Glenn M. Chertow
Norman S. Coplon/Satellite Healthcare Professor of Medicine and Professor, by courtesy, of Epidemiology and Population Health and of Health Policy
Medicine - Nephrology
Clinical Focus
- Nephrology
Academic Appointments
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Professor, Medicine - Nephrology
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Professor (By courtesy), Epidemiology and Population Health
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Professor (By courtesy), Health Policy
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Member, Bio-X
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Member, Cardiovascular Institute
Administrative Appointments
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Associate, Center for Health Policy, Center for Primary Care and Outcomes Research, Stanford University (2008 - Present)
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Professor of Medicine, Stanford University School of Medicine (2007 - Present)
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Professor of Epidemiology and Biostatistics, UCSF (2005 - 2007)
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Professor of Medicine in Residence, UCSF (2005 - 2007)
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Associate Professor of Epidemiology and Biostatistics, UCSF (2004 - 2005)
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Associate Professor of Medicine in Residence, UCSF (2001 - 2004)
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Assistant Professor of Medicine in Residence, University of California San Francisco School of Medicine, San Francisco, CA (UCSF) (1998 - 2001)
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Assistant Professor of Medicine, HMS (1997 - 1998)
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Instructor in Surgery, HMS (1966 - 1998)
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Instructor in Medicine, HMS (1995 - 1997)
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Research Fellow in Medicine, HMS (1992 - 1995)
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Clinical Fellow in Medicine, Harvard Medical School, Boston, MA (HMS) (1989 - 1992)
Honors & Awards
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Summa Cum Laude, University of Pennsylvania (1985)
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Phi Beta Kappa, University of Pennsylvania (1985)
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Hewlett Packard Outstanding Medical Graduate Award, HMS (1989)
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American Kidney Fund, Amgen Clinical Scientist in Nephrology (1993-95)
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Calvin and Sylvia Margolis Scholar in Internal Medicine, Department of Medicine, BWH (1996-97)
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Best Doctors in America designation, Woodward and White (1996)
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Best Doctors in Boston designation, Boston Magazine (1997-98)
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Top Doctors in Bay Area designation, San Francisco Magazine (1999-2000)
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Presidents Award, National Kidney Foundation (1999)
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Floyd C. Rector, Jr., Housestaff Teaching Award, Department of Medicine, UCSF (2001)
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Academic Senate Distinction in Teaching Award Honorable Mention, USCF School of Medicine (2002)
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Nominee, Kaiser Awards for Excellence in Teaching, UCSF School of Medicine (2002)
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"Top Doctors in Bay Area designation, San Francisco Magazine Inductee, American Society of Clinical Investigation (2002-2004)
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Member, American Society of Clinical Investigation (2004)
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Nominee, Kaiser Awards for Excellence in Teaching, UCSF School of Medicine (2005)
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Inductee, Society of Master Clinicians, UCSF Department of Medicine (2006)
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STAR Award, UCSF Medical Center (2006)
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National Torchbearer Award, American Kidney Fund (2007)
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Mentor of the Year, Bay Area Clinical Research Symposium (2007)
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Senior Mentor, Network of Minority Research Investigators, NIDDK (2008)
Professional Education
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Board Certification: American Board of Internal Medicine, Nephrology (2020)
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Board Certification: American Board of Internal Medicine, Internal Medicine (1992)
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Fellowship: Brigham and Women's Hospital Nephrology Fellowship (1995) MA
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Residency: Brigham and Women's Hospital Internal Medicine Residency (1992) MA
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Medical Education: Harvard Medical School (1989) MA
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MPH, Harvard School of Public Health, Epidemiology and Biostatistics (1995)
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MD, Harvard Medical School, Medicine (1989)
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BA, University of Pennsylvania (1985)
Current Research and Scholarly Interests
clinical epidemiology, health services research, decision sciences, clinical trials in acute and chronic kidney disease
Clinical Trials
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Neutrophil and Monocyte Deactivation Via the SeLective CytopheretIc Device - a Randomized Clinical Trial in Acute Kidney Injury
Recruiting
This randomized, controlled, pivotal study is intended to determine whether up to ten sequential 24-hour treatments with the Selective Cytopheretic Device (SCD) will improve survival in patients with Acute Kidney Injury (AKI) requiring continuous kidney replacement therapy (CKRT) when compared to CKRT alone (standard of care). This study is further intended to determine whether SCD therapy will reduce the duration of maintenance dialysis secondary to AKI. This study will enroll approximately 200 subjects across 30 US sites. Participants will be patients in an intensive care unit (ICU) setting with a diagnosis of AKI requiring CKRT.
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Sit Less, Interact and Move More (SLIMM) 2 Study
Recruiting
* Prolonged sitting (sedentary behavior) is a risk factor for decreased kidney function, obesity, diabetes and mortality. Prolonged sitting is associated with decreased kidney function and increased risk of diabetes, heart disease and death. * In a previous pilot study funded by NIH, it was shown that a Sit Less, Interact and Move More (SLIMM) intervention targeting sedentary behavior in people with kidney disease was able to decrease prolonged sitting but that effect was not sustained. * Therefore, the researchers are currently conducting a follow-up study named Sit Less, Interact and Move More (SLIMM) 2. * This NIH funded study is conducted at the University of Utah and Stanford University. * The purpose of this study is to see if guided resistance training (to improve muscle strength) and semaglutide (FDA approved diabetes and weight loss medication that might also improve physical function) can boost adherence to the SLIMM Intervention and reduce sedentary behavior.
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SARS-COV-2 Screening in Dialysis Facilities
Not Recruiting
Patients receiving dialysis are one of the highest risk groups for serious illness with SARS-CoV-2 infection. In addition to the inherent risks of travel to and dialysis within indoor facilities, patients receiving dialysis are more likely to be older, non-white, from disadvantaged backgrounds, and have impaired immune responses to viral infections and vaccinations. Universal testing offered at hemodialysis facilities could shield this vulnerable population from exposure, enable early identification and treatment for those affected, and reduce transmission to other patients and family members. In this pragmatic cluster randomized controlled trial as part of NIH RADx-UP Consortium, we will randomize 62 US Renal Care facilities with an estimated 2480 patients to static versus dynamic universal screening testing strategies. Static universal screening will involve offering patients SARS-CoV-2 screening tests every two weeks; the dynamic universal screening strategy will vary the frequency of testing from once every week to once every four weeks, depending on community COVID-19 case rates. We hypothesize that patients dialyzing at facilities randomized to a dynamic testing frequency responsive to community case rates will have higher test acceptability (primary outcome), experience lower rates of COVID-19 death and hospitalization, and report better experience-of-care metrics.
Stanford is currently not accepting patients for this trial. For more information, please contact Shuchi Anand, MD, (650) 725 - 2207.
2024-25 Courses
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Independent Studies (10)
- Directed Reading in Epidemiology
EPI 299 (Aut, Win, Spr, Sum) - Directed Reading in Health Research and Policy
HRP 299 (Aut, Win, Spr, Sum) - Directed Reading in Medicine
MED 299 (Aut, Win, Spr, Sum) - Early Clinical Experience in Medicine
MED 280 (Aut, Win, Spr, Sum) - Graduate Research
EPI 399 (Aut, Win, Spr, Sum) - Graduate Research
HRP 399 (Aut, Win, Spr, Sum) - Graduate Research
MED 399 (Aut, Win, Spr, Sum) - Medical Scholars Research
MED 370 (Aut, Win, Spr, Sum) - Undergraduate Research
EPI 199 (Aut, Win, Spr, Sum) - Undergraduate Research
MED 199 (Aut, Win, Spr, Sum)
- Directed Reading in Epidemiology
Graduate and Fellowship Programs
All Publications
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Pesticides and prostate cancer incidence and mortality: An environment-wide association study.
Cancer
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
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Chronic kidney disease in older adults: challenges and opportunities for the primary care provider.
BMC primary care
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
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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
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
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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
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
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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
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
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Variation in Urology Care after Urinary Stone Surgery among Veterans at High-risk for Recurrence.
Urology
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
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Prevalence of Mendelian Kidney Disease Among Patients With High-Risk APOL1 Genotypes Undergoing Commercial Genetic Testing in the United States
KIDNEY INTERNATIONAL REPORTS
2024; 9 (9): 2667-2676
View details for DOI 10.1016/j.ekir.2024.06.028
View details for Web of Science ID 001307959400001
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Acceptance of SARS-CoV-2 Surveillance Testing Among Patients Receiving Dialysis: A Cluster Randomized Trial.
JAMA network open
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
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Hexasodium fytate for the treatment of calciphylaxis: a randomised, double-blind, phase 3, placebo-controlled trial with an open-label extension
ECLINICALMEDICINE
2024; 75
View details for DOI 10.1016/j.eclinm.2024.102784
View details for Web of Science ID 001300972300001
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Hexasodium fytate for the treatment of calciphylaxis: a randomised, double-blind, phase 3, placebo-controlled trial with an open-label extension.
EClinicalMedicine
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
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Prevalence of Mendelian Kidney Disease Among Patients With High-Risk APOL1 Genotypes Undergoing Commercial Genetic Testing in the United States.
Kidney international reports
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
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Where Are Patients' Voices in Chronic Kidney Disease?
Clinical journal of the American Society of Nephrology : CJASN
2024
View details for DOI 10.2215/CJN.0000000581
View details for PubMedID 39213129
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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
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
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In memoriam: George L. Bakris, MD, 1952-2024.
Kidney international
2024
View details for DOI 10.1016/j.kint.2024.08.003
View details for PubMedID 39178909
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Hyperkalemia and risk of chronic kidney disease progression: A propensity score matched analysis.
Kidney360
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
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SGLT2 Inhibitor Use in Chronic Kidney Disease: Supporting Cardiovascular, Kidney, and Metabolic Health
KIDNEY MEDICINE
2024; 6 (8)
View details for DOI 10.1016/j.xkme.2024.100851
View details for Web of Science ID 001270728700001
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Prospective Study on Kidney Dysfunction Markers and Risk for Mortality among South Asians
KIDNEY INTERNATIONAL REPORTS
2024; 9 (8): 2537-2545
View details for DOI 10.1016/j.ekir.2024.05.025
View details for Web of Science ID 001289221400001
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Prospective Study on Kidney Dysfunction Markers and Risk for Mortality among South Asians.
Kidney international reports
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
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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
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
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Sodium-Glucose Cotransporter 2 Inhibitors in Older Patients with CKD.
Journal of the American Society of Nephrology : JASN
2024
View details for DOI 10.1681/ASN.0000000000000466
View details for PubMedID 39133046
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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
2024: 1-12
View details for DOI 10.1080/03007995.2024.2364824
View details for PubMedID 39041778
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Selonsertib in Patients with Diabetic Kidney Disease: A Phase 2b Randomized Active Run-In Clinical Trial.
Journal of the American Society of Nephrology : JASN
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
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Plasmapheresis in ANCA-Associated Vasculitis with Active Kidney Involvement in the United States (2016-2020): A Cross-Sectional Study.
Kidney360
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
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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
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
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Author Correction: IL-6 inhibition with clazakizumab in patients receiving maintenance dialysis: a randomized phase 2b trial.
Nature medicine
2024
View details for DOI 10.1038/s41591-024-03156-7
View details for PubMedID 38961226
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Patient Perspectives on Using Telemedicine During In-Center Hemodialysis: A Qualitative Study.
Kidney medicine
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
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Effects of Dapagliflozin in Patients with Membranous Nephropathy.
Glomerular diseases
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
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The Medical Costs of Determining Eligibility and Waiting for a Kidney Transplantation.
Medical care
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
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Revisiting a "Paradigm" in Cardiovascular and Kidney Disease.
Journal of the American College of Cardiology
2024; 83 (22): 2160-2162
View details for DOI 10.1016/j.jacc.2024.04.018
View details for PubMedID 38811093
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The Use of KDIGO AKI Definitions in AKI Research: PRO.
Kidney360
2024
View details for DOI 10.34067/KID.0000000000000486
View details for PubMedID 38833308
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Projecting the clinical burden of chronic kidney disease at the patient level (Inside CKD): a microsimulation modelling study.
EClinicalMedicine
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
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CALCIMIMETIC PRESCRIPTIONS FOLLOWING THE TRANSITIONAL DRUG ADD-ON PAYMENT ADJUSTMENT IN FEE-FOR-SERVICE MEDICARE PATIENTS ON DIALYSIS
ELSEVIER SCIENCE INC. 2024: S213
View details for Web of Science ID 001277006602073
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IL-6 inhibition with clazakizumab in patients receiving maintenance dialysis: a randomized phase 2b trial.
Nature medicine
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
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Association of Diabetes with Changes in Blood Pressure during Hemodialysis: A Secondary Analysis of the Frequent Hemodialysis Network Daily Trial.
American journal of nephrology
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
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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
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
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PESTICIDES AND PROSTATE CANCER INCIDENCE AND MORTALITY: AN ENVIRONMENTAL WIDE ASSOCIATION STUDY
LIPPINCOTT WILLIAMS & WILKINS. 2024: E620
View details for Web of Science ID 001263885302097
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Safety and efficacy of vadadustat vs darbepoetin alfa in patients on maintenance dialysis by prespecified subgroups of baseline ESA dose
OXFORD UNIV PRESS. 2024: I1421-I1422
View details for Web of Science ID 001267529301377
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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
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
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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
2024
View details for DOI 10.2215/CJN.0000000000000470
View details for PubMedID 38622766
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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
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
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SERUM BICARBONATE CONCENTRATIONS AND CKD PROGRESSION IN PATIENTS WITH METABOLIC ACIDOSIS: EVIDENCE FROM VALOR-CKD
W B SAUNDERS CO-ELSEVIER INC. 2024: S107
View details for Web of Science ID 001282605100349
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The Use of Telemedicine by US Nephrologists for In-Center Hemodialysis Care During the Pandemic: AnAnalysis of National Medicare Claims.
Kidney medicine
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
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A Prospective Clinical Study to EvaluAte the AbiliTy of the CloudCath System to Detect Peritonitis During In-Home Peritoneal Dialysis (CATCH).
Kidney international reports
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
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A Prospective Clinical Study to EvaluAte the AbiliTy of the CloudCath System to Detect Peritonitis During In-Home Peritoneal Dialysis (CATCH)
KIDNEY INTERNATIONAL REPORTS
2024; 9 (4): 929-940
View details for DOI 10.1016/j.ekir.2024.01.033
View details for Web of Science ID 001218441100001
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Bias and Accuracy of Glomerular Filtration Rate Estimating Equations in the US: A Systematic Review and Meta-Analysis.
JAMA network open
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
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Dapagliflozin and Blood Pressure in Patients with Chronic Kidney Disease and Albuminuria.
American heart journal
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
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Dapagliflozin in chronic kidney disease: cost-effectiveness beyond the DAPA-CKD trial.
Clinical kidney journal
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
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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
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
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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
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
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Antineutrophil Cytoplasmic Antibody-Associated Vasculitis with Active Kidney Involvement in the United States: 2016-2020.
Glomerular diseases
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
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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
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
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Population-Wide Screening for Chronic Kidney Disease.
Annals of internal medicine
2024; 177 (1): eL230370
View details for DOI 10.7326/L23-0370
View details for PubMedID 38224602
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Safety and Tolerability of the APOL1 Inhibitor, Inaxaplin, following Single- and Multiple-Ascending Doses in Healthy Adults.
Glomerular diseases
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
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Hexasodium fytate exposure-response correlations in a randomized, placebo-controlled study of patients on dialysis with cardiovascular calcification.
Frontiers in pharmacology
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
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Effects of Dapagliflozin in Chronic Kidney Disease Across the Spectrum of Age and by Sex.
Journal of general internal medicine
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
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Heterogeneous Treatment Effects of Intensive Glycemic Control on Kidney Microvascular Outcomes and Mortality in ACCORD.
Journal of the American Society of Nephrology : JASN
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
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Association of Bioimpedance Parameters with Increases in Blood Pressure during Hemodialysis.
Clinical journal of the American Society of Nephrology : CJASN
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
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Report From a Multidisciplinary Symposium on the Future of Living Kidney Donor Transplantation.
Progress in transplantation (Aliso Viejo, Calif.)
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
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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
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
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Tenapanor Improves Long-term Control of Hyperphosphatemia in Patients Receiving Maintenance Dialysis: the NORMALIZE Study.
Kidney360
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
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Muscle Mass and Serum Creatinine Concentration by Race and Ethnicity Among Hemodialysis Patients.
Journal of the American Society of Nephrology : JASN
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
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Implications of a Race Term in GFR Estimates Used to Predict AKI After Coronary Intervention.
JACC. Cardiovascular interventions
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
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Contemporary Methods for Predicting Acute Kidney Injury After Coronary Intervention.
JACC. Cardiovascular interventions
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
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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
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
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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
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
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Market Competition and Anemia Management in the United States following Dialysis Payment Reform.
Medical care
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
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Using Relative Survival to Estimate the Burden of Kidney Failure.
American journal of kidney diseases : the official journal of the National Kidney Foundation
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
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Hypocitraturia and Risk of Bone Disease in Patients With Kidney Stone Disease.
JBMR plus
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
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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
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
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Disparities in the Timing of Preoperative Hemodialysis Among Patients With End-Stage Kidney Disease.
JAMA network open
2023; 6 (7): e2326326
View details for DOI 10.1001/jamanetworkopen.2023.26326
View details for PubMedID 37505500
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Use of Wastewater Metrics to Track COVID-19 in the US.
JAMA network open
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
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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
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
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Effects of Dapagliflozin on Hospitalizations in Patients With Chronic Kidney Disease.
Annals of internal medicine
2023; 176 (7): eL230070
View details for DOI 10.7326/L23-0070
View details for PubMedID 37459628
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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
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
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Inaxaplin for Proteinuric Kidney Disease in Persons with Two <i>APOL1</i> Variants
NEW ENGLAND JOURNAL OF MEDICINE
2023; 388 (26): 2491
View details for Web of Science ID 001058999200021
View details for PubMedID 37379148
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Inaxaplin for Proteinuric Kidney Disease in Persons with Two APOL1 Variants. Reply.
The New England journal of medicine
2023; 388 (26): 2491
View details for DOI 10.1056/NEJMc2304780
View details for PubMedID 37379148
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Hypocitraturia and Risk of Bone Disease in Patients With Kidney Stone Disease
JBMR PLUS
2023
View details for DOI 10.1002/jbm4.10786
View details for Web of Science ID 001018463200001
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Heterogeneous treatment effects of intensive glycemic control on kidney microvascular outcomes in ACCORD.
medRxiv : the preprint server for health sciences
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
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Groundwater constituents and the incidence of kidney cancer.
Cancer
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
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Estimating Life Years from Transplant in Older Candidates
ELSEVIER SCIENCE INC. 2023: S681
View details for Web of Science ID 001087126902166
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Dapagliflozin and Anemia in Patients with Chronic Kidney Disease.
NEJM evidence
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
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APOL1 GENOTYPING AND PROTEINURIC KIDNEY DISEASE IN EUROPE
OXFORD UNIV PRESS. 2023: I144-I145
View details for Web of Science ID 001022961100136
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REASONS FOR DIALYSIS INITIATION AND SAFETY OF DAPAGLIFLOZIN AMONG DIALYSIS PARTICIPANTS: NEW INSIGHTS FROMDAPA-CKD
OXFORD UNIV PRESS. 2023: I52-I53
View details for Web of Science ID 001022961100049
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EFFECT OF DAPAGLIFLOZIN IN PATIENTS WITH CKD ACROSS THE SPECTRUM OF AGE AND BY SEX
OXFORD UNIV PRESS. 2023: I638-I639
View details for Web of Science ID 001022961102124
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AMBIENT HEAT EXPOSURE AND ESTIMATED GLOMERULAR FILTRATION RATE TRAJECTORY: A POST-HOC ANALYSIS OF THE DAPA-CKD TRIAL
OXFORD UNIV PRESS. 2023: I472
View details for Web of Science ID 001022961101270
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Population-Wide Screening for Chronic Kidney Disease : A Cost-Effectiveness Analysis.
Annals of internal medicine
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
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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
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
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Effects of Dapagliflozin in Chronic Kidney Disease, With and Without Other Cardiovascular Medications: DAPA-CKD Trial.
Journal of the American Heart Association
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
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Effects of newer kidney protective agents on kidney endpoints provide implications for future clinical trials.
Kidney international
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
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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
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
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Kidney Stone Events after Kidney Transplant in the United States.
Clinical journal of the American Society of Nephrology : CJASN
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
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Estimated Effect of Parathyroidectomy on Long-Term Kidney Function in Adults With Primary Hyperparathyroidism.
Annals of internal medicine
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
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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
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
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Clinically Indicated, Equitable Care for Ischemic Heart Disease in CKD: A Call to Action.
Journal of the American Society of Nephrology : JASN
2023; 34 (4): 525-526
View details for DOI 10.1681/ASN.0000000000000100
View details for PubMedID 37000953
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Feasibility and Acceptability of SARS-CoV-2 Screening among Patients Receiving Hemodialysis: A Pilot Study.
Clinical journal of the American Society of Nephrology : CJASN
2023
View details for DOI 10.2215/CJN.0000000000000137
View details for PubMedID 36976655
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Inaxaplin for Proteinuric Kidney Disease in Persons with Two APOL1 Variants.
The New England journal of medicine
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
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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
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
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Class I and II Human Leukocyte Antigen Serotypes Associated with End-Stage Kidney Disease due to Membranoproliferative Glomerulonephritis and Dense Deposit Disease
ELSEVIER SCIENCE INC. 2023: S1422-S1423
View details for Web of Science ID 000990969803123
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The potential roles of galectin-3 in AKI and CKD.
Frontiers in physiology
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
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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
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
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Cardiovascular Drug Use After Acute Kidney Injury Among Hospitalized Patients With a History of Myocardial Infarction.
Kidney international reports
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
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Efficacy of Dapagliflozin by Baseline Diabetes Medications: A Prespecified Analysis From the DAPA-CKD Study.
Diabetes care
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
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Association of Pretransplant Coronary Heart Disease Testing With Early Kidney Transplant Outcomes.
JAMA internal medicine
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
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Potassium reduction with sodium zirconium cyclosilicate in patients with heart failure.
ESC heart failure
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
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Effects of Dapagliflozin on Hospitalizations in Patients With Chronic Kidney Disease : A Post Hoc Analysis of DAPA-CKD.
Annals of internal medicine
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
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Association between cause of kidney failure and fracture incidence in a national US dialysis population cohort study.
Clinical kidney journal
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
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Overall Adverse Event Profile of Vadadustat for the Treatment of Anemia Associated With Chronic Kidney Disease in Phase 3 Trials
AMERICAN JOURNAL OF NEPHROLOGY
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
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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
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
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Effects of Bardoxolone Methyl in Alport Syndrome.
Clinical journal of the American Society of Nephrology : CJASN
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
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Apixaban for Patients with Atrial Fibrillation on Hemodialysis: A Multicenter Randomized Controlled Trial.
Circulation
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
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Risks for Anaphylaxis With Intravenous Iron Formulations.
Annals of internal medicine
2022; 175 (11): W143-W144
View details for DOI 10.7326/L22-0283
View details for PubMedID 36375166
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A Phase 2b Randomized Controlled Trial of Selonsertib in Moderate to Severe Diabetic Kidney Disease (MOSAIC)
AMER SOC NEPHROLOGY. 2022: 28
View details for Web of Science ID 001261054400095
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Effects of Dapagliflozin in People without Diabetes and with Microalbuminuria.
Clinical journal of the American Society of Nephrology : CJASN
2022; 17 (11): 1665-1668
View details for DOI 10.2215/CJN.07290622
View details for PubMedID 36344217
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Association Between Cause of Kidney Failure and Fracture Incidence in a National US Dialysis Population Cohort Study
AMER SOC NEPHROLOGY. 2022: 652
View details for Web of Science ID 001261054404215
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Risks for Anaphylaxis With Intravenous Iron Formulations.
Annals of internal medicine
2022; 175 (11): W143
View details for DOI 10.7326/L22-0282
View details for PubMedID 36375165
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National Imaging Trends for Suspected Urinary Stone Disease in the Emergency Department.
JAMA internal medicine
2022
View details for DOI 10.1001/jamainternmed.2022.4939
View details for PubMedID 36315134
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APOL1 G3 Variant Is Associated with Cardiovascular Mortality and Sudden Cardiac Death in Patients Receiving Maintenance Hemodialysis of European Ancestry.
Cardiorenal medicine
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
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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
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
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Effects of Dapagliflozin in People without Diabetes and with Microalbuminuria
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
2022
View details for DOI 10.2215/CJN.07290622
View details for Web of Science ID 000863520500001
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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
WILEY. 2022: 31
View details for Web of Science ID 000864433100054
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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
OXFORD UNIV PRESS. 2022: 2407
View details for Web of Science ID 000894947901652
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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
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
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Parathyroidectomy and Cinacalcet Use in Medicare-Insured Kidney Transplant Recipients.
American journal of kidney diseases : the official journal of the National Kidney Foundation
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
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Cardiovascular Effects of Home Dialysis Therapies: A Scientific Statement From the American Heart Association
CIRCULATION
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
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Association between cause of kidney failure and fracture incidence in a national US dialysis population cohort study
CLINICAL KIDNEY JOURNAL
2022
View details for DOI 10.1093/ckj/sfac193
View details for Web of Science ID 000855410400001
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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
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
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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
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
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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
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
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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
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
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Erythropoietic effects of vadadustat in patients with anemia associated with chronic kidney disease.
American journal of hematology
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
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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
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
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APOL1 INHIBITION BY VX-147 AS A TARGETED THERAPY FOR APOL1-MEDIATED KIDNEY DISEASE
W B SAUNDERS CO-ELSEVIER INC. 2022: 769
View details for Web of Science ID 000797690900026
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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
OXFORD UNIV PRESS. 2022: I386-I387
View details for Web of Science ID 000813350702002
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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
OXFORD UNIV PRESS. 2022: I392-I393
View details for Web of Science ID 000813350702006
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EFFECTS OF DAPAGLIFLOZIN IN PATIENTS WITH CHRONIC KIDNEY DISEASE ACCORDING TO BACKGROUND ANGIOTENSIN-CONVERTING ENZYME INHIBITOR AND ANGIOTENSIN RECEPTOR BLOCKER DOSE
OXFORD UNIV PRESS. 2022: I847-I848
View details for Web of Science ID 000813350704141
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Effect of dapagliflozin on kidney and cardiovascular outcomes by baseline KDIGO risk categories: a post hoc analysis of the DAPA-CKD trial.
Diabetologia
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 2022
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<p>Emerging Role of Clinical Genetics in CKD & nbsp;</p>
KIDNEY MEDICINE
2022; 4 (4)
View details for DOI 10.1016/ j.xkme.2022.100435
View details for Web of Science ID 000793559900004
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TABLO HEMODIALYSIS SYSTEMS COULD INCREASE RECOMMENDATIONS OF HOME HEMODIALYSIS FOR PATIENTS
W B SAUNDERS CO-ELSEVIER INC. 2022: S105
View details for Web of Science ID 000772365300347
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THE TABLO HEMODIALYSIS SYSTEM INCREASES PATIENT LIKELIHOOD FOR HHD ADOPTION
W B SAUNDERS CO-ELSEVIER INC. 2022: S108
View details for Web of Science ID 000772365300357
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Efficacy and Safety of Dapagliflozin in Patients With CKD Across Major Geographic Regions.
Kidney international reports
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
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Emerging Role of Clinical Genetics in CKD.
Kidney medicine
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
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Trends in Coronary Artery Disease Screening before Kidney Transplantation.
Kidney360
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
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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
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
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Dialysis Initiation in Patients With Chronic Coronary Disease and Advanced Chronic Kidney Disease in ISCHEMIA-CKD.
Journal of the American Heart Association
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
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Long-Term Clinical Impact of Contrast-Associated Acute Kidney Injury Following PCI: AnADAPT-DES Substudy.
JACC. Cardiovascular interventions
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
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Changing the Trajectory of Heart Failure and Kidney Disease.
Clinical journal of the American Society of Nephrology : CJASN
2022
View details for DOI 10.2215/CJN.00470122
View details for PubMedID 35232819
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Trends in Cost Attributable to Kidney Transplantation Evaluation and Waiting List Management in the United States, 2012-2017.
JAMA network open
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
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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
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
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Cost-Effectiveness of Dapagliflozin for Non-diabetic Chronic Kidney Disease.
Journal of general internal medicine
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
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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
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
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SARS-CoV-2 Neutralizing Monoclonal Antibodies for the Treatment of COVID-19 in Kidney Transplant Recipients.
Kidney360
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
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Quetelet (Body Mass) Index and Effects of Dapagliflozin in CKD.
Diabetes, obesity & metabolism
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
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Twenty-four-hour Urine Testing and Urinary Stone Disease Recurrence in Veterans
UROLOGY
2022; 159: 33-40
View details for DOI 10.1016/j.urology.2021.10.005
View details for Web of Science ID 000743888900008
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The CALCIPHYX study: a randomized, double-blind, placebo-controlled, Phase 3 clinical trial of SNF472 for the treatment of calciphylaxis.
Clinical kidney journal
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
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Breaking the Barriers to Innovation in Kidney Care.
Clinical journal of the American Society of Nephrology : CJASN
2022
View details for DOI 10.2215/CJN.15721221
View details for PubMedID 35168993
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INSIDE CKD: PROJECTING THE ECONOMIC BURDEN OF CHRONIC KIDNEY DISEASE USING PATIENT-LEVEL MICROSIMULATION
ELSEVIER SCIENCE INC. 2022: S73
View details for Web of Science ID 000746490200321
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Renal Morbidity Following Radical Cystectomy in Patients with Bladder Cancer.
European urology open science
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
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SARS-CoV-2 Vaccine Antibody Response and Breakthrough Infection in Patients Receiving Dialysis.
Annals of internal medicine
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
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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
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
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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
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
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Timing of Antihypertensive Medications on Key Outcomes in Hemodialysis: A Cluster Randomized Trial.
Kidney360
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
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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
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
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Challenging Assumptions of Outcomes and Costs Comparing Peritoneal and Hemodialysis.
Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research
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
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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
2021
View details for DOI 10.1053/j.ajkd.2021.08.008
View details for PubMedID 34728104
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Safety and Efficacy of Tenapanor for Long-term Serum Phosphate Control in Maintenance Dialysis: A 52-Week Randomized Phase 3 Trial (PHREEDOM)
KIDNEY360
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
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Vadadustat for Anemia in Patients with Dialysis-Dependent or Non-Dialysis-Dependent Chronic Kidney Disease
NEW ENGLAND JOURNAL OF MEDICINE
2021; 385 (16)
View details for Web of Science ID 000706806300028
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COVID19 Vaccine Type and Humoral Immune Response in Patients Receiving Dialysis.
Journal of the American Society of Nephrology : JASN
2021
View details for DOI 10.1681/ASN.2021070936
View details for PubMedID 34645698
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The Predialysis Serum Sodium Level Modifies the Effect of Hemodialysis Frequency on Left-Ventricular Mass: The Frequent Hemodialysis Network Trials.
Kidney & blood pressure research
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
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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
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
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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
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
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The effects of dapagliflozin on kidney and cardiovascular outcomes in patients with chronic kidney disease with and without heart failure
OXFORD UNIV PRESS. 2021: 2913
View details for Web of Science ID 000720456903214
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Inside CKD: modelling the clinical and economic impact of routine screening for albuminuria in people with type 2 diabetes
SPRINGER. 2021: 51
View details for Web of Science ID 000696550100093
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TWENTY-FOUR HOUR URINE TESTING AND URINARY STONE DISEASE RECURRENCE IN VETERANS
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
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Efficacy and safety of dapagliflozin on kidney and cardiovascular outcomes by baseline albuminuria: a secondary analysis of the DAPA-CKD trial
SPRINGER. 2021: 30
View details for Web of Science ID 000696550100053
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Inside CKD: modelling the future global burden of chronic kidney disease in patients with type 2 diabetes
SPRINGER. 2021: 322
View details for Web of Science ID 000696550100616
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Inside CKD: modelling the direct economic burden of concomitant chronic kidney disease and type 2 diabetes
SPRINGER. 2021: 322-323
View details for Web of Science ID 000696550100617
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The Contribution of Known Familial Cardiovascular Disease Genes to Sudden Cardiac Death in Patients Undergoing Hemodialysis
CARDIORENAL MEDICINE
2021
View details for DOI 10.1159/000517123
View details for Web of Science ID 000684289700001
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The Contribution of Known Familial Cardiovascular Disease Genes to Sudden Cardiac Death in Patients Undergoing Hemodialysis.
Cardiorenal medicine
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
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Effects of Dapagliflozin in Patients With Kidney Disease, With and Without HeartFailure.
JACC. Heart failure
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
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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
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
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THE EFFECT OF DAPAGLIFLOZIN IN PATIENTS WITH EGFR < 30 ML/MIN/1.73M2: FINDINGS FROM THE DAPA-CKD TRIAL
WILEY. 2021: 33-34
View details for Web of Science ID 000689277100097
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The potential roles of osmotic and non-osmotic sodium handling in mediating effects of SGLT2 inhibitors on heart failure.
Journal of cardiac failure
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
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Effects of Dapagliflozin in Stage 4 Chronic Kidney Disease.
Journal of the American Society of Nephrology : JASN
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
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Utility of Phosphate Binder Equivalent Dose Concept Reply
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
2021; 32 (7): 1824-1825
View details for DOI 10.1681/ASN.2021050606
View details for Web of Science ID 000753511400026
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Authors' Reply.
Journal of the American Society of Nephrology : JASN
2021; 32 (7): 1824-1825
View details for DOI 10.1681/ASN.2021050606
View details for PubMedID 36630522
View details for PubMedCentralID PMC8425642
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Karnofsky Performance Score-Failure to Thrive as a Frailty Proxy?
Transplantation direct
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
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Chronic Inflammation in Chronic Kidney Disease Progression: Role of Nrf2
KIDNEY INTERNATIONAL REPORTS
2021; 6 (7): 1775-1787
View details for DOI 10.1016/j.ekir.2021.04.023
View details for Web of Science ID 000671872900006
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Chronic Inflammation in Chronic Kidney Disease Progression: Role of Nrf2.
Kidney international reports
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
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SNF472: mechanism of action and results from clinical trials.
Current opinion in nephrology and hypertension
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
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Patient-Reported Experiences with Dialysis Care and Provider Visit Frequency.
Clinical journal of the American Society of Nephrology : CJASN
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
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Estimated SARS-CoV-2 Seroprevalence in US Patients Receiving Dialysis 1 Year After the Beginning of the COVID-19 Pandemic.
JAMA network open
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
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Patient-Reported Experiences with Dialysis Care and Provider Visit Frequency
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
2021; 16 (7): 1052-1060
View details for DOI 10.2215/CJN.16621020
View details for Web of Science ID 000675905100012
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Efficacy and Safety of Dapagliflozin by Baseline Glycemic Status: A Prespecified Analysis From the DAPA-CKD Trial.
Diabetes care
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
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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
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
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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
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
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Antibody Response to COVID-19 Vaccination in Patients Receiving Dialysis.
Journal of the American Society of Nephrology : JASN
2021
View details for DOI 10.1681/ASN.2021050611
View details for PubMedID 34117129
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Poor Reliability of Karnofsky Performance Score in Kidney Transplant Candidates
WILEY. 2021: 662
View details for Web of Science ID 000705310102383
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Invasive Management of Coronary Artery Disease in Advanced Renal Disease.
Kidney international reports
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
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HOSPITALIZATION IN PATIENTS RECEIVING MAINTENANCE DIALYSIS WITH HYPERPHOSPHATEMIA RANDOMIZED TO TENAPANOR OR SEVELAMER
ELSEVIER SCIENCE INC. 2021: S234
View details for Web of Science ID 000660039401286
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Performance versus Risk Factor-Based Approaches to Coronary Artery Disease Screening in Waitlisted Kidney Transplant Candidates.
Cardiorenal medicine
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
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Serial SARS-CoV-2 Receptor-Binding Domain Antibody Responses in Patients Receiving Dialysis.
Annals of internal medicine
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
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National Estimates of CKD Prevalence and Potential Impact of Estimating Glomerular Filtration Rate Without Race.
Journal of the American Society of Nephrology : JASN
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
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Barriers to ACEI/ARB Use in Proteinuric Chronic Kidney Disease: An Observational Study.
Mayo Clinic proceedings
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
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DAPAGLIFLOZIN DECREASES ALBUMINURIA IN PATIENTS WITH CHRONIC KIDNEY DISEASE WITH AND WITHOUT TYPE 2 DIABETES: INSIGHTS FROM THE DAPA-CKD TRIAL
OXFORD UNIV PRESS. 2021
View details for Web of Science ID 000713465601391
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SARS-COV-2 VACCINE ACCEPTABILITY IN PATIENTS ON DIALYSIS: A NATIONWIDE SURVEY
W B SAUNDERS CO-ELSEVIER INC. 2021: 831
View details for Web of Science ID 000642322000031
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INSIDE CKD: MODELLING THE ECONOMIC BURDEN OF CHRONIC KIDNEY DISEASE IN THE AMERICAS AND THE ASIA-PACIFIC REGION USING PATIENT-LEVEL MICROSIMULATION
OXFORD UNIV PRESS. 2021
View details for Web of Science ID 000713465600279
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INSIDE CKD: MODELLING THE IMPACT OF IMPROVED SCREENING FOR CHRONIC KIDNEY DISEASE IN THE AMERICAS AND ASIA-PACIFIC REGION
OXFORD UNIV PRESS. 2021
View details for Web of Science ID 000713465600247
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Body Composition Changes Following Dialysis Initiation and Cardiovascular and Mortality Outcomes in CRIC (Chronic Renal Insufficiency Cohort): A Bioimpedance Analysis Substudy.
Kidney medicine
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
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Safety and Efficacy of Vadadustat for Anemia in Patients Undergoing Dialysis.
The New England journal of medicine
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
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Vadadustat in Patients with Anemia and Non-Dialysis-Dependent CKD.
The New England journal of medicine
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
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SARS-CoV-2 Vaccine Acceptability in Patients on Hemodialysis: A Nationwide Survey.
Journal of the American Society of Nephrology : JASN
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
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Targeting Sedentary Behavior in CKD: A Pilot and Feasibility Randomized Controlled Trial.
Clinical journal of the American Society of Nephrology : CJASN
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
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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
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
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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
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
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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
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
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Removing Race from eGFR calculations: Implications for Urologic Care.
Urology
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
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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
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
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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
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
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Estimated Impact of Novel Coronavirus-19 and Transplant Center Inactivity on ESRD-related Patient Mortality in the United States.
Clinical transplantation
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
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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
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
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Chronic kidney disease, atherosclerotic plaque characteristics on carotid magnetic resonance imaging, and cardiovascular outcomes.
BMC nephrology
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
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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
2021
View details for DOI 10.1053/j.ajkd.2020.11.007
View details for PubMedID 33568321
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Cost Structures of US Organ Procurement Organizations.
Transplantation
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
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Race and Place in ESKD.
Kidney international reports
2021; 6 (2): 252–53
View details for DOI 10.1016/j.ekir.2020.11.027
View details for PubMedID 33617609
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And Then There Were Three: Effects of Pretransplant Dialysis on Multiorgan Transplantation.
Transplantation direct
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
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Association of 152 Biomarker Reference Intervals with All-Cause Mortality in Participants of a General United States Survey from 1999 to 2010.
Clinical chemistry
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
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SARS-CoV-2 vaccine antibody response and breakthrough infection in dialysis.
medRxiv : the preprint server for health sciences
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
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Kidney Disease, Hypertension Treatment, and Cerebral Perfusion and Structure.
American journal of kidney diseases : the official journal of the National Kidney Foundation
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
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Clinical laboratory tests associated with survival in patients with metastatic renal cell carcinoma: A Laboratory Wide Association Study (LWAS).
Urologic oncology
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
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Vadadustat for Anemia in Patients with Dialysis-Dependent or Non-Dialysis-Dependent Chronic Kidney Disease. Reply.
The New England journal of medicine
2021; 385 (16): e56
View details for DOI 10.1056/NEJMc2110095
View details for PubMedID 34644482
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Population-based identification and temporal trend of children with primary nephrotic syndrome: The Kaiser Permanente nephrotic syndrome study.
PloS one
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
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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
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
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COVID19 vaccine type and humoral immune response in patients receiving dialysis.
medRxiv : the preprint server for health sciences
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
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Laboratory correlates of SARS-CoV-2 seropositivity in a nationwide sample of patients on dialysis in the U.S.
PloS one
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
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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
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
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Aldosterone sensitivity: an opportunity for investigation into the pathogenesis of hypertension.
American journal of physiology. Renal physiology
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
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Combination treatment with tenapanor and sevelamer synergistically reduces urinary phosphorus excretion in rats.
American journal of physiology. Renal physiology
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
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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
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
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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
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
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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
2021; 9 (1): 22–31
View details for Web of Science ID 000600606200011
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Antibody Response to COVID-19 vaccination in Patients Receiving Dialysis.
medRxiv : the preprint server for health sciences
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
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AUTHOR REPLY.
Urology
2021; 155: 76
View details for DOI 10.1016/j.urology.2021.05.058
View details for PubMedID 34489006
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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
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
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Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD)
LIPPINCOTT WILLIAMS & WILKINS. 2020: E482–E483
View details for Web of Science ID 000639226400043
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Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD)
LIPPINCOTT WILLIAMS & WILKINS. 2020: E482–E483
View details for Web of Science ID 000598973900043
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Dapagliflozin And Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD)
CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS. 2020: 1111
View details for Web of Science ID 000599814300024
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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
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
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Laboratory-wide association study of survival with prostate cancer.
Cancer
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
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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
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
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Effect of Dapagliflozin on Clinical Outcomes in Patients with Chronic Kidney Disease, With and Without Cardiovascular Disease.
Circulation
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
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Factors Associated With Failure to Achieve the Intensive Blood Pressure Target in the Systolic Blood Pressure Intervention Trial (SPRINT).
Hypertension (Dallas, Tex. : 1979)
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
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Pharmacokinetics of apixaban in patients with end stage renal disease on hemodialysis and atrial fibrillation: results from the RENAL-AF trial
OXFORD UNIV PRESS. 2020: 3373
View details for Web of Science ID 000606106303380
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Cardiovascular Safety and Efficacy of Vadadust for the Treatment of Anemia in Non-Dialysis Dependent CKD: Design and Baseline Characteristics.
American heart journal
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
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Self-care training using the Tablo hemodialysis system.
Hemodialysis international. International Symposium on Home Hemodialysis
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
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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
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
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One-year safety and efficacy of intravenous etelcalcetide in patients on hemodialysis with secondary hyperparathyroidism
NEPHROLOGY DIALYSIS TRANSPLANTATION
2020; 35 (10): 1769–78
View details for DOI 10.1093/ndt/gfz039
View details for Web of Science ID 000607839600018
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Effects of Bardoxolone Methyl on Hepatic Enzymes in Patients with Type 2 Diabetes Mellitus and Stage 4 CKD.
Clinical and translational science
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
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Patient-reported outcomes from the investigational device exemption study of the Tablo hemodialysis system.
Hemodialysis international. International Symposium on Home Hemodialysis
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
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Drug Development in Kidney Disease: Proceedings From a Multistakeholder Conference.
American journal of kidney diseases : the official journal of the National Kidney Foundation
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
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Does really central venous pressure affect the risk of diuretic-associated acute kidney injury after cardiac surgery?
American heart journal
2020; 226: 252
View details for DOI 10.1016/j.ahj.2020.04.002
View details for PubMedID 32811639
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Analysis of Primary Hyperparathyroidism Screening Among US Veterans With Kidney Stones.
JAMA surgery
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
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Early Delays in Insurance Coverage and Long-term Use of Home-based Peritoneal Dialysis.
Medical care
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
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SNF472 CONSISTENTLY SLOWS PROGRESSION OF CORONARY CALCIFICATION IN PATIENTS ON HEMODIALYSIS: SUBGROUP ANALYSIS OF THE CALIPSO STUDY
OXFORD UNIV PRESS. 2020: 92
View details for Web of Science ID 000554536200413
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SNF472 CONSISTENTLY SLOWS PROGRESSION OF CORONARY CALCIFICATION IN PATIENTS ON HEMODIALYSIS: SUBGROUP ANALYSIS OF THE CALIPSO STUDY
OXFORD UNIV PRESS. 2020: 92
View details for Web of Science ID 000562392100622
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Baseline Diastolic Blood Pressure and Cardiovascular Outcomes in SPRINT Participants with Chronic Kidney Disease.
Kidney360
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
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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
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
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Targeting Vascular Calcification in Chronic Kidney Disease.
JACC. Basic to translational science
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
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OPEN-LABEL STUDY OF THE PHARMACOKINETICS, SAFETY, AND TOLERABILITY OF DM199 IN SUBJECTS WITH DIABETES AND CHRONIC KIDNEY DISEASE
W B SAUNDERS CO-ELSEVIER INC. 2020: 542–43
View details for Web of Science ID 000522408300035
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The Urine Albumin-Creatinine Ratio and Kidney Function after Nephrectomy.
The Journal of urology
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
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The ongoing search for a robust clinical prediction model of ICU AKI
CLINICAL NEPHROLOGY
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
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AKI-A Relevant Safety End Point?
American journal of kidney diseases : the official journal of the National Kidney Foundation
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
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Screening Rates for Primary Aldosteronism in Resistant Hypertension: A Cohort Study.
Hypertension (Dallas, Tex. : 1979)
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
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Outcomes after left ventricular assist device implantation in patients with acute kidney injury
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
2020; 159 (2): 477-+
View details for DOI 10.1016/j.jtcvs.2019.03.064
View details for Web of Science ID 000507380200052
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Effects of etelcalcetide on fibroblast growth factor 23 in patients with secondary hyperparathyroidism receiving hemodialysis.
Clinical kidney journal
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
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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
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
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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
2020
View details for DOI 10.1053/j.ajkd.2020.07.007
View details for PubMedID 32763259
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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
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
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Innovation in hemodialysis: Using the Biodesign process to identify unmet needs.
The journal of vascular access
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
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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
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
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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
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
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Toward telemedicine-compatible physical functioning assessments in kidney transplant candidates.
Clinical transplantation
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
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Health Status after Invasive or Conservative Care in Coronary and Advanced Kidney Disease.
The New England journal of medicine
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
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Alport Syndrome Classification and Management.
Kidney medicine
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
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Apixaban versus Warfarin in Patients with Atrial Fibrillation and Advanced Chronic Kidney Disease.
Circulation
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
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Prolonged Hospitalization Following Acute Respiratory Failure.
Chest
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
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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
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
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Management of Coronary Disease in Patients with Advanced Kidney Disease.
The New England journal of medicine
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
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Effects of SNF472, a Novel Inhibitor of Hydroxyapatite Crystallization in Patients Receiving Hemodialysis - Subgroup Analyses of the CALIPSO Trial.
Kidney international reports
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
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Preparing for Hemodialysis
CHRONIC RENAL DISEASE, 2ND EDITION
2020: 1157–73
View details for DOI 10.1016/B978-0-12-815876-0.00070-X
View details for Web of Science ID 000489824100070
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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
2020
View details for DOI 10.1053/j.ajkd.2020.10.007
View details for PubMedID 33271212
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Dapagliflozin in Patients with Chronic Kidney Disease.
The New England journal of medicine
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
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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)
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
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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
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
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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
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
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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
LIPPINCOTT WILLIAMS & WILKINS. 2019: E988–E989
View details for Web of Science ID 000508228600062
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Effect of SNF472 on Progression of Cardiovascular Calcification in Patients on Hemodialysis (Results of a Phase 2 Randomized Controlled Study: CaLIPSO)
LIPPINCOTT WILLIAMS & WILKINS. 2019: E967
View details for Web of Science ID 000508228600011
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A double-blind, randomized, placebo-controlled pilot trial to evaluate safety and efficacy of vorapaxar on arteriovenous fistula maturation.
The journal of vascular access
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
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Acute Kidney Injury in Children Hospitalized With Diarrheal Illness in the United States.
Hospital pediatrics
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
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Urinary Stone Disease in Pregnancy: A Claims-Based Analysis of 1.4 Million Patients.
The Journal of urology
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
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Slowing Progression of Cardiovascular Calcification with SNF472 in Patients on Hemodialysis: Results of a Randomized, Phase 2b Study.
Circulation
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
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Safety and efficacy of the Tablo hemodialysis system for in-center and home hemodialysis.
Hemodialysis international. International Symposium on Home Hemodialysis
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
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Antidiabetic medication use in patients with type 2 diabetes and chronic kidney disease
JOURNAL OF DIABETES AND ITS COMPLICATIONS
2019; 33 (11)
View details for DOI 10.1016/j.jdiacomp2019.107423
View details for Web of Science ID 000497890000003
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Angiotensin-related genetic determinants of cardiovascular disease in patients undergoing hemodialysis
NEPHROLOGY DIALYSIS TRANSPLANTATION
2019; 34 (11): 1924–31
View details for DOI 10.1093/ndt/gfy191
View details for Web of Science ID 000498168100018
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Chronic Kidney Disease and the Adiposity Paradox: Valid or Confounded?
JOURNAL OF RENAL NUTRITION
2019; 29 (6): 521–28
View details for DOI 10.1053/j.jrn.2018.11.011
View details for Web of Science ID 000493897600010
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Current Status of Angiotensin Receptor Blocker Recalls.
Hypertension (Dallas, Tex. : 1979)
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
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Percutaneous Kidney Biopsy and the Utilization of Blood Transfusion and Renal Angiography Among Hospitalized Adults
KIDNEY INTERNATIONAL REPORTS
2019; 4 (10): 1435–45
View details for DOI 10.1016/j.ekir.2019.07.008
View details for Web of Science ID 000488859300010
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Percutaneous Kidney Biopsy and the Utilization of Blood Transfusion and Renal Angiography Among Hospitalized Adults.
Kidney international reports
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
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Modification of eGFR-Based CKD Definitions: Perfect, or Enemy of the Good?
Journal of the American Society of Nephrology : JASN
2019
View details for DOI 10.1681/ASN.2019070743
View details for PubMedID 31506290
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Effects of Selonsertib in Patients with Diabetic Kidney Disease.
Journal of the American Society of Nephrology : JASN
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
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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
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
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A Pilot Randomized Trial of Ferric Citrate Coordination Complex for the Treatment of Advanced CKD.
Journal of the American Society of Nephrology : JASN
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
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A phase II trial showing improvements in calcific uraemic arteriolopathy wound healing, pain and quality of life during SNF472 treatment
WILEY. 2019: 39–40
View details for Web of Science ID 000474478800062
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Testing two (of several) intravenous iron dosing strategies in hemodialysis
ANNALS OF TRANSLATIONAL MEDICINE
2019; 7
View details for DOI 10.21037/atm.2019.05.75
View details for Web of Science ID 000483693200055
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Challenges in Assessing the Burden of Hospitalized Heart Failure in End-Stage Kidney Disease
JOURNAL OF CARDIAC FAILURE
2019; 25 (7): 534–36
View details for DOI 10.1016/j.cardfail.2019.05.001
View details for Web of Science ID 000479183600006
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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
2019; 34 (7): 1115–24
View details for DOI 10.1093/ndt/gfy318
View details for Web of Science ID 000484368300011
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Asymmetric dimethylarginine, erythropoietin resistance, and anemia in CKD.
Annals of translational medicine
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
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Testing two (of several) intravenous iron dosing strategies in hemodialysis.
Annals of translational medicine
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
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Asymmetric dimethylarginine, erythropoietin resistance, and anemia in CKD
ANNALS OF TRANSLATIONAL MEDICINE
2019; 7
View details for DOI 10.21037/atm.2019.04.22
View details for Web of Science ID 000483693200012
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Influence of prediabetes on the effects of intensive systolic blood pressure control on kidney events.
American journal of hypertension
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
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Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy
NEW ENGLAND JOURNAL OF MEDICINE
2019; 380 (24): 2295–2306
View details for DOI 10.1056/NEJMoa1811744
View details for Web of Science ID 000471299100008
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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)
OXFORD UNIV PRESS. 2019
View details for Web of Science ID 000495412900718
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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)
OXFORD UNIV PRESS. 2019
View details for Web of Science ID 000495412902046
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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
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
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Low testosterone is associated with frailty, muscle wasting and physical dysfunction among men receiving hemodialysis: a longitudinal analysis
NEPHROLOGY DIALYSIS TRANSPLANTATION
2019; 34 (5): 802–10
View details for DOI 10.1093/ndt/gfy252
View details for Web of Science ID 000473748300012
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Association of Hospitalization and Mortality Among Patients Initiating Dialysis With Hemodialysis Facility Ownership and Acquisitions
JAMA NETWORK OPEN
2019; 2 (5)
View details for DOI 10.1001/jamanetworkopen.2019.3987
View details for Web of Science ID 000476806200060
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Hypertension Hot Potato - Anatomy of the Angiotensin-Receptor Blocker Recalls
NEW ENGLAND JOURNAL OF MEDICINE
2019; 380 (17): 1589–91
View details for DOI 10.1056/NEJMp1901657
View details for Web of Science ID 000465598600004
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Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy.
The New England journal of medicine
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
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Treatment of metabolic acidosis with an intestinal binder
LANCET
2019; 393 (10179): 1387–88
View details for DOI 10.1016/S0140-6736(19)30230-2
View details for Web of Science ID 000463561000005
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Outcomes after left ventricular assist device implantation in patients with acute kidney injury.
The Journal of thoracic and cardiovascular surgery
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
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Efficacy and Safety of Tenapanor in Patients with Hyperphosphatemia Receiving Maintenance Hemodialysis: A Randomized Phase 3 Trial
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
2019; 30 (4): 641–52
View details for DOI 10.1681/ASN.2018080832
View details for Web of Science ID 000463913200013
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Updates in Management and Timing of Dialysis in Acute Kidney Injury
JOURNAL OF HOSPITAL MEDICINE
2019; 14 (4): 232–38
View details for DOI 10.12788/jhm.3105
View details for Web of Science ID 000462532700007
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Relative sarcopenia and mortality and the modifying effects of chronic kidney disease and adiposity
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
2019; 10 (2): 338–46
View details for DOI 10.1002/jcsm.12396
View details for Web of Science ID 000465092100008
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An integrated analysis of safety and tolerability of etelcalcetide in patients receiving hemodialysis with secondary hyperparathyroidism
PLOS ONE
2019; 14 (3)
View details for DOI 10.1371/journal.pone.0213774
View details for Web of Science ID 000461316400029
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Hypertension Hot Potato - Anatomy of the Angiotensin-Receptor Blocker Recalls.
The New England journal of medicine
2019
View details for PubMedID 30865819
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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
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
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Treatment of metabolic acidosis with an intestinal binder.
Lancet (London, England)
2019
View details for PubMedID 30857645
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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
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
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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
2019; 73 (3): 309–15
View details for DOI 10.1053/j.ajkd.2018.10.006
View details for Web of Science ID 000459248200005
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Long-term Trends and Clinical Outcomes of Inpatient Percutaneous Renal Biopsies in the United States, 2001-2013
NATURE PUBLISHING GROUP. 2019
View details for Web of Science ID 000478915503209
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Long-term Trends and Clinical Outcomes of Inpatient Percutaneous Renal Biopsies in the United States, 2001-2013
NATURE PUBLISHING GROUP. 2019
View details for Web of Science ID 000478081103084
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Paying for Hemodialysis in Kerala, India: A Description of Household Financial Hardship in the Context of Medical Subsidy
KIDNEY INTERNATIONAL REPORTS
2019; 4 (3): 390–98
View details for DOI 10.1016/j.ekir.2018.12.007
View details for Web of Science ID 000460067100007
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Paying for Hemodialysis in Kerala, India: A Description of Household Financial Hardship in the Context of Medical Subsidy.
Kidney international reports
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
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Frailty Among Patients Receiving Hemodialysis: Evolution of Components and Associations With Mortality
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
2019; 74 (3): 380–86
View details for DOI 10.1093/gerona/gly206
View details for Web of Science ID 000462192600014
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Updates in Management and Timing of Dialysis in Acute Kidney Injury.
Journal of hospital medicine
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
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Relative sarcopenia and mortality and the modifying effects of chronic kidney disease and adiposity.
Journal of cachexia, sarcopenia and muscle
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
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Frailty Among Patients Receiving Hemodialysis: Evolution of Components and Associations With Mortality.
The journals of gerontology. Series A, Biological sciences and medical sciences
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
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Trimethylamine N-Oxide and Cardiovascular Outcomes in Patients with ESKD Receiving Maintenance Hemodialysis
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
2019; 14 (2): 261–67
View details for DOI 10.2215/CJN.06190518
View details for Web of Science ID 000458400200015
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Prospective Biopsy-Based Study of CKD of Unknown Etiology in Sri Lanka
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
2019; 14 (2): 224–32
View details for DOI 10.2215/CJN.07430618
View details for Web of Science ID 000458400200011
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Excess Deaths Attributable to Influenza-Like Illness in the ESRD Population
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
2019; 30 (2): 346–53
View details for DOI 10.1681/ASN.2018060581
View details for Web of Science ID 000458398100014
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The effects of tenapanor on serum fibroblast growth factor 23 in patients receiving hemodialysis with hyperphosphatemia
NEPHROLOGY DIALYSIS TRANSPLANTATION
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
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Prior Hospitalization Burden and the Relatedness of 30-Day Readmissions in Patients Receiving Hemodialysis
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
2019; 30 (2): 323–35
View details for DOI 10.1681/ASN.2018080858
View details for Web of Science ID 000458398100012
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Differential Molecular Modeling Predictions of Mid and Conventional Dialysate Flows.
Blood purification
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
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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
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
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Excess Deaths Attributable to Influenza-Like Illness in the ESRD Population.
Journal of the American Society of Nephrology : JASN
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
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Fibroblast Growth Factor 23 Genotype and Cardiovascular Disease in Patients Undergoing Hemodialysis.
American journal of nephrology
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
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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
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
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Prospective Biopsy-Based Study of Chronic Kidney Disease of Unknown Etiology in Sri Lanka.
Clinical journal of the American Society of Nephrology : CJASN
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
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Prior Hospitalization Burden and the Relatedness of 30-Day Readmissions in Patients Receiving Hemodialysis.
Journal of the American Society of Nephrology : JASN
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
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Safety-Net Care for Maintenance Dialysis in the United States.
Journal of the American Society of Nephrology : JASN
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
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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
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
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Central venous pressure and the risk of diuretic-associated acute kidney injury in patients after cardiac surgery.
American heart journal
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
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Estimated effects of early diuretic use in critical illness.
Critical care explorations
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
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Antidiabetic medication use in patients with type 2 diabetes and chronic kidney disease.
Journal of diabetes and its complications
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
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Twenty-Four Hour Urine Testing and Prescriptions for Urinary Stone Disease-Related Medications in Veterans.
Clinical journal of the American Society of Nephrology : CJASN
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
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Exploring Care Attributes of Nephrologists Ranking Favorably on Measures of Value.
Journal of the American Society of Nephrology : JASN
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
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Intradialytic Symptoms and Recovery Time in Patients on Thrice-Weekly In-Center Hemodialysis: A Cross-sectional Online Survey.
Kidney medicine
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
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Market Consolidation and Mortality in Patients Initiating Hemodialysis.
Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research
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
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Effects of vadadustat on hemoglobin concentrations in patients receiving hemodialysis previously treated with erythropoiesis-stimulating agents
NEPHROLOGY DIALYSIS TRANSPLANTATION
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
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An integrated analysis of safety and tolerability of etelcalcetide in patients receiving hemodialysis with secondary hyperparathyroidism.
PloS one
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
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Patterns of diuretic use in the intensive care unit.
PloS one
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
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Association of Hospitalization and Mortality Among Patients Initiating Dialysis With Hemodialysis Facility Ownership and Acquisitions.
JAMA network open
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
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Market Consolidation and Mortality in Patients Initiating Hemodialysis
VALUE IN HEALTH
2019; 22 (1): 69–76
View details for DOI 10.1016/j.jval.2018.06.008
View details for Web of Science ID 000456090600010
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Fibroblast Growth Factor 23 Genotype and Cardiovascular Disease in Patients Undergoing Hemodialysis
AMERICAN JOURNAL OF NEPHROLOGY
2019; 49 (2): 125–32
View details for DOI 10.1159/000496060
View details for Web of Science ID 000459402800005
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Differential Molecular Modeling Predictions of Mid and Conventional Dialysate Flows
BLOOD PURIFICATION
2019; 47 (4): 369–76
View details for DOI 10.1159/000495022
View details for Web of Science ID 000468935700009
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Removing Disincentives to Kidney Donation: A Quantitative Analysis.
Journal of the American Society of Nephrology : JASN
2019
View details for DOI 10.1681/ASN.2019030242
View details for PubMedID 31345987
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Toward Greater Scrutiny of Dialysate Flow: Reply to the Letter to the Editor of Dr. Molano-Triviño and Colleagues.
Blood purification
2019: 1–2
View details for DOI 10.1159/000501842
View details for PubMedID 31340211
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Implications of Early Decline in eGFR due to Intensive BP Control for Cardiovascular Outcomes in SPRINT.
Journal of the American Society of Nephrology : JASN
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
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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
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
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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
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
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Etelcalcetide Is Effective at All Levels of Severity of Secondary Hyperparathyroidism in Hemodialysis Patients.
Kidney international reports
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
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Prevalence of twenty-four hour urine testing in Veterans with urinary stone disease.
PloS one
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
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Defining a willingness-to-transplant threshold in an era of organ scarcity: Simultaneous liver-kidney transplant as a case example.
Transplantation
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
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Challenges in Assessing the Burden of Hospitalized Heart Failure in End-stage Kidney Disease.
Journal of cardiac failure
2019
View details for PubMedID 31063825
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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
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
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PTH, FGF23, and Intensive Blood Pressure Lowering in Chronic Kidney Disease Participants in SPRINT
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
2018; 13 (12): 1816–24
View details for DOI 10.2215/CJN.05390518
View details for Web of Science ID 000452863400010
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Randomized trial of intravenous iron-induced hypophosphatemia.
JCI insight
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
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Randomized trial of intravenous iron-induced hypophosphatemia
JCI INSIGHT
2018; 3 (23)
View details for DOI 10.1172/jci.insight.124486
View details for Web of Science ID 000452436000011
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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
2018; 32 (12): 1113–17
View details for DOI 10.1016/j.jdiacomp.2018.09.005
View details for Web of Science ID 000455073400006
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The Terrible Toll of the Kidney Shortage
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
2018; 29 (12): 2775–76
View details for PubMedID 30420419
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Would government compensation of living kidney donors exploit the poor? An empirical analysis
PLOS ONE
2018; 13 (11)
View details for DOI 10.1371/journal.pone.0205655
View details for Web of Science ID 000451755800009
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Payer Type, Race/Ethnicity, and the Timing of Surgical Management of Urinary Stone Disease
JOURNAL OF ENDOUROLOGY
2019; 33 (2): 152–58
View details for DOI 10.1089/end.2018.0614
View details for Web of Science ID 000450757000001
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PTH, FGF23, and Intensive Blood Pressure Lowering in Chronic Kidney Disease Participants in SPRINT.
Clinical journal of the American Society of Nephrology : CJASN
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
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International Study of Comparative Health Effectiveness with Medical and Invasive Approaches-Chronic Kidney Disease (ISCHEMIA-CKD): Rationale and design
AMERICAN HEART JOURNAL
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
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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.)
2018; 20 (11): 1644–45
View details for PubMedID 30328272
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Prognostic relevance of visit-to-visit office blood pressure variability in Systolic Blood Pressure Intervention Trial: Same data, different conclusions?
JOURNAL OF CLINICAL HYPERTENSION
2018; 20 (11): 1644–45
View details for DOI 10.1111/jch.13395
View details for Web of Science ID 000449560100013
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Bioelectrical Impedance Analysis Measures and Clinical Outcomes in CKD
AMERICAN JOURNAL OF KIDNEY DISEASES
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
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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
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
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Payer Type, Race/Ethnicity, and the Timing of Surgical Management of Urinary Stone Disease.
Journal of endourology
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
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Market Competition and Health Outcomes in Heniodialysis
HEALTH SERVICES RESEARCH
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
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Patient-Reported Experiences of Dialysis Care Within a National Pay-for-Performance System
JAMA INTERNAL MEDICINE
2018; 178 (10): 1358–67
View details for DOI 10.1001/jamainternmed.2018.3756
View details for Web of Science ID 000446453500012
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Small increases in serum magnesium levels by dapagliflozin and normalisation of hypomagnesaemia in patients with type 2 diabetes
SPRINGER. 2018: S316
View details for Web of Science ID 000443556004017
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Pulse wave velocity and central aortic pressure in systolic blood pressure intervention trial participants
PLOS ONE
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
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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
2018; 7 (18)
View details for DOI 10.1161/JAHA.118.009326
View details for Web of Science ID 000452805400017
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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
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
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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
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
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Patient-Reported Experiences of Dialysis Care Within a National Pay-for-Performance System.
JAMA internal medicine
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
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Acute Kidney Injury Due to Diarrheal Illness Requiring Hospitalization: Data from the National Inpatient Sample
JOURNAL OF GENERAL INTERNAL MEDICINE
2018; 33 (9): 1520–27
View details for DOI 10.1007/s11606-018-4531-6
View details for Web of Science ID 000442642300024
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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
2018; 93 (9): E232–E233
View details for PubMedID 30016554
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Risk-benefit profile of intensive blood pressure treatment reply
LANCET DIABETES & ENDOCRINOLOGY
2018; 6 (8): 602
View details for PubMedID 30053986
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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
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
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Dialysis versus Medical Management at Different Ages and Levels of Kidney Function in Veterans with Advanced CKD
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
2018; 29 (8): 2169–77
View details for DOI 10.1681/ASN.2017121273
View details for Web of Science ID 000445764500017
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Use of Estimating Equations for Dosing Antimicrobials in Patients with Acute Kidney Injury Not Receiving Renal Replacement Therapy
JOURNAL OF CLINICAL MEDICINE
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
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Mandating Staffing Ratios in Hemodialysis Facilities California SB 349 and Unintended Consequences
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
2018; 13 (7): 1110–12
View details for PubMedID 29875201
View details for PubMedCentralID PMC6032581
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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
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
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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
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
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Unplanned Emergency Department Visits and Hospital Admissions Following Ureteroscopy: Do Ureteral Stents Make a Difference?
UROLOGY
2018; 117: 44–49
View details for DOI 10.1016/j.urology.2018.03.019
View details for Web of Science ID 000437729900013
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Effects of calcimimetics on long-term outcomes in dialysis patients: literature review and Bayesian meta-analysis
JOURNAL OF COMPARATIVE EFFECTIVENESS RESEARCH
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
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Benefits and risks of intensive blood-pressure lowering in advanced chronic kidney disease
JOURNAL OF INTERNAL MEDICINE
2018; 284 (1): 106–7
View details for PubMedID 29385288
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Acute Kidney Injury Due to Diarrheal Illness Requiring Hospitalization: Data from the National Inpatient Sample.
Journal of general internal medicine
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
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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
2018; 137 (24): 2668–69
View details for PubMedID 29891628
View details for PubMedCentralID PMC6003621
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Hemoglobin response to ferric citrate in patients with nondialysis-dependent chronic kidney disease and iron deficiency anemia
AMERICAN JOURNAL OF HEMATOLOGY
2018; 93 (6): E154–E156
View details for PubMedID 29575100
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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
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
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Incidence, predictors and therapeutic consequences of hypocalcemia in patients treated with cinacalcet in the EVOLVE trial
KIDNEY INTERNATIONAL
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
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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
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
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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
OXFORD UNIV PRESS. 2018
View details for Web of Science ID 000433059800076
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Comparing Simultaneous Liver-Kidney Transplant Strategies: A Modified Cost-Effectiveness Analysis
TRANSPLANTATION
2018; 102 (5): E219–E228
View details for DOI 10.1097/TP.0000000000002148
View details for Web of Science ID 000431423600006
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Comparative safety of intravenous ferumoxytol versus ferric carboxymaltose in iron deficiency anemia: A randomized trial
AMERICAN JOURNAL OF HEMATOLOGY
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
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DECREASES IN WEIGHT WITH BARDOXOLONE METHYL IN OBESE PATIENTS WITH CHRONIC KIDNEY DISEASE STAGE 4 AND TYPE 2 DIABETES - POST-HOC ANALYSES FROM BEACON
OXFORD UNIV PRESS. 2018
View details for Web of Science ID 000433059801225
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BARDOXOLONE METHYL PREVENTS EGFR DECLINE IN PATIENTS WITH CHRONIC KIDNEY DISEASE STAGE 4 AND TYPE 2 DIABETES - POST-HOC ANALYSES FROM BEACON
OXFORD UNIV PRESS. 2018
View details for Web of Science ID 000433059800023
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BASELINE LEVELS OF FGF23 AND EFFECTS OF ETELCALCETIDE
OXFORD UNIV PRESS. 2018
View details for Web of Science ID 000433059800443
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Associations of lipoproteins with cardiovascular and infection-related outcomes in patients receiving hemodialysis
JOURNAL OF CLINICAL LIPIDOLOGY
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
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PREOPERATIVE KIDNEY FUNCTION TRENDS: IMPROVING ESTIMATES OF BASELINE KIDNEY FUNCTION PRIOR TO KIDNEY CANCER SURGERY
ELSEVIER SCIENCE INC. 2018: E362
View details for Web of Science ID 000429166601066
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Updated guidelines for the diagnosis and management of high blood pressure: implications for clinical practice in nephrology
KIDNEY INTERNATIONAL
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
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Comparing Simultaneous Liver-Kidney Transplant Strategies: A Modified Cost-Effectiveness Analysis.
Transplantation
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
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Cost-effectiveness of multidisciplinary care in mild to moderate chronic kidney disease in the United States: A modeling study
PLOS MEDICINE
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
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IgA nephropathy: toward more specific diagnosis (and rescue of snails)
KIDNEY INTERNATIONAL
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
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Effects of Intensive Blood Pressure Treatment on Acute Kidney Injury Events in the Systolic Blood Pressure Intervention Trial (SPRINT)
AMERICAN JOURNAL OF KIDNEY DISEASES
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
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Causes of Death after a Hospitalization with AKI
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
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
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Chronic kidney disease care models in low- and middle-income countries: a systematic review
BMJ GLOBAL HEALTH
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
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Outcomes after Angiography with Sodium Bicarbonate and Acetylcysteine
NEW ENGLAND JOURNAL OF MEDICINE
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
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Antihypertensive medication withholding practices in hemodialysis: A survey study of patients and providers.
Hemodialysis international. International Symposium on Home Hemodialysis
2018
View details for DOI 10.1111/hdi.12640
View details for PubMedID 29436151
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Perioperative THR-184 and AKI after Cardiac Surgery
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
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
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Influence of Baseline Diastolic Blood Pressure on Effects of Intensive Compared With Standard Blood Pressure Control
CIRCULATION
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
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Unplanned Emergency Department Visits and Hospital Admissions Following Ureteroscopy: Do Ureteral Stents Make a Difference?
Urology
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
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Would government compensation of living kidney donors exploit the poor? An empirical analysis.
PloS one
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
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Ferumoxytol for the treatment of iron deficiency anemia
EXPERT REVIEW OF HEMATOLOGY
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
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Risk Factors, Incidence and Cost of Prolonged Hospitalization After Acute Respiratory Failure
AMER THORACIC SOC. 2018
View details for Web of Science ID 000449980301194
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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
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
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Clinical Outcomes by Race and Ethnicity in the Systolic Blood Pressure Intervention Trial (SPRINT): A Randomized Clinical Trial
AMERICAN JOURNAL OF HYPERTENSION
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
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Allogeneic Mesenchymal Stem Cells for Treatment of AKI after Cardiac Surgery
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
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
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Associations of Body Mass Index and Body Fat With Markers of Inflammation and Nutrition Among Patients Receiving Hemodialysis
AMERICAN JOURNAL OF KIDNEY DISEASES
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
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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
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
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Safety and efficacy of ferric citrate in patients with nondialysis-dependent chronic kidney disease
PLOS ONE
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
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Infrequent Provision of Palliative Care to Patients with Dialysis-Requiring AKI
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
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
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Declining Rates of Hip Fracture in End-Stage Renal Disease: Analysis From the 2003-2011 Nationwide Inpatient Sample
JOURNAL OF BONE AND MINERAL RESEARCH
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
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Receipt of Nephrology Care and Clinical Outcomes Among Veterans With Advanced CKD
AMERICAN JOURNAL OF KIDNEY DISEASES
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
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Effectiveness of Quality Improvement Strategies for the Management of CKD A Meta-Analysis
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
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
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Visit-to-Visit Office Blood Pressure Variability and Cardiovascular Outcomes in SPRINT (Systolic Blood Pressure Intervention Trial)
HYPERTENSION
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
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Effects of Intensive BP Control in CKD
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
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
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Clinical Outcomes by Race and Ethnicity in the Systolic Blood Pressure Intervention Trials (SPRINT): A Randomized Control Trial
LIPPINCOTT WILLIAMS & WILKINS. 2017
View details for Web of Science ID 000523486000047
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Screening Rates for the Diagnostic Workup of Resistant Hypertension
LIPPINCOTT WILLIAMS & WILKINS. 2017
View details for Web of Science ID 000523486000196
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Prehabilitation for kidney transplant candidates: Is it time?
CLINICAL TRANSPLANTATION
2017; 31 (8)
View details for DOI 10.1111/ctr.13020
View details for Web of Science ID 000407287900013
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Calcium-Sensing Receptor Genotype and Response to Cinacalcet in Patients Undergoing Hemodialysis
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
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
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Factors Associated with Frailty and Its Trajectory among Patients on Hemodialysis.
Clinical journal of the American Society of Nephrology
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
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Effect of Tenapanor on Serum Phosphate in Patients Receiving Hemodialysis
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
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
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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
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
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Effects of Ferric Citrate in Patients with Nondialysis-Dependent CKD and Iron Deficiency Anemia
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
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
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Prehabilitation for Kidney Transplant Candidates: Is it Time?
Clinical transplantation
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
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Dosing of Etelcalcetide and Cinacalcet for Secondary Hyperparathyroidism Reply
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
2017; 317 (20): 2132–33
View details for PubMedID 28535231
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Home Dialysis in the Prospective Payment System Era.
Journal of the American Society of Nephrology
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
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Utility in Treating Kidney Failure in End-Stage Liver Disease With Simultaneous Liver-Kidney Transplantation
TRANSPLANTATION
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
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Limited reduction in uremic solute concentrations with increased dialysis frequency and time in the Frequent Hemodialysis Network Daily Trial
KIDNEY INTERNATIONAL
2017; 91 (5): 1186–92
View details for DOI 10.1016/j.kint.2016.11.002
View details for Web of Science ID 000400541000020
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IMPACT OF ETELCALCETIDE ON FGF23 LEVELS DURING THE TREATMENT OF SECONDARY HYPERPARATHYROIDISM IN PATIENTS ON HEMODIALYSIS
OXFORD UNIV PRESS. 2017
View details for Web of Science ID 000469797100032
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Hyperprolactinemia in end-stage renal disease and effects of frequent hemodialysis
HEMODIALYSIS INTERNATIONAL
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
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ANALYSIS OF A SINGLE-ARM EXTENSION STUDY EVALUATING ETELCALETIDE STARTING DOSE FOR TREATMENT OF SECONDARY HYPERPARATHYROIDISM IN PATIENTS ON HEMODIALYSIS
W B SAUNDERS CO-ELSEVIER INC. 2017: A34
View details for Web of Science ID 000397702100086
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FERRIC CITRATE INCREASES HEMOGLOBIN IN PATIENTS WITH NON-DIALYSIS-DEPENDENT CHRONIC KIDNEY DISEASE AND IRON DEFICIENCY ANEMIA.
W B SAUNDERS CO-ELSEVIER INC. 2017: A76
View details for Web of Science ID 000397702100254
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THE INNO(2)VATE PHASE 3 PROGRAM OF VADADUSTAT FOR TREATMENT OF ANEMIA IN DIALYSIS-DEPENDENT CKD: RATIONALE AND STUDY DESIGN
W B SAUNDERS CO-ELSEVIER INC. 2017: A102
View details for Web of Science ID 000397702100360
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Glycovariations in Key HDL-Associated Glycoproteins Differentiate Between Clinical Groups and Affect the Immunomodulatory Capacity of HDL
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 2017