renal failure (ARF) must be accurately identified. Most epidemiological studies of ARF in the critically ill have been based at single centers, or have examined exposures at single time points using discrete outcomes (e.g., in-hospital mortality). We analyzed data from the Program to Improve Care in Acute Renal Disease (PICARD), a multi-center observational study of ARF. We determined correlates of mortality in 618 patients with ARF in intensive care units using three distinct analytic approaches. The predictive power of models using information obtained on the day of ARF diagnosis was extremely low. At the time of consultation, advanced age, oliguria, hepatic failure, respiratory failure, sepsis, and thrombocytopenia were associated with mortality. Upon initiation of dialysis for ARF, advanced age, hepatic failure, respiratory failure, sepsis, and thrombocytopenia were associated with mortality; higher blood urea nitrogen and lower serum creatinine were also associated with mortality in logistic regression models. Models incorporating time-varying covariates enhanced predictive power by reducing misclassification and incorporating day-to-day changes in extra-renal organ system failure and the provision of dialysis during the course of ARF. Using data from the PICARD multi-center cohort study of ARF in critically ill patients, we developed several predictive models for prognostic stratification and risk-adjustment. By incorporating exposures over time, the discriminatory power of predictive models in ARF can be significantly improved.

  View details for DOI 10.1038/sj.ki.5001579

  View details for Web of Science ID 000240370300027

  View details for PubMedID 16850028

• Correlates and outcomes of dementia among dialysis patients: the Dialysis Outcomes and Practice Patterns Study NEPHROLOGY DIALYSIS TRANSPLANTATION Kurella, M., Mapes, D. L., Port, F. K., Chertow, G. M. 2006; 21 (9): 2543-2548

  Abstract

  Recent studies suggest a high prevalence of cognitive impairment and dementia in persons with end-stage renal disease (ESRD), yet risk factors for dementia and its prognostic significance in persons with ESRD remain unclear. The goals of this study were to determine the prevalence, correlates and dialysis-related outcomes of dementia in an international sample of haemodialysis patients.We analysed data collected from a cohort of 16 694 patients in the Dialysis Outcomes and Practice Patterns Study. Dementia was defined as a diagnosis of dementia documented in the medical record. We used logistic regression to determine the baseline correlates of dementia and Cox proportional hazards models to determine the relative risk (RR) of death and dialysis withdrawal for patients with dementia, while adjusting for a number of confounding factors.Overall, 4% of the cohort had a recorded diagnosis of dementia. In the cross-sectional analyses, risk factors for dementia in the general population including age, black race, low educational attainment, cerebrovascular disease and diabetes, as well as modifiable uraemia-related factors, including markers of malnutrition and anaemia, were independently associated with dementia. After adjustment for a number of confounding factors, dementia was associated with an increased risk of death [RR 1.48, 95% confidence interval (CI) 1.32-1.66] and dialysis withdrawal (RR 2.01, 95% CI 1.57-2.57).Dementia is associated with adverse outcomes among ESRD patients. Dialysis providers should consider instituting routine screening for cognitive impairment among elderly patients in order to identify those at risk for associated adverse outcomes.

  View details for DOI 10.1093/ndt/gfl275

  View details for Web of Science ID 000240694200032

  View details for PubMedID 16751655

• Fetuin-A and kidney function in persons with coronary artery disease-data from the heart and soul study NEPHROLOGY DIALYSIS TRANSPLANTATION Ix, J. H., Chertow, G. M., Shlipak, M. G., Brandenburg, V. M., Ketteler, M., Whooley, M. A. 2006; 21 (8): 2144-2151

  Abstract

  Fetuin-A is a serum protein that inhibits ectopic vascular calcification and is present in lower concentrations in end-stage renal disease than in healthy controls. Whether fetuin-A concentrations are also lower in the setting of mild-to-moderate chronic kidney disease (CKD) is unknown.We evaluated the associations of several parameters of kidney function including measured 24 h urinary creatinine clearance (CrCl), estimated glomerular filtration rate (GFR) by the Mayo Clinic quadratic GFR equation (qGFR), serum cystatin-C concentrations, and urinary albumin-to-creatinine ratio with serum fetuin-A concentrations in 970 outpatients with coronary artery disease. We used general linear models to determine the adjusted mean fetuin-A concentrations within each kidney function category.The mean age of the study sample was 67 years, 82% were male, 71% had hypertension and 26% had diabetes mellitus. In adjusted analysis, we observed no significant differences in mean fetuin-A concentrations across groups defined by CrCl, qGFR, or albumin-to-creatinine ratio groups. For example, adjusted mean fetuin-A concentrations were 0.66 g/l in participants with CrCl > 90, 60-90 and 45-60 ml/min/1.73 m(2), and 0.65 g/l in participants with CrCl < 45 ml/min/1.73 m(2). Higher serum cystatin-C (indicating worse kidney function) was associated with higher adjusted mean serum fetuin-A concentrations (lowest quartile 0.62 g/l, highest quartile 0.68 g/l; P for trend <0.001).Among ambulatory patients with coronary artery disease, there is no evidence that mild-to-moderate CKD is associated with lower concentrations of serum fetuin-A compared with persons with normal renal function. The mechanisms explaining the association between CKD and vascular calcification remain elusive.

  View details for DOI 10.1093/ndt/gfl204

  View details for Web of Science ID 000239906500018

  View details for PubMedID 16644775

  View details for PubMedCentralID PMC2776687

• Renal function and heart failure risk in older black and white individuals - The health, aging, and body composition study ARCHIVES OF INTERNAL MEDICINE Bibbins-Domingo, K., Chertow, G. M., Fried, L. F., Odden, M. C., Newman, A. B., Kritchevsky, S. B., Harris, T. B., Satterfield, S., Cummings, S. R., Shlipak, M. G. 2006; 166 (13): 1396-1402

  Abstract

  Chronic kidney disease is a risk factor for heart failure, an association that may be particularly important in blacks who are disproportionately affected by both processes. Our objective was to determine whether the association of chronic kidney disease with incident heart failure differs between blacks and whites.The study population comprised participants in the Health, Aging, and Body Composition Study without a diagnosis of heart failure (1124 black and 1676 white community-dwelling older persons). The main predictors were quintiles of cystatin C and creatinine concentrations and estimated glomerular filtration rate. The main outcome measure was incident heart failure.Over a mean 5.7 years, 200 participants developed heart failure. High concentrations of cystatin C and low estimated glomerular filtration rate were each associated with heart failure, but the magnitude was greater for blacks than for whites (cystatin C concentration: adjusted hazard ratio for quintile 5 [> or =1.18 mg/dL] vs quintile 1 [<0.84 mg/dL] was 3.0 [95% confidence interval 1.4-6.5] in blacks and 1.4 [95% confidence interval, 0.8-2.5] in whites; estimated glomerular filtration rate: adjusted hazard ratio for quintile 5 (<59.2 mL/min) vs quintile 1 (>86.7 mL/min) was 2.7 [95% confidence interval, 1.4-4.9] in blacks and 1.8 [95% confidence interval, 0.9-3.6] in whites). For cystatin C, this association was observed at more modest decrements in kidney function among blacks as well. The population attributable risk of heart failure was 47% for blacks with moderate or high concentrations of cystatin C (> or =0.94 mg/dL) (56% prevalence) but only 5% among whites (64% prevalence).The association of kidney dysfunction with heart failure appears stronger in blacks than for whites, particularly when cystatin C is used to measure kidney function.

  View details for Web of Science ID 000238916500009

  View details for PubMedID 16832005

• The metabolic syndrome and chronic kidney disease CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION Peralta, C. A., Kurella, M., Lo, J. C., Chertow, G. M. 2006; 15 (4): 361-365

  Abstract

  The metabolic syndrome is a constellation of physical and laboratory abnormalities including hypertension, hyperglycemia, hyperlipidemia and abdominal obesity. Over the past decade, the metabolic syndrome has emerged as a critically important risk factor for cardiovascular disease.A large population-based cross-sectional analysis (the National Health and Nutrition Evaluation Survey III) found that the presence of the metabolic syndrome was associated with chronic kidney disease, defined as an estimated glomerular filtration rate of less than 60 ml/min per 1.73 m and was also associated with proteinuria. More recently, a prospective cohort study found that the presence of the metabolic syndrome was associated with incident chronic kidney disease by the same definition, even when excluding individuals with diabetes mellitus and hypertension. More studies are required to determine whether the relationship between the metabolic syndrome and chronic kidney disease is mainly mediated by hyperglycemia (with insulin resistance) and hypertension, or other metabolic or hemodynamic factors.The metabolic syndrome is associated with chronic kidney disease. Efforts aimed at determining the mechanisms underlying this association and strategies for the prevention of chronic kidney disease (or slowing the progression of chronic kidney disease) in affected patients should be research priorities in the future.

  View details for Web of Science ID 000239103000002

  View details for PubMedID 16775449

• The tortoise and hare on hemodialysis: Does slow and steady win the race? KIDNEY INTERNATIONAL Chertow, G. M., Kurella, M., Lowrie, E. G. 2006; 70 (1): 24-25

  Abstract

  The importance of hemodialysis session length relative to small solute (e.g., urea) clearance has been debated for many years. Longer session length augments clearance of larger molecules and may facilitate ultrafiltration; however, the independent effects of session length on survival and other outcomes are unknown. In this report, we review two recently published observational studies examining the association between hemodialysis session length and survival. Prospective clinical trials will be required to resolve the debate.

  View details for DOI 10.1038/sj.ki.5001544

  View details for Web of Science ID 000238969300012

  View details for PubMedID 16763569

• The case against calcium-based phosphate binders CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Moe, S. M., Chertow, G. M. 2006; 1 (4): 697-703

  Abstract

  Disturbances of mineral metabolism are associated with significant morbidity and mortality in patients with chronic kidney disease. Unfortunately, some of the treatments for these disturbances also have been found to be associated with morbidity. More recently, there is increasing evidence in the form of prospective, randomized trials that the use of calcium-based phosphate binders contributes to progressive coronary artery and aorta calcification compared with the non-calcium-containing binder sevelamer. Moreover, there is compelling biologic plausibility that hyperphosphatemia and excess exogenous calcium administration can accelerate vascular calcification. Unfortunately, there is no bedside test that can determine whether there is a dose of calcium salts (either as maintenance or as cumulative dose) that can be administered safely, and, unfortunately, the serum calcium concentration does not reflect calcium balance. Therefore, calcium-based phosphate binders should be avoided in many, if not most, patients who are undergoing dialysis.

  View details for DOI 10.2215/CJN.00560206

  View details for Web of Science ID 000242241700012

  View details for PubMedID 17699275

• Evolving practices in critical care and potential implications for management of acute kidney injury CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Liu, K. D., Matthay, M. A., Chertow, G. M. 2006; 1 (4): 869-873

  View details for DOI 10.2215/CJN.00450206

  View details for Web of Science ID 000242241700036

  View details for PubMedID 17699299

• Guidelines for disorders of mineral metabolism and secondary hyperparathyroidism should not yet be modified NATURE CLINICAL PRACTICE NEPHROLOGY Ix, J. H., Quarles, L. D., Chertow, G. M. 2006; 2 (6): 337-339

  Abstract

  This brief article is a response to the article by Monge et al. on page 326 entitled Reappraisal of 2003 NKF-K/DOQI guidelines for management of hyperparathyroidism in chronic kidney disease patients. We contend that there is insufficient evidence to support the changes to clinical practice and clinical practice guidelines proposed by Monge and colleagues. We recommend that clinical trials be conducted to resolve these points of contention and other critical issues in the management of disorders of mineral metabolism in chronic kidney disease, including secondary hyperparathyroidism. The focus should be on evaluating the effects of alternative strategies on survival, as well as clinical manifestations of cardiovascular and bone disease.

  View details for DOI 10.1038/hcpneph0190

  View details for Web of Science ID 000237901300014

  View details for PubMedID 16932455

• The enlarging body of evidence: Obesity and chronic kidney disease JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Chertow, G. M., Hsu, C., Johansen, K. L. 2006; 17 (6): 1501-1502

  View details for Web of Science ID 000237891100002

  View details for PubMedID 16672317

• Validity of International Classification of Diseases, Ninth Revision, Clinical Modification codes for acute renal failure JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Waikar, S. S., Wald, R., Chertow, G. M., Curhan, G. C., Winkelmayer, W. C., Liangos, O., Sosa, M., Jaber, B. L. 2006; 17 (6): 1688-1694

  Abstract

  Administrative and claims databases may be useful for the study of acute renal failure (ARF) and ARF that requires dialysis (ARF-D), but the validity of the corresponding diagnosis and procedure codes is unknown. The performance characteristics of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for ARF were assessed against serum creatinine-based definitions of ARF in 97,705 adult discharges from three Boston hospitals in 2004. For ARF-D, ICD-9-CM codes were compared with review of medical records in 150 patients with ARF-D and 150 control patients. As compared with a diagnostic standard of a 100% change in serum creatinine, ICD-9-CM codes for ARF had a sensitivity of 35.4%, specificity of 97.7%, positive predictive value of 47.9%, and negative predictive value of 96.1%. As compared with review of medical records, ICD-9-CM codes for ARF-D had positive predictive value of 94.0% and negative predictive value of 90.0%. It is concluded that administrative databases may be a powerful tool for the study of ARF, although the low sensitivity of ARF codes is an important caveat. The excellent performance characteristics of ICD-9-CM codes for ARF-D suggest that administrative data sets may be particularly well suited for research endeavors that involve patients with ARF-D.

  View details for DOI 10.1681/ASN.2006010073

  View details for Web of Science ID 000237891100020

  View details for PubMedID 16641149

• End stage renal disease. Clinical evidence Hall, Y. N., Chertow, G. M. 2006: 1171-1181

  View details for PubMedID 16973047

• Declining mortality in patients with acute renal failure, 1988 to 2002 38th Annual Meeting of the American-Society-of-Nephrology/Annual Renal Week Waikar, S. S., Curhan, G. C., Wald, R., McCarthy, E. P., Chertow, G. M. AMER SOC NEPHROLOGY. 2006: 1143–50

  Abstract

  Despite improvements in intensive care and dialysis, some experts have concluded that outcomes associated with acute renal failure (ARF) have not improved significantly over time. ARF was studied in hospitalized patients between 1988 and 2002 using the Nationwide Inpatient Sample, a nationally representative sample of discharges from acute-care, nonfederal hospitals. During a 15-yr period, 5,563,381 discharges with ARF and 598,768 with ARF that required dialysis (ARF-D) were identified. Between 1988 and 2002, the incidence of ARF rose from 61 to 288 per 100,000 population; the incidence of ARF-D increased from 4 to 27 per 100,000 population. Between 1988 and 2002, in-hospital mortality declined steadily in patients with ARF (40.4 to 20.3%; P < 0.001) and in those with ARF-D (41.3 to 28.1%; P < 0.001). Compared with 1988 to 1992, the multivariable-adjusted odds ratio (OR) of death was lower in 1993 to 1997 (ARF: OR 0.62, 95% confidence interval [CI] 0.61 to 0.64; ARF-D: OR 0.63, 95% CI 0.59 to 0.66) and 1998 to 2002 (ARF: OR 0.40, 95% CI 0.39 to 0.41; ARF-D: OR 0.47, 95% CI 0.45 to 0.50). The percentage of patients who had ARF with a Deyo-Charlson comorbidity index of 3 or more increased from 16.4% in 1988 to 26.6% in 2002 (P < 0.001). This study provides evidence from an administrative database that the incidence of ARF and ARF-D is rising. Despite an increase in the degree of comorbidity, in-hospital mortality has declined.

  View details for DOI 10.1681/ASN.2005091017

  View details for Web of Science ID 000242120600028

  View details for PubMedID 16495376

• Association of body size with health status in patients beginning dialysis AMERICAN JOURNAL OF CLINICAL NUTRITION Johansen, K. L., Kutner, N. G., Young, B., Chertow, G. M. 2006; 83 (3): 543-549

  Abstract

  Greater weight-for-height has been associated with prolonged survival in patients with end-stage renal disease (ESRD) but not in the general population. The association between body size and health status has not been carefully evaluated.We compared the self-reported health status of 2467 participants in the Dialysis Morbidity and Mortality Study Wave 2 by using body mass index (BMI; in kg/m2) to approximate body size and composition.BMI was categorized into 4 groups (<19, 19 to <25, 25 to <30, and > or = 30) corresponding to World Health Organization criteria for underweight, normal-weight, overweight, and obese status. We adjusted for demographic, clinical, and laboratory factors that may have confounded the association between body size and health status.Scores on the physical component summary and the physical functioning scale were significantly lower for obese subjects than for those with normal weight or moderately high BMI after adjustment for demographic factors, comorbidity, and laboratory markers of nutritional status. Mental component summary and symptom scores were unrelated to BMI. The underweight group scored lower on many Medical Outcomes Study 36-Item Short Form scales than did the normal-weight group.Whereas higher BMI has consistently been associated with enhanced dialysis-related survival, health status-particularly physical function-may be impaired by obesity. Additional longitudinal studies of body weight and composition are needed for a better understanding of the complex effects of obesity and undernutrition in persons with ESRD and advanced chronic kidney disease.

  View details for Web of Science ID 000236073100004

  View details for PubMedID 16522899

• Strategies for successful patient oriented research: Why did I (not) get funded? CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Agarwal, R., Chertow, G. M., Mehta, R. L. 2006; 1 (2): 340-343

  Abstract

  Writing grants that are subsequently funded is an integral part of the process of patient-oriented research. A catalogue of common deficiencies that are identified in the grant review process can yield valuable insights into the process of grant writing. This article provides the authors' opinion on the common pitfalls in the current patient-oriented research applications that if identified before submission can lead to a stronger application. The authors participated in the review of clinical research grants to the National Kidney Foundation and catalogued the weaknesses of the grants that were reviewed and discussed. The top five reasons identified with grants were problems with study design (76%); statistical issues (34%); general issues such as ownership of the work, mentor, and environment (29%); weak hypothesis (24%); and problems with the research question, such as novelty or lack of creation of new data (24%). Patient-oriented research grants that have strong mentoring, are hypothesis driven, and have a strong study design that addresses sample size, analysis, and confounding factors have an increased chance of yielding high-quality research and, therefore, successful funding.

  View details for Web of Science ID 000242172600023

  View details for PubMedID 17699226

• Acute renal failure after endovascular vs open repair of abdominal aortic aneurysm JOURNAL OF VASCULAR SURGERY Wald, R., Waikar, S. S., Liangos, O., Pereira, B. J., Chertow, G. M., Jaber, B. L. 2006; 43 (3): 460-466

  Abstract

  Endovascular aneurysm repair (EVAR) is an increasingly used alternative to open surgical repair of unruptured abdominal aortic aneurysms (AAAs). The effect of EVAR on postprocedure acute renal failure has not been determined. We hypothesized that EVAR would be associated with a lower risk of acute renal failure and acute renal failure requiring hemodialysis.A retrospective cohort study was conducted of the 2002 Nationwide Inpatient Sample, the largest all-payer inpatient care database in the United States, reflecting discharges from a representative sample of United States hospitals. We identified 6614 discharges with a primary diagnosis of unruptured AAA and a primary procedure code for open AAA repair or EVAR. We excluded 56 patients with end-stage renal disease and 42 patients who underwent concomitant aortorenal bypass. We compared EVAR vs open repair in this cohort. The main outcome measures were acute renal failure and acute renal failure requiring dialysis.A total of 6516 patient discharges met the inclusion criteria for the study, and postprocedure acute renal failure developed in 439 (6.7%). EVAR was associated with lower odds of acute renal failure (adjusted odds ratio, 0.42; 95% confidence interval, 0.33 to 0.53) and acute renal failure requiring dialysis (adjusted odds ratio, 0.30, 95% confidence interval, 0.15 to 0.63). Results were similar when EVAR and open AAA repair were compared within quintiles of the propensity score for the receipt of EVAR.Compared with open AAA repair, EVAR is associated with a lower risk of postprocedure acute renal failure.

  View details for DOI 10.1016/j.jvs.2005.11.053

  View details for Web of Science ID 000235848800006

  View details for PubMedID 16520155

• Cinacalcet hydrochloride (sensipar) in hemodialysis patients on active vitamin D derivatives with controlled PTH and elevated calcium x phosphate 37th Annual Meeting of the American-Society-of-Nephrology Chertow, G. M., Blumenthal, S., Turner, S., Roppolo, M., Stern, L., Chi, E. M., Reed, J. AMER SOC NEPHROLOGY. 2006: 305–12

  Abstract

  Active vitamin D derivatives attenuate the severity of secondary hyperparathyroidism but often increase serum calcium (Ca) and phosphorus (P) as a result of enhanced intestinal absorption. The calcimimetic cinacalcet HCl lowers parathyroid hormone (PTH) and tends to decrease Ca x P. A 16-wk, open-label clinical trial was conducted in adult hemodialysis patients who had controlled PTH (biointact PTH [biPTH] 80 to 160 pg/ml) and elevated Ca x P (> 55 mg2/dl2) and were receiving paricalcitol > 6 microg/wk (or an equipotent dose of an alternative active vitamin D derivative). At the start of the study, active vitamin D derivatives were decreased to a mean equivalent dose of paricalcitol 6 microg/wk, and cinacalcet was titrated from 30 mg/d to a maximum possible dose of 180 mg/d. Of the 72 study patients, 53 (74%) completed 8 wk of dose titration with cinacalcet. In response to cinacalcet, the following mean percentage changes were observed: biPTH, -1.8%; Ca, -9.7% (P < 0.0001), phosphorus, -11.1% (P < 0.0001), and Ca x P, -20.1% (P < 0.0001). At the end of the study, approximate Kidney Disease Outcomes Quality Initiative targets for biPTH (< or = 160 pg/ml) were achieved in 85% (45 of 53) of patients and for Ca x P (< or = 55 mg2/dl2) in 72% (38 of 53) of patients. Concurrent achievement of both targets occurred in 47% (25 of 53) of patients. In this open-label clinical trial, hemodialysis patients who had controlled PTH but elevated Ca x P and were taking moderate- to high-dose active vitamin D derivatives achieved improved control of mineral metabolism with a combination of low-dose active vitamin D derivatives and cinacalcet. The long-term effects of this treatment regimen on clinical outcomes should be tested prospectively.

  View details for DOI 10.2215/CJN.00870805

  View details for Web of Science ID 000242172600018

  View details for PubMedID 17699221

• Update on adverse drug events associated with parenteral iron NEPHROLOGY DIALYSIS TRANSPLANTATION Chertow, G. M., Mason, P. D., Vaage-Nilsen, O., Ahlmen, J. 2006; 21 (2): 378-382

  Abstract

  We previously compared the safety profile of three formulations of intravenous iron used during 1998-2000 and found higher rates of adverse drug events (ADEs) associated with the use of higher molecular weight iron dextran and sodium ferric gluconate complex compared with lower molecular weight iron dextran. Since that time, iron sucrose has become widely available and clinicians have gained additional experience with sodium ferric gluconate complex.We obtained data from the United States Food and Drug Administration (FDA) on ADEs attributed to the provision of four formulations of intravenous iron during 2001-2003, including higher and lower molecular weight iron dextran, sodium ferric gluconate complex and iron sucrose. We estimated the odds of intravenous iron-related ADEs using 2 x 2 tables and the chi(2) test.The total number of reported parenteral iron-related ADEs was 1141 among approximately 30,063,800 doses administered, yielding a rate of 3.8 x 10(-5), or roughly 38 per million. Eleven individuals died in association with the ADE. Relative to lower molecular weight iron dextran, total and life-threatening ADEs were significantly more frequent among recipients of higher molecular weight iron dextran and significantly less frequent among recipients of sodium ferric gluconate complex and iron sucrose. The absolute rates of life-threatening ADEs were 0.6, 0.9, 3.3 and 11.3 per million for iron sucrose, sodium ferric gluconate complex, lower molecular weight iron dextran and higher molecular weight iron dextran, respectively. Based on differences in the average wholesale price of iron sucrose and lower molecular weight iron dextran in the US, the cost to prevent one life-threatening ADE related to the use of lower molecular weight iron dextran was estimated to be 5.0-7.8 million dollars. The cost to prevent one lower molecular weight iron dextran-related death was estimated to be 33 million dollars.The frequency of intravenous iron-related ADEs reported to the FDA has decreased, and overall, the rates are extremely low. This is the fourth report suggesting increased risks associated with the provision of higher molecular weight iron dextran. Life-threatening and other ADEs appear to be lower with the use of non-dextran iron formulations, although the cost per ADE prevented is extremely high.

  View details for DOI 10.1093/ndt/gfi253

  View details for Web of Science ID 000234782900020

  View details for PubMedID 16286429

• Challenging the validity of the EPO index. American journal of kidney diseases Kaysen, G. A., Müller, H. G., Ding, J., Chertow, G. M. 2006; 47 (1): 166-?

  Abstract

  With use of recombinant erythropoietin (EPO) and intravenous iron, the majority of hemodialysis patients can achieve target hemoglobin concentrations. EPO resistance arises as a consequence of inflammation and other processes that can adversely affect survival. We hypothesized that the EPO dose-hematocrit (EPO/Hct) ratio, also known as the EPO index, may be a surrogate for inflammation and that greater EPO/Hct ratios would be associated with decreased survival.We used proportional hazards regression models and time-varying logistic models to analyze the association between EPO index and survival in US hemodialysis patients initiating hemodialysis therapy between January 1, 1999, and December 31, 2000, and followed up for up to 3 years until December 31, 2001.We found an unexpected and consistent association between greater EPO index and survival in all models. The associations of EPO/Hct ratio were most prominent at intermediate Hct values and with longer dialysis vintage. Iron administration was associated with a lower risk for death independent of Hct. Conversely, greater average prior EPO dose was associated with a greater risk for death.EPO resistance may be reflected better by total cumulative EPO dose than the EPO/Hct ratio. The mechanism(s) responsible for the association between a greater EPO/Hct ratio and survival remains to be established, but may be a result of nonerythrogenic effects of EPO.

  View details for PubMedID 16377397

• Challenging the validity of the EPO index AMERICAN JOURNAL OF KIDNEY DISEASES Kaysen, G. A., Muller, H. G., Ding, J., Chertow, G. M. 2006; 47 (1): 157-166

  View details for DOI 10.1053/j.ajkd.2005.09.013

  View details for Web of Science ID 000235036000019

• Cystatin C and mortality risk in the elderly: The health, aging, and body composition study JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Shlipak, M. G., Fyr, C. L., Chertow, G. M., Harris, T. B., Kritchevsky, S. B., Tylavsky, F. A., Satterfield, S., Cummings, S. R., Newman, A. B., Fried, L. F. 2006; 17 (1): 254-261

  Abstract

  Kidney dysfunction is known to decrease life expectancy in the elderly. Cystatin C is a novel biomarker of kidney function that may have prognostic utility in older adults. The association of cystatin C with mortality was evaluated in a biracial cohort of black and white ambulatory elderly and compared with that of serum creatinine concentrations. The Health, Aging and Body Composition study is a cohort of well-functioning elderly that was designed to evaluate longitudinal changes in weight, body composition, and function. A total of 3075 participants who were aged 70 to 79 yr and had no disability were recruited at sites in Memphis, TN, and Pittsburgh, PA, between April 1997 and June 1998 with a follow-up of 6 yr. At entry, the mean cystatin C was 1.05 mg/L and the mean creatinine was 1.06 mg/dl. After 6 yr of follow-up, 557 participants had died. The mortality rates in each ascending cystatin C quintile were 1.7, 2.7, 2.9, 3.1, and 5.4%/yr. After adjustment for demographic risk factors, comorbid health conditions, and inflammatory biomarkers (C-reactive protein, IL-6. and TNF-alpha), each quintile of cystatin C was significantly associated with increased mortality risk compared with the lowest: Hazard ratios (HR; 95% confidence intervals) quintile 1, -1.0 (referent); quintile 2, -1.74 (1.21 to 2.50); quintile 3, -1.51 (1.05 to 2.18); quintile 4, -1.49 (1.04 to 2.13); and quintile 5, -2.18 (1.53 to 3.10). These associations did not differ by gender or race. Results were consistent for cardiovascular and other-cause mortality, but not cancer mortality. Creatinine quintiles were not associated with mortality after multivariate adjustment (HR: 1.0 [referent], 1.00 [0.72 to 1.39], 0.95 [0.68 to 1.32], 1.11 [0.79 to 1.57], 1.16 [0.86 to 1.58]). Cystatin C is a strong, independent risk factor for mortality in the elderly. Future studies should investigate whether cystatin C has a role in clinical medicine.

  View details for DOI 10.1681/ASN.2005050545

  View details for Web of Science ID 000242120000032

  View details for PubMedID 16267155

• PTH and the risks for hip, vertebral, and pelvic fractures among patients on dialysis AMERICAN JOURNAL OF KIDNEY DISEASES Danese, M. D., Kim, J., Doan, Q. V., Dylan, M., Griffiths, R., Chertow, G. M. 2006; 47 (1): 149-156

  Abstract

  Few investigations have described fracture risk and its relation to disorders in calcium (Ca), phosphorus (P), and parathyroid hormone (PTH) metabolism in the end-stage renal disease population.Laboratory values for Ca, P, and PTH were obtained from Dialysis Morbidity and Mortality Study (DMMS) Waves 1 to 4. Additional data available from the US Renal Data System were used to determine the incidence and associated costs of hip, vertebral, and pelvic fractures in 9,007 patients with nonmissing laboratory values and Medicare as primary payor. Cox proportional hazards and Poisson models were used to analyze time to first fracture and numbers of fractures, respectively.There was no association between Ca or P values and risk for fracture; risks for vertebral and hip fractures and PTH concentrations were U shaped and weakly significant using Poisson regression (P = 0.03). The age- and sex-adjusted mortality rate after fracture was 2.7 times greater (580/1,000 person-years) than for general dialysis patients from the DMMS (217/1,000 person-years). Mean total episodic costs of hip, vertebral, and pelvic fractures were 20,810 dollars +/- 16,743 dollars (SD), 17,063 dollars +/- 26,201 dollars, and 14,475 dollars +/- 19,209 dollars, respectively.Using data from the DMMS, there were no associations between Ca and P concentrations and risk for fracture. Risks for hip and vertebral fracture were associated weakly with PTH concentration, with the lowest risk observed around a PTH concentration of 300 pg/mL (ng/L). Fractures were associated with high subsequent mortality and costs. Prospective studies are needed to determine whether therapies that maintain PTH concentrations within or near the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative range will result in fewer complications of disordered mineral metabolism.

  View details for DOI 10.1053/j.ajkd.2005.09.024

  View details for Web of Science ID 000235036000018

  View details for PubMedID 16377396

• Lessons for Medicare Part D in the hemodialysis community. BMC nephrology Nayeem, A. I., Chertow, G. M. 2006; 7: 11-?

  Abstract

  Medicare beneficiaries without prescription drug coverage consistently fill fewer prescriptions than beneficiaries with some form of drug coverage due to cost. ESRD patients, who are disproportionately poor and typically use multiple oral medications, would likely benefit substantially from any form of prescription drug coverage. Because most hemodialysis patients are Medicare-eligible, they as well as their providers would be expected to be well informed of changes in Medicare prescription drug coverage. By examining the level of understanding and use of the temporary Medicare Prescription Drug Discount Card Program in the hemodialysis population, we can gain a better understanding of the potential long-term utilization for Medicare Part D.We surveyed English-speaking adult hemodialysis patients with Medicare coverage from two urban hemodialysis centers affiliated with the University of California San Francisco (UCSF) during July and August 2005 (n = 70). We also surveyed University- and community-based nephrologists and non-physician dialysis health care professionals over the same time frame (n = 70).Fifty-nine percent of patients received prescription drug coverage through Medi-Cal, 20% through another insurance program, and 21% had no prescription drug coverage. Forty percent of patients with no prescription drug coverage reported "sometimes" or "rarely" being able to obtain medications vs. 22% of patients with some form of drug coverage. None of the patients surveyed actually had a Medicare-approved prescription drug card, and of those who intended to apply, only 10% reported knowing how to do so. Only 11% health care professionals knew the eligibility requirements of the drug discount cards.Despite a significant need, hemodialysis patients and providers were poorly educated about the Medicare Prescription Drug Discount Cards. This has broad implications for the dissemination of information about Medicare Part D.

  View details for PubMedID 16824211

  View details for PubMedCentralID PMC1526420

• Health-related quality of life and estimates of utility in chronic kidney disease KIDNEY INTERNATIONAL Gorodetskaya, I., Zenios, S., McCulloch, C. E., Bostrom, A., Hsu, C. Y., Bindman, A. B., Go, A. S., Chertow, G. M. 2005; 68 (6): 2801-2808

  Abstract

  Health-related quality of life and estimates of utility have been carefully evaluated in persons with end-stage renal disease. Fewer studies have examined these parameters in persons with chronic kidney disease (CKD).To determine the relations among kidney function, health-related quality of life, and estimates of utility, we administered the Kidney Disease Quality of Life Short Form 36 (KDQOL-36), Health Utilities Index (HUI)-3, and Time Trade-off (TTO) questionnaires to 205 persons with CKD. Persons with CKD stages 4 and 5 (estimated GFR <30 mL/min/1.73 m2, N= 115) were tested two to eight times over the subsequent two years. The relations among estimated glomerular filtration rate (eGFR), and changes in health-related quality of life and utility over time were estimated using mixed effect regression models. Models were adjusted for age, sex, race, and diabetes.Mean scores on the KDQOL-36 generic components, HUI-3, and TTO suggested considerable loss of function and well-being in CKD relative to population norms. On cross-sectional analysis, lower levels of kidney function were associated with significantly lower scores on the SF-12 Physical Health Composite (P= 0.002), the Burden of Kidney Disease subscale (P < 0.0001), and the Effects of Kidney Disease subscale (P < 0.0001) of the KDQOL-36trade mark. Kidney function was significantly associated with the TTO (P= 0.008) and global HUI-3 utility (P= 0.016) although these associations were attenuated after adjustment for diabetes. A decline in eGFR was associated with a significant increase in the reported Burden of Kidney Disease (5.0 point change per year per mL/min/1.73 m2 decline in eGFR) and with marginally significant changes in the Dexterity and Pain attributes of the HUI-3. Mean HUI-3 scores for persons with CKD stages 4 and 5, absent dialysis, were in the range previously reported for persons with stroke and severe peripheral vascular disease.Health-related quality of life and estimates of utility are distressingly low in persons with CKD. Self-reported outcomes should be considered when evaluating health policy decisions that affect this population.

  View details for Web of Science ID 000233204300036

  View details for PubMedID 16316356

• Prealbumin, mortality, and cause-specific hospitalization in hemodialysis patients KIDNEY INTERNATIONAL Chertow, G. M., Goldstein-Fuchs, D. J., Lazarus, J. M., Kaysen, G. A. 2005; 68 (6): 2794-2800

  Abstract

  Prealbumin (transthyretin) is a hepatic secretory protein thought to be important in the evaluation of nutritional deficiency and nutrition support. Prior studies have suggested that the serum prealbumin concentration is independently associated with mortality in hemodialysis patients, even with adjustment for serum albumin and other nutritional parameters.To determine whether prealbumin was independently associated with mortality and morbidity (cause-specific hospitalization) in hemodialysis patients, we analyzed data on 7815 hemodialysis patients with at least one determination of serum prealbumin during the last three months of 1997. Unadjusted, case mix-adjusted, and multivariable-adjusted relative risks of death were calculated for categories of serum prealbumin using proportional hazards regression. We also determined whether the prealbumin concentration was associated with all-cause, cardiovascular, infection-related, and vascular access-related hospitalization.The relative risk (RR) of death was inversely related to the serum prealbumin concentration. Relative to prealbumin > or =40 mg/dL, the adjusted RRs of death were 2.41, 1.85, 1.49, and 1.23 for prealbumin <15, 15-20, 20-25, and 25-30 mg/dL, respectively. The adjusted RRs of hospitalization due to infection were 2.97, 1.95, 1.81, and 1.61 for prealbumin <15, 15-20, 20-25, and 25-30 mg/dL, respectively. The adjusted RRs of vascular access-related hospitalization were 0.48, 0.52, 0.58, and 0.71 for prealbumin <15, 15-20, 20-25, and 25-30 mg/dL, respectively. While serum albumin was strongly associated with mortality and all-cause hospitalization, it was not associated with hospitalization due to infection, and lower levels were associated with higher rather than lower rates of vascular access-related hospitalization.In hemodialysis patients, lower prealbumin concentrations were associated with mortality and hospitalization due to infection, independent of serum albumin and other clinical characteristics. Higher prealbumin concentrations were associated with vascular access-related hospitalization. In light of these findings, more intensive study into the determinants and biological actions of prealbumin (transthyretin) in end-stage renal disease is warranted.

  View details for Web of Science ID 000233204300035

  View details for PubMedID 16316355

• Self-reported appetite, hospitalization and death in haemodialysis patients: findings from the hemodialysis (HEMO) study NEPHROLOGY DIALYSIS TRANSPLANTATION Burrowes, J. D., Larive, B., Chertow, G. M., Cockram, D. B., Dwyer, J. T., Greene, T., Kusek, J. W., Leung, J., Rocco, M. V. 2005; 20 (12): 2765-2774

  Abstract

  Anorexia is an important cause of protein-energy malnutrition (PEM) in haemodialysis patients. We investigated whether self-reported appetite was associated with death and hospitalization in subjects enrolled in the Hemodialysis (HEMO) Study.The HEMO Study was a 7-year, multicentre, randomized trial (N = 1846), which examined the effects of dialysis dose and membrane flux on mortality and morbidity. Three questions from the Appetite and Diet Assessment Tool (ADAT) were used to determine whether appetite had changed over time in the randomized treatment groups. The relations among ADAT scores, dietary protein and energy intakes, biochemical and anthropometric measures, and quality of life were assessed. We used Cox proportional hazards models to evaluate the relative risks of death and hospitalization associated with static and dynamic ADAT scores, adjusted for demographic factors, dose and flux assignments, and co-morbidity.The average length of follow-up was 2.84 years. After adjusting for demographic factors and randomized treatment assignments, there was a significant association between poorer self-reported appetite and death (RR 1.52, 95% CI 1.16-1.98); however, the association became non-significant with further adjustment for co-morbidity (RR 1.23, 95% CI 0.94-1.62). Poorer appetite was unequivocally associated with increased hospitalization rates (multivariable RR 1.35, 95% CI 1.13-1.61). The longitudinal effect of worsening appetite from baseline to 1 year was not associated with mortality or hospitalization rate after adjusting for co-morbidity.The association between appetite and death was confounded by co-morbidity. Self-reported appetite was associated with hospitalization rate in haemodialysis patients and, thus, it may be a useful screening tool for this outcome. Patients who report poor or very poor appetites should be monitored, and they should receive more comprehensive nutritional assessments.

  View details for DOI 10.1093/ndt/gfi132

  View details for Web of Science ID 000233361800029

  View details for PubMedID 16204298

• Differential mortality and transplantation rates among Asians and Pacific Islanders with ESRD JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Hall, Y. N., Sugihara, J. G., Go, A. S., Chertow, G. M. 2005; 16 (12): 3711-3720

  Abstract

  Few studies in patients with ESRD have examined outcomes in Asian or Pacific Islander subgroups compared with white individuals. The objective of this study was to assess ethnic disparities in mortality and kidney transplantation among a multiethnic cohort of incident dialysis patients. A total of 24,963 patients who initiated dialysis within the TransPacific Renal Network (Network 17) between April 1, 1995, and September 30, 2001, were studied to ascertain death and kidney transplantation through September 30, 2002. Overall, 12,902 deaths and 2258 kidney transplantations were observed during 59,075 person-years of follow-up. Mortality on dialysis among Asians and Pacific Islanders (except Chamorros) was lower than that of white individuals after controlling for differences in sociodemographic characteristics, comorbid conditions, and other risk factors for death (adjusted hazard ratio [95% confidence interval] versus white individuals: Japanese 0.64 [0.57 to 0.72], Chinese 0.64 [0.52 to 0.78], Filipino 0.64 [0.57 to 0.72], Native Hawaiian 0.84 [0.72 to 0.96], Samoan 0.62 [0.48 to 0.82], and Chamorro 0.96 [0.84 to 1.20]). In contrast, Asians and Pacific Islanders were much less likely to undergo kidney transplantation (adjusted rate ratio [95% confidence interval] versus white individuals: Japanese 0.34 [0.24 to 0.46], Chinese 0.54 [0.30 to 0.88], Filipino 0.32 [0.26 to 0.47], Native Hawaiian 0.17 [0.10 to 0.30], Samoan 0.17 [0.07 to 0.38], and Chamorro 0.04 [0.01 to 0.14]). Despite wide variations in primary cause of ESRD, clinical characteristics, and body size at dialysis initiation, Asians and Pacific Islanders experience better survival but substantially lower transplantation rates compared with white individuals. Strategies that are aimed at improving access to transplantation in Asian and Pacific Islander communities may further enhance survival among Asians and Pacific Islanders with ESRD.

  View details for DOI 10.1681/ASN.2005060580

  View details for Web of Science ID 000233893600032

  View details for PubMedID 16236803

• Acute kidney injury, mortality, length of stay, and costs in hospitalized patients JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Chertow, G. M., Burdick, E., Honour, M., Bonventre, J. V., Bates, D. W. 2005; 16 (11): 3365-3370

  Abstract

  The marginal effects of acute kidney injury on in-hospital mortality, length of stay (LOS), and costs have not been well described. A consecutive sample of 19,982 adults who were admitted to an urban academic medical center, including 9210 who had two or more serum creatinine (SCr) determinations, was evaluated. The presence and degree of acute kidney injury were assessed using absolute and relative increases from baseline to peak SCr concentration during hospitalization. Large increases in SCr concentration were relatively rare (e.g., >or=2.0 mg/dl in 105 [1%] patients), whereas more modest increases in SCr were common (e.g., >or=0.5 mg/dl in 1237 [13%] patients). Modest changes in SCr were significantly associated with mortality, LOS, and costs, even after adjustment for age, gender, admission International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis, severity of illness (diagnosis-related group weight), and chronic kidney disease. For example, an increase in SCr >or=0.5 mg/dl was associated with a 6.5-fold (95% confidence interval 5.0 to 8.5) increase in the odds of death, a 3.5-d increase in LOS, and nearly 7500 dollars in excess hospital costs. Acute kidney injury is associated with significantly increased mortality, LOS, and costs across a broad spectrum of conditions. Moreover, outcomes are related directly to the severity of acute kidney injury, whether characterized by nominal or percentage changes in serum creatinine.

  View details for DOI 10.1681/ASN.2004090740

  View details for Web of Science ID 000232847800026

  View details for PubMedID 16177006

• Effects of the calcimimetic cinacalcet HCl on cardiovascular disease, fracture, and health-related quality of life in secondary hyperparathyroidism KIDNEY INTERNATIONAL Cunningham, J., Danese, M., Olson, K., Klassen, P., Chertow, G. M. 2005; 68 (4): 1793-1800

  Abstract

  Secondary hyperparathyroidism (HPT) and abnormal mineral metabolism are thought to play an important role in bone and cardiovascular disease in patients with chronic kidney disease. Cinacalcet, a calcimimetic that modulates the calcium-sensing receptor, reduces parathyroid hormone (PTH) secretion and lowers serum calcium and phosphorus concentrations in patients with end-stage renal disease (ESRD) and secondary HPT.We undertook a combined analysis of safety data (parathyroidectomy, fracture, hospitalizations, and mortality) from 4 similarly designed randomized, double-blind, placebo-controlled clinical trials enrolling 1184 subjects (697 cinacalcet, 487 control) with ESRD and uncontrolled secondary HPT (intact PTH > or =300 pg/mL). Cinacalcet or placebo was administered to subjects receiving standard care for hyperphosphatemia and secondary HPT (phosphate binders and vitamin D). Relative risks (RR) and 95% CI were calculated using proportional hazards regression with follow-up times from 6 to 12 months. Health-related quality-of-life (HRQOL) data were obtained from the Medical Outcomes Study Short Form-36 (SF-36), and the Cognitive Functioning scale from the Kidney Disease Quality of Life instrument (KDQOL-CF).Randomization to cinacalcet resulted in significant reductions in the risk of parathyroidectomy (RR 0.07, 95% CI 0.01-0.55), fracture (RR 0.46, 95% CI 0.22-0.95), and cardiovascular hospitalization (RR 0.61, 95% CI 0.43-0.86) compared with placebo. Changes in HRQOL favored cinacalcet, with significant changes observed for the SF-36 Physical Component Summary score and the specific domains of Bodily Pain and General Health Perception.Combining results from 4 clinical trials, randomization to cinacalcet led to significant reductions in the risk of parathyroidectomy, fracture, and cardiovascular hospitalization, along with improvements in self-reported physical function and diminished pain. These data suggest that, in addition to its effects on PTH and mineral metabolism, cinacalcet had favorable effects on important clinical outcomes.

  View details for Web of Science ID 000231801300044

  View details for PubMedID 16164656

• Are nutritional status indicators associated with mortality in the Hemodialysis (HEMO) Study ? KIDNEY INTERNATIONAL Dwyer, J. T., Larive, B., Leung, J., Rocco, M. V., Greene, T., Burrowes, J., Chertow, G. M., Cockram, D. B., Chumlea, W. C., Daugirdas, J., Frydrych, A., Kusek, J. W. 2005; 68 (4): 1766-1776

  Abstract

  The purpose of this study was to determine if indicators of nutritional status were associated with subsequent mortality in hemodialysis patients.Twelve selected nutrition indicators were measured prior to randomization in the Mortality and Morbidity in Hemodialysis (HEMO) Study. Relative risks (RR) of mortality were assessed at <6 months and >6 months of follow-up using Cox regression after controlling for case mix, comorbidity, and treatment assignment (high vs. standard Kt/V and high vs. low membrane flux).Low values of most nutritional status indicators were associated with increased RR of mortality. RRs were greatest over the short term (<6 months) and diminished with increasing follow-up (>6 months). Increases in body mass index (BMI) at lower levels (e.g., < or =25 kg/m(2)) and increases in serum albumin at any level were associated with reduced short-term RR, even after adjusting for case mix, treatment assignment, and for the joint effects of equilibrated normalized protein catabolic rate, total cholesterol, and serum creatinine. For >6 months' follow-up, increases in values among those with lower levels of BMI and serum albumin (< or =3.635 g/dL) and increases in all serum creatinine levels were associated with lower RR.Nutrition indicators are associated with subsequent mortality in a time-dependent manner, with greatest effects at <6 months of follow-up. The RR for these indicators may also vary within different ranges of values.

  View details for Web of Science ID 000231801300041

  View details for PubMedID 16164653

• Insulin resistance in critically ill patients with acute renal failure 36th Annual Meeting of the American-Society-of-Nephrology Basi, S., Pupim, L. B., Simmons, E. M., Sezer, M. T., Shyr, Y., Freedman, S., Chertow, G. M., Mehta, R. L., Paganini, E., Himmelfarb, J., Ikizler, T. A. AMER PHYSIOLOGICAL SOC. 2005: F259–F264

  Abstract

  Mortality in critically ill patients with acute renal failure (ARF) remains high. Hyperglycemia associated with insulin resistance has been associated with adverse outcomes in critically ill intensive care unit (ICU) patients but has not been examined specifically in patients with ARF. We used data from a subcohort (n = 90) of the Program to Improve Care in Acute Renal Disease (PICARD), an observational study of 618 adult ICU patients with ARF in whom nephrology service consultation was obtained. We obtained simultaneous measurements of serum glucose, insulin, insulin-like growth factor (IGF)-I, and IGF-1 binding proteins (IGFBP) in 90 patients. Daily glucose determinations were obtained from a larger fraction of the PICARD cohort (n = 509). Among the 90 patients with intensive metabolic monitoring, glucose concentrations in survivors were significantly lower than in nonsurvivors throughout the 5-wk period (P = 0.008, adjusted P = 0.013). In the larger PICARD cohort (n = 509), hyperglycemia was also significantly associated with in-hospital mortality. Mean insulin concentrations were significantly higher (431 +/- 508 vs. 234 +/- 189 pmol/l, P = 0.03), mean homeostasis model of insulin resistance levels were significantly higher (24.1 +/- 30.0 vs. 11.7 +/- 12.5, P = 0.04), and IGFBP-3 concentrations were significantly lower (1,190 +/- 498 vs. 1,470 +/- 581 microg/l, P = 0.02) among nonsurvivors compared with survivors. Insulin resistance as defined by hyperglycemia in the setting of higher insulin concentrations may be associated with mortality in critically ill patients with ARF. The IGF-IGFBP axis may play an important role in this process.

  View details for DOI 10.1152/ajprenal.00002.2005

  View details for Web of Science ID 000230385900005

  View details for PubMedID 15840772

• Chronic kidney disease and cognitive impairment in the elderly: The health, aging, and body composition study JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Kurella, M., Chertow, G. M., Fried, L. F., Cummings, S. R., Harris, T., Simonsick, E., Satterfield, S., Ayonayon, H., Yaffe, K. 2005; 16 (7): 2127-2133

  Abstract

  Previous studies suggest a link between chronic kidney disease (CKD) and cognitive impairment. Whether the longitudinal course of cognitive impairment differs among people with or without CKD is unknown. Data collected in 3034 elderly individuals who participated in the Health, Aging, and Body Composition study were analyzed. Cognitive function was assessed with the Modified Mini-Mental State Exam (3MS) at baseline and then 2 and 4 yr after baseline. Cognitive impairment was defined as a 3MS score <80 or a decline in 3MS >5 points after 2 or 4 yr of follow-up among participants with baseline 3MS scores > or =80. Participants with CKD, defined as an estimated GFR (eGFR) <60 ml/min per 1.73 m2, were further divided into two eGFR strata. Unadjusted mean baseline 3MS scores and mean declines in 3MS scores over 4 yr were significantly more pronounced for participants with lower baseline eGFR. More advanced stages of CKD were associated with an increased risk for cognitive impairment: Odds ratio (OR) 1.32 (95% confidence interval [CI] 1.03 to 1.69) and OR 2.43 (95% CI, 1.38 to 4.29) for eGFR 45 to 59 ml/min per 1.73 m2 and <45 ml/min per 1.73 m2, respectively, adjusted for case mix, baseline 3MS scores, and other potential confounders. CKD is associated with an increased risk for cognitive impairment in the elderly that cannot be fully explained by other well-established risk factors. Studies aimed at understanding the mechanism(s) responsible for cognitive impairment in CKD and efforts to interrupt this decline are warranted.

  View details for Web of Science ID 000230046900032

  View details for PubMedID 15888561

• Metabolic syndrome and the risk for chronic kidney disease among nondiabetic adults JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Kurella, M., Lo, J. C., Chertow, G. M. 2005; 16 (7): 2134-2140

  Abstract

  The metabolic syndrome is a risk factor for the development of diabetes and cardiovascular disease; however, no prospective studies have examined the metabolic syndrome as a risk factor for chronic kidney disease (CKD). A total of 10,096 nondiabetic participants who were in the Atherosclerosis Risk in Communities study and had normal baseline kidney function composed the study cohort. The metabolic syndrome was defined according to recent guidelines from the National Cholesterol Education Program. Incident CKD was defined as an estimated GFR (eGFR) <60 ml/min per 1.73 m2 at study year 9 among those with an eGFR > or =60 ml/min per 1.73 m2 at baseline. After 9 yr of follow-up, 691 (7%) participants developed CKD. The multivariable adjusted odds ratio (OR) of developing CKD in participants with the metabolic syndrome was 1.43 (95% confidence interval [CI], 1.18 to 1.73). Compared with participants with no traits of the metabolic syndrome, those with one, two, three, four, or five traits of the metabolic syndrome had OR of CKD of 1.13 (95% CI, 0.89 to 1.45), 1.53 (95% CI, 1.18 to 1.98), 1.75 (95% CI, 1.32 to 2.33), 1.84 (95% CI, 1.27 to 2.67), and 2.45 (95% CI, 1.32 to 4.54), respectively. After adjusting for the subsequent development of diabetes and hypertension during the 9 yr of follow-up, the OR of incident CKD among participants with the metabolic syndrome was 1.24 (95% CI, 1.01 to 1.51). The metabolic syndrome is independently associated with an increased risk for incident CKD in nondiabetic adults.

  View details for Web of Science ID 000230046900033

  View details for PubMedID 15901764

• Serum blood urea nitrogen as an independent marker of subsequent mortality among patients with acute coronary syndromes and normal to mildly reduced glomerular filtration rates JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Kirtane, A. J., Leder, D. M., Waikar, S. S., Chertow, G. M., Ray, K. K., Pinto, D. S., Karmpaliotis, D., Burger, A. J., Murphy, S. A., Cannon, C. P., Braunwald, E., Gibson, C. M. 2005; 45 (11): 1781-1786

  Abstract

  We hypothesized that elevated blood urea nitrogen (BUN) would be associated with adverse outcomes independent of serum creatinine (sCr)-based estimates of kidney function in patients with acute coronary syndromes (ACS).Although lower glomerular filtration rates (GFR) have prognostic significance among patients with ACS, estimates of GFR based on sCr may perform less accurately among patients with milder kidney dysfunction. In this population in particular, BUN, which can reflect increased proximal tubular reabsorption in addition to decreased GFR, may have independent prognostic value.Data were drawn from 9,420 patients with unstable coronary syndromes from Orbofiban in Patients With Unstable Coronary Syndromes-Thrombolysis In Myocardial Infarction (OPUS-TIMI)-16, a trial that excluded patients with sCr >1.6 mg/dl or estimated creatinine clearance <40 ml/min.Patients with elevated BUN were older, had a higher prevalence of comorbidities, and had higher heart rates, lower systolic blood pressures, and an abnormal Killip class more often on admission. In univariate analyses, as well as in stratified and multivariable analyses including sCr-based estimates of GFR as a covariate, a stepwise increase in mortality occurred with increasing BUN (multivariable hazard ratio with BUN 20 to 25 mg/dl 1.9, 95% confidence interval 1.3 to 2.6; with BUN >/=25 mg/dl 3.2 [95% confidence interval 2.2 to 4.7]) compared with BUN

  View details for DOI 10.1016/j.jacc.2005.02.068

  View details for Web of Science ID 000229593000009

  View details for PubMedID 15936606

• Control of hypertension in adults with chronic kidney disease in the United States HYPERTENSION Peralta, C. A., Hicks, L. S., Chertow, G. M., Ayanian, J. Z., Vittinghoff, E., Lin, F., Shlipak, M. G. 2005; 45 (6): 1119-1124

  Abstract

  Although improved control of hypertension is known to attenuate progression of chronic kidney disease (CKD), little is known about the adequacy of hypertension treatment in adults with CKD in the United States. Using data from the Fourth National Health and Nutrition Survey, we assessed adherence to national hypertension guideline targets for patients with CKD (blood pressure <130/80 mm Hg), we assessed control of systolic (<130 mm Hg) and diastolic (<80 mm Hg) blood pressure, and we evaluated determinants of adequate blood pressure control. Presence of CKD was defined as glomerular filtration rate <60 mL/min per 1.73 m2 or presence of albuminuria (albumin:creatinine ratio >30 microg/mg). Multivariable logistic regression with appropriate weights was used to determine predictors of inadequate hypertension control and related outcomes. Among 3213 participants with CKD, 37% had blood pressure <130/80 mm Hg (95% confidence interval [CI], 34.5% to 41.8%). Of those with inadequate blood pressure control, 59% (95% CI, 54% to 64%) had systolic >130 mm Hg, with diastolic < or =80 mm Hg, whereas only 7% (95% CI, 3.9 to 9.8%) had a diastolic pressure >80 mm Hg, with systolic blood pressure < or =130 mm Hg. Non-Hispanic black race (odds ratio [OR], 2.4; 95% CI, 1.5 to 3.9), age >75 years (OR, 4.7; 95% CI, 2.7 to 8.2), and albuminuria (OR, 2.4; 95% CI, 1.4 to 4.1) were independently associated with inadequate blood pressure control. We conclude that control of hypertension is poor in participants with CKD and that lack of control is primarily attributable to systolic hypertension. Future guidelines and antihypertensive therapies for patients with CKD should target isolated systolic hypertension.

  View details for DOI 10.1161/01.HYP.0000164577.81087.70

  View details for Web of Science ID 000229396600017

  View details for PubMedID 15851626

• Beyond Framingham: Cardiovascular risk profiling in ESRD JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY McClellan, W. M., Chertow, G. M. 2005; 16 (6): 1539-1541

  View details for DOI 10.1681/ASN.2005040415

  View details for Web of Science ID 000229393900004

  View details for PubMedID 15872082

• End stage renal disease. Clinical evidence Hall, Y., Chertow, G. 2005: 1048-1059

  View details for PubMedID 16135286

• Potential antiatherogenic and anti-inflammatory properties of sevelamer in maintenance hemodialysis patients AMERICAN HEART JOURNAL Ferramosca, E., Burke, S., Chasan-Taber, S., Ratti, C., Chertow, G. M., Raggi, P. 2005; 149 (5): 820-825

  Abstract

  Patients affected by end-stage renal disease (ESRD) demonstrate a very high cardiovascular risk mediated by traditional cardiovascular risk factors as well as abnormal mineral metabolism and a state of chronic inflammation. Sevelamer is a nonabsorbable non-calcium-based hydrogel with potential antiatherosclerotic properties.One hundred eight patients undergoing maintenance hemodialysis were randomized to sevelamer or calcium acetate as treatment for hyperphosphatemia. A coronary artery calcium score, as a measure of plaque burden, was calculated at baseline and 1 year, along with serial measurements of serum lipoproteins, beta2-microglobulin, and high-sensitivity C-reactive protein (hs-CRP). At 1 year, coronary artery calcium score progressed significantly from baseline in calcium acetate-treated subjects ( P < .001) but not in sevelamer-treated patients (P = NS). Total cholesterol (P < .0001), low-density lipoprotein cholesterol (P < .0001), apolipoprotein B (P < .0001), beta2-microglobulin (P = .018), and hs-CRP (P < .002) decreased, and high-density lipoprotein increased significantly (P = .036) from baseline in the sevelamer-treated subjects but not in subjects treated with calcium acetate despite the more frequent use of statins in the latter group (46% vs 22%, P < .05). The changes in total and low-density lipoprotein cholesterol, apolipoprotein B, and hs-CRP were significantly different between treatment groups (all P < .01).Sevelamer leads to favorable changes in lipids and inflammatory markers with potentially useful antiatherogenic effects in hemodialysis patients.

  View details for DOI 10.1016/j.ahj.2004.07.023

  View details for Web of Science ID 000229560500011

  View details for PubMedID 15894962

• Medicare ESRD prospective payment system: Weighing the evidence JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Himmelfarb, J., Chertow, G. M. 2005; 16 (5): 1164-1165

  View details for DOI 10.1681/ASN.2005030315

  View details for Web of Science ID 000228715700001

  View details for PubMedID 15829705

• Decrease in thoracic vertebral bone attenuation with calcium-based phosphate binders in hemodialysis JOURNAL OF BONE AND MINERAL RESEARCH Raggi, P., James, G., Burke, S. K., Bommer, J., Chasan-Taber, S., Holzer, H., Braun, J., Chertow, G. M. 2005; 20 (5): 764-772

  Abstract

  We performed a post hoc analysis of a 52-week randomized trial conducted in adult hemodialysis patients that compared the effects of calcium-based phosphate binders and sevelamer, a nonabsorbable polymer, on parameters of mineral metabolism and vascular calcification by electron beam tomography. In this analysis, we evaluated the relative effects of calcium and sevelamer on thoracic vertebral attenuation by CT and markers of bone turnover. Subjects randomized to calcium salts experienced a significant reduction in trabecular bone attenuation and a trend toward reduction in cortical bone attenuation, in association with higher concentrations of serum calcium, lower concentrations of PTH, and reduced total and bone-specific alkaline phosphatase.In patients with chronic kidney disease, hyperphosphatemia is associated with osteodystrophy, vascular and soft tissue calcification, and mortality. Calcium-based phosphate binders are commonly prescribed to reduce intestinal phosphate absorption and to attenuate secondary hyperparathyroidism. Clinicians and investigators have presumed that, in hemodialysis patients, calcium exerts beneficial effects on bone.We performed a post hoc analysis of a 52-week randomized trial conducted in adult hemodialysis patients that compared the effects of calcium-based phosphate binders and sevelamer, a nonabsorbable polymer, on parameters of mineral metabolism and vascular calcification by electron beam tomography. In this analysis, we evaluated the relative effects of calcium and sevelamer on thoracic vertebral attenuation by CT and markers of bone turnover.The average serum phosphorus and calcium x phosphorus products were similar for both groups, although the average serum calcium concentration was significantly higher in the calcium-treated group. Compared with sevelamer-treated subjects, calcium-treated subjects showed a decrease in thoracic vertebral trabecular bone attenuation (p = 0.01) and a trend toward decreased cortical bone attenuation. More than 30% of calcium-treated subjects experienced a 10% or more decrease in trabecular and cortical bone attenuation. On study, sevelamer-treated subjects had higher concentrations of total and bone-specific alkaline phosphatase, osteocalcin, and PTH (p < 0.001). When used to correct hyperphosphatemia, calcium salts lead to a reduction in thoracic trabecular and cortical bone attenuation. Calcium salts may paradoxically decrease BMD in hemodialysis patients.

  View details for DOI 10.1359/JBMR.041221

  View details for Web of Science ID 000228679800007

  View details for PubMedID 15824849

• Bone disease and bottle caps JOURNAL OF RENAL NUTRITION Tichy, M., Garg, J. P., Cho, K. C., Chertow, G. M. 2005; 15 (2): 257-259

  View details for DOI 10.1053/j.jm.2005.01.006

  View details for Web of Science ID 000228782100009

  View details for PubMedID 15827900

• Frequent hemodialysis and psychosocial function SEMINARS IN DIALYSIS Kurella, M., Suri, R. S., Chertow, G. M. 2005; 18 (2): 132-136

  Abstract

  Studies suggest that more frequent hemodialysis (HD; short daily and long nocturnal dialysis) may be associated with a variety of clinical benefits, including improvement in blood pressure, anemia, and hyperphosphatemia, regression of left ventricular hypertrophy, and reduced rates of hospitalization. Whether these clinical benefits are paralleled by improvements in health-related quality of life (HRQOL) has been unclear. In addition, the psychosocial burden of more intensive HD schedules has not been critically evaluated. Recent reports have suggested beneficial effects of frequent HD on global HRQOL, dialysis-related and uremic symptoms, patient satisfaction, and psychosocial burden. However, the interpretation of many of these studies is restricted by limitations in study design, follow-up, and generalizability. This article reviews the current literature focusing on psychosocial and HRQOL effects of frequent HD and suggests future directions for research in this important area.

  View details for Web of Science ID 000227478200010

  View details for PubMedID 15771657

• Suicide in the United States end-stage renal disease program JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Kurella, M., Kimmel, P. L., Young, B. S., Chertow, G. M. 2005; 16 (3): 774-781

  Abstract

  Although depression and dialysis withdrawal are relatively common among individuals with ESRD, there have been few systematic studies of suicide in this population. The goals of this study were to compare the incidence of suicide with national rates and to contrast the factors associated with suicide with those associated with withdrawal in persons with ESRD. All individuals who were aged 15 yr and older and initiated dialysis between April 1, 1995, and November 30, 2000, composed the analytic cohort. Patients were censored at the time of death, transplantation, or October 31, 2001. Death as a result of suicide in the ESRD population and the general US population was ascertained from the Death Notification Form and the Centers for Disease Control and Prevention, respectively. Standardized incidence ratios for suicide among patient subgroups were computed using national data from the year 2000 as the reference population. The crude suicide rate from 1995 to 2001 was 24.2 suicides per 100,000 patient-years, and the overall standardized incidence ratio for suicide was 1.84 (95% confidence interval, 1.50 to 2.27). In multivariable models, age > or =75 yr, male gender, white or Asian race, geographic region, alcohol or drug dependence, and recent hospitalization with mental illness were significant independent predictors of death as a result of suicide. Persons with ESRD are significantly more likely to commit suicide than persons in the general population. Although relatively rare, risk assessment can be used to identify patients for whom counseling and other interventions might be beneficial.

  View details for DOI 10.1681/ASN.2004070550

  View details for Web of Science ID 000227372000026

  View details for PubMedID 15659561

• Dialysis session length ("t") as a determinant of the adequacy of dialysis SEMINARS IN NEPHROLOGY Kurella, M., Chertow, G. M. 2005; 25 (2): 90-95

  Abstract

  Several studies have shown an association between the hemodialysis session length (the t of Kt or Kt/V) and favorable outcomes for patients on maintenance hemodialysis. In a single randomized controlled trial that systematically varied hemodialysis session length, shorter session length was associated with an increased risk for morbidity and mortality, independent of the time-averaged concentration of urea. Observational studies of dialysis session length have yielded conflicting results, although virtually all studies have confounded hemodialysis session length with hemodialysis efficiency or dose. Limited observational data from nocturnal hemodialysis programs more strongly suggest an independent beneficial effect of longer session length. In aggregate, data on the effects of hemodialysis session length are inconclusive. Future studies should evaluate hemodialysis session length independent of efficiency, and should consider the evaluation of dose by using other clearance parameters and the adequacy of ultrafiltration in addition to solute kinetics.

  View details for DOI 10.1016/j.semnephrol.2004.09.015

  View details for Web of Science ID 000228545200005

  View details for PubMedID 15791560

• Increased prevalence of subclinical and clinical hypothyroidism in persons with chronic kidney disease KIDNEY INTERNATIONAL Lo, J. C., Chertow, G. M., Go, A. S., Hsu, C. Y. 2005; 67 (3): 1047-1052

  Abstract

  Previous studies have suggested a higher prevalence of thyroid abnormalities in persons with end-stage renal disease. However, little is known regarding the epidemiology of thyroid disorders in persons with less severe kidney dysfunction.We used data from the Third National Health and Nutrition Examination Survey to examine the prevalence of hypothyroidism (clinical and subclinical) at different levels of estimated glomerular filtration rate (GFR). We used multivariable logistic regression to evaluate the association between GFR and prevalent hypothyroidism.Among 14,623 adult participants with serum creatinine and thyroid function test results, the mean age was 48.7 years, and 52.6% were women. The prevalence of hypothyroidism increased with lower levels of GFR (in units of mL/min/1.73 m(2)), occurring in 5.4% of subjects with GFR >/=90, 10.9% with GFR 60-89, 20.4% with GFR 45-59, 23.0% with GFR 30-44, and 23.1% with GFR <30 (P < 0.001 for trend). Overall, 56% of hypothyroidism cases were considered subclinical. Compared with GFR >/=90 mL/min/1.73 m(2), reduced GFR was associated with an increased risk of hypothyroidism, after adjusting for age, gender, and race/ethnicity: adjusted odds ratio 1.07 (95% confidence interval: 0.86-1.32) for GFR 60-89, 1.57 (1.11-2.22) for GFR 45-59, 1.81 (1.04-3.16) for GFR 30-44, and 1.97 (0.69-5.61) for GFR <30 mL/min/1.73 m(2) (P= 0.008 for trend).Among a nationally representative sample of adults, reduced glomerular filtration rate was associated with a higher prevalence of hypothyroidism, with many subclinical cases. Future studies are needed to determine the potential adverse effects of subclinical and clinical hypothyroidism in persons with chronic kidney disease.

  View details for Web of Science ID 000227013500025

  View details for PubMedID 15698444

• Achieving NKF-K/DOQI (TM) bone metabolism and disease treatment goals with cinacalcet HCl KIDNEY INTERNATIONAL Moe, S. M., Chertow, G. M., Coburn, J. W., Quarles, L. D., Goodman, W. G., Block, G. A., Drueke, T. B., Cunningham, J., Sherrard, D. J., McCary, L. C., Olson, K. A., Turner, S. A., Martin, K. J. 2005; 67 (2): 760-771

  Abstract

  The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (NKF-K/DOQItrade mark) has established guidelines for treatment of secondary hyperparathyroidism (HPT). The ability of cinacalcet HCl (Sensipartrade mark) treatment to improve achievement of target levels of parathyroid hormone (PTH), calcium, phosphorus, and calcium-phosphorus product (Ca x P) was investigated in subjects on dialysis with secondary HPT.Data were combined from three placebo-controlled, double-blind, 26-week studies with similar design that randomized 1136 subjects on dialysis to receive traditional therapy plus cinacalcet or placebo. Oral cinacalcet was titrated from 30 to 180 mg/day. Achievement of K/DOQI goals was determined for each treatment group overall and for subgroups defined by baseline intact PTH (iPTH) and Ca x P levels.Cinacalcet-treated subjects were more likely to achieve a mean iPTH

  View details for Web of Science ID 000226420600041

  View details for PubMedID 15673327

• Calcification or classification? JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Chertow, G. M., Moe, S. M. 2005; 16 (2): 293-295

  View details for DOI 10.1681/ASN.2004121115

  View details for Web of Science ID 000226959400002

  View details for PubMedID 15647332

• Self-assessed sleep quality in chronic kidney disease. International urology and nephrology Kurella, M., Luan, J., Lash, J. P., Chertow, G. M. 2005; 37 (1): 159-165

  Abstract

  Although sleep complaints are commonly reported in persons with end stage renal disease (ESRD), little is known about the prevalence of sleep complaints in chronic kidney disease (CKD), and the relation of sleep quality to the severity of kidney disease.We administered the Kidney Disease Quality of Life (KDQOL) sleep scale to 156 subjects, 78 with ESRD and 78 with CKD. Glomerular filtration rate (GFR) was estimated using the six variable Modification of Diet in Renal Disease (MDRD) equation and used to stratify subjects with CKD as mild-moderate (GFR >25 ml/min/1.73 m(2)) and advanced (GFR <25 ml/min/1.73 m(2)). We used multivariable linear regression to determine independent predictors of KDQOL sleep scale scores. Higher scores indicate higher self-reported quality of sleep.Median scores on the KDQOL sleep scale were 59 (interquartile range 40-80) in subjects with ESRD and 69 (interquartile range 53-80) in subjects with CKD (P=0.04). Thirty-four percent of subjects with ESRD, 27% of subjects with advanced CKD, and 14% of subjects with mild to moderate CKD had sleep maintenance disturbances (P=0.05). Thirteen percent of subjects with ESRD, 11% of subjects with advanced CKD, and no subjects with mild-moderate CKD had complaints of daytime somnolence (P=0.03). There was no significant difference in the prevalence of sleep adequacy complaints in persons with ESRD versus CKD. In multivariable analyses, only age and ESRD status (vs. CKD) were significant predictors of lower KDQOL sleep scores. Among subjects with CKD, there was a significant direct association between estimated GFR and scores on the KDQOL sleep scale in non-African American subjects (P=0.01).Sleep complaints are common in persons with CKD and ESRD and may be associated with the severity of kidney disease.

  View details for PubMedID 16132780

• Influence of race on kidney transplant outcomes within and outside the department of veterans affairs JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Chakkera, H. A., O'Hare, A. M., Johansen, K. L., Hynes, D., Stroupe, K., Colin, P. M., Chertow, G. M. 2005; 16 (1): 269-277

  Abstract

  Inferior outcomes after kidney transplantation among African Americans are poorly understood. It was hypothesized that unequal access to medical care among transplant recipients might contribute to worse posttransplantation outcomes among African Americans and that racial disparities in kidney transplant outcomes would be less pronounced among patients who receive health care within versus outside the Department of Veterans Affairs (VA), because eligible veterans who receive care within the VA are entitled to receive universal access to care, including coverage of prescription drugs. A study cohort of 79,361 patients who were undergoing their first kidney transplant in the United States between October 1, 1991, and October 31, 2000, was assembled, with follow-up data on graft survival obtained through October 31, 2001. After multivariable proportional hazards adjustment for a wide range of recipient and donor characteristics, African-American patients were at increased risk for graft failure compared with non-African-American patients (relative risk [RR] 1.31; 95% confidence interval [CI] 1.26 to 1.36). African-American race was associated with a similarly increased risk for graft failure among patients who were VA users (RR 1.31; 95% CI 1.11 to 1.54) and non-VA users (RR 1.31; 95% CI 1.26 to 1.36). In conclusion, racial disparities in kidney transplant outcomes seem to persist even in a universal access-to-care system such as the VA. Reasons for worse outcomes among African Americans require further investigation.

  View details for Web of Science ID 000226008700036

  View details for PubMedID 15563568

• Effects of sevelamer and calcium-based phosphate binders on uric acid concentrations in patients undergoing hemodialysis - A randomized clinical trial ARTHRITIS AND RHEUMATISM Garg, J. P., Chasan-Taber, S., Blair, A., Plone, M., Bommer, J., Raggi, P., Chertow, G. M. 2005; 52 (1): 290-295

  Abstract

  Gout affects a large fraction of persons with advanced chronic kidney disease, and hyperuricemia may increase the risk of cardiovascular disease. Several hypouricemic agents are contraindicated in patients with end-stage renal disease. Sevelamer is a nonabsorbed hydrogel that binds phosphorus and bile acids in the intestinal tract. Results of short-term and open-label studies suggest that sevelamer might lower the concentration of uric acid, another organic anion. We undertook this study to test our hypothesis that the reduction in serum uric acid concentration induced by sevelamer would be confirmed in a long-term, randomized, clinical trial comparing sevelamer with calcium-based phosphate binders.Two hundred subjects undergoing maintenance hemodialysis were randomly assigned to receive either sevelamer or calcium-based phosphorus binders in an international, multicenter, clinical trial. Data on baseline and end-of-study uric acid concentrations were available in 169 subjects (85%); the change in uric acid concentration from baseline to the end of the study was the outcome of interest.Baseline clinical characteristics, including mean uric acid concentrations, were similar in subjects randomly assigned to receive sevelamer and calcium-based phosphate binders. The mean change in uric acid concentration (from baseline to the end of the study) was significantly larger in sevelamer-treated subjects (-0.64 mg/dl versus -0.26 mg/dl; P = 0.03). The adjusted mean change in uric acid concentration was more pronounced when the effects of age, sex, diabetes, vintage (time since initiation of dialysis), dialysis dose, and changes in blood urea nitrogen and bicarbonate concentrations were considered (-0.72 mg/dl versus -0.15 mg/dl; P = 0.001). Twenty-three percent of sevelamer-treated subjects experienced a study-related reduction in the concentration of uric acid equal to -1.5 mg/dl or more, compared with 10% of calcium-treated subjects (P = 0.02).In a randomized clinical trial comparing sevelamer and calcium-based phosphate binders, treatment with sevelamer was associated with a significant reduction in serum uric acid concentrations.

  View details for DOI 10.1002/art.20781

  View details for Web of Science ID 000226507700037

  View details for PubMedID 15641045

• Angiotensin receptor blockade and arterial compliance in chronic kidney disease: A pilot study AMERICAN JOURNAL OF NEPHROLOGY Garg, J. P., Ellis, R., Elliott, W. J., Hasabou, N., Chua, D., Chertowa, G. M., Bakris, G. L. 2005; 25 (4): 393-399

  Abstract

  Almost 20 million people in the US have chronic kidney disease (CKD). Cardiovascular disease and arterial wall abnormalities are common in this population. Because angiotensin II may have adverse effects on the arterial wall, we hypothesized that an angiotensin receptor blocker (ARB) would improve arterial compliance as compared with placebo in subjects with CKD.We performed a double-blinded, placebo-controlled pilot study in which 25 subjects with stages 2 or 3 CKD and proteinuria <1 g were randomized to either the ARB, eprosartan, or placebo and titrated to achieve a goal blood pressure (BP) <130/85 mm Hg. Arterial compliance was measured at baseline and at 8 weeks.Baseline characteristics were similar between the groups and included mean estimated glomerular filtration rate 63 +/- 14 ml/min/1.73 m(2), heart rate 76 +/- 10 beats/min, BP 142 +/- 12/81 +/- 8 mm Hg, 64% diabetic, 44% male, and 40% white, though subjects in the eprosartan group were younger (60 +/- 12 vs. 70 +/- 6 years, p = 0.01). There were no significant differences between the groups in large or small artery compliance measurements either at baseline or at 8 weeks, but there was a statistically significant improvement from baseline in small artery compliance in the eprosartan group (from median 2.5 ml/mm Hg x 100 [90% CI (1.1, 4.7)] to 4.0 ml/mm Hg x 100 [90% CI (1.9, 6.7)] (p = 0.01)) not seen in the placebo group.Use of an ARB to achieve recommended BP is associated with improved small artery compliance in people with CKD, though larger studies are needed to confirm these findings.

  View details for DOI 10.1159/000087211

  View details for Web of Science ID 000231389400010

  View details for PubMedID 16088080

• Chronic kidney disease and cognitive impairment in menopausal women AMERICAN JOURNAL OF KIDNEY DISEASES Kurella, M., Yaffe, K., Shlipak, M. G., Wenger, N. K., Chertow, G. M. 2005; 45 (1): 66-76

  Abstract

  Although end-stage renal disease has been associated with cognitive impairment, the relation between lesser degrees of chronic kidney disease (CKD) and cognitive impairment is less well understood.Data for 1,015 women enrolled at 10 of the 20 Heart Estrogen/Progestin Replacement Study clinical sites were analyzed. All participants were younger than 80 years and had established coronary artery disease at study entry. Participants underwent 6 standard tests of cognitive function evaluating various domains. Unadjusted, residual age- and race-adjusted, and multivariable-adjusted linear and logistic regression models were used. Glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease regression equation. In addition to analyses across the spectrum of GFRs, CKD was categorized as mild (estimated GFR [eGFR], 45 to 60 mL/min/1.73 m2), moderate (eGFR, 30 to 44 mL/min/1.73 m2), and severe (eGFR, <30 mL/min/1.73 m2) according to a modification of recently established classification guidelines.Mean eGFR was 57 +/- 14 mL/min/1.73 m2. In multivariable analyses, eGFR was associated significantly with impairment in global cognition, executive function, language, and memory (approximately 15% to 25% increase in risk for dysfunction/10-mL/min/1.73 m2 decrement in eGFR). Associations among eGFR and cognitive function were independent of residual effects of age and race (2 key determinants of GFR) and the contributions of education, lifestyle factors, stroke, diabetes, and other laboratory variables.CKD is associated with cognitive impairment in menopausal women with coronary artery disease.

  View details for DOI 10.1053/j.ajkd.2004.08.044

  View details for Web of Science ID 000226517300009

  View details for PubMedID 15696445

• Chronic kidney disease, cardiovascular risk, and response to angiotensin-converting enzyme inhibition after myocardial infarction - The Survival and Ventricular Enlargement (SAVE) study CIRCULATION Tokmakova, M. P., Skali, H., Kenchaiah, S., Braunwald, E., Rouleau, J. L., Packer, M., Chertow, G. M., Moye, L. A., Pfeffer, M. A., Solomon, S. D. 2004; 110 (24): 3667-3673

  Abstract

  Persons with end-stage renal disease and those with lesser degrees of chronic kidney disease (CKD) have an increased risk of death after myocardial infarction (MI) that is not fully explained by associated comorbidities. Future cardiovascular event rates and the relative response to therapy in persons with mild to moderate CKD are not well characterized.We calculated the estimated glomerular filtration rate (eGFR) using the 4-variable Modification of Diet in Renal Disease method in 2183 Survival And Ventricular Enlargement (SAVE) trial subjects. SAVE randomized post-MI subjects (3 to 16 days after MI) with left ventricular ejection fraction < or =40% and serum creatinine <2.5 mg/dL to captopril or placebo. Cox proportional hazards models were used to evaluate the relative hazard rates for death and cardiovascular events associated with reduced eGFR. Subjects with reduced eGFR were older and had more extensive comorbidities. The multivariable adjusted risk ratio for total mortality associated with reduced eGFR from 60 to 74, 45 to 59, and <45 mL x min(-1) x 1.73 m(-2) (compared with eGFR > or =75 mL x min(-1) x 1.73 m(-2)) was 1.11 (0.86 to 1.42), 1.24 (0.96 to 1.60) and 1.81 (1.32 to 2.48), respectively (P for trend =0.001). Similar adjusted trends were present for CV mortality (P=0.001), recurrent MI (P=0.017), and the combined CV mortality and morbidity outcome (P=0.002). The absolute benefit of captopril tended to be greater in subjects with CKD: 12.4 versus 5.5 CV events prevented per 100 subjects with (n=719) and without (n=1464) CKD, respectively.CKD was associated with a heightened risk for all major CV events after MI, particularly among subjects with an estimated glomerular filtration rate <45 mL x min(-1) x 1.73 m(-2). Randomization to captopril resulted in a reduction of CV events irrespective of baseline kidney function.

  View details for DOI 10.1161/01.CIR.0000149806.01354.BF

  View details for Web of Science ID 000225706600009

  View details for PubMedID 15569840

• Validation of the kidney disease quality of life (KDQOL) cognitive function subscale KIDNEY INTERNATIONAL Kurella, M., Luan, J., Yaffe, K., Chertow, G. M. 2004; 66 (6): 2361-2367

  Abstract

  Formal cognitive function testing is cumbersome, and no self-administered instruments for estimating cognitive function in persons with chronic kidney disease (CKD) and end-stage renal disease (ESRD) have been validated. The goal of this study was to determine the validity of the Kidney Disease Quality of Life Cognitive Function scale (KDQOL-CF) for the assessment of cognitive impairment in persons with kidney disease.We administered the KDQOL-CF to 157 subjects, 79 with ESRD and 78 with CKD participating in a cross-sectional study of cognitive function. Scores on the Modified Mini-Mental State Exam (3MS) were considered the gold standard measure of global cognitive function. Performance characteristics of the KDQOL-CF were assessed using correlation coefficients, Bland-Altman plots, and receiver operating characteristic curves.Median scores on the KDQOL-CF were 73 (interquartile range 60-87) for subjects with ESRD and 87 (interquartile range 73-100) for subjects with CKD (P < 0.0001). Scores on the KDQOL-CF were directly correlated with scores on the 3MS (r = 0.31, P = 0.0001). Defining global cognitive impairment as a 3MS score < 80, a cut-point of 60 on the KDQOL-CF accurately classified 76% of subjects, with 52% sensitivity and 81% specificity. On multivariable analysis, cerebral and peripheral vascular disease, benzodiazepine use, and higher serum phosphorus concentrations were associated with lower KDQOL-CF scores, while beta blocker use, education, and higher serum albumin concentrations were associated with higher KDQOL-CF scores.The KDQOL-CF is a valid instrument for estimating cognitive function in patients with CKD and ESRD. KDQOL-CF screening followed by 3MS testing in selected individuals may prove to be an effective and efficient strategy for identifying cognitive impairment in patients with kidney disease.

  View details for Web of Science ID 000225026200028

  View details for PubMedID 15569327

• Cognitive impairment in chronic kidney disease JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Kurella, M., Chertow, G. M., Luan, J., Yaffe, K. 2004; 52 (11): 1863-1869

  Abstract

  To assess the prevalence of cognitive impairment in persons with chronic kidney disease (CKD) and its relation to the severity of CKD.Cross-sectional study.University-affiliated ambulatory nephrology and dialysis practices.Eighty subjects with CKD Stages III and IV not requiring dialysis (CKD) and 80 subjects with CKD Stage V on hemodialysis (end-stage renal disease (ESRD)) with a mean age+/-standard deviation of 62.5+/-14.3.Three standardized cognitive tests, the Modified Mini-Mental State Examination (3MS), Trailmaking Test B (Trails B), and California Verbal Learning Trial (CVLT). Glomerular filtration rate was estimated in subjects with CKD using the six-variable Modification of Diet in Renal Disease equation.There was a graded relation between cognitive function and severity of CKD. Mean scores on the 3MS, Trails B, and CVLT immediate and delayed recall were significantly worse for subjects with ESRD than for subjects with CKD or published norms (P<.001 for all comparisons). Scores on the Trails B (P<.001) and CVLT immediate (P=.01) and delayed (P<.001) recall were significantly worse for subjects with CKD not requiring dialysis than for published norms. In addition, the fraction of subjects with impairment on the 3MS and Trails B increased with decreasing kidney function.Cognitive impairment is associated with the severity of kidney disease. Further studies are needed to determine the reasons for cognitive impairment in subjects with CKD and ESRD.

  View details for Web of Science ID 000224594100010

  View details for PubMedID 15507063

• Theophylline for the prevention of radiocontrast nephropathy: a meta-analysis NEPHROLOGY DIALYSIS TRANSPLANTATION Ix, J. H., McCulloch, C. E., Chertow, G. M. 2004; 19 (11): 2747-2753

  Abstract

  Radiocontrast nephropathy is a common cause of acute renal failure in hospitalized patients. Several studies have examined the capacity of theophylline or aminophylline to prevent radiocontrast nephropathy, with conflicting results. We conducted a meta-analysis of published randomized controlled trials to determine if the pre-procedural administration of theophylline or aminophylline prevents radiocontrast-induced declines in kidney function.We searched MEDLINE, EMBASE, the Cochrane Collaboration Database, bibliographies of retrieved articles, and consulted with experts to identify relevant studies. Randomized controlled trials of theophylline or aminophylline in hospitalized patients receiving radiocontrast were included. Studies were excluded if they did not report changes in serum creatinine or creatinine clearance within 48 h after radiocontrast exposure.Seven randomized controlled trials satisfied all inclusion criteria and were included in the analysis (pooled sample size n = 480). The difference in mean change in serum creatinine was 11.5 micromol/l (95% confidence intervals 5.3-19.4 micromol/l, P = 0.004) lower in the theophylline- or aminophylline-treated groups than controls. One participant (0.6%) required dialysis.Prophylactic administration of theophylline or aminophylline appears to protect against radiocontrast-induced declines in kidney function. Whether these agents reduce the proportion of patients who experience large decrements in serum creatinine concentration, or require dialysis, is unknown.

  View details for Web of Science ID 000225115400011

  View details for PubMedID 15328384

• Spectrum of acute renal failure in the intensive care unit: The PICARD experience 12th World Congress of Nephrology Mehta, R. L., Pascual, M. T., Soroko, S., Savage, B. R., Himmelfarb, J., Ikizler, T. A., Paganini, E. P., Chertow, G. M. NATURE PUBLISHING GROUP. 2004: 1613–21

  Abstract

  Acute renal failure (ARF) in the critically ill is associated with extremely high mortality rates. Understanding the changing spectrum of ARF will be necessary to facilitate quality improvement efforts and to design successful interventional trials.We conducted an observational cohort study of 618 patients with ARF in intensive care units at five academic medical centers in the United States. Participants were required to sign (or have a proxy sign) informed consent for data collection. A comprehensive data collection instrument captured more than 800 variables, most on a daily basis, throughout the course of ARF. Patient characteristics, dialysis status, and major outcomes were determined and stratified by clinical site.The mean age was 59.5 years, 41% were women, and 20% were of minority race or ethnicity. There was extensive comorbidity; 30% had chronic kidney disease, 37% had coronary artery disease, 29% had diabetes mellitus, and 21% had chronic liver disease. Acute renal failure was accompanied by extrarenal organ system failure in most patients, even those who did not require dialysis. Three hundred and ninety-eight (64%) patients required dialysis. The in-hospital mortality rate was 37%, and the rate of mortality or nonrecovery of renal function was 50%. The median hospital length of stay was 25 days (26 days, excluding patients who died).There is a changing spectrum of ARF in the critically ill, characterized by a large burden of comorbid disease and extensive extrarenal complications, obligating the need for dialysis in the majority of patients. There is wide variation across institutions in patient characteristics and practice patterns. These differences highlight the need for additional multicenter observational and interventional studies in ARF.

  View details for Web of Science ID 000223821000036

  View details for PubMedID 15458458

• Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization 36th Annual Meeting of the American-Society-of-Nephrology Go, A. S., Chertow, G. M., Fan, D. J., McCulloch, C. E., Hsu, C. Y. MASSACHUSETTS MEDICAL SOC. 2004: 1296–1305

  Abstract

  End-stage renal disease substantially increases the risks of death, cardiovascular disease, and use of specialized health care, but the effects of less severe kidney dysfunction on these outcomes are less well defined.We estimated the longitudinal glomerular filtration rate (GFR) among 1,120,295 adults within a large, integrated system of health care delivery in whom serum creatinine had been measured between 1996 and 2000 and who had not undergone dialysis or kidney transplantation. We examined the multivariable association between the estimated GFR and the risks of death, cardiovascular events, and hospitalization.The median follow-up was 2.84 years, the mean age was 52 years, and 55 percent of the group were women. After adjustment, the risk of death increased as the GFR decreased below 60 ml per minute per 1.73 m2 of body-surface area: the adjusted hazard ratio for death was 1.2 with an estimated GFR of 45 to 59 ml per minute per 1.73 m2 (95 percent confidence interval, 1.1 to 1.2), 1.8 with an estimated GFR of 30 to 44 ml per minute per 1.73 m2 (95 percent confidence interval, 1.7 to 1.9), 3.2 with an estimated GFR of 15 to 29 ml per minute per 1.73 m2 (95 percent confidence interval, 3.1 to 3.4), and 5.9 with an estimated GFR of less than 15 ml per minute per 1.73 m2 (95 percent confidence interval, 5.4 to 6.5). The adjusted hazard ratio for cardiovascular events also increased inversely with the estimated GFR: 1.4 (95 percent confidence interval, 1.4 to 1.5), 2.0 (95 percent confidence interval, 1.9 to 2.1), 2.8 (95 percent confidence interval, 2.6 to 2.9), and 3.4 (95 percent confidence interval, 3.1 to 3.8), respectively. The adjusted risk of hospitalization with a reduced estimated GFR followed a similar pattern.An independent, graded association was observed between a reduced estimated GFR and the risk of death, cardiovascular events, and hospitalization in a large, community-based population. These findings highlight the clinical and public health importance of chronic renal insufficiency.

  View details for Web of Science ID 000223997700007

  View details for PubMedID 15385656

• Race/ethnicity and disease severity in IgA nephropathy. BMC nephrology Hall, Y. N., Fuentes, E. F., Chertow, G. M., Olson, J. L. 2004; 5: 10-?

  Abstract

  Relatively few U.S.-based studies in chronic kidney disease have focused on Asian/Pacific Islanders. Clinical reports suggest that Asian/Pacific Islanders are more likely to be affected by IgA nephropathy (IgAN), and that the severity of disease is increased in these populations.To explore whether these observations are borne out in a multi-ethnic, tertiary care renal pathology practice, we examined clinical and pathologic data on 298 patients with primary glomerular lesions (IgAN, focal segmental glomerulosclerosis, membranous nephropathy and minimal change disease) at the University of California San Francisco Medical Center from November 1994 through May 2001. Pathologic assessment of native kidney biopsies with IgAN was conducted using Haas' classification system.Among individuals with IgAN (N = 149), 89 (60%) were male, 57 (38%) white, 53 (36%) Asian/Pacific Islander, 29 (19%) Hispanic, 4 (3%) African American and 6 (4%) were of other or unknown ethnicity. The mean age was 37 +/- 14 years and median serum creatinine 1.7 mg/dL. Sixty-six patients (44%) exhibited nephrotic range proteinuria at the time of kidney biopsy. The distributions of age, gender, mean serum creatinine, and presence or absence of nephrotic proteinuria and/or hypertension at the time of kidney biopsy were not significantly different among white, Hispanic, and Asian/Pacific Islander groups. Of the 124 native kidney biopsies with IgAN, 10 (8%) cases were classified into Haas subclass I, 12 (10%) subclass II, 23 (18%) subclass III, 30 (25%) subclass IV, and 49 (40%) subclass V. The distribution of Haas subclass did not differ significantly by race/ethnicity. In comparison, among the random sample of patients with non-IgAN glomerular lesions (N = 149), 77 (52%) patients were male, 51 (34%) white, 42 (28%) Asian/Pacific Islander, 25 (17%) Hispanic, and 30 (20%) were African American.With the caveats of referral and biopsy biases, the race/ethnicity distribution of IgAN differs significantly from that of other major glomerulonephridities. However, among individuals undergoing native kidney biopsy, we see no evidence of a race/ethnicity association with severity of disease in IgAN by clinical and IgAN-specific histopathologic criteria. Further studies are needed to identify populations at higher risk for progressive disease in IgAN.

  View details for PubMedID 15341669

  View details for PubMedCentralID PMC517500

• Diminishing significance of HLA matching in kidney transplantation AMERICAN JOURNAL OF TRANSPLANTATION Su, X. M., Zenios, S. A., Chakkera, H., Milford, E. L., Chertow, G. M. 2004; 4 (9): 1501-1508

  Abstract

  To determine trends in the significance of HLA matching and other risk factors in kidney transplantation, we analyzed data on graft survival in a consecutive sample of 33 443 transplant recipients who received deceased donor kidneys from December 1994 to December 1998 with a mean follow-up time of 2.2 years. HLA matching and other risk factors (peak panel reactive antibody, donor age, sex and cause of death, cold ischemia time, donor and recipient body size) were examined. Mean likelihood ratios of models, fit with and without each variable of interest, were calculated by generating bootstrapped samples from each single year cohort. Pooled censored and uncensored graft survival rates were 90.6% and 89.9% at 1 year, 85.8% and 84.5% at 2 years, and 80.7% and 78.6% at 3 years. HLA matching declined in significance while other factors retained similar levels of statistical significance over the four yearly cohorts. With evolving clinical practice, including the provision of safer and more potent immunosuppressive therapy, the significance of HLA matching has diminished. Non-immunologic factors continue to impede more marked improvements in long-term graft survival. Recognizing these trends, organ allocation algorithms may need to be revised.

  View details for DOI 10.1111/j.1600-6143.2004.00535.x

  View details for PubMedID 15307838

• Vector length as a proxy for the adequacy of ultrafiltration in hemodialysis KIDNEY INTERNATIONAL Pillon, L., Piccoli, A., Lowrie, E. G., Lazarus, J. M., Chertow, G. M. 2004; 66 (3): 1266-1271

  Abstract

  Evaluation of dialysis adequacy has focused on parameters of solute (principally urea) clearance. Relatively little attention has been paid to the adequacy of ultrafiltration. At a given phase angle, the bioimpedance vector length reflects the degree of tissue hydration, as the vector lengthens with ultrafiltration.We determined the relative risk of death associated with different bioimpedance vector lengths in a 3009 patient hemodialysis cohort using proportional hazards regression.The mean phase angle was 4.8 degrees, and the mean vector length 300 +/- 70 ohm/m (range 140 to 630 ohm/m). Vector length was much longer in women than men (mean 340 vs. 270 ohm/m) and significantly longer in African Americans and patients without diabetes. Adjusted for the effects of age, gender, race, diabetes, vintage, weight, albumin, prealbumin, creatinine, hemoglobin, ferritin, and dialysis dose, the relative risk (RR) of death was 0.75 (95% CI 0.57 to 0.88) per 100 ohm/m decrease in vector length. The effect of vector length on RR was somewhat more pronounced among men (vector length x gender interaction, P= 0.07). Considering vector length of 300 to 350 ohm/m as the referent category, the RRs of death were 1.54 (95% CI 1.08 to 2.21) and 2.83 (95% CI 1.55 to 5.14) for patients with vector length 200 to 250 and <200 ohm/m, respectively.Shorter predialysis bioimpedance vectors, indicating greater soft tissue hydration, were associated with diminished survival in hemodialysis patients. These findings validate clinical observations linking longevity to maintenance of dry body weight.

  View details for Web of Science ID 000223217700052

  View details for PubMedID 15327426

• "Renalism": Inappropriately low rates of coronary angiography in elderly individuals with renal insufficiency JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Chertow, G. M., Normand, S. L., McNeil, B. J. 2004; 15 (9): 2462-2468

  Abstract

  Higher risk patients (including the elderly) receive more conservative therapy for cardiovascular diseases, even though the relative benefits of therapy tend to be greater. The perceived risk of radiocontrast-associated nephrotoxicity may influence the provision of coronary angiography and subsequent revascularization, especially among individuals with chronic kidney disease (CKD). The aim of this study was to determine whether there is excessive variation in the provision of coronary angiography after acute myocardial infarction on the basis of the presence of CKD and whether there is an association between angiography and mortality. Elderly (age 65 to 89 yr) individuals with acute myocardial infarction from the Cooperative Cardiovascular Project were classified by the presence or absence of CKD (defined as a baseline serum creatinine of 1.5 to 5.0 mg/dl). In CKD patients, the propensity to undergo coronary angiography was determined and the effect of coronary angiography on mortality was estimated using multivariable logistic regression and stratification. Mortality was significantly higher with CKD (52.6 versus 26.4%). Fewer patients with CKD underwent coronary angiography (25.2 versus 46.8%) despite the observation that a similar proportion of patients were deemed appropriate for angiography by standard, published criteria. When limiting the analysis to CKD patients who are considered appropriate, the multivariable estimate of the odds of death associated with coronary angiography was 0.58 (95% confidence interval, 0.50 to 0.67). With adjustment using propensity scores, the odds ratio averaged across propensity score quintiles was 0.62 (95% confidence interval, 0.54 to 0.70). Results were qualitatively similar when patients were stratified by CKD stage IV (estimated GFR <30 ml/min per 1.73 m(2)). There is a large relative decrease in utilization of coronary angiography among patients with CKD. Alteration in practice because of an aversion to the risk of radiocontrast-associated nephrotoxicity ("renalism") is inappropriate, even if the true relative benefit of invasive strategies is a fraction of what is estimated here.

  View details for DOI 10.1097/01.ASN.0000135969.33773.0B

  View details for Web of Science ID 000223668200025

  View details for PubMedID 15339996

• Mineral metabolism, mortality, and morbidity in maintenance hemodialysis JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Block, G. A., Klassen, P. S., Lazarus, J. M., Ofsthun, N., Lowrie, E. G., Chertow, G. M. 2004; 15 (8): 2208-2218

  Abstract

  Mortality rates in ESRD are unacceptably high. Disorders of mineral metabolism (hyperphosphatemia, hypercalcemia, and secondary hyperparathyroidism) are potentially modifiable. For determining associations among disorders of mineral metabolism, mortality, and morbidity in hemodialysis patients, data on 40,538 hemodialysis patients with at least one determination of serum phosphorus and calcium during the last 3 mo of 1997 were analyzed. Unadjusted, case mix-adjusted, and multivariable-adjusted relative risks of death were calculated for categories of serum phosphorus, calcium, calcium x phosphorus product, and intact parathyroid hormone (PTH) using proportional hazards regression. Also determined was whether disorders of mineral metabolism were associated with all-cause, cardiovascular, infection-related, fracture-related, and vascular access-related hospitalization. After adjustment for case mix and laboratory variables, serum phosphorus concentrations >5.0 mg/dl were associated with an increased relative risk of death (1.07, 1.25, 1.43, 1.67, and 2.02 for serum phosphorus 5.0 to 6.0, 6.0 to 7.0, 7.0 to 8.0, 8.0 to 9.0, and >/=9.0 mg/dl). Higher adjusted serum calcium concentrations were also associated with an increased risk of death, even when examined within narrow ranges of serum phosphorus. Moderate to severe hyperparathyroidism (PTH concentrations >/=600 pg/ml) was associated with an increase in the relative risk of death, whereas more modest increases in PTH were not. When examined collectively, the population attributable risk percentage for disorders of mineral metabolism was 17.5%, owing largely to the high prevalence of hyperphosphatemia. Hyperphosphatemia and hyperparathyroidism were significantly associated with all-cause, cardiovascular, and fracture-related hospitalization. Disorders of mineral metabolism are independently associated with mortality and morbidity associated with cardiovascular disease and fracture in hemodialysis patients.

  View details for DOI 10.1097/01.ASN.0000133041.27682.A2

  View details for Web of Science ID 000223106600028

  View details for PubMedID 15284307

• Association of body size with outcomes among patients beginning dialysis AMERICAN JOURNAL OF CLINICAL NUTRITION Johansen, K. L., Young, B., Kaysen, G. A., Chertow, G. M. 2004; 80 (2): 324-332

  Abstract

  Although obesity confers an increased risk of mortality in the general population, observational reports on the dialysis population have suggested that obesity is associated with improved survival. These reports have generally not examined extremely high values of body mass index (BMI; in kg/m(2)), survival >1 y, or alternative measures of adiposity.We sought to clarify the relation between body size and outcomes among a large cohort of patients beginning dialysis.Data on 418 055 patients beginning dialysis between 1 April 1995 and 1 November 2000 were analyzed by using US Renal Data System data. BMI was divided into 8 categories in increments of 3 units, ranging from < 19 to > or =37, and the relation between survival and BMI was examined by using proportional hazards regression with adjustment for demographic, laboratory, and comorbidity data.High BMI was associated with increased survival in this cohort, even at extremely high BMI, after adjustment, and over a 2-y average follow-up time. This was true for whites, African Americans, and Hispanics but not for Asians. High BMI was also associated with a reduced risk of hospitalization and a lower rate of mortality in all mortality categories. Alternative estimates of adiposity, including the Benn index and estimated fat mass, yielded similar results, and adjustments for lean body mass did not substantially alter the findings.High BMI is not associated with increased mortality among patients beginning dialysis. This finding does not appear to be a function of lean body mass and, although modified by certain patient characteristics, it is a robust finding.

  View details for Web of Science ID 000222912800013

  View details for PubMedID 15277152

• Coronary and aortic calcifications in patients new to dialysis. Hemodialysis international. International Symposium on Home Hemodialysis Spiegel, D. M., Raggi, P., Mehta, R., Lindberg, J. S., Chonchol, M., Ehrlich, J., James, G., Chertow, G. M., Block, G. A. 2004; 8 (3): 265-272

  Abstract

  Vascular calcification has been associated with all cause and cardiovascular mortality in patients with end-stage kidney disease (ESRD). Whether vascular calcification is present in persons with advanced chronic kidney disease starting dialysis or develops in patients on dialysis is unknown. The purpose of this study was to examine the prevalence of vascular and coronary calcification in patients new to hemodialysis.A total of 129 subjects new to dialysis were evaluated using electron beam computed tomography. The primary outcome was the presence and extent of coronary artery, aortic, and valvular calcification.Forty-three percent of subjects had no significant coronary artery calcification (total score

  View details for DOI 10.1111/j.1492-7535.2004.01104.x

  View details for PubMedID 19379426

• Incorporating recipient choice in kidney transplantation JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Su, X. M., Zenios, S. A., Chertow, G. M. 2004; 15 (6): 1656-1663

  Abstract

  Despite the acute shortage of cadaveric organs for kidney transplantation, more than 10% of cadaveric kidneys are discarded each year because of marginal quality. Transplant recipients' access to these kidneys and to information about their quality is limited. A Monte Carlo model was developed to simulate the operations of an organ procurement organization over a 10-yr period. Donor and recipient characteristics were generated from the United States Renal Data System. Kidneys were assigned one of five possible grades, which were determined by calculating the relative risk of graft failure associated with donor characteristics and HLA matching for every donor-candidate pair. Modeled were recipient decisions to accept or reject a kidney on the basis of the relative change in quality-adjusted life years (QALY). Compared were the United Network of Organ Sharing (UNOS) policy, the UNOS expanded donor criteria policy, two benchmark policies (one equity driven and the other efficiency driven), and a hybrid policy that incorporated recipient choice into the UNOS algorithm. Sensitivity analyses for major input variables were performed. Compared with UNOS, an algorithm that incorporated recipient choice predicted a 6% increase in QALY, a 12% decrease in median waiting time, a 39% increase in the likelihood of transplantation, and a 56% reduction in the number of discarded kidneys. Benefits were observed across categories of age, gender, and race. Incorporating recipient choice in kidney transplantation would improve equity, efficiency, and QALY of the end-stage renal disease population.

  View details for DOI 10.1097/01.ASN.0000127866.34592.60

  View details for PubMedID 15153578

• On the relative safety of parenteral iron formulations World Congress of Nephrology Chertow, G. M., Mason, P. D., Vaage-Nilsen, O., Ahlmen, J. OXFORD UNIV PRESS. 2004: 1571–75

  Abstract

  Intravenous iron is usually required to optimize the correction of anaemia in persons with advanced chronic kidney disease and end-stage renal disease. Randomized clinical trials may have insufficient power to detect differences in the safety profiles of specific formulations.We obtained data from the US Food and Drug Administration on reported adverse drug events (ADEs) related to the provision of three formulations of intravenous iron during 1998-2000. We estimated the relative risks [odds ratios (OR)] of ADEs associated with the use of higher molecular weight iron dextran and sodium ferric gluconate complex compared with lower molecular weight iron dextran using 2 x 2 tables.The total number of reported parenteral iron-related ADEs was 1981 among approximately 21,060,000 doses administered, yielding a rate of 9.4 x 10(-5), or approximately 94 per million. Total major ADEs were significantly increased among recipients of higher molecular weight iron dextran (OR 5.5, 95% CI 4.9-6.0) and sodium ferric gluconate complex (OR 6.2, 95% CI 5.4-7.2) compared with recipients of lower molecular weight iron dextran. We observed significantly higher rates of life-threatening ADEs, including death, anaphylactoid reaction, cardiac arrest and respiratory depression among users of higher molecular weight compared with lower molecular weight iron dextran. There was insufficient power to detect differences in life-threatening ADEs when comparing lower molecular weight iron dextran with sodium ferric gluconate complex.Parenteral iron-related ADEs are rare. Using observational data, overall and most specific ADE rates were significantly higher among recipients of higher molecular weight iron dextran and sodium ferric gluconate complex than among recipients of lower molecular weight iron dextran. These data may help to guide clinical practice, as head-to-head clinical trials comparing different formulations of intravenous iron have not been conducted.

  View details for DOI 10.1093/ndt/gfh185

  View details for Web of Science ID 000221868600036

  View details for PubMedID 15150356

• Determinants of progressive vascular calcification in haemodialysis patients NEPHROLOGY DIALYSIS TRANSPLANTATION Chertow, G. M., Raggi, P., Chasan-Taber, S., Bommer, J., Holzer, H., Burke, S. K. 2004; 19 (6): 1489-1496

  Abstract

  We determined recently that targeted treatment with calcium-based phosphate binders (calcium acetate and carbonate) led to progressive coronary artery and aortic calcification by electron beam tomography (EBT), while treatment with the non-calcium-containing phosphate binder, sevelamer, did not. Aside from the provision of calcium, we hypothesized that other factors might be related to the likelihood of progressive calcification in both or either treatment groups.We explored potential determinants of progressive vascular calcification in 150 randomized study subjects who underwent EBT at baseline and at least once during follow-up (week 26 or 52).Among calcium-treated subjects, higher time-averaged concentrations of calcium, phosphorus and the calcium-phosphorus product were associated with more pronounced increases in EBT scores; no such associations were demonstrated in sevelamer-treated subjects. The relation between parathyroid hormone (PTH) and the progression of calcification was more complex. Lower PTH was associated with more extensive calcification in calcium-treated subjects, whereas higher PTH was associated with calcification in sevelamer-treated subjects. Serum albumin was inversely correlated with progression in aortic calcification. Sevelamer was associated with favourable effects on lipids, although the link between these effects and the observed attenuation in vascular calcification remains to be elucidated.Calcium-based phosphate binders are associated with progressive coronary artery and aortic calcification, especially when mineral metabolism is not well controlled. Calcium may directly or indirectly (via PTH) adversely influence the balance of skeletal and extraskeletal calcification in haemodialysis patients.

  View details for DOI 10.1093/ndt.gfh125

  View details for Web of Science ID 000221868600025

  View details for PubMedID 15102961

• Prevention of radiocontrast nephropathy - Back to basics JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Chertow, G. M. 2004; 291 (19): 2376-2377

  View details for Web of Science ID 000221455400026

  View details for PubMedID 15150210

• Screening to prevent coronary events or screening to detect obstruction? AMERICAN JOURNAL OF KIDNEY DISEASES Raggi, P., Budoff, M. J., Chertow, G. M. 2004; 43 (5): 940-940

  View details for DOI 10.1053/j.ajkd.2004.03.014

  View details for Web of Science ID 000221104800023

  View details for PubMedID 15112188

• Physical and sexual function in women with chronic kidney disease AMERICAN JOURNAL OF KIDNEY DISEASES Kurella, M., Ireland, C., Hlatky, M. A., Shlipak, M. G., Yaffe, K., Hulley, S. B., Chertow, G. M. 2004; 43 (5): 868-876

  Abstract

  Cross-sectional studies suggest an association between functional status and chronic kidney disease (CKD). Whether physical function deteriorates with progression of CKD is unknown.To determine associations among CKD, physical function, and sexual function in women, we conducted cross-sectional and longitudinal analyses of 2,761 women enrolled in the Heart and Estrogen/Progestin Replacement Study. Physical and sexual function were evaluated using the Duke Activity Status Index (DASI) and the Sexual Problems Scale of the Medical Outcomes Study, respectively. Glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease regression equation. In addition to analyses across the spectrum of GFR, CKD was categorized as mild (estimated GFR, 45 to 60 mL/min/1.73 m2), moderate (estimated GFR, 30 to 44 mL/min/1.73 m2), and severe (estimated GFR, <30 mL/min/1.73 m2) according to a modification of recently established classification guidelines.Mean age of study participants was 67 +/- 7 years, and mean estimated GFR was 61 +/- 14 mL/min/1.73 m2. In unadjusted analyses, mean baseline DASI score was 10 points lower in women with an estimated GFR less than 30 mL/min/1.73 m2 than in women with an estimated GFR of 60 mL/min/1.73 m2 or greater (P < 0.0001). Estimated GFR remained significantly associated with DASI score after multivariable adjustment. In longitudinal analyses, a decline in estimated GFR was associated with a significant decline in DASI score independent of baseline estimated GFR and other factors. There were no significant associations between estimated GFR and psychosocial aspects of sexual function.CKD is associated with impaired physical function, and a decline in estimated GFR is associated with a decline in physical function.

  View details for DOI 10.1053/j.ajkd.2003.12.050

  View details for Web of Science ID 000221104800013

  View details for PubMedID 15112178

• The influence of patient- and facility-specific factors on nutritional status and survival in hemodialysis JOURNAL OF RENAL NUTRITION Kaysen, G. A., Muller, H. G., Young, B. S., Leng, X. Y., Chertow, G. M. 2004; 14 (2): 72-81

  Abstract

  Parameters of nutritional status, including serum albumin, serum creatinine, and body mass index (BMI), are powerful predictors of mortality and hospitalization in patients with end stage renal disease (ESRD). Patient-specific characteristics and facility-related practice patterns modify certain parameters of nutritional status. We aimed to determine whether patient and facility characteristics modify the risk profiles associated with malnutrition in hemodialysis patients.We analyzed data on 5,234 prevalent hemodialysis patients from the Dialysis Morbidity and Mortality Study (DMMS) Wave 1 for whom information on demographic, clinical, nutritional, and facility-related characteristics were available. We evaluated the associations among facility characteristics and serum albumin, serum creatinine, and BMI, adjusting for the effects of age, sex, race/ethnicity, diabetes, and dialysis vintage. We determined correlates of mortality and hospitalization, focusing on nutritional parameters, facility effects, and the interactions among patient-specific and facility-specific characteristics, albumin, creatinine, and BMI.Serum albumin was lower with older age, diabetes, nonblack race, and hemodialysis using a catheter. Serum albumin was higher with annual vascular access surveillance, higher BMI among women, higher urea reduction ratio, among patients in whom dialyzers were reprocessed (particularly with bleach), among dialysis units in which water purification was used, and when vascular access blood flow rates were > or =350 mL/min. Overall survival was decreased with lower albumin, creatinine, and BMI. There were interactions among albumin, age, and vintage. Whereas lower serum albumin concentrations consistently were associated with an increased risk of death, the differences were attenuated among older patients and accentuated among patients of longer vintage.Some facility-specific factors are associated with nutritional parameters including serum albumin, serum creatinine, and BMI. The associations of nutritional parameters with mortality and hospitalization vary by age, sex, and vintage but not by facility-specific factors, including those associated with the nutritional parameters themselves.

  View details for DOI 10.1053/j.jm.2004.01.006

  View details for Web of Science ID 000221104700003

  View details for PubMedID 15060871

• Plasma cytokine levels predict mortality in patients with acute renal failure KIDNEY INTERNATIONAL Simmons, E. M., Himmelfarb, J., Sezer, M. T., Chertow, G. M., Mehta, R. L., Paganini, E. P., Soroko, S., Freedman, S., Becker, K., Spratt, D., Shyr, Y., Ikizler, T. A. 2004; 65 (4): 1357-1365

  Abstract

  Critically ill patients with acute renal failure (ARF) experience a high mortality rate. Animal and human studies suggest that proinflammatory cytokines lead to the development of a systemic inflammatory response syndrome (SIRS), which is temporally followed by a counter anti-inflammatory response syndrome (CARS). This process has not been specifically described in critically ill patients with ARF.The Program to Improve Care in Acute Renal Disease (PICARD) is a prospective, multicenter cohort study designed to examine the natural history, practice patterns, and outcomes of treatment in critically ill patients with ARF. In a subset of 98 patients with ARF, we measured plasma proinflammatory cytokines [interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha)], the acute-phase reactant C-reactive protein (CRP), and the anti-inflammatory cytokine IL-10 at study enrollment and over the course of illness.When compared with healthy subjects and end-stage renal disease patients on maintenance hemodialysis, patients with ARF had significantly higher plasma levels of all measured cytokines. Additionally, the proinflammatory cytokines IL-6 and IL-8 were significantly higher in nonsurvivors versus survivors [median 234.7 (interdecile range 64.8 to 1775.9) pg/mL vs. 113.5 (46.1 to 419.3) pg/mL, P= 0.02 for IL-6; 35.5 (14.1 to 237.9) pg/mL vs. 21.2 (8.5 to 87.1) pg/mL, P= 0.03 for IL-8]. The anti-inflammatory cytokine IL-10 was also significantly higher in nonsurvivors [3.1 (0.5 to 41.9) pg/mL vs. 2.4 (0.5 to 16.9) pg/mL, P= 0.04]. For each natural log unit increase in the levels of IL-6, IL-8, and IL-10, the odds of death increased by 65%, 54%, and 34%, respectively, corresponding to increases in relative risk of approximately 30%, 25%, and 15%. The presence or absence of SIRS or sepsis was not a major determinant of plasma cytokine concentration in this group of patients.There is evidence of ongoing SIRS with concomitant CARS in critically ill patients with ARF, with higher levels of plasma IL-6, IL-8, and IL-10 in patients with ARF who die during hospitalization. Strategies to modulate inflammation must take into account the complex cytokine biology in patients with established ARF.

  View details for Web of Science ID 000220135700024

  View details for PubMedID 15086475

• A 43-year-old woman with chronic renal insufficiency JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Chertow, G. M. 2004; 291 (10): 1252-1259

  View details for Web of Science ID 000220061900027

  View details for PubMedID 15010448

• Valvular calcification in hemodialysis patients randomized to calcium-based phosphorus, binders or sevelamer JOURNAL OF HEART VALVE DISEASE Raggi, P., Bommer, J., Chertow, G. M. 2004; 13 (1): 134-141

  Abstract

  Valvular calcification is common in patients with end-stage renal disease, and is associated with an unfavorable prognosis. It was hypothesized that sevelamer, a non-calcium-based phosphorus binder, might attenuate the progression of valvular calcification.Two hundred subjects on maintenance hemodialysis received either sevelamer or calcium-based phosphorus binders. To assess the extent of calcification, 186 subjects underwent baseline electron beam tomography (EBT) of the coronary arteries, aorta and mitral and aortic valves, and 132 had follow up EBT scans at week 52. Changes in valvular calcification and combined valvular/vascular calcification were monitored and compared.At baseline, mitral valve calcification was seen in 46% of subjects, aortic valve calcification in 33%. Most subjects with zero values at baseline failed to progress over one year. Aortic valve calcification was significantly increased in calcium-treated subjects. Changes in mitral valve calcification, and combined mitral + aortic valve calcification were less in sevelamer-treated than in calcium-treated subjects, but not significantly so. When combining valvular and vascular calcification, the median (10%, 90%) change in sevelamer-treated subjects was significantly lower than in calcium-treated subjects (6, -5084 to 1180 versus 81, -1150 to 2944, p = 0.04). The effect of sevelamer remained significant after adjustment for baseline calcification and the time-averaged calcium-phosphorus product, and was independent of the calcium preparation (acetate versus carbonate), geographic region (US versus Europe), LDL- or HDL-cholesterol, C-reactive protein and statin use. Significantly more sevelamer-treated subjects experienced an arrest (45 versus 28%, p = 0.047) or regression (26 versus 10%, p = 0.02) in total valvular and vascular calcification.Sevelamer arrested the progression of valvular and vascular calcification in almost 50% of hemodialysis subjects. Sevelamer treatment, plus intensive control of calcium and phosphorus levels, may attenuate progression of, or achieve regression in, cardiac valvular calcification.

  View details for Web of Science ID 000188195400026

  View details for PubMedID 14765851

• Multi-attribute utility and health-related quality of life in persons with CKD stages IV-V. 36th Annual Meeting of the American-Society-of-Nephrology Gorodetskaya, I., Young, B. S., Hsu, C. Y., Zenios, S. A., Chertow, G. M. AMER SOC NEPHROLOGY. 2003: 810A–810A

  View details for Web of Science ID 000186219103733

• Anthropometrically estimated total body water volumes are larger than modeled urea volume in chronic hemodialysis patients: Effects of age, race, and gender KIDNEY INTERNATIONAL Daugirdas, J. T., Greene, T., Depner, T. A., Chumlea, C., Rocco, M. J., Chertow, G. M. 2003; 64 (3): 1108-1119

  Abstract

  The modeled volume of urea distribution (Vm) in intermittently hemodialyzed patients is often compared with total body water (TBW) volume predicted from population studies of patient anthropometrics (Vant).Using data from the HEMO Study, we compared Vm determined by both blood-side and dialysate-side urea kinetic models with Vant as calculated by the Watson, Hume-Weyers, and Chertow anthropometric equations.Median levels of dialysate-based Vm and blood-based Vm agreed (43% and 44% of body weight, respectively). These volumes were lower than anthropometric estimates of TBW, which had median values of 52% to 55% of body weight for the three formulas evaluated. The difference between the Watson equation for TBW and modeled urea volume was greater in Caucasians (19%) than in African Americans (13%). Correlations between Vm and Vant determined by each of the three anthropometric estimation equations were similar; but Vant derived from the Watson formula had a slightly higher correlation with Vm. The difference between Vm and the anthropometric formulas was greatest with the Chertow equation, less with the Hume-Weyers formula, and least with the Watson estimate. The age term in the Watson equation for men that adjusts Vant downward with increasing age reduced an age effect on the difference between Vant and Vm in men.The findings show that kinetically derived values for V from blood-side and dialysate-side modeling are similar, and that these modeled urea volumes are lower by a substantial amount than anthropometric estimates of TBW. The higher values for anthropometry-derived TBW in hemodialyzed patients could be due to measurement errors. However, the possibility exists that TBW space is contracted in patients with end-stage renal disease (ESRD) or that the TBW space and the urea distribution space are not identical.

  View details for Web of Science ID 000184732300039

  View details for PubMedID 12911564

• Reasons for non-enrollment in a cohort study of ARF: The program to improve care in acute renal disease (PICARD) experience and implications for a clinical trials network 34th Annual Meeting of the American-Society-of-Nephrology Chertow, G. M., Pascual, M. T., Soroko, S., Savage, B. R., Himmelfarb, J., Ikizler, T. A., Paganini, E. P., Mehta, R. L. W B SAUNDERS CO-ELSEVIER INC. 2003: 507–12

  Abstract

  Acute renal failure (ARF) is associated strongly with in-hospital mortality and morbidity. Previous clinical trials of ARF have been hampered by the heterogeneous population affected, difficulty defining ARF, delays in identification of ARF, and significant comorbid conditions, among other factors.The Program to Improve Care in Acute Renal Disease (PICARD) phase I was a multicenter cohort study aimed to identify clinical characteristics and practice patterns associated with adverse and favorable outcomes in patients with ARF in intensive care units. Although PICARD used no interventions, signed informed consent was required of all study subjects or their proxies.Signed informed consent was obtained in 645 of 1,243 ARF episodes (52%). The fraction of patients not enrolled and reasons for non-enrollment varied widely across the 5 PICARD centers. Refusal by potential study subjects was infrequent, although the absence of family or proxy (15%) and refusal by family or proxy (18%) accounted for large fractions of non-enrolled subjects. Death (23%) and discharge (11%) before study personnel could evaluate patients were additional important reasons for non-enrollment.Understanding reasons for non-enrollment may help rationalize mortality and other outcome differences seen in clinical trials and cohort studies that require informed consent compared with historic reports of "all comers" with ARF.

  View details for DOI 10.1016/S0272-6386(03)00745-5

  View details for Web of Science ID 000185518500008

  View details for PubMedID 12955678

• The effects of sevelamer and calcium acetate on proxies of atherosclerotic and arteriosclerotic vascular disease in hemodialysis patients AMERICAN JOURNAL OF NEPHROLOGY Chertow, G. M., Raggi, P., McCarthy, J. T., Schulman, G., Silberzweig, J., Kuhlik, A., Goodman, W. G., Boulay, A., Burke, S. K., Toto, R. D. 2003; 23 (5): 307-314

  Abstract

  We recently determined that in hemodialysis patients, the use of calcium salts to correct hyperphosphatemia led to progressive coronary artery and aortic calcification as determined by sequential electron beam tomography (EBT) while the use of the non-calcium-containing binder sevelamer did not. Whether the specific calcium preparation (acetate vs. carbonate) might influence the likelihood of progressive calcification was debated.To determine whether treatment with calcium acetate was specifically associated with hypercalcemia and progressive vascular calcification, we conducted an analysis restricted to 108 hemodialysis patients randomized to calcium acetate or sevelamer and followed for one year.The reduction in serum phosphorus was roughly equivalent with both agents (calcium acetate -2.5 +/- 1.8 mg/dl vs. sevelamer -2.8 +/- 2.0 mg/dl, p = 0.53). Subjects given calcium acetate were more likely to develop hypercalcemia (defined as an albumin-corrected serum calcium > or =10.5 mg/dl) (36 vs. 13%, p = 0.015). Treatment with calcium acetate (mean 4.6 +/- 2.1 g/day - equivalent to 1.2 +/- 0.5 g of elemental calcium) led to a significant increase in EBT-determined calcification of the coronary arteries (mean change 182 +/- 350, median change +20, p = 0.002) and aorta (mean change 181 +/- 855, median change +73, p < 0.0001). These changes were similar in magnitude to those seen with calcium carbonate. There were no significant changes in calcification among sevelamer-treated subjects.Despite purported differences in safety and efficacy relative to calcium carbonate, calcium acetate led to hypercalcemia and progressive vascular calcification in hemodialysis patients.

  View details for DOI 10.1159/000072822

  View details for Web of Science ID 000185391200004

  View details for PubMedID 12915774

• Slowing the progression of vascular calcification in hemodialysis JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Chertow, G. M. 2003; 14 (9): S310-S314

  Abstract

  Hyperphosphatemia and secondary hyperparathyroidism are common complications of ESRD (chronic kidney disease stage 5) that, when untreated, may result in increased morbidity and mortality. Hyperphosphatemia and hypercalcemia have been associated with increased coronary artery calcification. Achieving control of serum phosphorus without increasing serum calcium is an important goal for patients with ESRD. Although calcium-based phosphate binders effectively reduce serum phosphorus and parathyroid hormone concentrations, these agents can lead to hypercalcemia and have been associated with increased vascular calcification. The phosphorus binder sevelamer was developed to overcome the limitations associated with the usual management of hyperphosphatemia and secondary hyperparathyroidism (i.e., mineral salts). Sevelamer, a nonabsorbable hydrogel, is as efficacious as calcium-based phosphate binders for reducing serum phosphorus but does not cause hypercalcemia or other adverse metabolic effects. Sevelamer also exhibits beneficial effects on lipids, consistently and significantly decreasing LDL cholesterol and increasing HDL cholesterol in most studies. In a head-to-head randomized clinical trial, sevelamer and calcium-based binders achieved similarly excellent phosphorus control, but the use of calcium-based binders led to significantly higher serum calcium concentrations and an increased incidence of hypercalcemia and unintended suppression of parathyroid hormone. Treatment with calcium-based binders also led to the progression of coronary artery and aortic calcification, whereas sevelamer attenuated or arrested progression. Strategies that use oral calcium and vitamin D in patients with ESRD should be reexamined, and the potential advantages of sevelamer should be considered when selecting a primary agent to reduce serum phosphorus in hemodialysis patients.

  View details for DOI 10.1097/01.ASN.0000081666.10967.05

  View details for Web of Science ID 000185131600004

  View details for PubMedID 12939387

• Acute renal failure definitions and classification: Time for change? JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Mehta, R. L., Chertow, G. M. 2003; 14 (8): 2178-2187

  View details for DOI 10.1097/01.ASN.0000079042.13465.1A

  View details for Web of Science ID 000184352600026

  View details for PubMedID 12874474

• Analgesia in patients with ESRD: A review of available evidence AMERICAN JOURNAL OF KIDNEY DISEASES Kurella, M., Bennett, W. M., Chertow, G. M. 2003; 42 (2): 217-228

  Abstract

  Moderate to severe pain frequently accompanies chronic diseases in general and end-stage renal disease (ESRD) in particular. Several analgesic agents and associated metabolites show altered pharmacokinetics in the presence of reduced glomerular filtration rate. Drug-related side effects may exacerbate symptoms frequently observed in persons with chronic kidney disease (CKD; eg, fatigue, nausea, vomiting, and constipation) or those often attributed to hemodialysis therapy (eg, orthostatic hypotension and impaired cognition). Persons with advanced CKD and ESRD are at increased risk for adverse effects of analgesic agents because of enhanced drug sensitivity, comorbid conditions, and concurrent medication use. Dose adjustment and avoidance of certain analgesics may be required in patients with advanced CKD and ESRD. We review the available evidence on pharmacokinetics and adverse drug effects of various analgesic agents commonly used in patients with advanced CKD and ESRD. Determining an optimal approach to the control of pain in patients with advanced CKD and ESRD will require additional research.

  View details for DOI 10.1016/S0272-6386(03)00645-0

  View details for Web of Science ID 000184557300001

  View details for PubMedID 12900801

• Inflammatory markers are unrelated to physical activity, performance, and functioning in hemodialysis 34th Annual Meeting of the American-Society-of-Nephrology Hung, A. M., Chertow, G. A., Young, B. S., Carey, S., Johansen, K. L. W B SAUNDERS CO-ELSEVIER INC. 2003: 232–40

  Abstract

  To determine the associations among dietary intake and inflammatory cytokines with physical activity, function, and performance in maintenance dialysis patients.Cross-sectional analysis of cohort study.University-affiliated dialysis units, general clinical research center.Multiethnic cohort of maintenance hemodialysis patients.Physical activity by accelerometry; physical performance by gait speed, stair climbing, and chair raising; physical functioning by the Medical Outcomes Study Short Form 36-item questionnaire subscale scores; and maximal and adjusted activity scores of human activity profile.Levels of inflammatory cytokines were uniformly high. Tumor necrosis factor-alpha was directly correlated with dietary protein and energy intake; no other cytokines were directly or inversely correlated with intake. Dietary intake was associated with physical activity, as expected, and not significantly associated with performance or function (with the exception of gait speed). There were no significant associations among inflammatory cytokines and physical activity, performance, or function.Although dietary intake and inflammation may independently influence traditional proxies of nutritional status, this analysis provides no evidence for a link between cytokines and physical activity, performance, or function in hemodialysis patients. More research is required to understand the role of cytokines in protein energy malnutrition and the mechanisms of wasting and functional decline in the dialysis population.

  View details for DOI 10.1053/j.arrt.2003.10.002

  View details for Web of Science ID 000187800300010

  View details for PubMedID 14708079

• The Chronic Renal Insufficiency Cohort (CRIC) study: Design and methods 1st International Summit on Kidney Disease Prevention Feldman, H. I., Appel, L. J., Chertow, G. M., Cifelli, D., Cizman, B., Daugirdas, J., Fink, J. C., Franklin-Becker, E. D., Go, A. S., Hamm, L. L., He, J. A., Hostetter, T., Hsu, C. Y., Jamerson, K., Joffe, M., Kusek, J. W., Landis, J. R., Lash, J. P., Miller, E. R., MOHLER, E. R., Muntner, P., Ojo, A. O., Rahman, M., Townsend, R. R., Wright, J. T. AMER SOC NEPHROLOGY. 2003: S148–S153

  Abstract

  Insights into end-stage renal disease have emerged from many investigations but less is known about the epidemiology of chronic renal insufficiency (CRI) and its relationship to cardiovascular disease (CVD). The Chronic Renal Insufficiency Cohort (CRIC) Study was established to examine risk factors for progression of CRI and CVD among CRI patients and develop models to identify high-risk subgroups, informing future treatment trials, and increasing application of preventive therapies. CRIC will enroll approximately 3000 individuals at seven sites and follow participants for up to 5 yr. CRIC will include a racially and ethnically diverse group of adults aged 21 to 74 yr with a broad spectrum of renal disease severity, half of whom have diagnosed diabetes mellitus. CRIC will exclude subjects with polycystic kidney disease and those on active immunosuppression for glomerulonephritis. Subjects will undergo extensive clinical evaluation at baseline and at annual clinic visits and via telephone at 6 mo intervals. Data on quality of life, dietary assessment, physical activity, health behaviors, depression, cognitive function, health care resource utilization, as well as blood and urine specimens will be collected annually. (125)I-iothalamate clearances and CVD evaluations including a 12-lead surface electrocardiogram, an echocardiogram, and coronary electron beam or spiral CT will be performed serially. Analyses planned in CRIC will provide important information on potential risk factors for progressive CRI and CVD. Insights from CRIC should lead to the formulation of hypotheses regarding therapy that will serve as the basis for targeted interventional trials focused on reducing the burden of CRI and CVD.

  View details for DOI 10.1097/01.ASN.0000070149.78399.CE

  View details for Web of Science ID 000183900700018

  View details for PubMedID 12819321

• Longitudinal study of nutritional status, body composition, and physical function in hemodialysis patients 34th Annual Meeting of the American-Society-of-Nephrology Johansen, K. L., Kaysen, G. A., Young, B. S., Hung, A. M., Da Silva, M., Chertow, G. M. AMER SOC NUTRITION-ASN. 2003: 842–46

  Abstract

  Cross-sectional studies have shown an association between the duration (y) of dialysis and nutritional status, providing evidence of wasting.The aim was to determine the extent, pace, determinants, and optimal methods of assessing wasting in patients undergoing hemodialysis.Laboratory variables, body composition, and physical activity, function, and performance were tested 4 times over 1 y in 54 hemodialysis patients. Changes in repeated measures were evaluated, with adjustment for baseline differences by age, sex, race, diabetes status, and dialysis vintage (ie, time since initiation of dialysis).No significant changes in body weight, fat mass, lean body mass, or laboratory variables were observed. Phase angle, a bioelectrical impedance analysis-derived variable related to body cell mass, decreased significantly (linear estimate: -0.043 degrees /mo, or approximately 0.5 degrees/y; P = 0.001). Physical activity measured by accelerometry declined 3.4%/mo (P = 0.01). The Maximum Activity Score of the Human Activity Profile (HAP) also declined significantly (linear estimate: -0.50/mo, or approximately 6 points/y; P = 0.025). Higher interleukin 1beta (IL-1beta) concentrations were associated with a narrower phase angle (P = 0.004) and with a more rapid decline in phase angle with time (time x IL-1beta interaction, P = 0.01); similar effects of IL-1beta on physical activity were observed. Dietary protein and energy intakes were associated with changes in the HAP.Evidence of adverse changes in body composition and physical activity, function, and performance and of a modest influence of inflammation and dietary intake on these changes was observed in this cohort. Tools such as bioelectrical impedance analysis, accelerometry, and the HAP may be required to identify subtle changes.

  View details for Web of Science ID 000181747600015

  View details for PubMedID 12663281

• Beware the rising creatinine level JOURNAL OF CARDIAC FAILURE Shlipak, M. G., Chertow, G. C., Massie, B. M. 2003; 9 (1): 26-28

  View details for DOI 10.1054/jcaf.2003.10

  View details for Web of Science ID 000181373700004

  View details for PubMedID 12612869

• In critically ill patients with acute renal failure, outcomes, not dollars, should drive modality choice CRITICAL CARE MEDICINE Mehta, R. L., Chertow, G. M. 2003; 31 (2): 644-646

  View details for DOI 10.1097/01.CCM.0000045183.74244.14

  View details for Web of Science ID 000180919700048

  View details for PubMedID 12576983

• The decline in residual renal function in hemodialysis is slow and age dependent. Hemodialysis international. International Symposium on Home Hemodialysis Hung, A. M., Young, B. S., Chertow, G. M. 2003; 7 (1): 17-22

  Abstract

  Persons on peritoneal dialysis and hemodialysis with preserved residual renal function experience lower mortality rates than those without. Previous studies have shown slower rates of decline of residual renal function for peritoneal dialysis (PD)(2 to 3% decrease/month), compared with hemodialysis (HD)(6 to 7% decrease/month). However, our clinical observations suggested a lower rate of decline in hemodialysis patients.We evaluated data in 174 hemodialysis patients cared for from January 2000 through October 2001. Eighty-seven (50%) patients had at least two timed quarterly urine collections to estimate the rate of change of residual renal function over time (urea clearance, or KrU). All patients underwent thrice-weekly hemodialysis using polysulfone dialyzers with formaldehyde reprocessing. The rate of decline of residual renal function and the effect of KrU on laboratory variables were estimated using a random effects (MIXED) model, adjusting for the effects of age, sex, race, diabetes, and dialysis vintage.The mean KrU at baseline was 3.5 mL/min. Men (P < 0.001) and persons of shorter vintage (P < 0.0001) had more residual renal function at baseline. The estimated rate of decline of residual renal function was - 0.07 mL/min/month (- 1.9% decrease/month). The rate of decline in residual renal function was unaffected by sex, race, diabetes, or vintage, although the rate of decline was significantly attenuated among older individuals (age x time interaction, P = 0.01). Serum phosphorus (P = 0.03) and the calcium x phosphorus product (P = 0.009) increased over time and were influenced by the level of residual renal function (P = 0.06 and P = 0.006, respectively). Residual renal function did not influence the rate of change of other laboratory variables.In an ethnically diverse cohort of hemodialysis patients, the rate of decline of residual renal function was relatively slow and age dependent, as well as consistent with values others have reported for patients on peritoneal dialysis. Universal use of biocompatible dialyzers and bicarbonate dialysate may have contributed to differences discussed in prior reports. Residual renal function attenuated the increase in calcium-phosphorus product over time. A better understanding of the determinants of the rate of decline in residual renal function, and the specific benefits afforded to patients via maintenance of residual renal function, would help to inform the debates on timing of initiation and various dosing strategies in hemodialysis.

  View details for DOI 10.1046/j.1492-7535.2003.00006.x

  View details for PubMedID 19379338

• Diuretics, mortality, and nonrecovery of renal function in acute renal JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Mehta, R. L., Pascual, M. T., Soroko, S., Chertow, G. M. 2002; 288 (20): 2547-2553

  Abstract

  Acute renal failure is associated with high mortality and morbidity. Diuretic agents continue to be used in this setting despite a lack of evidence supporting their benefit.To determine whether the use of diuretics is associated with adverse or favorable outcomes in critically ill patients with acute renal failure.Cohort study conducted from October 1989 to September 1995.A total of 552 patients with acute renal failure in intensive care units at 4 academic medical centers affiliated with the University of California. Patients were categorized by the use of diuretics on the day of nephrology consultation and, in companion analyses, by diuretic use at any time during the first week following consultation.All-cause hospital mortality, nonrecovery of renal function, and the combined outcome of death or nonrecovery.Diuretics were used in 326 patients (59%) at the time of nephrology consultation. Patients treated with diuretics on or before the day of consultation were older and more likely to have a history of congestive heart failure, nephrotoxic (rather than ischemic or multifactorial) origin of acute renal failure, acute respiratory failure, and lower serum urea nitrogen concentrations. With adjustment for relevant covariates and propensity scores, diuretic use was associated with a significant increase in the risk of death or nonrecovery of renal function (odds ratio, 1.77; 95% confidence interval, 1.14-2.76). The risk was magnified (odds ratio, 3.12; 95% confidence interval, 1.73-5.62) when patients who died within the first week following consultation were excluded. The increased risk was borne largely by patients who were relatively unresponsive to diuretics.The use of diuretics in critically ill patients with acute renal failure was associated with an increased risk of death and nonrecovery of renal function. Although observational data prohibit causal inference, it is unlikely that diuretics afford any material benefit in this clinical setting. In the absence of compelling contradictory data from a randomized, blinded clinical trial, the widespread use of diuretics in critically ill patients with acute renal failure should be discouraged.

  View details for Web of Science ID 000179394500021

  View details for PubMedID 12444861

• The severity of secondary hyperparathyroidism in chronic renal insufficiency is GFR-dependent, race-dependent, and associated with cardiovascular disease JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY de Boer, I. H., Gorodetskaya, I., Young, B., Hsu, C. Y., Chertow, G. M. 2002; 13 (11): 2762-2769

  Abstract

  Secondary hyperparathyroidism (SHPT) is an important complication of end-stage renal disease. However, SHPT begins during earlier stages of chronic renal insufficiency (CRI), and little is known about risk factors for SHPT in this population. This study evaluated 218 patients in an ethnically diverse ambulatory nephrology practice at the University of California San Francisco during calendar years 1999 and 2000. Demographic data, comorbid diseases, medications, and laboratory parameters were collected, and independent correlates of intact parathyroid hormone (PTH) were identified by using multiple linear regression. The mean estimated GFR was 34 ml/min per 1.73 m(2) (10%-90% range, 13 to 61 ml/min per 1.73 m(2)); PTH was inversely related to GFR (P < 0.0001). The adjusted mean PTH was higher among African Americans and lower among Asian/Pacific Islanders compared with white patients (233 versus 95 versus 139 pg/ml; P < 0.0001). Moreover, among the 196 patients with GFR <60 ml/min per 1.73 m(2), the slope of GFR versus PTH was significantly steeper among African Americans than among white patients (10.6 versus 3.9 pg/ml per ml per min per 1.73 m(2); P = 0.01). After adjusting for age and diabetes, PTH was associated with a history of myocardial infarction (OR, 1.6; 95% CI, 1.1 to 2.3 per unit natural log PTH) and congestive heart failure (OR, 2.0; 95% CI, 1.3 to 2.9 per unit natural log PTH) and not associated with other co-morbid conditions. These factors should be considered when screening and managing SHPT in CRI.

  View details for DOI 10.1097/01.ASN.0000034202.91413.EB

  View details for Web of Science ID 000178821400017

  View details for PubMedID 12397047

• Nephrology consultation in acute renal failure: Does timing matter? AMERICAN JOURNAL OF MEDICINE Mehta, R. L., McDonald, B., Gabbai, F., Pahl, M., Farkas, A., Pascual, M. T., Zhuang, S. P., Kaplan, R. M., Chertow, G. M. 2002; 113 (6): 456-461

  Abstract

  Patients who develop acute renal failure in the intensive care unit (ICU) have extremely high rates of mortality and morbidity. The goals of this study were to identify correlates of the timing of nephrology consultation in acute renal failure, and to explore the relation between timing of consultation and outcomes.We explored associations among timing of nephrology consultation and in-hospital mortality, lengths of hospital and ICU stay, and recovery of renal function in 215 ICU patients with acute renal failure at four U.S. teaching hospitals. We used multivariable logistic regression and propensity scores to adjust for confounding and selection effects.Nephrology consultation was delayed (>or=48 hours) in 61 patients (28%) (median time to consultation, 4 days). Lower serum creatinine levels (P <0.0001) and higher urine output (P = 0.002) were associated with delayed consultation. Delayed consultation was associated with increased mortality among dialyzed (31/42 [74%] vs. 50/103 [49%], P = 0.006) and nondialyzed patients (10/19 [53%] vs. 11/51 [22%], P = 0.01), and increases in lengths of hospital (median, 19 days vs. 16 days, P = 0.01) and ICU stay (17 days vs. 6 days, P <0.0001). The association between delayed consultation and mortality was attenuated by covariate adjustment, and was no longer statistically significant after adjustment for propensity score (odds ratio = 2.0; 95% confidence interval: 0.8 to 5.1).In acute renal failure, delayed nephrology consultation was associated with increased mortality and morbidity, whether or not dialysis was ultimately required. Using observational data, we cannot determine whether these findings reflect residual confounding, selection bias, adverse effects of delayed recognition of acute renal failure, or the benefits of nephrology consultation.

  View details for Web of Science ID 000179148600002

  View details for PubMedID 12427493

• Association of renal insufficiency with treatment and outcomes after myocardial infarction in elderly patients ANNALS OF INTERNAL MEDICINE Shlipak, M. G., Heidenreich, P. A., Noguchi, H., Chertow, G. M., Browner, W. S., McClellan, M. B. 2002; 137 (7): 555-562

  Abstract

  Patients with end-stage renal disease are known to have decreased survival after myocardial infarction, but the association of less severe renal dysfunction with survival after myocardial infarction is unknown.To determine how patients with renal insufficiency are treated during hospitalization for myocardial infarction and to determine the association of renal insufficiency with survival after myocardial infarction.Cohort study.All nongovernment hospitals in the United States.130 099 elderly patients with myocardial infarction hospitalized between April 1994 and July 1995.Patients were categorized according to initial serum creatinine level: no renal insufficiency (creatinine level < 1.5 mg/dL [<132 micromol/L]; n = 82 455), mild renal insufficiency (creatinine level, 1.5 to 2.4 mg/dL [132 to 212 micromol/L]; n = 36 756), or moderate renal insufficiency (creatinine level, 2.5 to 3.9 mg/dL [221 to 345 micromol/L]; n = 10 888). Vital status up to 1 year after discharge was obtained from Social Security records.Compared with patients with no renal insufficiency, patients with moderate renal insufficiency were less likely to receive aspirin, beta-blockers, thrombolytic therapy, angiography, and angioplasty during hospitalization. One-year mortality was 24% in patients with no renal insufficiency, 46% in patients with mild renal insufficiency, and 66% in patients with moderate renal insufficiency (P < 0.001). After adjustment for patient and treatment characteristics, mild (hazard ratio, 1.68 [95% CI, 1.63 to 1.73]) and moderate (hazard ratio, 2.35 [CI, 2.26 to 2.45]) renal insufficiency were associated with substantially elevated risk for death during the first month of follow-up. This increased mortality risk continued until 6 months after myocardial infarction.Renal insufficiency was an independent risk factor for death in elderly patients after myocardial infarction. Targeted interventions may be needed to improve treatment for this high-risk population.

  View details for Web of Science ID 000178355100001

  View details for PubMedID 12353942

• Elevations of serum phosphorus and potassium in mild to moderate chronic renal insufficiency NEPHROLOGY DIALYSIS TRANSPLANTATION Hsu, C. Y., Chertow, G. M. 2002; 17 (8): 1419-1425

  Abstract

  Reduced renal function is associated with a variety of biochemical abnormalities. However, the extent of these changes and their magnitude in relation to renal function is not well defined, especially among individuals with mild to moderate chronic renal insufficiency (CRI).We analysed the Third National Health and Nutrition Examination Survey (NHANES III; 1988-1994) data for 14722 adults aged >/=17 years with measurements of serum creatinine and all electrolytes including ionized calcium. General linear models were used to determine the relationship between mean concentrations of electrolytes and different levels of Cockcroft-Gault creatinine clearance (CrCl). Sample weights were used to produce weighted regression parameters.Changes in mean serum phosphorus and potassium concentration were evident at relatively modest reductions in CrCl (around 50 to 60 ml/min). Changes in the anion gap and mean levels of ionized calcium and bicarbonate were not apparent until CRI was advanced (CrCl 80 ml/min, those with CrCl 60-50, 50-40, 40-30, 30-20 and

  View details for Web of Science ID 000177372900013

  View details for PubMedID 12147789

• Inflammatory markers are unrelated to physical activity, performance, and functioning in hemodialysis 34th Annual Meeting of the American-Society-of-Nephrology Hung, A. M., Chertow, G. M., Young, B. S., Carey, S., Johansen, K. L. W B SAUNDERS CO-ELSEVIER INC. 2002: 170–76

  Abstract

  To determine the associations among dietary intake and inflammatory cytokines with physical activity, function, and performance in maintenance dialysis patients.Cross-sectional analysis of cohort study.University-affiliated dialysis units, general clinical research center.Multiethnic cohort of maintenance hemodialysis patients.Physical activity by accelerometry; physical performance by gait speed, stair climbing, and chair raising; physical functioning by the Medical Outcomes Study Short Form 36-item questionnaire subscale scores; and maximal and adjusted activity scores of human activity profile.Levels of inflammatory cytokines were uniformly high. Tumor necrosis factor-alpha was directly correlated with dietary protein and energy intake; no other cytokines were directly or inversely correlated with intake. Dietary intake was associated with physical activity, as expected, and not significantly associated with performance or function (with the exception of gait speed). There were no significant associations among inflammatory cytokines and physical activity, performance, or function.Although dietary intake and inflammation may independently influence traditional proxies of nutritional status, this analysis provides no evidence for a link between cytokines and physical activity, performance, or function in hemodialysis patients. More research is required to understand the role of cytokines in protein energy malnutrition and the mechanisms of wasting and functional decline in the dialysis population.

  View details for DOI 10.1053/jren.2002.33513

  View details for Web of Science ID 000176676800005

  View details for PubMedID 12105814

• Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients KIDNEY INTERNATIONAL Chertow, G. M., Burke, S. K., Raggi, P. 2002; 62 (1): 245-252

  Abstract

  Cardiovascular disease is frequent and severe in patients with end-stage renal disease. Disorders of mineral metabolism may contribute by promoting cardiovascular calcification.We conducted a randomized clinical trial comparing sevelamer, a non-absorbed polymer, with calcium-based phosphate binders in 200 hemodialysis patients. Study outcomes included the targeted concentrations of serum phosphorus, calcium, and intact parathyroid hormone (PTH), and calcification of the coronary arteries and thoracic aorta using a calcification score derived from electron beam tomography.Sevelamer and calcium provided equivalent control of serum phosphorus (end-of-study values 5.1 +/- 1.2 and 5.1 +/- 1.4 mg/dL, respectively, P = 0.33). Serum calcium concentration was significantly higher in the calcium-treated group (P = 0.002), and hypercalcemia was more common (16% vs. 5% with sevelamer, P = 0.04). More subjects in the calcium group had end-of-study intact PTH below the target of 150 to 300 pg/mL (57% vs. 30%, P = 0.001). At study completion, the median absolute calcium score in the coronary arteries and aorta increased significantly in the calcium treated subjects but not in the sevelamer-treated subjects (coronary arteries 36.6 vs. 0, P = 0.03 and aorta 75.1 vs. 0, P = 0.01, respectively). The median percent change in coronary artery (25% vs. 6%, P = 0.02) and aortic (28% vs. 5%, P = 0.02) calcium score also was significantly greater with calcium than with sevelamer.Compared with calcium-based phosphate binders, sevelamer is less likely to cause hypercalcemia, low levels of PTH, and progressive coronary and aortic calcification in hemodialysis patients.

  View details for Web of Science ID 000176397500027

  View details for PubMedID 12081584

• Methodological issues in studying the epidemiology of mild to moderate chronic renal insufficiency KIDNEY INTERNATIONAL Hsu, C. Y., Chertow, G. M., Curhan, G. C. 2002; 61 (5): 1567-1576

  Abstract

  There is increasing interest in studying the epidemiology of subjects with mild to moderate chronic renal insufficiency (CRI), defined as reduced glomerular filtration rate (GFR) not requiring renal replacement therapy. This review discusses some of the methodological challenges presented by the epidemiological study of mild to moderate CRI that have not been adequately addressed in the literature. Issues that relate to defining the prevalence of CRI include between-laboratory differences in serum creatinine (SCr) assays, within-person measurement errors in SCr, and differences in SCr in different demographic groups that are independent of GFR. Issues that relate to examining CRI as an outcome include the choice between a "slope" or "threshold" analysis. Issues that relate to examining CRI as an exposure include the choice of renal function measure (for example, SCr vs. estimated GFR) in multivariable analysis, whether to normalize renal function to body surface area or other body size parameters, potential effect modification of the association between CRI and the outcome and the complex relation between CRI, adverse outcomes, potential confounders and intermediary variables. As we enter an era of more intensive study of mild to moderate CRI, recognition of these potential pitfalls should guide researchers toward improving the quality of epidemiological research in this field.

  View details for Web of Science ID 000175054200001

  View details for PubMedID 11967006

• Refining predictive models in critically ill patients with acute renal failure JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Mehta, R. L., Pascual, M. T., Gruta, C. G., Zhuang, S. P., Chertow, G. M. 2002; 13 (5)

  Abstract

  Mortality rates in acute renal failure remain extremely high, and risk-adjustment tools are needed for quality improvement initiatives and design (stratification) and analysis of clinical trials. A total of 605 patients with acute renal failure in the intensive care unit during 1989-1995 were evaluated, and demographic, historical, laboratory, and physiologic variables were linked with in-hospital death rates using multivariable logistic regression. Three hundred and fourteen (51.9%) patients died in-hospital. The following variables were significantly associated with in-hospital death: age (odds ratio [OR], 1.02 per yr), male gender (OR, 2.36), respiratory (OR, 2.62), liver (OR, 3.06), and hematologic failure (OR, 3.40), creatinine (OR, 0.71 per mg/dl), blood urea nitrogen (OR, 1.02 per mg/dl), log urine output (OR, 0.64 per log ml/d), and heart rate (OR, 1.01 per beat/min). The area under the receiver operating characteristic curve was 0.83, indicating good model discrimination. The model was superior in all performance metrics to six generic and four acute renal failure-specific predictive models. A disease-specific severity of illness equation was developed using routinely available and specific clinical variables. Cross-validation of the model and additional bedside experience will be needed before it can be effectively applied across centers, particularly in the context of clinical trials.

  View details for DOI 10.1097/01.ASN.0000014692.19351.52

  View details for Web of Science ID 000175210800025

  View details for PubMedID 11961023

• Bone mineral density is not diminished by mild to moderate chronic renal insufficiency KIDNEY INTERNATIONAL Hsu, C. Y., Cummings, S. R., McCulloch, C. E., Chertow, G. A. 2002; 61 (5): 1814-1820

  Abstract

  Persons with end-stage renal disease are at higher risk for osteopenia and hip fracture relative to the age-matched general population. Persons with mild to moderate chronic renal insufficiency (CRI) may have reduced bone mineral density (BMD) as a result of abnormalities in acid-base and vitamin D-parathyroid hormone homeostasis.We analyzed data on 13,848 adults aged 20 and above from the Third National Health and Nutrition Examination Survey (NHANES III; 1988-1994). Regression models were used to determine the relationship between femoral BMD and renal function, the latter assessed using serum creatinine, blood urea nitrogen or Cockcroft-Gault creatinine clearance. To control for confounding, we fit sex-stratified models that adjusted for age, weight, height, race-ethnicity, menopausal status, estrogen use, activity level, family history of osteoporosis, diuretic use, and dietary intake of calcium and alcohol.Although subjects with reduced renal function had significantly lower femoral BMD in unadjusted analysis, the association between CRI and bone mineral density was extinguished after adjustment in the multivariate models. In fact, controlling for only sex, age and weight was sufficient to extinguish any negative association between decreased renal function and decreased bone mineral density.Although subjects with worse renal function have significantly lower femoral BMD, this association can be explained by confounding, principally by sex, age and weight. After taking into account the facts that women, older individuals and smaller individuals have less renal function and lower BMD, renal function itself is not independently associated with BMD.

  View details for Web of Science ID 000175054200027

  View details for PubMedID 11967032

• With bioimpedance spectroscopy, the errors get fat when the patients get slim JOURNAL OF PARENTERAL AND ENTERAL NUTRITION Chertow, G. M. 2002; 26 (2): 128-129

  View details for Web of Science ID 000174000200011

  View details for PubMedID 11871736

• Cardiac calcification in adult Hemodialysis patients - A link between end-stage renal disease and cardiovascular disease? JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Raggi, P., Boulay, A., Chasan-Taber, S., Amin, N., Dillon, M., Burke, S. K., Chertow, G. M. 2002; 39 (4): 695-701

  Abstract

  We sought to determine clinical and laboratory correlates of calcification of the coronary arteries (CAs), aorta and mitral and aortic valves in adult subjects with end-stage renal disease (ESRD) receiving hemodialysis.Vascular calcification is known to be a risk factor for ischemic heart disease in non-uremic individuals. Patients with ESRD experience accelerated vascular calcification, due at least in part to dysregulation of mineral metabolism. Clinical correlates of the extent of calcification in ESRD have not been identified. Moreover, the clinical relevance of calcification as measured by electron-beam tomography (EBT) has not been determined in the ESRD population.We conducted a cross-sectional analysis of 205 maintenance hemodialysis patients who received baseline EBT for evaluation of vascular and valvular calcification. We compared subjects with and without clinical evidence of atherosclerotic vascular disease and determined correlates of the extent of vascular and valvular calcification using multivariable linear regression and proportional odds logistic regression analyses.The median coronary artery calcium score was 595 (interquartile range, 76 to 1,600), values consistent with a high risk of obstructive coronary artery disease in the general population. The CA calcium scores were directly related to the prevalence of myocardial infarction (p < 0.0001) and angina (p < 0.0001), and the aortic calcium scores were directly related to the prevalence of claudication (p = 0.001) and aortic aneurysm (p = 0.02). The extent of coronary calcification was more pronounced with older age, male gender, white race, diabetes, longer dialysis vintage and higher serum concentrations of calcium and phosphorus. Total cholesterol (and high-density lipoprotein and low-density lipoprotein subfractions), triglycerides, hemoglobin and albumin were not significantly related to the extent of CA calcification. Only dialysis vintage was significantly associated with the prevalence of valvular calcification.Coronary artery calcification is common, severe and significantly associated with ischemic cardiovascular disease in adult ESRD patients. The dysregulation of mineral metabolism in ESRD may influence vascular calcification risk.

  View details for Web of Science ID 000173904800021

  View details for PubMedID 11849871

• Renal insufficiency with monoclonal gammopathy and urticarial vasculitis AMERICAN JOURNAL OF KIDNEY DISEASES O''Hare, A., Olson, J. L., Connolly, M. K., Ward, J. W., Stein, P., Wisnieski, J. J., Chertow, G. M. 2002; 39 (1): 203-207

  View details for DOI 10.1053/ajkd.2002.29918

  View details for Web of Science ID 000173141700029

  View details for PubMedID 11774123

• Guided medication dosing for inpatients with renal insufficiency 31st Congress of the American-Society-of-Nephrology Chertow, G. M., Lee, J., Kuperman, G. J., Burdick, E., Horsky, J., Seger, D. L., LEE, R., Mekala, A., Song, J., Komaroff, A. L., Bates, D. W. AMER MEDICAL ASSOC. 2001: 2839–44

  Abstract

  Usual drug-prescribing practices may not consider the effects of renal insufficiency on the disposition of certain drugs. Decision aids may help optimize prescribing behavior and reduce medical error.To determine if a system application for adjusting drug dose and frequency in patients with renal insufficiency, when merged with a computerized order entry system, improves drug prescribing and patient outcomes.Four consecutive 2-month intervals consisting of control (usual computerized order entry) alternating with intervention (computerized order entry plus decision support system), conducted in September 1997-April 1998 with outcomes assessed among a consecutive sample of 17 828 adults admitted to an urban tertiary care teaching hospital.Real-time computerized decision support system for prescribing drugs in patients with renal insufficiency. During intervention periods, the adjusted dose list, default dose amount, and default frequency were displayed to the order-entry user and a notation was provided that adjustments had been made based on renal insufficiency. During control periods, these recommended adjustments were not revealed to the order-entry user, and the unadjusted parameters were displayed.Rates of appropriate prescription by dose and frequency, length of stay, hospital and pharmacy costs, and changes in renal function, compared among patients with renal insufficiency who were hospitalized during the intervention vs control periods.A total of 7490 patients were found to have some degree of renal insufficiency. In this group, 97 151 orders were written on renally cleared or nephrotoxic medications, of which 14 440 (15%) had at least 1 dosing parameter modified by the computer based on renal function. The fraction of prescriptions deemed appropriate during the intervention vs control periods by dose was 67% vs 54% (P<.001) and by frequency was 59% vs 35% (P<.001). Mean (SD) length of stay was 4.3 (4.5) days vs 4.5 (4.8) days in the intervention vs control periods, respectively (P =.009). There were no significant differences in estimated hospital and pharmacy costs or in the proportion of patients who experienced a decline in renal function during hospitalization.Guided medication dosing for inpatients with renal insufficiency appears to result in improved dose and frequency choices. This intervention demonstrates a way in which computer-based decision support systems can improve care.

  View details for Web of Science ID 000172655400032

  View details for PubMedID 11735759

• "Wishing don't make it so" - Why we need a randomized clinical trial of high-intensity hemodialysis JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Chertow, G. M. 2001; 12 (12): 2850-2853

  View details for Web of Science ID 000172412900036

  View details for PubMedID 11729257

• Determinants of physical performance in ambulatory patients on hemodialysis KIDNEY INTERNATIONAL Johansen, K. L., Chertow, G. M., Da Silva, M., Carey, S., Painter, P. 2001; 60 (4): 1586-1591

  Abstract

  Physical performance measures, particularly gait speed, have been useful as predictors of loss of independence, institutionalization, and mortality in older nonuremic individuals. Gait speed has not been evaluated as a predictor of these important outcomes in patients on hemodialysis, nor have the determinants of gait speed in the dialysis population been studied.We performed a cross-sectional analysis to determine whether demographic, clinical, or nutritional status variables were related to physical performance in a group of 46 hemodialysis patients treated at three University of California San Francisco-affiliated dialysis units. Three physical performance measures were examined, including gait speed, time to climb stairs, and time to rise from a chair five times in succession. Forward stepwise linear-regression analysis was performed with each physical performance measure as the dependent variable and the following candidate predictor variables: age, gender, body mass index, dialysis vintage, Kt/V, albumin, blood urea nitrogen, creatinine, hematocrit, lean body mass, phase angle, ferritin, and the following comorbidities: hypertension, diabetes mellitus, coronary artery disease, peripheral vascular disease, and cerebrovascular disease.Subjects included 31 men and 15 women aged 22 to 87 years (mean +/- SD, 52 +/- 17). The mean gait speed for the group was 113.1 +/- 34.5 cm/s (low compared with norms established for persons of similar age). Results of multivariable regression showed that age, albumin, and Kt/V were important determinants of gait speed in this population. Overall, the model explained 52% of the variability in gait speed (r = 0.72, P < 0.0001). Qualitatively similar results were obtained using stair-climbing time or chair-rising time as the dependent variables, except that comorbidity was more important than age for stair climbing. The addition of physical activity level to the models did not eliminate the associations of albumin or Kt/V with physical performance.Physical performance is significantly impaired in ambulatory hemodialysis patients and is related to age, serum albumin, and dialysis dose. Prospective studies are needed to determine whether modification of dialysis dose or nutritional interventions can improve physical performance in patients on hemodialysis.

  View details for Web of Science ID 000171127000043

  View details for PubMedID 11576377

• Correlates of acute renal failure in patients receiving parenteral amphotericin B 9th International Conference of Infectious Diseases Bates, D. W., Su, L., Yu, D. T., Chertow, G. M., Seger, D. L., Gomes, D. R., Platt, R. NATURE PUBLISHING GROUP. 2001: 1452–59

  Abstract

  While parenteral amphotericin B is an effective therapy for serious fungal infections, it frequently causes acute renal failure (ARF). This study identified correlates of ARF in amphotericin B therapy and used them to develop clinical prediction rules.All 643 inpatients receiving parenteral amphotericin B therapy at one tertiary care hospital were included. Data regarding correlates were obtained both electronically and from manual chart review in a subsample of 231 patients. ARF was defined as a 50% increase in the baseline creatinine with a peak > or =2.0 mg/dL.Among 643 episodes, ARF developed in 175 (27%). In the larger group, the only independent correlate of ARF was male gender (OR = 2.2, 95% CI, 1.5 to 3.3). In the subsample (N = 231), independent correlates of ARF were maximum daily amphotericin dosage, location at the time of initiation of amphotericin therapy, and concomitant use of cyclosporine. These data were used to develop two clinical prediction rules. A rule using only data available at initiation of therapy stratified patients into groups with probability of ARF ranging from 15 to 54%, while a rule including data available during therapy (maximum daily dose) stratified patients into groups with probability of ARF ranging from 4 to 80%.Acute renal failure occurred in a quarter of the patients. Correlates of ARF at the beginning and during the course of amphotericin therapy were identified and then combined to allow stratification according to ARF risk. These data also provide evidence for guidelines for the selection of patients for alternative therapies.

  View details for Web of Science ID 000171127000025

  View details for PubMedID 11576359

• Inflammation and dietary protein intake exert competing effects on serum albumin and creatinine in hemodialysis patients KIDNEY INTERNATIONAL Kaysen, G. A., Chertow, G. M., Adhikarla, R., Young, B., Ronco, C., Levin, N. W. 2001; 60 (1): 333-340

  Abstract

  Cross-sectional studies have shown an inverse correlation between serum C-reactive protein (CRP) and serum albumin concentration in hemodialysis patients. The net effects of inflammation and dietary protein intake on nutritional markers over time are unknown.To explore the effects of CRP and normalized protein catabolic rate (nPCR) on serum albumin and creatinine, we analyzed six consecutive months of laboratory data from 364 hemodialysis patients, using a multivariable Mixed model with conservative biases.The overall trend over time in serum albumin was slightly positive (0.039 g/dL/month) and in serum creatinine slightly negative (-0.052 mg/dL/month). With increasing CRP, serum albumin declined significantly (-0.124 g/dL/month per unit increase in log CRP, adjusted for age, gender, race, diabetes, and nPCR, P < 0.0001). Serum albumin increased with increasing nPCR (0.021 g/dL/month per 0.1 g/kg/day, P < 0.0001). The effect of CRP on albumin was attenuated in African Americans and at a higher nPCR. Corresponding values for creatinine mirrored those for albumin. With increasing CRP, creatinine declined significantly [-0.142 mg/dL/month per unit increase in log CRP, adjusted for age, gender, race, diabetes (time since initiation of dialysis; vintage), Kt/V, and nPCR, P = 0.002]. Serum creatinine increased with increasing nPCR (0.183 mg/dL/month per g/kg/day, P < 0.0001).Proxies of inflammation and dietary protein intake exert competing effects on serum albumin and creatinine in hemodialysis patients. These data provide a rationale for prospective testing of dietary protein supplementation in hemodialysis patients with biochemical evidence of ongoing inflammation and "malnutrition."

  View details for Web of Science ID 000169496000039

  View details for PubMedID 11422769

• Cardiac arrest and sudden death in dialysis units 33rd Annual Meeting of the American-Society-of-Nephrology Karnik, J. A., Young, B. S., Lew, N. L., Herget, M., Dubinsky, C., Lazarus, J. M., Chertow, G. M. NATURE PUBLISHING GROUP. 2001: 350–57

  Abstract

  For patients with end-stage renal disease and their providers, dialysis unit-based cardiac arrest is the most feared complication of hemodialysis. However, relatively little is known regarding its frequency or epidemiology, or whether a fraction of these events could be prevented.To explore clinical correlates of dialysis unit-based cardiac arrest, 400 reported arrests over a nine-month period from October 1998 through June 1999 were reviewed in detail. Clinical characteristics of patients who suffered cardiac arrest were compared with a nationally representative cohort of> 77,000 hemodialysis patients dialyzed at Fresenius Medical Care North America-affiliated facilities.The cardiac arrest rate was 400 out of 5,744,708, corresponding to a rate of 7 per 100,000 hemodialysis sessions. Cardiac arrest was more frequent during Monday dialysis sessions than on other days of the week. Case patients were nearly twice as likely to have been dialyzed against a 0 or 1.0 mEq/L potassium dialysate on the day of cardiac arrest (17.1 vs. 8.8%). Patients who suffered a cardiac arrest were on average older (66.3 +/- 12.9 vs. 60.2 +/- 15.4 years), more likely to have diabetes (61.8 vs. 46.8%), and more likely to use a catheter for vascular access (34.1 vs. 27.8%) than the general hemodialysis population. Sixteen percent of patients experienced a drop in systolic pressure of 30 mm Hg or more prior to the arrest. Thirty-seven percent of patients who suffered cardiac arrest had been hospitalized within the past 30 days. Sixty percent of patients died within 48 hours of the arrest, including 13% while in the dialysis unit.Cardiac arrest is a relatively infrequent but devastating complication of hemodialysis. To reduce the risk of adverse cardiac events on hemodialysis, the dialysate prescription should be evaluated and modified on an ongoing basis, especially following hospitalization in high-risk patients.

  View details for Web of Science ID 000169496000041

  View details for PubMedID 11422771

• Suspected iron dextran-related adverse drug events in hemodialysis patients 9th Annual Clinical Meeting of the National-Kidney-Foundation Fletes, R., Lazarus, J. M., Gage, J., Chertow, G. M. W B SAUNDERS CO-ELSEVIER INC. 2001: 743–49

  Abstract

  Despite the use of recombinant erythropoietin, anemia remains a significant problem for patients with end-stage renal disease, in part related to chronic dialysis-related blood loss and resultant iron deficiency. Because oral iron preparations have been relatively ineffective and poorly tolerated in this population, intravenous (IV) iron dextran has been widely prescribed, despite a finite risk for adverse effects associated with its use. We analyzed data from Fresenius Medical Care North America (FMCNA) clinical variance reports to determine the incidence of suspected iron dextran-related adverse drug events (ADEs) and associated patient characteristics, dialysis practice patterns, and outcomes. We used a case-cohort study design, comparing individuals who experienced suspected ADEs with the overall FMCNA population. Among 841,252 IV iron dextran administrations from October 1998 through March 1999, there were 165 reported suspected ADEs, corresponding to an overall rate of 0.000196%, or approximately 20 per 100,000 doses. Forty-three patients (26%) required an independent emergency department evaluation, 18 patients (11%) required hospitalization, and 1 patient (0.6%) died. Dyspnea (43%), hypotension (23%), and neurological symptoms (23%) were the most common major ADEs; nausea (34%), vomiting (23%), flushing (27%), and pruritus (25%) were the most common other ADEs. ADEs were 8.1-fold more common among patients administered Dexferrum (American Regent Laboratories, Inc, Shirley, NY) compared with those administered InFed (Watson Pharmaceuticals, Phoenix, AZ). In summary, serious adverse reactions to IV iron dextran are rare in clinical practice. The risk appears to depend on the specific formulation of IV iron dextran. Otherwise, iron dextran-related ADEs are difficult to predict.

  View details for Web of Science ID 000169905400010

  View details for PubMedID 11273874

• Mortality and costs of acute renal failure associated with amphotericin B therapy CLINICAL INFECTIOUS DISEASES Bates, D. W., Su, L., Yu, D. T., Chertow, G. M., Seger, D. L., Gomes, D. R., Dasbach, E. J., Platt, R. 2001; 32 (5): 686-693

  Abstract

  To assess the mortality and resource utilization that results from acute renal failure associated with amphotericin B therapy, 707 adult admissions in which parenteral amphotericin B therapy was given were studied at a tertiary-care hospital. Main outcome measures were mortality, length of stay, and costs; we controlled for potential confounders, including age, sex, insurance status, baseline creatinine level, length of stay before beginning amphotericin B therapy, and severity of illness. Among 707 admissions, there were 212 episodes (30%) of acute renal failure. When renal failure developed, the mortality rate was much higher: 54% versus 16% (adjusted odds of death, 6.6). When acute renal failure occurred, the mean adjusted increase in length of stay was 8.2 days, and the adjusted total cost was $29,823. Although residual confounding exists despite adjustment, the increases in resource utilization that we found are large and the associated mortality is high when acute renal failure occurs following amphotericin B therapy.

  View details for Web of Science ID 000167201200002

  View details for PubMedID 11229835

• beta(2)-microglobulin modified with advanced glycation end products delays monocyte apoptosis KIDNEY INTERNATIONAL Hou, F. F., Miyata, T., Boyce, J., Yuan, Q., Chertow, G. M., Kay, J., Schmidt, A. M., Owen, W. F. 2001; 59 (3): 990-1002

  Abstract

  A local inflammatory reaction to beta(2)-microglobulin (beta(2)m) amyloid deposits by monocytes/macrophages is a characteristic histologic feature of dialysis-related amyloidosis (DRA). Since beta(2)m modified with advanced glycation end products (AGE-beta(2)m) is a major constituent of amyloid in DRA, we tested the hypothesis that AGE-beta(2)m affects apoptosis and phenotype of human monocytes.Human peripheral blood monocytes were incubated with or without in vitro-derived AGE-beta(2)m, and their viability, extent of apoptosis, morphology, and function examined over the subsequent four days.AGE-modified but not unmodified beta(2)m significantly delayed spontaneous apoptosis of human peripheral blood monocytes in adherent and nonadherent cultures. The effect of AGE-beta(2)m on monocytes apoptosis was time- and dose-dependent and was attenuated by a blocking antibody directed against the human AGE receptor (RAGE). There was no difference in effect between AGE-beta(2)m and that of AGE-modified human serum albumin. Culture of monocytes with AGE-beta(2)m did not alter membrane expression of Fas or Fas ligand. Monocytes cultured with AGE-beta(2)m underwent substantial changes in morphology similar to those observed when monocytes differentiate into macrophages. The cultured cells increased in size and vacuolization, and their content of beta-glucuronidase and acid phosphatase increased by 5- to 10-fold at day 4. Expression of the monocyte--macrophage membrane antigens HLA-DR, CD11b, and CD11c also increased at day 4. Although exhibiting phenotypic characteristics of macrophages, monocytes cultured with AGE-beta(2)m functioned differently than macrophages cultured with serum. Superoxide production in response to phorbol myristic acetate was maintained in monocytes cultured with AGE-beta(2)m, but declined with time in cells cultured with serum. Constitutive synthesis of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and prostaglandin E2 (PGE2) increased in monocytes cultured for four to six days with AGE-beta(2)m.These findings support a novel role for AGE-modified proteins such as AGE-beta(2)m that may contribute to the development of a local inflammatory response, with predominant accumulation of monocytes/macrophages, in DRA.

  View details for Web of Science ID 000167434200018

  View details for PubMedID 11231354

• Validation of questionnaires to estimate physical activity and functioning in end-stage renal disease KIDNEY INTERNATIONAL Johansen, K. L., Painter, P., Kent-Braun, J. A., Ng, A. V., Carey, S., Da Silva, M., Chertow, G. M. 2001; 59 (3): 1121-1127

  Abstract

  Patients on dialysis are less physically active than sedentary persons with normal kidney function. To assess the consequences of inactivity and the results of efforts to increase activity in the end-stage renal disease (ESRD) population, valid instruments to measure physical activity and physical functioning in this group are needed.We performed a cross-sectional study to establish the validity in ESRD of several questionnaires designed to measure physical activity or physical functioning in the general population. Questionnaires studied included the Stanford 7-day Physical Activity Recall questionnaire (PAR), the Physical Activity Scale for the Elderly (PASE), the Human Activity Profile (HAP), and the Medical Outcomes Study Short Form 36-item questionnaire (SF-36). Physical activity was measured using three-dimensional activity monitors (accelerometers) over a seven-day period (the "gold standard"). Patients also underwent physical performance tests, including measurement of gait speed, stair climbing time, and chair rising time. Study questionnaires were administered, and questionnaire results were compared with each other and with activity monitor and physical performance test results.Thirty-nine maintenance hemodialysis patients participated in the study. Dialysis patients scored worse than previously published healthy norms on all tests. All questionnaires correlated with seven-day accelerometry and with at least one measure of physical performance. The HAP correlated best with accelerometry (r = 0.78, P < 0.0001). Seventy-five percent of the variability in physical activity measured by accelerometry could be explained by a model that combined information from the HAP and the PASE. The HAP and the physical functioning scale of the SF-36 were about equally well correlated with physical performance measures.These questionnaires are valid in patients on hemodialysis and should be used to study the physical activity and rehabilitation efforts in this population further.

  View details for Web of Science ID 000167434200033

  View details for PubMedID 11231369

• Gridlock on the road to kidney transplantation AMERICAN JOURNAL OF KIDNEY DISEASES Chertow, G. M., Zenios, S. A. 2001; 37 (2): 435-437

  View details for DOI 10.1053/ajkd.2001.22502

  View details for Web of Science ID 000166647400026

  View details for PubMedID 11157389

• Mechanisms underlying renoprotection during renin-angiotensin system blockade AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY Taal, M. W., Chertow, G. M., Rennke, H. G., Gurnani, A., Jiang, T., Shahsafaei, A., Troy, J. L., BRENNER, B. M., Mackenzie, H. S. 2001; 280 (2): F343-F355

  Abstract

  Potential determinants of chronic renal disease (CRD) progression were studied in male Munich-Wistar rats subjected to 5/6 nephrectomy and treated with candesartan (Csn; n = 30) or enalapril (Ena; n = 27) from 5 wk postsurgery. Despite control of systolic blood pressure (SBP; 24 wk: Csn = 143 +/- 9; Ena = 148 +/- 8 mmHg), urinary protein excretion rates (U(pr)V) increased over 24 wk (Csn = 92 +/- 10; Ena = 99 +/- 8mg/day). Glomerulosclerosis scores (GS) at 24 wk were similar for Csn (42 +/- 7%) vs. Ena (42 +/- 4%), values close to those of untreated controls at 12 wk (43 +/- 4%). At 24 wk, SBP and UprV correlated strongly with GS, together accounting for 72% of the variance in GS. Renal cortex mRNA levels (determined by competitive RT-PCR) for transforming growth factor (TGF)-beta1 and monocyte chemoattractant protein (MCP)-1 were elevated in Csn and Ena at 12 wk and remained higher at 24 wk vs. sham. Strong correlations were evident among TGF-beta1, MCP-1, and interleukin-1beta and renal injury at 24 wk. Cns and Ena are thus equally effective renoprotective agents in this model. During renin-angiotensin system inhibition, renoprotection is dependent on control of both SBP and UprV. Incomplete suppression of renal cytokine gene expression may also contribute to CRD progression.

  View details for Web of Science ID 000166449600018

  View details for PubMedID 11208610

• Prealbumin is as important as albumin in the nutritional assessment of hemodialysis patients 32nd Annual Meeting of the American-Society-of-Nephrology Chertow, G. M., Ackert, K., Lew, N. L., Lazarus, J. M., Lowrie, E. G. NATURE PUBLISHING GROUP. 2000: 2512–17

  Abstract

  Although serum prealbumin is considered a valid indicator of nutritional status in hemodialysis patients, there is relatively little evidence that its determination is of major prognostic significance. In this study, we aimed to determine the independent association of serum prealbumin with survival in hemodialysis patients, after adjusting for serum albumin and other indicators of protein energy nutritional status.Serum prealbumin was measured in more than 1600 maintenance hemodialysis patients. We determined the correlations among prealbumin and other indicators of nutritional status, including serum albumin, and bioimpedance-derived indicators of body composition. The relationship between serum prealbumin and survival was determined using proportional hazards regression.The serum albumin was directly correlated with the serum prealbumin (r = 0.47, P < 0.0001), but still explained <25% of the variability in prealbumin. Prealbumin was inversely related to mortality, with a relative risk reduction of 6% per 1 mg/dL increase in prealbumin, even after adjusting for case mix, serum albumin, and other nutritional indicators. The increase in risk with lower serum prealbumin concentrations was observed whether the serum albumin was high or low.In hemodialysis patients, the serum prealbumin provides prognostic value independent of the serum albumin and other established predictors of mortality in this population.

  View details for Web of Science ID 000165665100026

  View details for PubMedID 11115085

• Hyperparathyroidism and dialysis vintage CLINICAL NEPHROLOGY Chertow, G. M., Plone, M., DILLON, M. A., Burke, S. K., Slatopolsky, E. 2000; 54 (4): 295-300

  Abstract

  Secondary hyperparathyroidism and its effects on bone and viscera are among the most important complications of end-stage renal disease. Despite its ubiquity, little is known about the treated natural history of the disorder.We assembled a cohort of 310 patients with endstage renal disease on hemodialysis who were participants in one of four clinical trials of the phosphate binder sevelamer. Baseline parathyroid hormone levels were collected, and the relation between dialysis vintage and other clinical variables with parathyroid hormone were described.There was a direct relation between dialysis vintage and the severity of hyperparathyroidism. Other variables that were significantly associated with PTH on univariate analysis included age, African American race, Kt/V, and the serum concentrations of calcium, phosphate, and bicarbonate. Multivariable linear regression analysis yielded three significant predictors of PTH: calcium, phosphorus, and vintage (5.8% (4.0-7.5%) expected increase in PTH per year of vintage). The model R2 was 0.22.Dialysis vintage is a key determinant of the severity of secondary hyperparathyroidism. Vintage and certain laboratory variables should be considered in the evaluation of therapies aimed at modifying the treated natural history of this disorder.

  View details for Web of Science ID 000089804600006

  View details for PubMedID 11076105

• Atrial natriuretic factor in oliguric acute renal failure AMERICAN JOURNAL OF KIDNEY DISEASES Lewis, J., Salem, M. M., Chertow, G. M., Weisberg, L. S., McGrew, F., Marbury, T. C., Allgren, R. L. 2000; 36 (4): 767-774

  Abstract

  Atrial natriuretic peptide (ANP), an endogenous hormone synthesized by the cardiac atria, has been shown to improve renal function in multiple animal models of acute renal failure. In a recent multicenter clinical trial of 504 patients with acute tubular necrosis (oliguric and nonoliguric), ANP decreased the need for dialysis only in the oliguric patients. In the present study, 222 patients with oliguric acute renal failure were enrolled into a multicenter, randomized, double-blind, placebo-controlled trial designed to assess prospectively the safety and efficacy of ANP compared with placebo. Subjects were randomized to treatment with a 24-hour infusion of ANP (anaritide, 0.2 microgram/kg/min; synthetic form of human ANP) or placebo. Dialysis and mortality status were followed up for 60 days. The primary efficacy end point was dialysis-free survival through day 21. Dialysis-free survival rates were 21% in the ANP group and 15% in the placebo group (P = 0.22). By day 14 of the study, 64% and 77% of the ANP and placebo groups had undergone dialysis, respectively (P = 0.054), and 9 additional patients (7 patients, ANP group; 2 patients, placebo group) needed dialysis but did not receive it. Although a trend was present, there was no statistically significant beneficial effect of ANP in dialysis-free survival or reduction in dialysis in these subjects with oliguric acute renal failure. Mortality rates through day 60 were 60% versus 56% in the ANP and placebo groups, respectively (P = 0.541). One hundred two of 108 (95%) versus 63 of 114 (55%) patients in the ANP and placebo groups had systolic blood pressures less than 90 mm Hg during the study-drug infusion (P < 0.001). The maximal absolute decrease in systolic blood pressure was significantly greater in the anaritide group than placebo group (33.6 versus 23.9 mm Hg; P < 0.001). This well-characterized population with oliguric acute renal failure had an overall high morbidity and mortality.

  View details for Web of Science ID 000089552300014

  View details for PubMedID 11007679

• Reply from the authors Kidney international Chertow, G. M. 2000; 58 (3): 1358-9

  View details for PubMedID 10972705

• Crystalloids versus colloids for resuscitation in shock CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION Waikar, S. S., Chertow, G. M. 2000; 9 (5): 501-504

  Abstract

  The optimal composition of fluid for volume resuscitation in critically ill patients has been the subject of controversy for decades. Clinicians are faced with several options, including crystalloid solutions of varying tonicity, several colloid preparations (albumin and others), and blood products. Some of these solutions may be differentially distributed between the intra- and extravascular, and intra- and extracellular compartments, accounting for a variety of physiological effects. Two recently published meta-analyses concluded that colloids afford no survival benefit in critically ill patients compared with crystalloids. Albumin infusion may be of more value in patients with cirrhosis, or in those at high risk of acute renal failure. Additional randomized trials will be needed to establish the optimal composition and volume of colloid or crystalloid solutions for resuscitation in shock.

  View details for Web of Science ID 000089074200007

  View details for PubMedID 10990368

• Chronic renal confusion: Insufficiency, failure, dysfunction, or disease AMERICAN JOURNAL OF KIDNEY DISEASES Hsu, C., Chertow, G. M. 2000; 36 (2): 415-418

  Abstract

  The terms routinely used to describe states of reduced glomerular filtration rate (GFR) not requiring renal replacement therapy are poorly defined. With increasing interest in the epidemiology of chronic renal insufficiency and the timing of initiation of dialysis, terms such as "pre-ESRD" and "pre-dialysis" have been popularized, again without clear definition. Unambiguous terminology should be adopted. The authors favor using the term chronic renal insufficiency to describe states of reduced GFR not severe enough to require dialysis or transplantation. The authors propose classifying patients with GFR of 60 to 41 mL/min, 40 to 21 mL/min, and 20 mL/min or below as having mild, moderate, and advanced degrees of chronic renal insufficiency, respectively. The use of this terminology will facilitate communication among nephrologists and other physicians and provide a framework for comparison of populations across cohort studies and clinical trials.

  View details for Web of Science ID 000089227100025

  View details for PubMedID 10922323

• Dynamic allocation of kidneys to candidates on the transplant waiting list OPERATIONS RESEARCH Zenios, S. A., Chertow, G. M., Wein, L. M. 2000; 48 (4): 549-569

  View details for Web of Science ID 000088906700005

• Sevelamer with and without calcium and vitamin D: observations from a long-term open-label clinical trial. Journal of renal nutrition Chertow, G. M., DILLON, M. A., Amin, N., Burke, S. K. 2000; 10 (3): 125-132

  Abstract

  To determine the effects of sevelamer hydrochloride on serum phosphorus, calcium, calcium x phosphate product, and parathyroid hormone (PTH) in patients treated with and without vitamin D metabolites and calcium supplementation.Long-term, open-label clinical trial.Hemodialysis units.One hundred ninety-two adult patients with end-stage renal disease on hemodialysis.An extended treatment period of sevelamer hydrochloride, preceded and followed by phosphate binder washout periods.Treatment-related changes in serum phosphorus, calcium, calcium x phosphate product, and PTH.Subjects treated with sevelamer alone, sevelamer with vitamin D metabolites (with or without calcium), and sevelamer with calcium without vitamin D experienced significant reductions in mean serum phosphorus (range, 2.1 to -2.9 mg/dL) and the calcium x phosphate product (range, -16.3 to -23.4 mg2/dL2). The mean serum calcium concentration increased in all subgroups except those treated with sevelamer alone (range, +0.3 to +0.5 mg/dL). In contrast, only subjects treated concurrently with vitamin D metabolites experienced a reduction in PTH. Subjects treated with sevelamer alone or sevelamer with calcium without vitamin D experienced an increase in PTH with treatment.Sevelamer hydrochloride is a safe and effective phosphate binder in hemodialysis patients. Sevelamer should be used in combination with vitamin D metabolites to jointly control hyperphosphatemia and hyperparathyroidism. Randomized clinical trials will be required to determine the optimal management strategies for metabolic bone disease in end-stage renal disease, as well as less advanced stages of chronic renal insufficiency.

  View details for PubMedID 10921533

• Ochrobactrum anthropi bacteremia in a patient on hemodialysis AMERICAN JOURNAL OF KIDNEY DISEASES Chertow, G. M. 2000; 35 (6)

  Abstract

  Although newer tunneled dialysis catheters offer improved capacity for blood flow and efficiency of dialysis, catheter-associated bacteremia remains an extremely important complication of this access strategy. This is a report of a case of catheter-associated bacteremia with Ochrobactrum anthropi, a water-borne gram-negative rod with an unusual pattern of antibiotic resistance. Given the organism's hydrophilic property and the frequency of catheter use in debilitated individuals with end-stage renal disease, Ochrobactrum anthropi infection should be considered in the differential diagnosis of a hemodialysis patient with unexplained fever.

  View details for Web of Science ID 000087559100035

  View details for PubMedID 10845846

• Predicting acute renal failure after coronary bypass surgery: Cross-validation of two risk-stratification algorithms KIDNEY INTERNATIONAL Fortescue, E. B., Bates, D. W., Chertow, G. M. 2000; 57 (6): 2594-2602

  Abstract

  Acute renal failure (ARF) requiring dialysis after coronary artery bypass grafting (CABG) occurs in 1 to 5% of patients and is independently associated with postoperative mortality, even after case-mix adjustment. A risk-stratification algorithm that could reliably identify patients at increased risk of ARF could help improve outcomes.To assess the validity and generalizability of a previously published preoperative renal risk-stratification algorithm, we analyzed data from the Quality Measurement and Management Initiative (QMMI)1 patient cohort. The QMMI includes all adult patients (N = 9498) who underwent CABG at 1 of 12 academic tertiary care hospitals from August 1993 to October 1995. ARF requiring dialysis was the outcome of interest. Cross-validation of a recursive partitioning algorithm developed from the VA Continuous Improvement in Cardiac Surgery Program (CICSP) was performed on the QMMI. An additive severity score derived from logistic regression was also cross-validated on the QMMI.The CICSP recursive partitioning algorithm discriminated well (ARF vs. no ARF) in QMMI patients, even though the QMMI cohort was more diverse. Rates of ARF were similar among risk subgroups in the CICSP tree, as was the overall ranking of subgroups by risk. Using logistic regression, independent predictors of ARF in the QMMI cohort were similar to those found in the CICSP. The CICSP additive severity score performed well in the QMMI cohort, successfully stratifying patients into low-, medium-, high-, and very high-risk groups.The CICSP preoperative renal-risk algorithms are valid and generalizable across diverse populations.

  View details for Web of Science ID 000087346100041

  View details for PubMedID 10844629

• Physical activity levels in patients on hemodialysis and healthy sedentary controls 32nd Annual Meeting of the American-Society-of-Nephrology Johansen, K. L., Chertow, G. M., Ng, A. V., Mulligan, K., Carey, S., Schoenfeld, P. Y., Kent-Braun, J. A. NATURE PUBLISHING GROUP. 2000: 2564–70

  Abstract

  Patients on dialysis have reduced exercise tolerance compared with age-matched sedentary controls. The reasons for this debility have not been fully elucidated, but physical inactivity could be a contributing factor. The purpose of the current study was to determine whether patients on hemodialysis are less active than healthy sedentary controls and to explore clinical correlates of physical activity level in a group of hemodialysis patients.Thirty-four hemodialysis patients and 80 healthy sedentary individuals participated in the study. Physical activity was measured for seven days with a three-dimensional accelerometer and with an activity questionnaire.Vector magnitude values from the accelerometer for the dialysis and control subjects were 104,718 +/- 9631 and 161,255 +/- 6792 arbitrary units per day, respectively (P < 0.0001, mean +/- SEM). The estimated energy expenditure values derived from the questionnaire were 33.6 +/- 0.5 kcal/kg/day and 36.2 +/- 0.5 kcal/kg/day (P = 0.002). The difference between patients on dialysis and controls increased with advancing age. Among the dialysis subjects, some measures of nutritional status correlated with physical activity level, including serum albumin concentration (r = 0.58, P = 0.003), serum creatinine concentration (r = 0.37, P = 0. 03), and phase angle derived from bioelectrical impedance analysis (r = 0.40, P = 0.02).Patients on hemodialysis are less active than healthy sedentary controls, and this difference is more pronounced among older individuals. There is an association between the level of physical activity and nutritional status among patients on dialysis. These findings are of great concern, given the trend toward increasing age in incident dialysis patients and the well-known association between inactivity and increased mortality in the general population.

  View details for Web of Science ID 000087346100038

  View details for PubMedID 10844626

• Leveling the "paying" field in end-stage renal disease AMERICAN JOURNAL OF MEDICINE Chertow, G. M. 2000; 108 (8): 666-668

  View details for Web of Science ID 000087466900010

  View details for PubMedID 10856417

• Survival after acute myocardial infarction in patients with end-stage renal disease: Results from the Cooperative Cardiovascular Project AMERICAN JOURNAL OF KIDNEY DISEASES Chertow, G. M., Normand, S. L., Silva, L. R., McNeil, B. J. 2000; 35 (6): 1044-1051

  Abstract

  Cardiovascular disease (CVD) is the most common cause of death in patients with end-stage renal disease (ESRD). The optimal management strategy in this population is unknown. We studied 640 patients with ESRD and acute myocardial infarction during 1994 to 1995 as part of the Health Care Financing Administration's Cooperative Cardiovascular Project. The majority of patients were treated with medical therapy alone, 46 patients (7%) were treated with percutaneous transluminal coronary angioplasty (PTCA), and 29 patients (5%) underwent coronary artery bypass grafting (CABG). Patient characteristics and comorbid conditions were similar among the three groups. The overall 1-year mortality rate was 53%. Advanced age, low or high body mass index, history of peripheral vascular disease or stroke, the inability to walk independently, and several indicators of cardiac dysfunction were associated with an increased relative risk (RR) for death. Survival curves differed significantly by treatment modality, with 1-year survival rates of 45%, 54%, and 69% in the medical therapy alone, PTCA, and CABG groups, respectively (P = 0.03). After adjustment for confounding variables, the RR for death was less (but not significantly so) in the CABG group (RR, 0.6; 95% confidence interval, 0.3 to 1.1). There are no randomized clinical trial data to guide therapy of CVD in patients with ESRD. On the basis of these and other available data, CABG may be the optimal therapy for CVD in ESRD. In light of the exceptionally poor outcomes observed for patients treated with medical therapy alone, it may be premature to dismiss PTCA as a therapeutic option in this population.

  View details for Web of Science ID 000087559100004

  View details for PubMedID 10845815

• Long-term effects of sevelamer hydrochloride on the calcium x phosphate product and lipid profile of haemodialysis patients Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association Chertow, Burke, Dillon, Slatopolsky 2000; 15 (4): 559-?

  View details for PubMedID 10727558

• Issues in renal nutrition for persons from the former Soviet Union. Journal of renal nutrition Gorodetskaya, I., Matel, J., Chertow, G. M. 2000; 10 (2): 98-102

  Abstract

  Dietary practices differ greatly among individuals by race and ethnicity. The importance of these differences is accentuated in patients with end-stage renal disease, a population for whom dietary restrictions are often prescribed. In addition to the known variation in dietary practices among US-born whites and African-Americans, persons of other ethnicities often present new and unique challenges to the dialysis-nutrition care team. The UCSF-Mt. Zion Dialysis Unit (San Francisco, CA) is a university-affiliated dialysis unit that serves an ethnically diverse population in San Francisco's Western Addition neighborhood. Ten percent to 15% of patients are recent immigrants from the former Soviet Union. This report highlights the dietary practices of this immigrant community and the need for ethnicity-specific renal nutrition recommendations in modern dialysis practice.

  View details for PubMedID 10757823

• Acute renal failure with interstitial nephritis in a patient with AIDS AMERICAN JOURNAL OF KIDNEY DISEASES Mouratoff, J. G., Tokumoto, J., Olson, J. L., Chertow, G. M. 2000; 35 (3): 557-561

  View details for Web of Science ID 000085583200029

  View details for PubMedID 10692288

• Vintage, nutritional status, and survival in hemodialysis patients 32nd Annual Meeting of the American-Society-of-Nephrology Chertow, G. M., Johansen, K. L., Lew, N., Lazarus, J. M., Lowrie, E. G. NATURE PUBLISHING GROUP. 2000: 1176–81

  Abstract

  The link between dialysis "vintage" (length of time on dialysis in months to years) and survival has been difficult to define, largely because of selection effects. End-stage renal disease (ESRD) is thought to be a wasting illness, but there are no published reports describing the associations between vintage and body composition in hemodialysis patients.We explored the relationships among vintage, nutritional status, and survival in a 3009 patient cohort of prevalent hemodialysis patients. Body weight, total body water, body cell mass, and phase angle by bioelectrical impedance analysis were the body composition parameters of interest. We examined vintage as an explanatory variable in multiple linear regression analyses (adjusted for age, gender, race, and diabetes) using body composition parameters and biochemical indicators of nutritional status as dependent variables. Proportional hazards regression was used to evaluate the association of vintage and survival with and without adjustment for case mix and laboratory variables.Dialysis vintage was 3.8 +/- 3.7 (median 2.6) years. Body composition parameters tended to be lower after dialysis year 2. Linear estimates per year of vintage beyond year 2 include -0.66 kg body wt (P < 0.0001), -0.17 kg total body water (P = 0.0003), -0.14 kg body cell mass (P < 0.0001), and -0.07 degrees phase angle (P < 0.0001). In unadjusted analyses, vintage was not associated with survival, either as a linear or higher order term. The adjustment for case mix yielded a vintage term associated with an increased relative risk (RR) of death (RR 1.04 (95% CI, 1.01 to 1.07 per year). A further adjustment for laboratory data yielded a RR of 1.06 (95% CI, 1.03 to 1.09 per year).Dialysis vintage is related to nutritional status in hemodialysis patients, with vintage of more than years associated with a significant decline in all measured nutritional parameters. Cross-sectional analyses probably underestimate these effects. A year accrued on dialysis is associated with a 6% increase in the risk of death, all else equal. Longitudinal assessments of nutritional status, including body composition, are required to better understand the natural history of wasting with ESRD and its implications for long-term survival.

  View details for Web of Science ID 000085461500045

  View details for PubMedID 10720970

• Renal nutrition in the new millennium. Journal of renal nutrition Chertow, G. M. 2000; 10 (1): 1-?

  View details for PubMedID 10671625

• Exploring the reverse J-shaped curve between urea reduction ratio and mortality KIDNEY INTERNATIONAL Chertow, G. M., Owen, W. F., Lazarus, J. M., Lew, N. L., Lowrie, E. G. 1999; 56 (5): 1872-1878

  Abstract

  Although accepted worldwide as valid measures of dialysis adequacy, neither the Kt/V (urea clearance determined by kinetic modeling) nor the urea reduction ratio (URR) have unambiguously predicted survival in hemodialysis patients. Because the ratio Kt/V can be high with either high Kt (clearance x time) or low V (urea volume of distribution) and V may be a proxy for skeletal muscle mass and nutritional health, we hypothesized that the increase in the relative risk of death observed among individuals dialyzed in the top 10 to 20% of URR or Kt/V values might reflect a competing risk of malnutrition.A total of 3,009 patients who underwent bioelectrical impedance analysis were stratified into quintiles of URR. Laboratory indicators of nutritional status and two bioimpedance-derived parameters, phase angle and estimated total body water, were compared across quintiles. The relationship between dialysis dose and mortality was explored, with a focus on how V influenced the structure of the dose-mortality relationship.There were statistically significant differences in all nutritional parameters across quintiles of URR or Kt/V, indicating that patients in the fifth quintile (mean URR, 74.4 +/- 3.1%) were more severely malnourished on average than patients in all or some of the other quintiles. The relationship between URR and mortality was decidedly curvilinear, resembling a reverse J shape that was confirmed by statistical analysis. An adjustment for the influence of V on URR or Kt/V was performed by evaluating the Kt-mortality relationship. There was no evidence of an increase in the relative risk of death among patients treated with high Kt. Higher Kt was associated with a better nutritional status.We conclude that the increase in mortality observed among those patients whose URR or Kt/V are among the top 10 to 20% of patients reflects a deleterious effect of malnutrition (manifest by a reduced V) that overcomes whatever benefit might be derived from an associated increase in urea clearance. Identification of patients who achieve extremely high URR (>75%) or single-pooled Kt/V (>1.6) values using standard dialysis prescriptions should prompt a careful assessment of nutritional status. Confounding by protein-calorie malnutrition may limit the utility of URR or Kt/V as a population-based measure of dialysis dose.

  View details for Web of Science ID 000083328500026

  View details for PubMedID 10571796

• Bioelectrical impedance methods in clinical research: A follow-up to the NIH technology assessment conference NUTRITION Ellis, K. J., Bell, S. J., Chertow, G. M., Chumlea, W. C., Knox, T. A., Kotler, D. P., Lukaski, H. C., Schoeller, D. A. 1999; 15 (11-12): 874-880

  Abstract

  In 1994, the National Institutes of Health (NIH) convened a Technology Assessment Conference "to provide physicians with a responsible assessment of bioelectrical impedance analysis (BIA) technology for body composition measurement." In 1997, Serono Symposia USA, Inc., organized an invited panel of scientists and clinicians, with extensive research and clinical experience with BIA, to provide an update. Panel members presented reviews based on their own work and published studies for the intervening years. Updates were provided on the single and multifrequency BIA methods and models; continued clinical research experiences; efforts toward establishing population reference norms; and the feasibility of establishing guidelines for potential diagnostic use of BIA in a clinical setting. This report provides a summary of the panel's findings including a consensus on several technical and clinical issues related to the research use of BIA, and those areas that are still in need of additional study.

  View details for Web of Science ID 000083497300011

  View details for PubMedID 10575664

• The urea {clearance x dialysis time} product (Kt) as an outcome-based measure of hemodialysis dose KIDNEY INTERNATIONAL Lowrie, E. G., Chertow, G. M., Lew, N. L., Lazarus, J. M., Owen, W. F. 1999; 56 (2): 729-737

  Abstract

  The normalized treatment ratio [Kt/V = the ratio of the urea clearance x time product to total body water] and the urea reduction ratio (URR) have become widely accepted measures of dialysis dose. Both are related to and derived from pharmacokinetic models of blood urea concentration during the dialysis cycle. Theoretical reconsideration of the models revealed that the premise about V on which they rest (that is, that V is a passive diluent with no survival-associated properties of its own) is flawed if the intended use of the models is for profiling clinical outcome (for example, mortality) rather than estimating urea concentration. As a proxy for body mass, V has survival-associated properties of its own. Thus, indexing clearance x time to body size could create an offsetting combination whereby one measure favorably associated with survival (Kt) is divided by another (for example, V). Observed clinical paradoxes support that interpretation. For example, patients with a low body mass have both higher URR and higher mortality than heavier patients. Increasing mortality is often observed at high URR, suggesting the possibility of "over-dialysis." Black patients tend to be treated at lower URR than whites but enjoy better survival on dialysis. Therefore, clearance x time was evaluated as an outcome-based measure of dialysis dose, not indexed to V, and various body size estimates were evaluated as separate and distinct measures.The retrospective sample included 17,141 black and white hemodialysis patients treated three times per week. Logistic regression analysis was used to evaluate death odds in age-, gender-, race-, and diabetes-adjusted models. Kt and five body size estimates (total body water or V, body weight, body weight adjusted for height, body surface area, and body mass index) were evaluated using two analytical strategies. First, all of the measures were treated as continuous variables to explore different statistical models. Second, Kt and the body size measures were divided into groups to construct risk profiles.All evaluations revealed improving death odds with increasing Kt (whether adjusted for the body size estimates or not) and also with increasing body size (whether adjusted for Kt or not) for each estimate of size. Significant statistical interactions of Kt with gender, but not Kt with race, were observed in all models. There were no statistical interactions, suggesting that higher Kt was routinely required with increasing body size. Separate risk profiles for males and females suggested a higher Kt threshold for males.The urea clearance x time is a valid outcome-based measure of dialysis dose and is not confounded by indexing it to an estimate of body size, which has outcome-associated properties of its own. Dialysis prescriptions for males and females should be regarded separately, but there appears no need to make a distinction between the races.

  View details for Web of Science ID 000081601200040

  View details for PubMedID 10432415

• Aggravated renal dysfunction during intensive therapy for advanced chronic heart failure AMERICAN HEART JOURNAL Weinfeld, M. S., Chertow, G. M., Stevenson, L. W. 1999; 138 (2): 285-290

  Abstract

  Chronic heart failure is associated with impaired renal function, which may worsen during therapy. The incidence, predictors, and consequences of aggravated renal dysfunction (ARD) in patients undergoing intensive therapy for advanced chronic heart failure are unknown.We reviewed the experience of 48 consecutive patients hospitalized for treatment of advanced chronic heart failure who underwent intravenous diuretic therapy with a weight loss of >/=2 kg. Evaluation included baseline renal function and echocardiography in all patients and hemodynamic measurements in 38 (79%) patients.ARD, defined as >/=25% increase in serum creatinine concentration to >/=2 mg/dL, developed in 10 (21%) patients. Patients with ARD developing were older (aged 58 +/- 16 years vs 51 +/- 13 years; P =.006) and had lower baseline creatinine clearance (49 +/- 21 mL/min vs 74 +/- 26 mL/min; P =.01) but had the same serum creatinine at baseline. They were more likely to have atrial fibrillation (70% vs 29%, P =.02) but did not have lower filling pressures, cardiac output, or estimated renal perfusion pressure. Length of stay was longer if ARD developed (median 17 vs 9 days, P =.02). Mortality rate after discharge was increased in the patients with ARD (relative risk 5.3, P =.002).In patients undergoing intensive treatment for heart failure, ARD is common and clinically significant. The relation among baseline factors, ARD, and worsened outcome may reflect complex cardiorenal interactions. Better understanding of the causes and prevention of ARD during heart failure therapy may in the future lead to better outcomes.

  View details for Web of Science ID 000081922200016

  View details for PubMedID 10426840

• Estimates of body composition as intermediate outcome variables: are DEXA and BIA ready for prime time? Journal of renal nutrition Chertow, G. M. 1999; 9 (3): 138-141

  View details for PubMedID 10431033

• Evidence-based organ allocation AMERICAN JOURNAL OF MEDICINE Zenios, S. A., Wein, L. M., Chertow, G. M. 1999; 107 (1): 52-61

  Abstract

  There are not enough cadaveric kidneys to meet the demands of transplant candidates. The equity and efficiency of alternative organ allocation strategies have not been rigorously compared.We developed a five-compartment Monte Carlo simulation model to compare alternative organ allocation strategies, accommodating dynamic changes in recipient and donor characteristics, patient and graft survival rates, and quality of life. The model simulated the operations of a single organ procurement organization and attempted to predict the evolution of the transplant waiting list for 10 years. Four allocation strategies were compared: a first-come first-transplanted system; a point system currently utilized by the United Network of Organ Sharing; an efficiency-based algorithm that incorporated correlates of patient and graft survival; and a distributive efficiency algorithm, which had an additional goal of promoting equitable allocation among African-American and other candidates.A 10-year computer simulation was performed. The distributive efficiency policy was associated with a 3.5%+/-0.8% (mean +/- SD) increase in quality-adjusted life expectancy (33.9 months vs 32.7 months), a decrease in the median waiting time to transplantation among those who were transplanted (6.6 months vs 16.3 months), and an increase in the overall likelihood of transplantation (61% vs 45%), compared with the United Network of Organ Sharing algorithm. Improved equity and efficiency were also seen by race (African-American vs other), sex, and age (<50 or > or =50 years). Sensitivity analyses did not appreciably change the qualitative results.Evidence-based organ allocation strategies in cadaveric kidney transplantation would yield improved equity and efficiency measures compared with existing algorithms.

  View details for PubMedID 10403353

• Metabolic and monetary casts of avoidable parenteral nutrition use JOURNAL OF PARENTERAL AND ENTERAL NUTRITION Trujillo, E. B., Young, L. S., Chertow, G. M., Randall, S., Clemons, T., Jacobs, D. O., Robinson, M. K. 1999; 23 (2): 109-113

  Abstract

  We prospectively collected data on in patients receiving parenteral nutrition to determine the magnitude of potentially preventable metabolic and monetary costs associated with parenteral nutrition.Parenteral nutrition was prescribed by the treating physicians with optional consultation from a multidisciplinary metabolic support service. Days on parenteral nutrition, appropriateness of parenteral nutrition, metabolic complications, and avoidable parenteral nutrition charges were determined. Parenteral nutrition use was considered "indicated" or "not indicated" based on the American Society for Parenteral and Enteral Nutrition guidelines and "preventable" if the gastrointestinal tract was functional but not accessed when possible.Of the 209 parenteral nutrition starts, 62% were indicated, 23% were preventable, and 15% were not indicated. Parenteral nutrition starts were deemed indicated in 82% of instances in which a metabolic support service consult was obtained, compared with 56% in which a consultation was not obtained (p = .004). Hyperglycemia was the most common metabolic complication, with an overall incidence of 20%. Metabolic complications occurred less frequently in patients who received a metabolic support service consultation compared with patients who did not (34% vs 66% of parenteral nutrition days, respectively; p = .004). Parenteral nutrition use of < or =5 days duration was significantly less frequent among patients who received metabolic support service consultation (16% vs 35%; p = .002). Parenteral nutrition that was not indicated or preventable resulted in excess annualized patient charges of more than one half million dollars not accounting for charges related to treatment of potentially avoidable parenteral nutrition complications.This study illustrates that not-indicated and preventable parenteral nutrition initiation, short-term parenteral nutrition use, and metabolic complications are less likely when patients receive consultation by a multidisciplinary team with expertise in nutrition and metabolic support. Furthermore, the avoidance of inappropriate parenteral nutrition use translates into substantial cost savings.

  View details for Web of Science ID 000078963500011

  View details for PubMedID 10082002

• Modality-specific nutrition support in ESRD: Weighing the evidence AMERICAN JOURNAL OF KIDNEY DISEASES Chertow, G. M. 1999; 33 (1): 193-197

  Abstract

  Protein-calorie malnutrition affects a large fraction of patients with end-stage renal disease (ESRD) and contributes significantly to the high rates of mortality and morbidity observed in this population. Observational studies of specific interventions, including intradialytic parenteral nutrition (IDPN), suggest that aggressive nutrition support may be of some benefit to some patients with ESRD. Due in part to lack of data derived from prospective, randomized clinical trials, and to the large expense associated with these therapies, Medicare and other payers have strongly discouraged the prescription of IDPN and other intermittent, dialysis-specific methods of nutrition support, such as intraperitoneal nutrition (IPN). The "burden of proof" has been placed on the dialysis community. In response, we must continue to emphasize the importance of securing nutritional health for all patients on or anticipating renal replacement therapy. Intradialytic parenteral nutrition should be reserved for patients who are taking in sufficient calories yet are unable to tolerate oral or enteral protein-rich foods or formulas designed to meet daily protein requirements (> or = 1.5 g/kg in some patients). Intradialytic parenteral nutrition should not be prescribed in place of total parenteral nutrition (TPN) if the latter is truly needed. Creative methods of nutrition support, including the use of dietary supplements at dialysis (intradialytic oral or enteral nutrition), should be explored. Prospective clinical trials investigating the effects of nutrition support on survival, hospitalization rates, health-related quality of life, and functional status, are urgently needed.

  View details for Web of Science ID 000077966700033

  View details for PubMedID 9915290

• A randomized trial of sevelamer hydrochloride (RenaGel) with and without supplemental calcium - Strategies for the control of hyperphosphatemia and hyperparathyroidism in hemodialysis patients CLINICAL NEPHROLOGY Chertow, G. M., Dillon, M., Burke, S. K., Steg, M., Bleyer, A. J., Garrett, B. N., Domoto, D. T., Wilkes, B. M., Wombolt, D. G., Slatopolsky, E. 1999; 51 (1): 18-26

  Abstract

  We have previously shown sevelamer hydrochloride (RenaGel) to be an effective and well-tolerated treatment for hyperphosphatemia in hemodialysis patients.We performed a randomized clinical trial to compare the efficacy of RenaGel alone and RenaGel with calcium, using the serum phosphorus concentration and intact parathyroid hormone (PTH) as the principal outcomes of interest. Calcium (900 mg elemental) was provided as a once-nightly dose on an empty stomach. 71 patients were randomized and included in the intent-to-treat population; 55 completed the 16-week study period (2 weeks washout, 12 weeks treatment, 2 weeks washout). 49% of subjects were taking vitamin D metabolites.Serum phosphorus and PTH rose significantly when patients stopped their phosphate binders during both washout periods. RenaGel and RenaGel with calcium were equally effective at reducing serum phosphorus (mean change -2.4 mg/dL vs. -2.3 mg/dL). RenaGel with calcium was associated with a small increase in serum calcium (mean change 0.3 mg/dL vs. 0.0 mg/dL in RenaGel group, P = 0.09) that was not statistically significant. During the treatment phase, the reduction in PTH tended to be greater in the RenaGel with calcium group (median change -67.0 vs. -22.5 pg/mL in RenaGel group, P = 0.07). Non-users of vitamin D metabolites treated with RenaGel with calcium experienced a significant decrease in PTH (median change -114.5 vs. -22 pg/mL in RenaGel group, P = 0.006). Adverse events were seen with equal frequency in both groups, being generally mild in intensity, and rarely attributable to the drugs.We conclude that RenaGel and RenaGel with calcium are similarly effective in the treatment of ESRD-related hyperphosphatemia. Provision of supplemental calcium or metabolites of vitamin D with RenaGel may enhance control of hyperparathyroidism.

  View details for Web of Science ID 000078661200003

  View details for PubMedID 9988142

• Dose of hemodialysis and survival - Differences by race and sex JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Owen, W. F., Chertow, G. M., Lazarus, J. M., Lowrie, E. G. 1998; 280 (20): 1764-1768

  Abstract

  Although blacks receive lower doses of hemodialysis than whites, their survival when receiving dialysis treatment is better than that for whites. Previous studies of the relationship between the dose of dialysis and patient survival have not controlled for differences in patient characteristics.To examine the association of mortality with the dose of hemodialysis for clusters of patients categorized by race and sex.Retrospective analysis of laboratory data and mortality outcomes from 1994, using a national database of hemodialysis patients.A total of 18144 black and white patients receiving hemodialysis 3 times weekly who either lived the entire year receiving hemodialysis or died.The fractional reduction of urea in a single dialysis session as the measured hemodialysis dose (urea reduction ratio [URR]) after controlling for race, sex, age, and diabetes mellitus. Mortality was determined by strata of URRs and albumin and creatinine levels.Across all age categories, blacks had lower URRs than whites, and men had lower URRs than women. In an age-adjusted model for evaluating interactions among URRs, race, sex, and diabetes, the association of URR with mortality risk was weak among blacks, particularly black men. After adjustment for age and diabetes, death probability curves were most steep for white women with URR values less than 60%. The death probability curves were least steep for black men. There was no meaningful difference between death probability and albumin or creatinine concentration among the race by sex clusters.Using URR, the usual measure of hemodialysis dose, the assumption that the association between dialysis dose and survival is uniform across demographic groups appears incorrect. Comparisons of the quality of dialysis patient care should not rely on URR alone to predict patient survival.

  View details for Web of Science ID 000077081400032

  View details for PubMedID 9842952

• Clearance of Pneumocystis carinii cysts in acute P carinii pneumonia - Assessment by serial sputum induction CHEST O'Donnell, W. J., Pieciak, W., Chertow, G. M., Sanabria, J., Lahive, K. C. 1998; 114 (5): 1264-1268

  Abstract

  To determine the feasibility of repeat sputum induction in acute Pneumocystis carinii pneumonia (PCP) and to define the rate of clearance of P carinii cysts from the respiratory tract of HIV-seropositive patients with acute PCP.Prospective cohort evaluation.University medical center.Twenty-four HIV-seropositive subjects with acute PCP.Sputum induction for P carinii 2, 3, 4, and 6 weeks after initial diagnosis, and follow-up for 1 year.Eighty-eight percent of subjects had residual cysts at 2 weeks, 76% at 3 weeks, 29% at 4 weeks, and 24% at 6 weeks postdiagnosis. A prior AIDS-defining illness (p = 0.033) or prior PCP (p = 0.004) predicted relapse within 6 months, but persistent cysts at 3 weeks did not; 8 of 16 sputum-positive subjects and 1 of 5 sputum-negative subjects experienced a relapse within 6 months (p = 0.34). Secondary prophylaxis with trimethoprim-sulfamethoxazole was associated with a reduced risk of relapse.Serial sputum induction coupled with direct fluorescent antibody staining is a feasible, noninvasive method of respiratory tract surveillance for the eradication of P carinii during and after acute PCP. Three-quarters of HIV-seropositive patients with acute PCP have persistent cysts in their lungs at the end of antimicrobial treatment, despite clinical recuperation, but only one quarter have residual cysts 6 weeks postdiagnosis. A prior AIDS-defining illness and prior PCP are positively associated, and subsequent trimethoprim-sulfamethoxazole prophylaxis is negatively associated, with relapse within 6 months, while persistent organisms at 3 weeks do not appear to be a significant predictor of relapse risk.

  View details for Web of Science ID 000077001200011

  View details for PubMedID 9823999

• Effects of estrogen replacement therapy on the lipoprotein profile in postmenopausal women with ESRD KIDNEY INTERNATIONAL Ginsburg, E. S., Walsh, B., Greenberg, L., Price, D., Chertow, G. M., Owen, W. F. 1998; 54 (4): 1344-1350

  Abstract

  Patients with ESRD have excessive cardiovascular morbidity and mortality. In postmenopausal women with normal renal function, estrogen replacement therapy decreases cardiovascular mortality by 50%, in part because of their beneficial effects on the lipoprotein profile. Because of similarities in the lipoprotein profile between healthy, postmenopausal women, and women with ESRD, we examined the effects of estrogen replacement on lipoproteins in 11 postmenopausal women with ESRD.In a randomized, placebo-controlled crossover study (8 week treatment arms) using 2 mg daily of oral, micronized estradiol, 11 postmenopausal women with ESRD were treated. Neither baseline lipid nor lipoprotein abnormalities were used as entry criteria for study participation.Blood estradiol levels were 19 +/- 4 with placebo and 194 +/- 67 pg/ml (P = 0.024) with estradiol treatment. Total HDL cholesterol concentrations increased from 52 +/- 19 mg/dl to 61 +/- 20 mg/dl (16%), with placebo and estradiol treatments, respectively (P = 0.002). Apolipoprotein A1 increased by 24.6% (P = 0.0002) with estradiol intervention. HDL2 concentrations were 19 +/- 13 with placebo and 24 +/- 16 with estradiol treatment (P = 0.046). There were no differences in total or LDL cholesterol, other lipoprotein fractions including Lp(a), and triglycerides with 2 mg daily estradiol treatment. No significant side effects were observed.Therefore, using standard dosage regimens for estrogen replacement therapy in postmenopausal women with ESRD, HDL cholesterol is increased to an extent that would be expected to improve their cardiovascular risk profile. Further studies are needed to assess whether estrogen replacement therapy decreases the incidence or severity of cardiovascular disease in ESRD patients to a similar degree compared with other women.

  View details for Web of Science ID 000076096900036

  View details for PubMedID 9767554

• Cancer screening and detection in patients with end-stage renal disease INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS Gornik, H. L., Lazarus, J. M., Chertow, G. M. 1998; 21 (9): 495-500

  View details for Web of Science ID 000076823500001

  View details for PubMedID 9828052

• Haemobilia mimicking acute cholecystitis following percutaneous renal biopsy NEPHROLOGY DIALYSIS TRANSPLANTATION Lee, M. C., Jacobs, D. O., Chertow, G. M. 1998; 13 (8): 2118-2120

  View details for Web of Science ID 000075315700046

  View details for PubMedID 9719179

• beta 2-microglobulin modified with advanced glycation end products modulates collagen synthesis by human fibroblasts 14th International Congress of Nephrology Owen, W. F., Hou, F. F., Stuart, R. O., Kay, J., Boyce, J., Chertow, G. M., Schimidt, A. M. NATURE PUBLISHING GROUP. 1998: 1365–73

  Abstract

  Beta 2-microglobulin amyloidosis (A beta 2m) is a serious complication for patients undergoing long-term dialysis. beta 2-microglobulin modified with advanced glycation end products (beta 2m-AGE) is a major component of the amyloid in A beta 2m. It is not completely understood whether beta 2m-AGE plays an active role in the pathogenesis of A beta 2m, or if its presence is a secondary event of the disease. beta 2-microglobulin amyloid is mainly located in tendon and osteo-articular structures that are rich in collagen, and local fibroblasts constitute the principal cell population in the synthesis and metabolism of collagen. Recent identification of AGE binding proteins on human fibroblasts lead to the hypothesis that the fibroblast may be a target for the biological action of beta 2m-AGE. The present study demonstrated that two human fibroblast cell lines exhibited a decrease in procollagen type I mRNA and type I collagen synthesis after exposure to beta 2m-AGE for 72 hours. Similar results were observed using AGE-modified albumin. Antibody against the RAGE, the receptor for AGE, attenuated this decrease in synthesis, indicating that the response was partially mediated by RAGE. In addition, antibody against epidermal growth factor (EGF) attenuated the decrease in type I procollagen mRNA and type I collagen induced by beta 2m-AGE, suggesting that EGF acts as an intermediate factor. These findings support the hypothesis that beta 2m-AGE actively participates in connective tissue and bone remodeling via a pathway involving fibroblast RAGE, and at least one interposed mediator, the growth factor EGF.

  View details for Web of Science ID 000073168500031

  View details for PubMedID 9573554

• Predictors of mortality and the provision of dialysis in patients with acute tubular necrosis 27th Annual Meeting of the American-Society-of-Nephrology Chertow, G. M., Lazarus, J. M., Paganini, E. P., Allgren, R. L., Lafayette, R. A., Sayegh, M. H. AMER SOC NEPHROLOGY. 1998: 692–98

  Abstract

  To explore the natural history of critically ill patients with acute renal failure due to acute tubular necrosis, we evaluated 256 patients enrolled in the placebo arm of a randomized clinical trial. Death and the composite outcome, death or the provision of dialysis, were determined with follow-up to 60 d. The relative risks (RR) and 95% confidence intervals (95% CI) associated with routinely available demographic, clinical, and laboratory variables were estimated using proportional hazards regression. Ninety-three (36%) deaths were documented; an additional 52 (20%) patients who survived received dialysis. Predictors of mortality included male gender (RR, 2.01; 95% CI, 1.21 to 3.36), oliguria (RR, 2.25; 95% CI, 1.43 to 3.55), mechanical ventilation (RR, 1.86; 95% CI, 1.18 to 2.93), acute myocardial infarction (RR, 3.14; 95% CI, 1.85 to 5.31), acute stroke or seizure (RR, 3.08; 95% CI, 1.56 to 6.06), chronic immunosuppression (RR, 2.37; 95% CI, 1.16 to 4.88), hyperbilirubinemia (RR, 1.06; 95% CI, 1.03 to 1.08 per 1 mg/dl increase in total bilirubin) and metabolic acidosis (RR, 0.95; 95% CI, 0.90 to 0.99 per 1 mEq/L increase in serum bicarbonate concentration). Predictors of death or the provision of dialysis were oliguria (RR, 5.95; 95% CI, 3.96 to 8.95), mechanical ventilation (RR, 1.53; 95% CI, 1.07 to 2.21), acute myocardial infarction (RR, 1.95; 95% CI, 1.24 to 3.07), arrhythmia (RR, 1.51; 95% CI, 1.04 to 2.19), and hypoalbuminemia (RR, 0.56; 95% CI, 0.42 to 0.74 per 1 g/dl increase in serum albumin concentration). Neither mortality nor the provision of dialysis was related to patient age. These observations can be used to estimate risk early in the course of acute tubular necrosis. Furthermore, these and related models may be used to adjust for case-mix variation in quality improvement efforts, and to objectively stratify patients in future intervention trials aimed at favorably altering the course of hospital-acquired acute renal failure.

  View details for Web of Science ID 000072776600020

  View details for PubMedID 9555672

• Independent association between acute renal failure and mortality following cardiac surgery AMERICAN JOURNAL OF MEDICINE Chertow, G. M., Levy, E. M., Hammermeister, K. E., Grover, F., Daley, J. 1998; 104 (4): 343-348

  Abstract

  To determine whether there is an independent association of acute renal failure requiring dialysis with operative mortality after cardiac surgery.The 42,773 patients who underwent coronary artery bypass or valvular heart surgery at 43 Department of Veterans Affairs Medical Centers between 1987 and 1994 were evaluated to determine the association between acute renal failure sufficient to require dialysis and operative mortality, with and without adjustment for comorbidity and postoperative complications. Crude and adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were derived from logistic regression analysis.Acute renal failure occurred in 460 (1.1%) patients. Overall operative mortality was 63.7% in these patients, compared with 4.3% in patients without this complication. The unadjusted OR for death was 39 (95% CI 32 to 48). After adjustment for comorbid factors related to the development of acute renal failure (surgery type, baseline renal function, preoperative intraaortic balloon pump, prior heart surgery, NYHA class IV status, peripheral vascular disease, pulmonary rales, left ventricular ejection fraction below 35%, chronic obstructive pulmonary disease, systolic blood pressure, and the cross-product of systolic blood pressure and surgery type), the OR was 27 (95% CI 22 to 34). Further adjustment was made for seven postoperative complications (low cardiac output, cardiac arrest, perioperative myocardial infarction, prolonged mechanical ventilation, reoperation for bleeding or repeat cardiopulmonary bypass, stroke or coma, and mediastinitis), that were independently associated with operative mortality. The OR adjusted for comorbidity and postoperative complications associated with acute renal failure was 7.9 (95% CI 6 to 10).Acute renal failure was independently associated with early mortality following cardiac surgery, even after adjustment for comorbidity and postoperative complications. Interventions to prevent or improve treatment of this condition are urgently needed.

  View details for Web of Science ID 000073229200006

  View details for PubMedID 9576407

• Olecranon bursitis caused by infection with Candida lusitaniae JOURNAL OF RHEUMATOLOGY Behar, S. M., Chertow, G. H. 1998; 25 (3): 598-600

  Abstract

  We describe a 59-year-old woman with diabetes and chronic asthma treated with prednisone and methotrexate who developed chronic olecranon bursitis caused by Candida lusitaniae. Infection, especially with unusual microbial pathogens, should be considered in cases of chronic bursitis in patients taking immunosuppressive medicine, even if the classic signs of septic bursitis are absent. Infection with C. lusitaniae, a component of the normal mycoflora, may be a marker of serious immunosuppression, as this patient ultimately died of a Pneumocystis carinii infection.

  View details for Web of Science ID 000072245800035

  View details for PubMedID 9517788

• Dialysis: Cost-effective "SUPPORT" for patients with acute renal failure AMERICAN JOURNAL OF KIDNEY DISEASES Chertow, G. M. 1998; 31 (3): 545-548

  View details for Web of Science ID 000072338000023

  View details for PubMedID 9506696

• Aminoguanidine inhibits advanced glycation end products formation on beta 2-microglobulin JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Hou, F. F., Boyce, J., Chertow, G. M., Kay, J., Owen, W. F. 1998; 9 (2): 277-283

  Abstract

  Because advanced glycation end products (AGE)-modified beta2-microglobulin (AGE-beta2M) is a dominant constituent of amyloid in dialysis-related amyloidosis (DRA), AGE-beta2M may be directly involved in the pathobiology of DRA. In experimental diabetes mellitus, blocking the formation of AGE prevents AGE-mediated tissue damage. In this study, it is postulated that similar pharmacologic intervention may be beneficial in DRA. Aminoguanidine, a nucleophilic hydrazine compound that prevents AGE formation on collagen, may have a similar effect on the advanced glycation of beta2M. To test this hypothesis, beta2M was incubated in vitro with 50 or 100 mM D-glucose for 3 wk in the presence and absence of incremental concentrations of aminoguanidine. On the basis of enzyme-linked immunosorbent assay and immunoblots using anti-AGE-keyhole limpet hemocyanin antibody, aminoguanidine inhibited glucose-induced N(epsilon)-(carboxymethyl)lysine formation on beta2M. At aminoguanidine-glucose molar ratios of 1:8 to 1:1, 26 to 53% inhibition occurred. Fluorospectrometry examination showed that aminoguanidine also inhibited the formation of fluorescent AGE on beta2M in a dose-dependent manner. At aminoguanidine-glucose molar ratios of 1:8 to 1:1, fluorescent product generation was inhibited by 30 to 70%. Furthermore, aminoguanidine suppressed the AGE formation on beta2M bound to AGE-modified collagen. If aminoguanidine is similarly active in vivo, this compound may be of clinical utility for treating DRA in patients on maintenance dialysis.

  View details for Web of Science ID 000071726600014

  View details for PubMedID 9527404

• Allocation of kidneys to patients on the transplant waiting list: a simulation-based policy model 30th Conference on Transplantation and Clinical Immunology - Organ Allocation Zenios, S. A., Chertow, G. M., Wein, L. M. KLUWER ACADEMIC PUBL. 1998: 133–133

  View details for Web of Science ID 000074633700014

• Bioimpedance norms for the hemodialysis population 28th Annual Meeting of the American-Society-of-Nephrology Chertow, G. M., Lazarus, J. M., Lew, N. L., Ma, L. H., Lowrie, E. G. NATURE PUBLISHING GROUP. 1997: 1617–21

  Abstract

  More than 3,000 hemodialysis patients were examined with single-frequency bioelectrical impedance analysis (BIA). Distributions of resistance, reactance, phase angle (PA), and estimates of total body water (TBW) and body cell mass (BCM) by BIA were determined, and compared with traditional laboratory markers of nutritional status. Bioimpedance parameters and body composition estimates differed significantly by age, sex, race, and diabetic status. PA and BCM correlated directly with serum creatinine, albumin, and prealbumin concentrations. Population-based norms for bioimpedance parameters and estimates of body composition are provided.

  View details for Web of Science ID A1997YH57300019

  View details for PubMedID 9407508

• Antigen-independent determinants of graft survival in living-related kidney transplantation Symposium on Progression of Renal Disease - Clinical Patterns, Therapeutic Options and What We Have Learned from Clinical Trials Chertow, G. M., BRENNER, B. M., Mori, M., Mackenzie, H. S., Milford, E. L. NATURE PUBLISHING GROUP. 1997: S84–S86

  Abstract

  We used the United Network of Organ Sharing database to define the antigen independent risk factors which contributed to the survival of 8,582 kidney transplants performed in the U.S. between October 1987 and December 1991, using multivariable regression techniques. In this analysis, death with a functioning graft was censored. The risk ratio for graft loss was high when recipients were African-American or had high body surface area, or when donors were older or female. The analysis shows that antigen independent factors that are associated with lower donor kidney mass or increased recipient size play a significant role in living donor kidney transplant loss, as they do in cadaver kidney transplantation.

  View details for Web of Science ID A1997YJ60500022

  View details for PubMedID 9407430

• On the design and analysis of multicenter trials in acute renal failure 2nd International Conference on Continuous Renal Replacement Therapy Chertow, G. M. W B SAUNDERS CO-ELSEVIER INC. 1997: S96–S101

  Abstract

  Improving outcomes for patients with acute renal failure (ARF) is one of the most urgent tasks for 21st century nephrologists and other critical care physicians. The incidence of hospital-acquired ARF is rising (to 5% or more), partly because of changes in the demographic and clinical characteristics of the hospitalized patient population. When ARF is severe enough to require dialysis, in-hospital mortality rates are distressingly high, in excess of 50% in most published studies. In the past several years, a number of attempts have been made to influence the course of ARF, either relatively early (eg, atrial natriuretic peptide [ANP], insulin growth factor-1 [IGF-1]) or coincident with the dialysis procedure in severe cases (eg, variations in dialysis membrane and modality). Several lessons can be learned from these efforts. This article will briefly address issues in the design and analysis of clinical trials, focusing on elements of special interest to practitioners of renal medicine.

  View details for Web of Science ID A1997YE17200016

  View details for PubMedID 9372986

• Renal vasculitis with HIV seropositivity: Potential manifestation of cytomegalovirus infection AMERICAN JOURNAL OF KIDNEY DISEASES Chertow, G. M., Rennke, H. G., Curhan, G. C., Brady, H. R. 1997; 30 (3): 428-432

  Abstract

  The associations among human immunodeficiency virus (HIV) infection, focal segmental glomerulosclerosis, and its variant, "collapsing glomerulopathy," often leading to chronic renal failure, are well described. HIV-seropositive patients may also develop a variety of immune complex-mediated glomerular diseases, including postinfectious glomerulonephritis, IgA nephropathy, and membranoproliferative glomerulonephritis. Herein we describe a case of pauci-immune necrotizing renal vasculitis in an HIV-seropositive patient, thereby expanding the differential diagnosis of acute renal failure in this setting.

  View details for Web of Science ID A1997XU87900018

  View details for PubMedID 9292573

• Allocation of kidneys to patients on the transplant waiting list. Assessing the trade-off between equity and efficiency. Zenios, S. A., Chertow, G. M., Wein, L. M. AMER SOC NEPHROLOGY. 1997: A3291–A3291

  View details for Web of Science ID A1997XY10303288

• The rise and fall of atrial natriuretic peptide for acute renal failure CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION Brenner, R. M., Chertow, G. M. 1997; 6 (5): 474-476

  Abstract

  Atrial natriuretic peptide can increase glomerular filtration rate and filtration fraction and can promote natriuresis, effects that would logically seem to improve renal function after acute tubular necrosis from ischemic or toxic injury. Early human trials suggested a beneficial effect of atrial natriuretic peptide on creatinine clearance, and a reduction in the need for dialysis in treated patients. However, randomized, placebo-controlled trials have failed to show a clinically relevant benefit on survival, dialysis-free survival, or renal function in patients treated with this agent.

  View details for Web of Science ID A1997XX75600011

  View details for PubMedID 9327207

• Nephrology JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Chertow, G. M. 1997; 277 (23): 1872-1873

  View details for Web of Science ID A1997XD54400028

  View details for PubMedID 9185809

• Development of a population-specific regression equation to estimate total body water in hemodialysis patients ISN Forefronts in Nephrology Symposium on Cytokines and Adhesion Molecules in Tissue Injury and Repair Chertow, G. M., Lazarus, J. M., Lew, N. L., Ma, L. H., Lowrie, E. G. NATURE PUBLISHING GROUP. 1997: 1578–82

  Abstract

  We have previously shown that the impedance index (height corrected resistance) is a valid and reliable correlate of total body water (TBW) in hemodialysis patients. We estimated TBW by single frequency bioelectrical impedance analysis (BIA) in 3009 in-center hemodialysis patients, and developed an ESRD-specific TBW equation from routinely available demographic and anthropometric variables. The mean +/- SD age was 60.5 +/- 15.5 years; 47% were female, 47% African-American, and 36% diabetic. Dialysis duration was 3.8 +/- 3.7 years. Mean TBW was 40.8 +/- 9.3 kg, 56 +/- 9% of body weight. A stepwise linear regression equation was fit on a two-thirds random sample, deriving significant parameter estimates for the variables age, gender, height, weight, diabetic status, weight squared, and the cross-products of age and gender, age and weight, gender and weight, and height and weight. The equation was then validated in the remaining one-third sample, and compared with TBW estimates by the Watson and Hume-Weyer formulae. TBW estimated by our equation (40.6 +/- 8.6 kg) was not significantly different from the BIA TBW (40.5 +/- 9.3 kg). In contrast, TBW estimated by the Watson (37.0 +/- 7.6 kg) and Hume-Weyer (37.9 +/- 7.7 kg) formulae underestimated TBW by a mean of 3.5 and 2.6 kg, respectively. A population-specific equation provides superior prediction of TBW in hemodialysis patients. The use of formulae developed and validated in non-uremic populations may result in underestimates of TBW in patients with ESRD, and potentially, overestimates of dialysis dose approximated by the clearance-time to TBW ratio (Kt/V).

  View details for Web of Science ID A1997WX90600035

  View details for PubMedID 9150475

• Interaction between beta 2-microglobulin and advanced glycation end products in the development of dialysis related amyloidosis ISN Forefronts in Nephrology Symposium on Cytokines and Adhesion Molecules in Tissue Injury and Repair Hou, F. F., Chertow, G. M., Kay, J., Boyce, J., Lazarus, J. M., Braatz, J. A., Owen, W. F. NATURE PUBLISHING GROUP. 1997: 1514–19

  Abstract

  Dialysis related amyloidosis (DRA) is a progressive debilitating complication of long-term dialysis. beta 2-microglobulin (beta 2m) amyloid deposition occurs preferentially in older patients and initially is located in collagen-rich osteo-articular tissues. Since an age-dependent increase in the formation of advanced glycation end products (AGE) has been observed in collagen-containing structures, we hypothesized that AGE-modified beta 2m in the amyloid of DRA may be formed locally in osteo-articular structures as a subsequent event of its binding to collagen-AGE. Based on this hypothesis, we investigated the binding between beta 2m and AGE-modified collagen (collagen-AGE) in vitro. Significantly larger amounts of human beta 2m were bound to types I to IV of immobilized collagen-AGE than to unmodified collagens (P < 0.0001). The quantity of beta 2m bound to collagen-AGE was dependent on the concentrations of both beta 2m and of AGE contained in collagen (P < 0.01). Unmodified beta 2m was more avidly bound to collagen-AGE or collagen in comparison to AGE-modified beta 2m (P < 0.0001). beta 2m bound to collagen-AGE could be modified further by nonenzymatic glycosylation during three weeks of incubation with physiologic concentrations of glucose. Similar processes in vivo may be important in the pathobiology of DRA.

  View details for Web of Science ID A1997WX90600027

  View details for PubMedID 9150467

• A practical approach to acute renal failure MEDICAL CLINICS OF NORTH AMERICA Mindell, J. A., Chertow, G. M. 1997; 81 (3): 731-?

  Abstract

  Acute renal failure represents a wide variety of renal diseases, which may be challenging to diagnose and even more challenging to treat. As understanding of these diseases improves, so perhaps will clinicians' ability to treat them.

  View details for Web of Science ID A1997XA50100010

  View details for PubMedID 9167655

• Preoperative renal risk stratification CIRCULATION Chertow, G. M., Lazarus, J. M., Christiansen, C. L., Cook, E. F., Hammermeister, K. E., Grover, F., Daley, J. 1997; 95 (4): 878-884

  Abstract

  After cardiac surgery, acute renal failure (ARF) requiring dialysis develops in 1% to 5% of patients and is strongly associated with perioperative morbidity and mortality. Prior studies have attempted to identify predictors of ARF but have had insufficient power to perform multivariable analyses or to develop risk stratification algorithms.We conducted a prospective cohort study of 43 642 patients who underwent coronary artery bypass or valvular heart surgery in 43 Department of Veterans Affairs medical centers between April 1987 and March 1994. Logistic regression analysis was used to identify independent predictors of ARF requiring dialysis. A risk stratification algorithm derived from recursive partitioning was constructed and was validated on an independent sample of 3795 patients operated on between April and December 1994. The overall risk of ARF requiring dialysis was 1.1%. Thirty-day mortality in patients with ARF was 63.7%, compared with 4.3% in patients without ARF. Ten clinical variables related to baseline cardiovascular disease and renal function were independently associated with the risk of ARF. A risk stratification algorithm partitioned patients into low-risk (0.4%), medium-risk (0.9% to 2.8%), and high-risk (> or = 5.0%) groups on the basis of several of these factors and their interactions.The risk of ARF after cardiac surgery can be accurately quantified on the basis of readily available preoperative data. These findings may be used by physicians and surgeons to provide patients with improved risk estimates and to target high-risk subgroups for interventions aimed at reducing the risk and ameliorating the consequences of this serious complication.

  View details for Web of Science ID A1997WJ28200024

  View details for PubMedID 9054745

• Poorer graft survival in African-American transplant recipients cannot be explained by HLA mismatching. Advances in renal replacement therapy Chertow, G. M., Milford, E. L. 1997; 4 (1): 40-45

  Abstract

  African-American kidney-transplant recipients have exhibited a higher rate of graft failure than whites and other patient groups. Many have attributed this discrepancy to disparities in HLA matching against a predominantly white donor pool. We compared the relative risks of cadaveric and living-related graft failure in African-American, white, Hispanic, and Asian transplant recipients, adjusting for a variety of demographic and clinical covariates. The relative risks of graft failure were increased by 44% and 73% in African-American recipients of cadaveric and living-related organs, respectively. Although Asians were subject to a comparable degree of HLA mismatching, cadaveric graft survival in Asian recipients was superior to that in whites. These results suggest that other variables not captured by registry data account for the increase in graft failure observed in African-Americans. More focused investigation into the causes and prevention of graft failure in African-Americans is required.

  View details for PubMedID 8996619

• Poly[allylamine hydrochloride] (RenaGel): A noncalcemic phosphate binder for the treatment of hyperphosphatemia in chronic renal failure AMERICAN JOURNAL OF KIDNEY DISEASES Chertow, G. M., Burke, S. K., Lazarus, J. M., Stenzel, K. H., Wombolt, D., Goldberg, D., Bonventre, J. V., Slatopolsky, E. 1997; 29 (1): 66-71

  Abstract

  Dietary phosphate restriction and the oral administration of calcium and aluminum salts have been the principal means of controlling hyperphosphatemia in individuals with end-stage renal disease over the past decade. Although relatively well-tolerated, a large fraction of patients treated with calcium develop hypercalcemia, particularly when administered concurrently with calcitriol, despite a lowering of the dialysate calcium concentration. We evaluated the efficacy of cross-linked poly[allylamine hydrochloride] (RenaGel; Geltex Pharmaceuticals, Waltham, MA), a nonabsorbable calcium- and aluminum-free phosphate binder, in a randomized, placebo-controlled, double-blind trial of 36 maintenance hemodialysis patients followed over an 8-week period. RenaGel was found to be as effective as calcium carbonate or acetate as a phosphate binder. The reduction in serum phosphorus was significantly greater after 2 weeks of treatment with RenaGel (6.6 +/- 2.1 mg/dL to 5.4 +/- 1.5 mg/dL) compared with placebo (7.0 +/- 2.1 mg/dL to 7.2 +/- 2.4 mg/dL; P = 0.037). There was no significant change in serum calcium concentration in either treatment group. The total serum cholesterol and low-density lipoprotein cholesterol fraction were significantly reduced in RenaGel-treated patients compared with placebo-treated patients (P = 0.013 and P = 0.003, respectively) without a concomitant reduction in high-density lipoprotein cholesterol (P = 0.93). There was no difference among recipients of RenaGel and placebo in terms of adverse events. RenaGel is a safe and effective alternative to oral calcium for the management of hyperphosphatemia in end-stage renal disease.

  View details for Web of Science ID A1997WD53300007

  View details for PubMedID 9002531

• Antigen-independent determinants of cadaveric kidney transplant failure JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Chertow, G. M., Milford, E. L., Mackenzie, H. S., BRENNER, B. M. 1996; 276 (21): 1732-1736

  Abstract

  To determine the association of various antigen-independent factors with long-term cadaveric kidney transplant failure.Cohort analytic study.Kidney transplant centers (N=131) in the United States.A total of 31 515 patients who received cadaveric kidney transplants between October 1987 and December 1991. Patients with unknown or uninterpretable vital status or graft survival time (n=264 [0.8%]) were excluded.Graft failure, estimated at 2 extremes, depending on whether the death of a patient with a functioning graft was censored ("censored graft failure") or not ("uncensored graft failure").During the 62-month study period, 5883 patients required the reinstitution of dialysis because of graft failure, 2404 patients died with graft failure, and 2041 patients died with a functioning graft. The relative risks of censored and uncensored graft failure were significantly associated with donor age, sex, and race and recipient body surface area, after adjusting for recipient age, sex, race, diabetes, cold ischemia time, panel cross-reactivity, pretransplant blood transfusions, previous renal transplantation, functional status, and HLA antigen mismatch.In cadaveric kidney transplantation, selected demographic and anthropometric factors are significantly related to long-term graft outcomes, even after adjusting for well-known antigen-dependent risk factors. These results support the hypothesis that the supply of viable donor nephrons and the physiologic demands of the transplant recipient are important determinants of long-term graft failure. Antigen-independent factors such as donor age should be incorporated into organ allocation algorithms to optimize equity and efficiency.

  View details for Web of Science ID A1996VV56600030

  View details for PubMedID 8940321

• Intensity of dialysis in established acute renal failure SEMINARS IN DIALYSIS Chertow, G. M., Lazarus, J. M. 1996; 9 (6): 476-480

  View details for Web of Science ID A1996VV40200008

• Grafts vs fistulas for hemodialysis patients - Equal access for all? JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Chertow, G. M. 1996; 276 (16): 1343-1344

  View details for Web of Science ID A1996VM82500040

  View details for PubMedID 8861996

• Fanconi's syndrome and tubulointerstitial nephritis in association with L-lysine ingestion AMERICAN JOURNAL OF KIDNEY DISEASES Lo, J. C., Chertow, G. M., Rennke, H., Seifter, J. L. 1996; 28 (4): 614-617

  Abstract

  We report a case of a 44-year-old woman who developed Fanconi's syndrome in association with the oral ingestion of L-lysine. L-lysine is widely available in health food stores and has been recommended in the lay press for the treatment and prevention of recurrent herpes simplex. The development of a severe tubulointerstitial nephritis, and eventual progression to chronic renal failure, underscores the importance of this entity, heretofore unrecognized in humans.

  View details for Web of Science ID A1996VL78600021

  View details for PubMedID 8840955

• Birth weight and adult hypertension and obesity in women CIRCULATION Curhan, G. C., Chertow, G. M., Willett, W. C., Spiegelman, D., Colditz, G. A., Manson, J. E., Speizer, F. E., Stampfer, M. J. 1996; 94 (6): 1310-1315

  Abstract

  Low birth weight has been associated with an increased risk of hypertension, and high birth weight has been associated with increased adult body mass index. Published studies on adults have included only a small number of women.We studied 71 100 women in the Nurses Health Study I (NHS I) who were 30 to 55 years of age in 1976 and 92 940 women in the Nurses' Health Study II (NHS II) who were 25 to 42 years of age in 1989. Information on birth weight, blood pressure, physician-diagnosed hypertension, and other relevant variables was collected by biennial mailed questionnaire. Ninety-five percent of the women were white. Compared with women in the middle category of birth weight (NHS I, 7.1 to 8.5 lb; NHS II, 7.0 to 8.4 lb), the age-adjusted odds ratio of hypertension in NHS I women with birth weights < 5.0 lb was 1.39 (95% CI, 1.29 to 1.50); in NHS II, for birth weights < 5.5 lb, the age-adjusted odds ratio was 1.43 (95% CI, 1.31 to 1.56). There was no material change in the estimates after adjustment for other risk factors. In addition, compared with women in NHS I who weighed 7.1 to 8.5 lb at birth, those who weighed > 10 lb had an age-adjusted odds ratio of 1.62 (95% CI, 1.38 to 1.90) of being in the highest (> 29.2 kg/m2) versus the lowest (< 21.9 kg/ m2) quintile of body mass index in midlife. Similar results were seen in the NHS II cohort.Early life exposures affecting birth weight may be important in the development of hypertension and obesity in adults.

  View details for Web of Science ID A1996VG35000025

  View details for PubMedID 8822985

• Restless legs syndrome in end-stage renal disease AMERICAN JOURNAL OF KIDNEY DISEASES Winkelman, J. W., Chertow, G. M., Lazarus, J. M. 1996; 28 (3): 372-378

  Abstract

  The aim of this study was to evaluate the prevalence of restless legs syndrome (RLS) in patients with end-stage renal disease (ESRD), and to determine its association with sleep disorders and premature discontinuation of dialysis ("sign-offs"). End-stage renal disease patients (N = 204) and a control group of patients with heart disease (N = 129) completed a self-administered questionnaire regarding symptoms of RLS, sleep habits, pruritus, and adherence to dialysis therapy. Laboratory measures and sensory nerve amplitudes were collected on the ESRD patients. Twenty percent of the ESRD patients and 6% of the cardiac patients reported moderate to severe RLS symptomatology. Sleep onset was delayed and total sleep time was diminished in ESRD patients compared with cardiac patients. Symptoms of RLS were directly correlated with all sleep measures as well as with pruritus. Symptoms of RLS, sleep onset latency, and transferrin saturation were independently associated with premature discontinuation of dialysis. Significantly increased risk for mortality was observed in patients with RLS at the 2.5-year follow-up. Restless legs syndrome is a common finding in patients with ESRD and is associated with substantial morbidity.

  View details for Web of Science ID A1996VG42900008

  View details for PubMedID 8804235

• Trimethoprim-sulfamethoxazole and hypouricemia CLINICAL NEPHROLOGY Chertow, G. M., Seifter, J. L., Christiansen, C. L., ODONNELL, W. J. 1996; 46 (3): 193-198

  Abstract

  Hypouricemia has been reported in a substantial fraction of patients with AIDS and attributed to an HIV-related renal urate transport defect. We tested the alternative hypothesis that hypouricemia was associated with the administration of high-dose trimethoprim-sulfamethoxazole (TMP-SMX).Sociodemographic, clinical, and repeated laboratory data on 45 hospitalized patients with Pneumocystis carinii pneumonia (PCP) with and without HIV infection, were abstracted by a blinded reviewer. The primary outcome of interest was the percent change in serum uric acid concentration from baseline to hospital day 5 +/- 1.Subjects who received TMP-SMX were older (mean age 44.8 vs. 37.0, p = 0.02), less likely to be HIV-seropositive (61% vs. 94%, p = 0.01), and more likely to have received glucocorticoid therapy (75% vs. 35%, p = 0.01) than those who received pentamidine, dapsone-trimethoprim, clindamycin-primaquine, sulfadiazine-pyramethamine, or a combination of these agents. The administration of TMP-SMX was associated with a 37% +/- 12% reduction in serum uric acid concentration, adjusting for the effects of age, sex, race, HIV antibody status, renal function, serum sodium, and the use of diuretics and glucocorticoids (p = 0.005).Among a diverse cohort of hospitalized patients with PCP, treatment with high-dose TMP-SMX was strongly associated with a reduction in serum uric acid concentration over time.

  View details for Web of Science ID A1996VG96300006

  View details for PubMedID 8879855

• Performance characteristics of a dialysis-related amyloidosis questionnaire JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Chertow, G. M., TRIMBUR, T., Karlson, E. W., Lazarus, J. M., Kay, J. 1996; 7 (8): 1235-1240

  Abstract

  To evaluate the effects of beta-2 microglobulin amyloidosis on functional status, a 19-item self-administered questionnaire exploring two major domains-symptoms and disability-was developed as part of this study. Fifteen patients with dialysis-related amyloidosis (DRA) were identified and compared with 15 age-matched control subjects who had been on hemodialysis for less than 24 months. Demographic data, Charlson comorbidity scores, and other clinical and laboratory variables were recorded. Total dialysis-related amyloidosis questionnaire (DRAQ) score (52.1 +/- 16.3 versus 24.4 +/- 6.2, P < 0.0001) and the scores of the symptom (24.5 +/- 7.0 versus 11.5 +/- 2.3, P < 0.0001) and disability (27.5 +/- 10.8 versus 12.9 +/- 4.0, P < 0.0001) subscales were markedly increased among patients with DRA. Baseline characteristics among case and control subjects were similar, except for serum creatinine concentration, which tended to be lower among patients with DRA (8.9 +/- 2.6 versus 11.5 +/- 2.3 mg/dL, P = 0.07). Instrument reliability and internal consistency were high. With a total DRAQ score of 30 or more, the sensitivity and specificity of the instrument were 93% and 80%, respectively. The DRAQ is a reliable, internally consistent, and valid instrument that may be suitable for population screening and clinical practice.

  View details for Web of Science ID A1996VD59600020

  View details for PubMedID 8866418

• ''Renal-dose'' dopamine for the treatment of acute renal failure: Scientific rationale, experimental studies and clinical trials KIDNEY INTERNATIONAL Denton, M. D., Chertow, G. M., Brady, H. R. 1996; 50 (1): 4-14

  View details for Web of Science ID A1996UT64500002

  View details for PubMedID 8807566

• Is the administration of dopamine associated with adverse or favorable outcomes in acute renal failure? AMERICAN JOURNAL OF MEDICINE Chertow, G. M., Sayegh, M. H., Allgren, R. L., Lazarus, J. M. 1996; 101 (1): 49-53

  Abstract

  To explore the relationship between the administration of low-dose dopamine and outcomes in acute renal failure.Two hundred and fifty-six patients with acute renal failure randomized to the placebo arm of a multicenter intervention trial were examined. Independent correlates of low-dose (arbitrarily defined as < 3 micrograms/kg/min) and high-dose (arbitrarily defined as > or = 3 micrograms/kg/min) dopamine administration were identified. The relative risks of death, and the combined outcome of death or dialysis, were estimated using proportional hazards regression with and without adjustment for potential confounding and bias.There were 93 (36%) deaths documented; an additional 52 (20%) patients who survived required dialysis during the 60-day study period. The relative risk (RR) of death associated with the administration of low-dose dopamine was 1.11 (95% confidence interval [95% Cl] 0.66 to 1.89). The RR of death was modestly but not significantly reduced, after adjustment for the probability of treatment assignment and for relevant covariates (RR 0.82, 95% Cl 0.42 to 1.60). The RR of death or dialysis associated with the administration of low-dose dopamine was 1.10 (95% Cl 0.71 to 1.71). The RR of death or dialysis was attenuated by adjustment, but not significantly (RR 0.95, 95% Cl 0.58 to 1.58).There is insufficient evidence that the administration of low-dose dopamine improves survival or obviates the need for dialysis in persons with acute renal failure. The routine use of low-dose dopamine should be discouraged until a prospective, randomized, placebo-controlled trial establishes its safety and efficacy.

  View details for Web of Science ID A1996UY64700008

  View details for PubMedID 8686714

• Cost-effectiveness of cancer screening in end-stage renal disease ARCHIVES OF INTERNAL MEDICINE Chertow, G. M., Paltiel, A. D., Owen, W. F., Lazarus, J. M. 1996; 156 (12): 1345-1350

  Abstract

  Limited evidence suggests that persons with end-stage renal disease (ESRD) may be at increased risk for malignancy. The appropriateness of screening procedures in this population has not been evaluated.To determine the relative cost-effectiveness of hypothetical cancer screening programs in the population with ESRD compared with the general population.We performed a cost-effectiveness analysis, employing the declining exponential approximation of life expectancy. Assumptions were put forth to bias the model in favor of cancer screening. Secondary comparisons were made between cancer screening and other interventions targeted to patients with ESRD.The costs per unit of survival benefit conferred by cancer screening were 1.6 to 19.3 times greater among patients with ESRD than in the general population, depending on age, sex, and race, and assumptions outlined herein. For persons with ESRD, the net gain in life expectancy from a typical cancer screening program was calculated to be 5 days or less. Similar survival gains could be obtained via a reduction of 0.02% or less in the baseline ESRD-related mortality rate.These analyses suggest that routine cancer screening in the population with ESRD is a relatively inefficient allocation of financial resources. Direction of funds toward improving the quality of dialysis could attain such an objective at substantially lower cost. Furthermore, these findings highlight the importance of competing risks as a consideration in the evaluation of screening strategies and other interventions targeted to patients with ESRD and to other populations with chronic diseases associated with reduced survival.

  View details for Web of Science ID A1996UT70300014

  View details for PubMedID 8651845

• Nutrition and the dialysis prescription AMERICAN JOURNAL OF NEPHROLOGY Chertow, G. M., Bullard, A., Lazarus, J. M. 1996; 16 (1): 79-89

  Abstract

  Malnutrition is common among patients with acute and chronic renal failure. The efficiency of modern dialytic techniques has allowed for more liberal administration of nutrients to patients with renal failure, particularly with regard to protein and amino acids. Protein restriction is not indicated for patients on dialysis, and should be employed cautiously, if at all, in patients with renal insufficiency. The 'nutrition prescription' should be considered a vital part of the comprehensive medical, surgical, and dialytic care provided to patients with renal disease.

  View details for Web of Science ID A1996TL22100010

  View details for PubMedID 8719769

• Non-immunologic predictors of chronic renal allograft failure: data from the United Network of Organ Sharing. Kidney international. Supplement Chertow, G. M., BRENNER, B. M., Mackenzie, H. S., Milford, E. L. 1995; 52: S48-51

  Abstract

  Experimental evidence and clinical experience suggest that non-immunologic factors are important predictors of long-term renal allograft survival. It has been suggested that chronic allograft failure may in some cases by mediated by non-immunologic factors implicated in the pathobiology of other forms of progressive renal disease. Donor age, sex, and race may influence the "dose" of nephrons delivered in cadaveric renal transplantation. The United Network of Organ Sharing 1994 Public Use Data Tape was used to evaluate these and other risk factors in more than 31,000 recipients of cadaver allografts followed between 1987 and 1992. Female sex and African American race of the donor were important predictors of allograft failure. There was a markedly increased risk of allograft failure at both extremes of donor age. Recipients of large body size had accelerated graft loss. Stratified analyses suggested an interaction between donor and recipient race; nevertheless, all non-immunologic factors examined expressed independent associations with allograft survival. In sum, antigen-independent factors appear to be important determinants of allograft performance. Additional multivariable analyses are required to assess the relative importance of these factors compared with other known immunologic factors, such as HLA antigen mismatch. These findings may have important biomedical and health care policy implications.

  View details for PubMedID 8587283

• NONIMMUNOLOGICAL PREDICTORS OF CHRONIC RENAL-ALLOGRAFT FAILURE - DATA FROM THE UNITED-NETWORK-OF-ORGAN-SHARING Chronic Renal Allograft Failure Satellite Symposium to the XIIIth Meeting of the International Congress of Nephrology Chertow, G. M., BRENNER, B. M., Mackenzie, H. S., Milford, E. L. BLACKWELL SCIENCE PUBL INC CAMBRIDGE. 1995: S48–S51

  Abstract

  Experimental evidence and clinical experience suggest that non-immunologic factors are important predictors of long-term renal allograft survival. It has been suggested that chronic allograft failure may in some cases by mediated by non-immunologic factors implicated in the pathobiology of other forms of progressive renal disease. Donor age, sex, and race may influence the "dose" of nephrons delivered in cadaveric renal transplantation. The United Network of Organ Sharing 1994 Public Use Data Tape was used to evaluate these and other risk factors in more than 31,000 recipients of cadaver allografts followed between 1987 and 1992. Female sex and African American race of the donor were important predictors of allograft failure. There was a markedly increased risk of allograft failure at both extremes of donor age. Recipients of large body size had accelerated graft loss. Stratified analyses suggested an interaction between donor and recipient race; nevertheless, all non-immunologic factors examined expressed independent associations with allograft survival. In sum, antigen-independent factors appear to be important determinants of allograft performance. Additional multivariable analyses are required to assess the relative importance of these factors compared with other known immunologic factors, such as HLA antigen mismatch. These findings may have important biomedical and health care policy implications.

  View details for Web of Science ID A1995TH91700011

• MULTIFREQUENCY BIOELECTRICAL-IMPEDANCE ESTIMATES THE DISTRIBUTION OF BODY-WATER JOURNAL OF APPLIED PHYSIOLOGY Cha, K. C., Chertow, G. M., Gonzalez, J., Lazarus, J. M., Wilmore, D. W. 1995; 79 (4): 1316-1319

  Abstract

  Multifrequency bioelectrical impedance analysis was used to estimate the ratio of extracellular water (ECW) to total body water in subjects with end-stage renal disease. The body's resistance was measured at frequencies ranging from 1 kHz to 1 MHz. The impedance index (height2/resistance) determined at low frequency (5 kHz) correlated most closely with ECW (r = 0.886) using sodium bromide dilution as the standard of comparison. In contrast, the ratio of height squared to resistance determined at high frequency (500 kHz) correlated most closely with total body water (r = 0.974) using deuterium oxide dilution as the standard of comparison. The ratio of resistance at 500 kHz to resistance at 5 kHz was directly correlated (r = 0.767) with the ratio of ECW to total body water. Multifrequency bioelectrical impedance analysis may assist in the evaluation of body water distribution in endstage renal disease and other clinical disorders of fluid volume and/or distribution.

  View details for Web of Science ID A1995TA62000036

  View details for PubMedID 8567578

• PROGNOSTIC STRATIFICATION IN CRITICALLY ILL PATIENTS WITH ACUTE-RENAL-FAILURE REQUIRING DIALYSIS ARCHIVES OF INTERNAL MEDICINE Chertow, G. M., Christiansen, C. L., Cleary, P. D., Munro, C., Lazarus, J. M. 1995; 155 (14): 1505-1511

  Abstract

  Despite the widespread availability of dialytic and intensive care unit technology, the probability of early mortality in critically ill persons with acute renal failure is distressingly high. Previous efforts to predict outcome in this population have been limited by small sample size and the absence of uniform exclusion criteria. Additionally, data obtained decades ago may not apply today owing to changes in case mix.The medical records of 132 consecutive patients in the intensive care unit with acute renal failure who required dialysis from 1991 through 1993 were evaluated by a blinded reviewer.The overall in-hospital mortality rate was 70%. Twelve readily available historical, clinical, and laboratory variables were significantly associated with in-hospital mortality. Multivariate logistic regression analysis showed that mechanical ventilation, malignancy, and nonrespiratory organ system failure were independently associated with in-hospital mortality. Using a 95% positivity criterion, this model identified 24% of high-risk patients who died, without misclassification of any survivors. Of those who survived to hospital discharge, 33% were dialysis dependent and 28% were institutionalized long-term.Among critically ill patients, acute renal failure requiring dialysis is an ominous condition with a high risk of in-hospital mortality. This risk appears to depend largely on comorbid conditions, such as the need for mechanical ventilation and underlying malignancy. While this prognostic model requires prospective validation, it appears to identify a substantial fraction of patients for whom dialysis may be of limited or no benefit.

  View details for Web of Science ID A1995RJ62100006

  View details for PubMedID 7605152

• NUTRITIONAL ASSESSMENT WITH BIOELECTRICAL-IMPEDANCE ANALYSIS IN MAINTENANCE HEMODIALYSIS-PATIENTS JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Chertow, G. M., Lowrie, E. G., Wilmore, D. W., Gonzalez, J., Lew, N. L., Ling, J., LeBoff, M. S., GOTTLIEB, M. N., Huang, W., Zebrowski, B., College, J., Lazarus, J. M. 1995; 6 (1): 75-81

  Abstract

  Protein energy malnutrition is common among persons with ESRD and contributes substantially to morbidity and mortality. The usual methods of nutritional assessment, such as anthropometry, can be misleading because of altered tissue hydration. Bioelectrical impedance analysis (BIA) has been recommended by some as a practical nutritional assessment tool but has not been validated in patients with ESRD. Thirty-three stable patients on maintenance hemodialysis were evaluated in an ambulatory clinical research center with simultaneous BIA, dual-energy x-ray absorptiometry, and deuterium oxide (D2O) and sodium bromide (NaBr) isotope dilution studies. Standard determinations of total body water (TBW) and body cell mass (BCM) were obtained and compared with values estimated by BIA. Two separate outpatient BIA measurements were also obtained approximately 2 wk before and after the clinical research center evaluation. BCM estimated by BIA was directly correlated (r = 0.92, P < 0.0001) with BCM determined by DEXA and NaBr. TBW estimated by BIA was directly correlated (r = 0.96, P < 0.0001) with TBW determined by deuterium oxide dilution. The reactance to resistance ratio (Xc/R) derived from BIA was inversely correlated (r = -0.73, P < 0.0001) with the extracellular water/TBW ratio determined by NaBr/D2O. Bland-Altman analyses showed that for TBW, BIA was in excellent agreement with D2O dilution. BCM was modestly underestimated by BIA compared with the dual-energy x-ray absorptiometry/NaBr standard and was adjusted by linear regression. The coefficients of variation on repeated BIA measurements were below 4%, demonstrating test-retest reliability. BIA is a valid and reliable method of nutritional assessment in maintenance hemodialysis patients.

  View details for Web of Science ID A1995RK19000009

  View details for PubMedID 7579073

• THE ASSOCIATION OF INTRADIALYTIC PARENTERAL-NUTRITION ADMINISTRATION WITH SURVIVAL IN HEMODIALYSIS-PATIENTS AMERICAN JOURNAL OF KIDNEY DISEASES Chertow, G. M., Ling, J., Lew, N. L., Lazarus, J. M., Lowrie, E. G. 1994; 24 (6): 912-920

  Abstract

  Hemodialysis patients who had received intradialytic parenteral nutrition (IDPN) during 1991 were identified. These patients were compared with unexposed controls after adjusting for demographic variables, baseline renal diagnosis, diabetic status, serum albumin (ALB), creatinine (CRE), and urea reduction ratio. At lower levels of ALB (< or = 3.4 g/dL), treatment with IDPN was associated with a reduction in the odds of death at 1 year, an effect that became stronger at lower levels of CRE (< or = 8.0 mg/dL). In contrast, treatment with IDPN in patients with normal ALB was associated with increased mortality. Time trend analyses of ALB and CRE demonstrated progressive increases toward pretreatment levels in IDPN recipients that were not evident in control subjects. These time trend data suggest that in undernourished hemodialysis patients, IDPN can effect the serum levels of valid biochemical surrogates of visceral and somatic protein nutrition. Albeit retrospective, the improvement in survival at year's end among patients with ALB < or = 3.4 g/dL suggests that malnutrition and its attendant ill effects in hemodialysis patients may respond to aggressive therapeutic intervention, such as IDPN. These important findings should be prospectively confirmed in a randomized clinical trial.

  View details for Web of Science ID A1994PW00100006

  View details for PubMedID 7985668

• POTENTIAL IDENTIFIABILITY AND PREVENTABILITY OF ADVERSE EVENTS USING INFORMATION-SYSTEMS Meeting of the Society-of-General-Internal-Medicine Bates, D. W., ONEIL, A. C., Boyle, D., Teich, J., Chertow, G. M., Komaroff, A. L., Brennan, T. A. HANLEY & BELFUS INC. 1994: 404–11

  Abstract

  To evaluate the potential ability of computerized information systems (ISs) to identify and prevent adverse events in medical patients.Clinical descriptions of all 133 adverse events identified through chart review for a cohort of 3,138 medical patients were evaluated by two reviewers.For each adverse event, three hierarchical levels of IS sophistication were considered: Level 1--demographics, results for all diagnostic tests, and current medications would be available on-line; Level 2--all orders would be entered on-line by physicians; and Level 3--additional clinical data, such as automated problem lists, would be available on-line. Potential for event identification and potential for event prevention were scored by each reviewer according to two distinct sets of event monitors.Of all the adverse events, 53% were judged identifiable using Level 1 information, 58% were judged identifiable using Level 2 information, and 89% were judged identifiable using Level 3 information. The highest-yield event monitors for identifying adverse events were "panic" laboratory results, unexpected transfer to an intensive care unit, and hospital-incurred trauma. With information from Levels 1, 2, and 3, 5%, 13%, and 23% of the adverse events, respectively, were judged preventable. For preventing these adverse events, guided-dose algorithms, drug-laboratory checks, and drug-patient characteristic checks held the most potential.

  View details for Web of Science ID A1994QE64100005

  View details for PubMedID 7850564

  View details for PubMedCentralID PMC116222

• CONGENITAL OLIGONEPHROPATHY AND THE ETIOLOGY OF ADULT HYPERTENSION AND PROGRESSIVE RENAL INJURY Symposium in Honor of Neal S Bricker: The Pathophysiology of Chronic Renal Disease BRENNER, B. M., Chertow, G. M. W B SAUNDERS CO-ELSEVIER INC. 1994: 171–75

  Abstract

  Based on the associations reviewed in this report, we have hypothesized that retardation of renal development as occurs in individuals of low birth weight gives rise to increased postnatal risks for systemic and glomerular hypertension as well as enhanced risk of expression of renal disease. This hypothesis draws on observations suggesting (1) a direct relationship between birth weight and nephron number, (2) an inverse relationship between birth weight and later-life hypertension, and (3) an inverse relationship between nephron number and blood pressure, irrespective of whether nephron number is reduced congenitally or in postnatal life (as from partial renal ablation or acquired renal disease). Additional clinical and epidemiologic studies are needed to assess these initial impressions.

  View details for Web of Science ID A1994MX24700003

  View details for PubMedID 8311070

• Congenital oligonephropathy: an inborn cause of adult hypertension and progressive renal injury? Current opinion in nephrology and hypertension BRENNER, B. M., Chertow, G. M. 1993; 2 (5): 691-695

  View details for PubMedID 7922212

• BENIGN PLEURAL EFFUSIONS IN LONG-STANDING DIABETES-MELLITUS CHEST Chertow, B. S., KADZIELAWA, R., Burger, A. J. 1991; 99 (5): 1108-1111

  Abstract

  We studied intractable pleural effusions in five patients with long-standing diabetes mellitus and an additional 40 patients with left ventricular systolic dysfunction to determine whether the frequency of pleural effusions is increased in diabetic patients and, if so, the relation of pleural effusions to left ventricular dysfunction. In our initial observations, effusions were benign, were not always associated with congestive heart failure (CHF), and reaccumulated following thoracentesis. Effusions associated with CHF persisted despite medical treatment and improvement of CHF. In our study of 40 patients with similar degrees of left ventricular dysfunction, the incidence of pleural effusions in diabetic patients was 83 percent and in our nondiabetic patients was 14 percent (p less than 0.001). We conclude that pleural effusions occur more commonly in diabetic than nondiabetic patients and may be related to left ventricular dysfunction and possibly other factors leading to increased effusion.

  View details for Web of Science ID A1991FK42100013

  View details for PubMedID 2019165