Clinical Focus


  • Nephrology

Academic Appointments


Administrative Appointments


  • Associate, Center for Health Policy, Center for Primary Care and Outcomes Research, Stanford University (2008 - Present)
  • Professor of Medicine, Stanford University School of Medicine (2007 - Present)
  • Professor of Epidemiology and Biostatistics, UCSF (2005 - 2007)
  • Professor of Medicine in Residence, UCSF (2005 - 2007)
  • Associate Professor of Epidemiology and Biostatistics, UCSF (2004 - 2005)
  • Associate Professor of Medicine in Residence, UCSF (2001 - 2004)
  • Assistant Professor of Medicine in Residence, University of California San Francisco School of Medicine, San Francisco, CA (UCSF) (1998 - 2001)
  • Assistant Professor of Medicine, HMS (1997 - 1998)
  • Instructor in Surgery, HMS (1966 - 1998)
  • Instructor in Medicine, HMS (1995 - 1997)
  • Research Fellow in Medicine, HMS (1992 - 1995)
  • Clinical Fellow in Medicine, Harvard Medical School, Boston, MA (HMS) (1989 - 1992)

Honors & Awards


  • Summa Cum Laude, University of Pennsylvania (1985)
  • Phi Beta Kappa, University of Pennsylvania (1985)
  • Hewlett Packard Outstanding Medical Graduate Award, HMS (1989)
  • American Kidney Fund, Amgen Clinical Scientist in Nephrology (1993-95)
  • Calvin and Sylvia Margolis Scholar in Internal Medicine, Department of Medicine, BWH (1996-97)
  • “Best Doctors in America” designation, Woodward and White (1996)
  • “Best Doctors in Boston” designation, Boston Magazine (1997-98)
  • “Top Doctors in Bay Area” designation, San Francisco Magazine (1999-2000)
  • President’s Award, National Kidney Foundation (1999)
  • Floyd C. Rector, Jr., Housestaff Teaching Award, Department of Medicine, UCSF (2001)
  • Academic Senate Distinction in Teaching Award Honorable Mention, USCF School of Medicine (2002)
  • Nominee, Kaiser Awards for Excellence in Teaching, UCSF School of Medicine (2002)
  • "Top Doctors in Bay Area” designation, San Francisco Magazine Inductee, American Society of Clinical Investigation (2002-2004)
  • Member, American Society of Clinical Investigation (2004)
  • Nominee, Kaiser Awards for Excellence in Teaching, UCSF School of Medicine (2005)
  • Inductee, Society of Master Clinicians, UCSF Department of Medicine (2006)
  • STAR Award, UCSF Medical Center (2006)
  • National Torchbearer Award, American Kidney Fund (2007)
  • Mentor of the Year, Bay Area Clinical Research Symposium (2007)
  • Senior Mentor, Network of Minority Research Investigators, NIDDK (2008)

Professional Education


  • Fellowship:Brigham and Women's Hospital Nephrology Fellowship (1995) MA
  • Residency:Brigham and Women's Hospital Internal Medicine Residency (1992) MA
  • Board Certification: Internal Medicine, American Board of Internal Medicine (1992)
  • Board Certification: Nephrology, American Board of Internal Medicine (1994)
  • Medical Education:Harvard Medical School (1989) MA
  • MPH, Harvard School of Public Health, Epidemiology and Biostatistics (1995)
  • MD, Harvard Medical School, Medicine (1989)
  • 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


  • Rituximab in Progressive Immunoglobulin A (IgA) Nephropathy Recruiting

    This study was about IgA nephropathy, a form of kidney disease characterized by the presence of blood and protein in the urine. This study was done to determine if the medication rituximab could reduce protein in the patient's urine. Hypothesis: In patients with progressive IgA nephropathy an intravenous infusion of 1000 mg of rituximab on Day 1 and Day 15 and Days 168 and 182 is superior to conventional therapy in reducing 24 hour proteinuria, and slowing progression of chronic kidney disease.

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  • Safety and Efficacy of Polymyxin B Hemoperfusion (PMX) for Septic Shock Recruiting

    To compare the safety and efficacy of the PMX cartridge based on mortality at 28-days in subjects with septic shock who have high levels of endotoxin and are treated with standard medical care plus use of the PMX cartridge, versus subjects who receive standard medical care alone.

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  • Systolic Pressure Intervention Trial Factors Affecting Factors Affecting Atherosclerosis Study Recruiting

    Systolic Pressure Intervention Trial (SPRINT) is a large scale randomized trial of ~ 9250 adults aged 50 years or older with high cardiovascular risk sponsored by NIH. The study is designed to recruit 45% of the study population with Chronic Kidney Disease (CKD). The trial will test the effects of low systolic blood pressure (SBP) goal of < 120 mm Hg versus the standard goal of < 140 mm Hg on the primary composite of cardiovascular events and death. One of the pre-specified secondary outcome is the progression of kidney disease. In this ancillary named SPRINT - Factors affecting Atherosclerosis STudy (FAST), the investigators plan to take advantage of the unique opportunities afforded by the parent study to examine issues that are of significant public health importance. This is an observational study in SPRINT participants. This study will examine mechanistically, the factors affecting the progression of atherosclerosis in CKD.

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2018-19 Courses


All Publications


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

    Abstract

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

    View details for DOI 10.1093/ndt/gfz120

    View details for PubMedID 31302696

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

    Abstract

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

    View details for DOI 10.1681/ASN.2018101016

    View details for PubMedID 31278194

  • A phase II trial showing improvements in calcific uraemic arteriolopathy wound healing, pain and quality of life during SNF472 treatment McMullen, E., Sinha, S., Gould, L., Brandenburg, V., Chertow, G., Miller, S., Canals, A., Bahr, D., Salcedo, C., Garg, R., Gold, A., Perello, J. WILEY. 2019: 39–40
  • Influence of prediabetes on the effects of intensive systolic blood pressure control on kidney events. American journal of hypertension Rathi, N., Whelton, P. K., Chertow, G. M., Cushman, W. C., Cheung, A. K., Wei, G., Boucher, R., Kimmel, P. L., Bress, A., Kramer, H. J., Al-Marji, C., Greene, T., Beddhu, S. 2019

    Abstract

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

    View details for DOI 10.1093/ajh/hpz105

    View details for PubMedID 31257407

  • Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy NEW ENGLAND JOURNAL OF MEDICINE Perkovic, V., Jardine, M. J., Neal, B., Bompoint, S., Heerspink, H. L., Charytan, D. M., Edwards, R., Agarwal, R., Bakris, G., Bull, S., Cannon, C. P., Capuano, G., Chu, P., De Zeeuw, D., Greene, T., Levin, A., Pollock, C., Wheeler, D. C., Yavin, Y., Zhang, H., Zinman, B., Meininger, G., Brenner, B. M., Mahaffey, K. W., CREDENCE Trial Investigators 2019; 380 (24): 2295–2306
  • The effect of increased frequency of hemodialysis on vitamin C concentrations: an ancillary study of the randomized Frequent Hemodialysis Network (FHN) daily trial BMC NEPHROLOGY Raimann, J. G., Abbas, S. R., Liu, L., Larive, B., Beck, G., Kotanko, P., Levin, N. W., Handelman, G., Kliger, A., Eggers, P., Briggs, J., Hostetter, T., Narva, A., Star, R., Augustine, B., Mohr, P., Beck, G., Fu, Z., Gassman, J., Greene, T., Daugirdas, J., Hunsicker, L., Larive, B., Li, M., MacKrell, J., Wiggins, K., Sherer, S., Weiss, B., Rajagopalan, S., Sanz, J., Dellagrottaglie, S., Kariisa, M., Tran, T., West, J., Unruh, M., Keene, R., Schlarb, J., Chan, C., McGrath-Chong, M., Frome, R., Higgins, H., Ke, S., Mandaci, O., Owens, C., Snell, C., Eknoyan, G., Appel, L., Cheung, A., Derse, A., Kramer, C., Geller, N., Grimm, R., Henderson, L., Prichard, S., Roecker, E., Chertow, G., James, S., Tamura, M., Hall, Y., McCulloch, C., Painter, P., Gorodetskaya, Tichy, M., Humphreys, M., Luan, J., Escalada, R., Rodriquez, R., Depner, T., Kaysen, G., Suter, M., Sonico, J., Anderson, S., Ting, G., Schiller, B., Coplon, N., Doss, S., Rogers, J., Dominguez, A., Atwal, J., Lemus, D., Rastogi, A., Nissenson, A., Goodman, W., Salusky, Schweitzer, S., Rivas, M., Smith, M., Gayda, P., Hernandez, A., Rashid, M., Mehta, R., Pepas, J., Bharti, B., Nabali, A., Manaster, R., Mathew, R., Shah, S., Sanz, G., Wei, J., Ayus, J., Achinger, S., Gutierrez, M., Levin, N., Bay, W., Carter, M., Geronemus, R., Kuhlmann, M., Handelman, G., Gotch, F., Finkelstein, F., Kimmel, P., Lacson, E., Ornt, D., Greenwood, R., Vassalotti, J., Burrowes, J., Kotanko, P., Kaufman, A., Winchester, J., Meisels, Radbill, B., Chang, J., Fofie, Y., Ramos, R., Sergeyeva, O., Callegari, J., Arthur, B., Tarallo, M., Ulloa, D., Apruzzese, R., Lindsay, R., Suri, R., Garg, A., Mazzorato, B. A., Rocco, M., Burkart, J., Moossavi, S., Mauck, Kaufman, T., Coppley, A., Schulman, G., McLeroy, S., Sika, M., Leavell, E., Miller, B., Schussler, R., Bardsley, J., Skelton, R., Riley, J., Schuessler, R., Lockridge, R., Pipkin, M., Peterson, C., Hoy, C., Fensterer, A., Steigerwald, D., Stokes, J., Somers, D., Hilkin, A., Lilli, K., Wallace, W., Franzwa, B., Waterman, E., Copland, M., Levin, A., Sioson, L., Cabezon, E., Kwan, S., Roger, D., Champagne, J., Bullas, R., Mazzorato, A., Spanner, E., Pierratos, A., Chan, W., Regozo, K., Kwok, S., FHN Trial 2019; 20: 179

    Abstract

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

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

    View details for Web of Science ID 000468306900004

    View details for PubMedID 31101018

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

    View details for DOI 10.1093/ndt/gfy252

    View details for Web of Science ID 000473748300012

  • Hypertension Hot Potato - Anatomy of the Angiotensin-Receptor Blocker Recalls NEW ENGLAND JOURNAL OF MEDICINE Byrd, J., Chertow, G. M., Bhalla, V. 2019; 380 (17): 1589–91
  • Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. The New England journal of medicine Perkovic, V., Jardine, M. J., Neal, B., Bompoint, S., Heerspink, H. J., Charytan, D. M., Edwards, R., Agarwal, R., Bakris, G., Bull, S., Cannon, C. P., Capuano, G., Chu, P., de Zeeuw, D., Greene, T., Levin, A., Pollock, C., Wheeler, D. C., Yavin, Y., Zhang, H., Zinman, B., Meininger, G., Brenner, B. M., Mahaffey, K. W., CREDENCE Trial Investigators 2019

    Abstract

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

    View details for PubMedID 30990260

  • Treatment of metabolic acidosis with an intestinal binder LANCET Song, S., Chertow, G. M. 2019; 393 (10179): 1387–88
  • Outcomes after left ventricular assist device implantation in patients with acute kidney injury. The Journal of thoracic and cardiovascular surgery Silver, S. A., Long, J., Zheng, Y., Goldstone, A. B., Franz, D., Chang, T. I., Chertow, G. M. 2019

    Abstract

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

    View details for PubMedID 31053433

  • Efficacy and Safety of Tenapanor in Patients with Hyperphosphatemia Receiving Maintenance Hemodialysis: A Randomized Phase 3 Trial JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Block, G. A., Rosenbaum, D. P., Yan, A., Chertow, G. M. 2019; 30 (4): 641–52
  • Updates in Management and Timing of Dialysis in Acute Kidney Injury JOURNAL OF HOSPITAL MEDICINE Yu, M. K., Kamal, F., Chertow, G. M. 2019; 14 (4): 232–38

    View details for DOI 10.12788/jhm.3105

    View details for Web of Science ID 000462532700007

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

    View details for DOI 10.1002/jcsm.12396

    View details for Web of Science ID 000465092100008

  • An integrated analysis of safety and tolerability of etelcalcetide in patients receiving hemodialysis with secondary hyperparathyroidism PLOS ONE Block, G. A., Chertow, G. M., Sullivan, J. T., Deng, H., Mather, O., Tomlin, H., Serenko, M. 2019; 14 (3)
  • Hypertension Hot Potato - Anatomy of the Angiotensin-Receptor Blocker Recalls. The New England journal of medicine Byrd, J. B., Chertow, G. M., Bhalla, V. 2019

    View details for PubMedID 30865819

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

    Abstract

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

    View details for PubMedID 30859218

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

    View details for PubMedID 30857645

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

    Abstract

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

    View details for PubMedID 30846557

  • Treatment of Anemia With Darbepoetin Prior to Dialysis Initiation and Clinical Outcomes: Analyses From the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT) AMERICAN JOURNAL OF KIDNEY DISEASES Mc Causland, F. R., Claggett, B., Burdmann, E. A., Chertow, G. M., Cooper, M. E., Eckardt, K., Ivanovich, P., Levey, A. S., Lewis, E. F., McGill, J. B., McMurray, J. V., Parfrey, P., Parving, H., Remuzzi, G., Singh, A. K., Solomon, S. D., Toto, R. D., Pfeffer, M. A. 2019; 73 (3): 309–15
  • Paying for Hemodialysis in Kerala, India: A Description of Household Financial Hardship in the Context of Medical Subsidy KIDNEY INTERNATIONAL REPORTS Bradshaw, C., Gracious, N., Narayanan, R., Narayanan, S., Safeer, M., Nair, G. M., Murlidharan, P., Sundaresan, A., Santhi, S., Prabhakaran, D., Tamura, M., Jha, V., Chertow, G. M., Jeemon, P., Anand, S. 2019; 4 (3): 390–98
  • Frailty Among Patients Receiving Hemodialysis: Evolution of Components and Associations With Mortality JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Johansen, K. L., Delgado, C., Kaysen, G. A., Chertow, G. M., Chiang, J., Dalrymple, L. S., Segal, M. R., Grimes, B. A. 2019; 74 (3): 380–86
  • Updates in Management and Timing of Dialysis in Acute Kidney Injury. Journal of hospital medicine Yu, M. K., Kamal, F., Chertow, G. M. 2019; 14: E1–E7

    Abstract

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

    View details for PubMedID 30794134

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

    Abstract

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

    View details for PubMedID 30784237

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

    Abstract

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

    View details for PubMedID 30192916

  • Trimethylamine N-Oxide and Cardiovascular Outcomes in Patients with ESKD Receiving Maintenance Hemodialysis CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Stubbs, J. R., Stedman, M. R., Liu, S., Long, J., Franchetti, Y., West, R. E., Prokopienko, A. J., Mahnken, J. D., Chertow, G. M., Nolin, T. D. 2019; 14 (2): 261–67
  • Prospective Biopsy-Based Study of CKD of Unknown Etiology in Sri Lanka CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Anand, S., Montez-Rath, M. E., Adasooriya, D., Ratnatunga, N., Kambham, N., Wazil, A., Wijetunge, S., Badurdeen, Z., Ratnayake, C., Karunasena, N., Schensul, S. L., Valhos, P., Haider, L., Bhalla, V., Levin, A., Wise, P. H., Chertow, G. M., Barry, M., Fire, A. Z., Nanayakkara, N. 2019; 14 (2): 224–32
  • Excess Deaths Attributable to Influenza-Like Illness in the ESRD Population JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Gilbertson, D. T., Rothman, K. J., Chertow, G. M., Bradbury, B. D., Brookhart, M., Liu, J., Winkelmayer, W. C., Stuermer, T., Monda, K. L., Herzog, C. A., Ashfaq, A., Collins, A. J., Wetmore, J. B. 2019; 30 (2): 346–53
  • The effects of tenapanor on serum fibroblast growth factor 23 in patients receiving hemodialysis with hyperphosphatemia NEPHROLOGY DIALYSIS TRANSPLANTATION Block, G. A., Rosenbaum, D. P., Yan, A., Greasley, P. J., Chertow, G. M., Wolf, M. 2019; 34 (2): 339–46

    Abstract

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

    View details for PubMedID 29617976

  • Prior Hospitalization Burden and the Relatedness of 30-Day Readmissions in Patients Receiving Hemodialysis JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Lin, E., Bhattacharya, J., Chertow, G. M. 2019; 30 (2): 323–35
  • Differential Molecular Modeling Predictions of Mid and Conventional Dialysate Flows. Blood purification Leypoldt, J. K., Prichard, S., Chertow, G. M., Alvarez, L. 2019: 1–8

    Abstract

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

    View details for PubMedID 30699416

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

    Abstract

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

    View details for PubMedID 30709713

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

    Abstract

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

    View details for PubMedID 30679380

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

    Abstract

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

    View details for PubMedID 30669147

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

    Abstract

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

    View details for PubMedID 30665924

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

    Abstract

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

    View details for PubMedID 30659059

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

    Abstract

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

    View details for PubMedID 30606782

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

    View details for PubMedID 31063825

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

    Abstract

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

    View details for DOI 10.1371/journal.pone.0220768

    View details for PubMedID 31393935

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

    Abstract

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

    View details for PubMedID 30661636

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

    Abstract

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

    View details for PubMedID 29672740

    View details for PubMedCentralID PMC6322440

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

    Abstract

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

    View details for PubMedID 30875390

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

    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 PubMedID 30899866

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

    Abstract

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

    View details for DOI 10.1371/journal.pone.0217911

    View details for PubMedID 31150512

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

    Abstract

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

    View details for PubMedID 31099872

  • Market Consolidation and Mortality in Patients Initiating Hemodialysis VALUE IN HEALTH Erickson, K. F., Winkelmayer, W. C., Ho, V., Bhattacharya, J., Chertow, G. M. 2019; 22 (1): 69–76
  • Fibroblast Growth Factor 23 Genotype and Cardiovascular Disease in Patients Undergoing Hemodialysis AMERICAN JOURNAL OF NEPHROLOGY Schwantes-An, T., Liu, S., Stedman, M., Decker, B. S., Wetherill, L., Edenberg, H. J., Vatta, M., Foroud, T. M., Chertow, G. M., Moe, S. M. 2019; 49 (2): 125–32

    View details for DOI 10.1159/000496060

    View details for Web of Science ID 000459402800005

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

    View details for DOI 10.1159/000495022

    View details for Web of Science ID 000468935700009

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

    View details for DOI 10.1681/ASN.2019030242

    View details for PubMedID 31345987

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

    View details for DOI 10.1159/000501842

    View details for PubMedID 31340211

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

    Abstract

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

    View details for DOI 10.1681/ASN.2018121261

    View details for PubMedID 31324734

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

    Abstract

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

    View details for DOI 10.1016/j.jdiacomp.2019.06.007

    View details for PubMedID 31375422

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

    Abstract

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

    View details for DOI 10.1016/j.kint.2019.04.027

    View details for PubMedID 31377056

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

    Abstract

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

    View details for DOI 10.1016/j.ekir.2019.04.010

    View details for PubMedID 31317120

    View details for PubMedCentralID PMC6611952

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

    Abstract

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

    View details for PubMedID 30578152

  • PTH, FGF23, and Intensive Blood Pressure Lowering in Chronic Kidney Disease Participants in SPRINT CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Ginsberg, C., Craven, T. E., Chonchol, M. B., Cheung, A. K., Sarnak, M. J., Ambrosius, W. T., Killeen, A. A., Raphael, K. L., Bhatt, U. Y., Chen, J., Chertow, G. M., Freedman, B. I., Oparil, S., Papademetriou, V., Wall, B. M., Wright, C. B., Ix, J. H., Shlipak, M. G., SPRINT Res Grp 2018; 13 (12): 1816–24
  • Randomized trial of intravenous iron-induced hypophosphatemia. JCI insight Wolf, M., Chertow, G. M., Macdougall, I. C., Kaper, R., Krop, J., Strauss, W. 2018; 3 (23)

    Abstract

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

    View details for PubMedID 30518682

  • Randomized trial of intravenous iron-induced hypophosphatemia JCI INSIGHT Wolf, M., Chertow, G. M., Macdougall, L. C., Kaper, R., Krop, J., Strauss, W. 2018; 3 (23)
  • Effects of bardoxolone methyl on body weight, waist circumference and glycemic control in obese patients with type 2 diabetes mellitus and stage 4 chronic kidney disease JOURNAL OF DIABETES AND ITS COMPLICATIONS Chertow, G. M., Appel, G. B., Block, G. A., Chin, M. P., Coyne, D. W., Goldsberry, A., Kalantar-Zadeh, K., Meyer, C. J., Molitch, M. E., Pergola, P. E., Raskin, P., Silva, A. L., Spinowitz, B., Sprague, S. M., Rossing, P. 2018; 32 (12): 1113–17
  • The Terrible Toll of the Kidney Shortage JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY McCormick, F., Held, P. J., Chertow, G. M. 2018; 29 (12): 2775–76

    View details for PubMedID 30420419

  • Would government compensation of living kidney donors exploit the poor? An empirical analysis PLOS ONE Held, P. J., McCormick, F., Chertow, G. M., Peters, T. G., Roberts, J. P. 2018; 13 (11)
  • Payer Type, Race/Ethnicity, and the Timing of Surgical Management of Urinary Stone Disease JOURNAL OF ENDOUROLOGY Brubaker, W. D., Dallas, K. B., Elliott, C. S., Pao, A. C., Chertow, G. M., Leppert, J. T., Conti, S. L. 2019; 33 (2): 152–58
  • PTH, FGF23, and Intensive Blood Pressure Lowering in Chronic Kidney Disease Participants in SPRINT. Clinical journal of the American Society of Nephrology : CJASN Ginsberg, C., Craven, T. E., Chonchol, M. B., Cheung, A. K., Sarnak, M. J., Ambrosius, W. T., Killeen, A. A., Raphael, K. L., Bhatt, U. Y., Chen, J., Chertow, G. M., Freedman, B. I., Oparil, S., Papademetriou, V., Wall, B. M., Wright, C. B., Ix, J. H., Shlipak, M. G., SPRINT Research Group 2018

    Abstract

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

    View details for PubMedID 30425104

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

    Abstract

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

    View details for PubMedID 29885923

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

    View details for PubMedID 30328272

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

    Abstract

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

    View details for PubMedID 30172098

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

    View details for DOI 10.1111/jch.13395

    View details for Web of Science ID 000449560100013

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

    Abstract

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

    View details for PubMedID 30380116

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

    Abstract

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

    View details for PubMedID 30343603

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

    Abstract

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

    View details for PubMedID 29468675

    View details for PubMedCentralID PMC6153181

  • Patient-Reported Experiences of Dialysis Care Within a National Pay-for-Performance System JAMA INTERNAL MEDICINE Brady, B. M., Zhao, B., Niu, J., Winkelmayer, W. C., Milstein, A., Chertow, G. M., Erickson, K. F. 2018; 178 (10): 1358–67
  • Small increases in serum magnesium levels by dapagliflozin and normalisation of hypomagnesaemia in patients with type 2 diabetes Toto, R., Goldenberg, R., Chertow, G. M., Cain, V., Stefansson, B. V., Sjostrom, C. D., Sartipy, P. SPRINGER. 2018: S316
  • Pulse wave velocity and central aortic pressure in systolic blood pressure intervention trial participants PLOS ONE Supiano, M. A., Lovato, L., Ambrosius, W. T., Bates, J., Beddhu, S., Drawz, P., Dwyer, J. P., Hamburg, N. M., Kitzman, D., Lash, J., Lustigova, E., Miracle, C. M., Oparil, S., Raj, D. S., Weiner, D. E., Taylor, A., Vita, J. A., Yunis, R., Chertow, G. M., Chonchol, M. 2018; 13 (9): e0203305

    Abstract

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

    View details for PubMedID 30256784

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

    Abstract

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

    View details for PubMedID 30371182

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

    Abstract

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

    View details for PubMedID 30318163

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

    Abstract

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

    View details for PubMedID 30208398

  • Acute Kidney Injury Due to Diarrheal Illness Requiring Hospitalization: Data from the National Inpatient Sample JOURNAL OF GENERAL INTERNAL MEDICINE Bradshaw, C., Zheng, Y., Silver, S. A., Chertow, G. M., Long, J., Anand, S. 2018; 33 (9): 1520–27
  • A response by Strauss et al. to "a comment on the comparative safety of intravenous ferumoxytol versus ferric carboxymaltose in iron deficiency anemia" AMERICAN JOURNAL OF HEMATOLOGY Strauss, W. E., Adkinson, N., Macdougall, I. C., Auerbach, M., Kaper, R. F., Chertow, G. M., Krop, J. S. 2018; 93 (9): E232–E233

    View details for PubMedID 30016554

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

    View details for PubMedID 30053986

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

    Abstract

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

    View details for PubMedID 30085235

  • Dialysis versus Medical Management at Different Ages and Levels of Kidney Function in Veterans with Advanced CKD JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Tamura, M., Desai, M., Kapphahn, K. I., Thomas, I., Asch, S. M., Chertow, G. M. 2018; 29 (8): 2169–77
  • Use of Estimating Equations for Dosing Antimicrobials in Patients with Acute Kidney Injury Not Receiving Renal Replacement Therapy JOURNAL OF CLINICAL MEDICINE Awdishu, L., Connor, A., Bouchard, J., Macedo, E., Chertow, G. M., Mehta, R. L. 2018; 7 (8)

    Abstract

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

    View details for PubMedID 30103503

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

    View details for PubMedID 29875201

    View details for PubMedCentralID PMC6032581

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

    Abstract

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

    View details for PubMedID 29982608

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

    Abstract

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

    View details for PubMedID 29685860

  • Unplanned Emergency Department Visits and Hospital Admissions Following Ureteroscopy: Do Ureteral Stents Make a Difference? UROLOGY Mittakanti, H. R., Conti, S. L., Pao, A. C., Chertow, G. M., Liao, J. C., Leppert, J. T., Elliott, C. S. 2018; 117: 44–49
  • Effects of calcimimetics on long-term outcomes in dialysis patients: literature review and Bayesian meta-analysis JOURNAL OF COMPARATIVE EFFECTIVENESS RESEARCH Lozano-Ortega, G., Waser, N., Bensink, M. E., Goring, S., Bennett, H., Block, G. A., Chertow, G. M., Trotman, M., Cooper, K., Levy, A. R., Belozeroff, V. 2018; 7 (7): 693–707

    Abstract

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

    View details for PubMedID 29762046

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

    View details for PubMedID 29385288

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

    Abstract

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

    View details for PubMedID 29916026

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

    View details for PubMedID 29891628

    View details for PubMedCentralID PMC6003621

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

    View details for PubMedID 29575100

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

    Abstract

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

    View details for PubMedID 29496260

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

    Abstract

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

    View details for PubMedID 29525393

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

    Abstract

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

    View details for PubMedID 29789430

  • EFFECT OF BARDOXOLONE METHYL TREATMENT ON URINARY ALBUMIN IN PATIENTS WITH TYPE 2 DIABETES AND CHRONIC KIDNEY DISEASE - POST-HOC ANALYSIS FROM BEAM AND BEACON Rossing, P., Block, G., Chertow, G., Chin, M., Goldsberry, A., McCullough, P., Meyer, C., Packham, D., Spinowitz, B., Sprague, S., Warnock, D., Pergola, P. OXFORD UNIV PRESS. 2018
  • Comparing Simultaneous Liver-Kidney Transplant Strategies: A Modified Cost-Effectiveness Analysis TRANSPLANTATION Cheng, X. S., Kim, W., Tan, J. C., Chertow, G. M., Goldhaber-Fiebert, J. 2018; 102 (5): E219–E228
  • Comparative safety of intravenous ferumoxytol versus ferric carboxymaltose in iron deficiency anemia: A randomized trial AMERICAN JOURNAL OF HEMATOLOGY Adkinson, N., Strauss, W. E., Macdougall, I. C., Bernard, K. E., Auerbach, M., Kaper, R. F., Chertow, G. M., Krop, J. S. 2018; 93 (5): 683–90

    Abstract

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

    View details for PubMedID 29417614

  • DECREASES IN WEIGHT WITH BARDOXOLONE METHYL IN OBESE PATIENTS WITH CHRONIC KIDNEY DISEASE STAGE 4 AND TYPE 2 DIABETES - POST-HOC ANALYSES FROM BEACON Rossing, P., Appel, G., Block, G., Chertow, G., Chin, M., Coyne, D., Goldsberry, A., Meyer, C., Molitch, M., Pergola, P., Spinowitz, B., Sprague, S., Raskin, P. OXFORD UNIV PRESS. 2018
  • BARDOXOLONE METHYL PREVENTS EGFR DECLINE IN PATIENTS WITH CHRONIC KIDNEY DISEASE STAGE 4 AND TYPE 2 DIABETES - POST-HOC ANALYSES FROM BEACON Wanner, C., Bakris, G., Block, G., Chin, M., Goldsberry, A., Inker, L., Meyer, C., O'Grady, M., Pergola, P., Warnock, D., Chertow, G. OXFORD UNIV PRESS. 2018
  • BASELINE LEVELS OF FGF23 AND EFFECTS OF ETELCALCETIDE Vervloet, M., Cooper, K., Block, G., Chertow, G., Fouqueray, B., Moe, S., Sun, Y., Tomlin, H., Wolf, M., Oberbauer, R. OXFORD UNIV PRESS. 2018
  • Associations of lipoproteins with cardiovascular and infection-related outcomes in patients receiving hemodialysis JOURNAL OF CLINICAL LIPIDOLOGY Kaysen, G. A., Grimes, B., Dalrymple, L. S., Chertow, G. M., Ishida, J. H., Delgado, C., Segal, M., Chiang, J., Dwyer, T., Johansen, K. L. 2018; 12 (2): 481–87

    Abstract

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

    View details for PubMedID 29361496

    View details for PubMedCentralID PMC5880742

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

    View details for DOI 10.1016/j.kint.2018.01.017

    View details for Web of Science ID 000428169200001

    View details for PubMedID 29475561

  • PREOPERATIVE KIDNEY FUNCTION TRENDS: IMPROVING ESTIMATES OF BASELINE KIDNEY FUNCTION PRIOR TO KIDNEY CANCER SURGERY Sun, A., Thomas, C., Ganesan, C., Sylman, J., Pao, A., Wagner, T., Brooks, J., Chertow, G., Leppert, J. ELSEVIER SCIENCE INC. 2018: E362
  • Comparing Simultaneous Liver-Kidney Transplant Strategies: A Modified Cost-Effectiveness Analysis. Transplantation Cheng, X. S., Kim, W. R., Tan, J. C., Chertow, G. M., Goldhaber-Fiebert, J. 2018

    Abstract

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

    View details for PubMedID 29554056

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

    Abstract

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

    View details for PubMedID 29629191

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

    Abstract

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

    View details for DOI 10.1016/j.kint.2017.10.028

    View details for Web of Science ID 000425713400005

    View details for PubMedID 29475546

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

    Abstract

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

    View details for PubMedID 29162340

    View details for PubMedCentralID PMC5828778

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

    Abstract

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

    View details for PubMedID 29584720

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

    Abstract

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

    View details for PubMedID 29242248

    View details for PubMedCentralID PMC5827605

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

    Abstract

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

    View details for PubMedID 29130810

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

    View details for DOI 10.1111/hdi.12640

    View details for PubMedID 29436151

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

    Abstract

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

    View details for PubMedID 29203473

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

    Abstract

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

    View details for PubMedID 29021322

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

    Abstract

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

    View details for PubMedID 28985268

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

    Abstract

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

    View details for PubMedID 30485269

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

    Abstract

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

    View details for PubMedID 30188740

  • Risk Factors, Incidence and Cost of Prolonged Hospitalization After Acute Respiratory Failure Marmor, M., Liu, S., Long, J., Chertow, G., Rogers, A. AMER THORACIC SOC. 2018
  • Bardoxolone Methyl Improves Kidney Function in Patients with Chronic Kidney Disease Stage 4 and Type 2 Diabetes: Post-Hoc Analyses from Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes Study AMERICAN JOURNAL OF NEPHROLOGY Chin, M. P., Bakris, G. L., Block, G. A., Chertow, G. M., Goldsberry, A., Inker, L. A., Heerspink, H. L., O'Grady, M., Pergola, P. E., Wanner, C., Warnock, D. G., Meyer, C. J. 2018; 47 (1): 40–47

    Abstract

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

    View details for PubMedID 29402767

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

    Abstract

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

    View details for PubMedID 29038286

    View details for PubMedCentralID PMC5748899

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

    Abstract

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

    View details for PubMedID 29601836

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

    Abstract

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

    View details for PubMedID 28870376

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

    Abstract

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

    View details for PubMedID 29071132

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

    Abstract

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

    View details for PubMedID 29186198

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

    Abstract

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

    View details for PubMedID 29042462

    View details for PubMedCentralID PMC5672958

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

    Abstract

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

    View details for PubMedID 28639740

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

    Abstract

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

    View details for PubMedID 28811048

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

    Abstract

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

    View details for PubMedID 28877926

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

    Abstract

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

    View details for PubMedID 28760939

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

    Abstract

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

    View details for PubMedID 28642330

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

    View details for DOI 10.1111/ctr.13020

    View details for Web of Science ID 000407287900013

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

    Abstract

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

    View details for DOI 10.2215/CJN.11141016

    View details for Web of Science ID 000404992800014

    View details for PubMedID 28630081

    View details for PubMedCentralID PMC5498355

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

    Abstract

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

    View details for DOI 10.2215/CJN.12131116

    View details for PubMedID 28576906

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

    Abstract

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

    View details for PubMedID 28159782

    View details for PubMedCentralID PMC5461797

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

    Abstract

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

    View details for PubMedID 28545622

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

    Abstract

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

    View details for PubMedID 28082519

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

    Abstract

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

    View details for DOI 10.1111/ctr.13020

    View details for PubMedID 28564126

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

    View details for PubMedID 28535231

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

    Abstract

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

    View details for DOI 10.1681/ASN.2017010041

    View details for PubMedID 28490435

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

    Abstract

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

    View details for DOI 10.1097/TP.0000000000001491

    View details for PubMedID 28437790

  • IMPACT OF ETELCALCETIDE ON FGF23 LEVELS DURING THE TREATMENT OF SECONDARY HYPERPARATHYROIDISM IN PATIENTS ON HEMODIALYSIS Wolf, M., Block, G., Chertow, G., Cooper, K., Fouqueray, B., Moe, S., Sun, Y., Tomlin, H., Vervloet, M., Oberbauer, R. OXFORD UNIV PRESS. 2017
  • Hyperprolactinemia in end-stage renal disease and effects of frequent hemodialysis HEMODIALYSIS INTERNATIONAL Lo, J. C., Beck, G. J., Kaysen, G. A., Chan, C. T., Kliger, A. S., Rocco, M. V., Chertow, G. M. 2017; 21 (2): 190-196

    Abstract

    Introduction End-stage renal disease is associated with elevations in circulating prolactin concentrations, but the association of prolactin concentrations with intermediate health outcomes and the effects of hemodialysis frequency on changes in serum prolactin have not been examined. Methods The FHN Daily and Nocturnal Dialysis Trials compared the effects of conventional thrice weekly hemodialysis with in-center daily hemodialysis (6 days/week) and nocturnal home hemodialysis (6 nights/week) over 12 months and obtained measures of health-related quality of life, self-reported physical function, mental health and cognition. Serum prolactin concentrations were measured at baseline and 12-month follow-up in 70% of the FHN Trial cohort to examine the associations among serum prolactin concentrations and physical, mental and cognitive function and the effects of hemodialysis frequency on serum prolactin. Findings Among 177 Daily Trial and 60 Nocturnal Trial participants with baseline serum prolactin measurements, the median serum prolactin concentration was 65 ng/mL (25th-75th percentile 48-195 ng/mL) and 81% had serum prolactin concentrations >30 ng/mL. While serum prolactin was associated with sex (higher in women), we observed no association between baseline serum prolactin and age, dialysis vintage, and baseline measures of physical, mental and cognitive function. Furthermore, there was no significant effect of hemodialysis frequency on serum prolactin in either of the two trials. Discussion Serum prolactin concentrations were elevated in the large majority of patients with ESRD, but were not associated with several measures of health status. Circulating prolactin levels also do not appear to decrease in response to more frequent hemodialysis over a one-year period.

    View details for DOI 10.1111/hdi.12489

    View details for Web of Science ID 000398574500011

  • ANALYSIS OF A SINGLE-ARM EXTENSION STUDY EVALUATING ETELCALETIDE STARTING DOSE FOR TREATMENT OF SECONDARY HYPERPARATHYROIDISM IN PATIENTS ON HEMODIALYSIS Cheng, S., Block, G., Dehmel, B., Deng, H., Chertow, G. W B SAUNDERS CO-ELSEVIER INC. 2017: A34
  • FERRIC CITRATE INCREASES HEMOGLOBIN IN PATIENTS WITH NON-DIALYSIS-DEPENDENT CHRONIC KIDNEY DISEASE AND IRON DEFICIENCY ANEMIA. Pergola, P. E., Fishbane, S., Neylan, J. F., Uhlig, K., Chertow, G. M. W B SAUNDERS CO-ELSEVIER INC. 2017: A76
  • THE INNO(2)VATE PHASE 3 PROGRAM OF VADADUSTAT FOR TREATMENT OF ANEMIA IN DIALYSIS-DEPENDENT CKD: RATIONALE AND STUDY DESIGN Winkelmayer, W., Block, G., Chertow, G., Fishbane, S., Komatsu, Y., McCullough, P., Pergola, P., Rosenberger, C., Williamson, D., Yee, J., Collins, A., Khawaja, Z., Sharma, A., Zuraw, Q., Maroni, B. W B SAUNDERS CO-ELSEVIER INC. 2017: A102
  • Glycovariations in Key HDL-Associated Glycoproteins Differentiate Between Clinical Groups and Affect the Immunomodulatory Capacity of HDL Zivkovic, A. M., Krishnan, S., Shimoda, M., Sacchi, R., Muchena, J. K., Luxardi, G., Kaysen, G. A., Parikh, A. N., Ngassam, V., Johansen, K., Chertow, G., Grimes, B., Smilowitz, J. T., Maverakis, E., Lebrilla, C. B. FEDERATION AMER SOC EXP BIOL. 2017
  • Thyroid function in end stage renal disease and effects of frequent hemodialysis. Hemodialysis international. International Symposium on Home Hemodialysis Lo, J. C., Beck, G. J., Kaysen, G. A., Chan, C. T., Kliger, A. S., Rocco, M. V., Li, M., Chertow, G. M. 2017

    Abstract

    End-stage renal disease (ESRD) is associated with perturbations in thyroid hormone concentrations and an increased prevalence of hypothyroidism. Few studies have examined the effects of hemodialysis dose or frequency on endogenous thyroid function.Within the Frequent Hemodialysis Network (FHN) trials, we examined the prevalence of hypothyroidism in patients with ESRD. Among those with endogenous thyroid function (without overt hyper/hypothyroidism or thyroid hormone supplementation), we examined the association of thyroid hormone concentration with multiple parameters of self-reported health status, and physical and cognitive performance, and the effects of hemodialysis frequency on serum thyroid stimulating hormone (TSH), free thyroxine (FT4), and free tri-iodothyronine (FT3) levels. Conventional thrice-weekly hemodialysis was compared to in-center (6 d/wk) hemodialysis (Daily Trial) and Nocturnal (6 nights/wk) home hemodialysis (Nocturnal Trial) over 12 months.Among 226 FHN Trial participants, the prevalence of hypothyroidism was 11% based on thyroid hormone treatment and/or serum TSH ≥8 mIU/mL. Among the remaining 195 participants (147 Daily, 48 Nocturnal) with endogenous thyroid function, TSH concentrations were modestly (directly) correlated with age (r = 0.16, P = 0.03) but not dialysis vintage. Circulating thyroid hormone levels were not associated with parameters of health status or physical and cognitive performance. Furthermore, frequent in-center and nocturnal hemodialysis did not significantly change (baseline to month 12) TSH, FT4, or FT3 concentrations in patients with endogenous thyroid function.Among patients receiving hemodialysis without overt hyper/hypothyroidism or thyroid hormone treatment, thyroid indices were not associated with multiple measures of health status and were not significantly altered with increased dialysis frequency.

    View details for DOI 10.1111/hdi.12527

    View details for PubMedID 28301073

  • Sarcopenia and its individual criteria are associated, in part, with mortality among patients on hemodialysis. Kidney international Kittiskulnam, P., Chertow, G. M., Carrero, J. J., Delgado, C., Kaysen, G. A., Johansen, K. L. 2017

    Abstract

    The relative importance of sarcopenia and its individual components as independent predictors of mortality in the dialysis population has not been determined. We estimated whole-body muscle mass using pre-dialysis bioimpedance spectroscopy measurements in 645 ACTIVE/ADIPOSE-enrolled prevalent hemodialysis patients from San Francisco and Atlanta. Low muscle mass was defined as two standard deviations below sex-specific means for young adults from NHANES and indexed to height(2), body weight, body surface area, or body mass index. We evaluated the association of sarcopenia (low muscle mass) by four indexing methods, weak hand grip strength, and slow gait speed with mortality. Seventy-eight deaths were observed during a mean follow-up of 1.9 years. Sarcopenia was not significantly associated with mortality after adjusting for covariates. No muscle mass criteria were associated with death, regardless of indexing metrics. In contrast, having weak grip strength or slow walking speed was associated with mortality in the adjusted model. Only gait slowness significantly improved the predictive accuracy for death with an increase in C-statistic from 0.63 to 0.68. However, both gait slowness and hand grip weakness significantly improved the net reclassification index compared to models without performance measures (50.5% for slowness and 33.7% for weakness), whereas models with muscle size did not. Neither sarcopenia nor low muscle mass by itself was a better predictor of mortality than functional limitation alone in patients receiving hemodialysis. Thus, physical performance measures, including slow gait speed and weak hand grip strength, were associated with mortality even after adjustment for muscle size and other confounders.

    View details for DOI 10.1016/j.kint.2017.01.024

    View details for PubMedID 28318630

  • Prevalence of chronic kidney disease and risk factors for its progression: A cross-sectional comparison of Indians living in Indian versus US cities PLOS ONE Anand, S., Kondal, D., Montez-Rath, M., Zheng, Y., Shivashankar, R., Singh, K., Gupta, P., Gupta, R., Ajay, V. S., Mohan, V., Pradeepa, R., Tandon, N., Ali, M. K., Narayan, K. M., Chertow, G. M., Kandula, N., Prabhakaran, D., Kanaya, A. M. 2017; 12 (3)

    Abstract

    While data from the latter part of the twentieth century consistently showed that immigrants to high-income countries faced higher cardio-metabolic risk than their counterparts in low- and middle-income countries, urbanization and associated lifestyle changes may be changing these patterns, even for conditions considered to be advanced manifestations of cardio-metabolic disease (e.g., chronic kidney disease [CKD]).Using cross-sectional data from the Center for cArdiometabolic Risk Reduction in South Asia (CARRS, n = 5294) and Mediators of Atherosclerosis in South Asians Living in America (MASALA, n = 748) studies, we investigated whether prevalence of CKD is similar among Indians living in Indian and U.S. cities. We compared crude, age-, waist-to-height ratio-, and diabetes- adjusted CKD prevalence difference. Among participants identified to have CKD, we compared management of risk factors for its progression. Overall age-adjusted prevalence of CKD was similar in MASALA (14.0% [95% CI 11.8-16.3]) compared with CARRS (10.8% [95% CI 10.0-11.6]). Among men the prevalence difference was low (prevalence difference 1.8 [95% CI -1.6,5.3]) and remained low after adjustment for age, waist-to-height ratio, and diabetes status (-0.4 [-3.2,2.5]). Adjusted prevalence difference was higher among women (prevalence difference 8.9 [4.8,12.9]), but driven entirely by a higher prevalence of albuminuria among women in MASALA. Severity of CKD--i.e., degree of albuminuria and proportion of participants with reduced glomerular filtration fraction--was higher in CARRS for both men and women. Fewer participants with CKD in CARRS were effectively treated. 4% of CARRS versus 51% of MASALA participants with CKD had A1c < 7%; and 7% of CARRS versus 59% of MASALA participants blood pressure < 140/90 mmHg. Our analysis applies only to urban populations. Demographic--particularly educational attainment--differences among participants in the two studies are a potential source of bias.Prevalence of CKD among Indians living in Indian and U.S. cities is similar. Persons with CKD living in Indian cities face higher likelihood of experiencing end-stage renal disease since they have more severe kidney disease and little evidence of risk factor management.

    View details for DOI 10.1371/journal.pone.0173554

    View details for PubMedID 28296920

  • HDL Glycoprotein Composition and Site-Specific Glycosylation Differentiates Between Clinical Groups and Affects IL-6 Secretion in Lipopolysaccharide-Stimulated Monocytes SCIENTIFIC REPORTS Krishnan, S., Shimoda, M., Sacchi, R., Kailemia, M. J., Luxardi, G., Kaysen, G. A., Parikh, A. N., Ngassam, V. N., Johansen, K., Chertow, G. M., Grimes, B., Smilowitz, J. T., Maverakis, E., Lebrilla, C. B., Zivkovic, A. M. 2017; 7

    Abstract

    The goal of this pilot study was to determine whether HDL glycoprotein composition affects HDL's immunomodulatory function. HDL were purified from healthy controls (n = 13), subjects with metabolic syndrome (MetS) (n = 13), and diabetic hemodialysis (HD) patients (n = 24). Concentrations of HDL-bound serum amyloid A (SAA), lipopolysaccharide binding protein (LBP), apolipoprotein A-I (ApoA-I), apolipoprotein C-III (ApoC-III), α-1-antitrypsin (A1AT), and α-2-HS-glycoprotein (A2HSG); and the site-specific glycovariations of ApoC-III, A1AT, and A2HSG were measured. Secretion of interleukin 6 (IL-6) in lipopolysaccharide-stimulated monocytes was used as a prototypical assay of HDL's immunomodulatory capacity. HDL from HD patients were enriched in SAA, LBP, ApoC-III, di-sialylated ApoC-III (ApoC-III2) and desialylated A2HSG. HDL that increased IL-6 secretion were enriched in ApoC-III, di-sialylated glycans at multiple A1AT glycosylation sites and desialylated A2HSG, and depleted in mono-sialylated ApoC-III (ApoC-III1). Subgroup analysis on HD patients who experienced an infectious hospitalization event within 60 days (HD+) (n = 12), vs. those with no event (HD-) (n = 12) showed that HDL from HD+ patients were enriched in SAA but had lower levels of sialylation across glycoproteins. Our results demonstrate that HDL glycoprotein composition, including the site-specific glycosylation, differentiate between clinical groups, correlate with HDL's immunomodulatory capacity, and may be predictive of HDL's ability to protect from infection.

    View details for DOI 10.1038/srep43728

    View details for Web of Science ID 000396421300001

    View details for PubMedID 28287093

  • Patients receiving frequent hemodialysis have better health-related quality of life compared to patients receiving conventional hemodialysis. Kidney international Garg, A. X., Suri, R. S., Eggers, P., Finkelstein, F. O., Greene, T., Kimmel, P. L., Kliger, A. S., Larive, B., Lindsay, R. M., Pierratos, A., Unruh, M., Chertow, G. M. 2017; 91 (3): 746-754

    Abstract

    Most patients with end-stage kidney disease value their health-related quality of life (HRQoL) and want to know how it will be affected by their dialysis modality. We extended the findings of two prior clinical trial reports to estimate the effects of frequent compared to conventional hemodialysis on additional measures of HRQoL. The Daily Trial randomly assigned 245 patients to receive frequent (six times per week) or conventional (three times per week) in-center hemodialysis. The Nocturnal Trial randomly assigned 87 patients to receive frequent nocturnal (six times per week) or conventional (three times per week) home hemodialysis. All patients were on conventional hemodialysis prior to randomization, with an average feeling thermometer score of 70 to 75 (a visual analog scale from 0 to 100 where 100 is perfect health), an average general health scale score of 40 to 47 (a score from 0 to 100 where 100 is perfect health), and an average dialysis session recovery time of 2 to 3 hours. Outcomes are reported as the between-treatment group differences in one-year change in HRQoL measures and analyzed using linear mixed effects models. After one year in the Daily Trial, patients assigned to frequent in-center hemodialysis reported a higher feeling thermometer score, better general health, and a shorter recovery time after a dialysis session compared to standard thrice-weekly dialysis. After one year in the Nocturnal Trial, patients assigned to frequent home hemodialysis also reported a shorter recovery time after a dialysis session, but no statistical difference in their feeling thermometer or general health scores compared to standard home dialysis schedules. Thus, patients receiving day or nocturnal hemodialysis on average recovered approximately one hour earlier from a frequent compared to conventional hemodialysis session. Patients treated in an in-center dialysis facility reported better HRQoL with frequent compared to conventional hemodialysis.

    View details for DOI 10.1016/j.kint.2016.10.033

    View details for PubMedID 28094031

  • Net Budgetary Impact of Ferric Citrate as a First-Line Phosphate Binder for the Treatment of Hyperphosphatemia: A Markov Microsimulation Model DRUGS IN R&D Brunelli, S. M., Sibbel, S. P., Van Wyck, D., Sharma, A., Hsieh, A., Chertow, G. M. 2017; 17 (1): 159–66

    Abstract

    Ferric citrate (FC) has demonstrated efficacy as a phosphate binder and reduces the requirements for erythropoiesis-stimulating agents (ESAs) and intravenous (IV) iron in dialysis patients. We developed a net budgetary impact model to evaluate FC vs. other phosphate binders from the vantage of a large dialysis provider. We used a Markov microsimulation model to simulate mutually referential longitudinal effects between serum phosphate and phosphate binder dose; categories of these defined health states. Health states probabilistically determined treatment attendance and utilization of ESA and IV iron. We derived model inputs from a retrospective analysis of incident phosphate binder users from a large dialysis organization (January 2011-June 2013) and incorporated treatment effects of FC from a phase III trial. The model was run over a 1-year time horizon. We considered fixed costs of providing dialysis; costs of administering ESA and IV iron; and payment rates for dialysis, ESAs, and IV iron. In the base-case model, FC had a net budgetary impact (savings) of +US$213,223/year per 100 patients treated vs. standard of care. One-way sensitivity analyses showed a net budgetary impact of up to +US$316,296/year per 100 patients treated when higher hemoglobin levels observed with FC translated into a 30% additional ESA dose reduction, and up to +US$223,281/year per 100 patients treated when effects on missed treatment rates were varied. Two-way sensitivity analyses in which acquisition costs for ESA and IV iron were varied showed a net budgetary impact of +US$104,840 to +US$213,223/year per 100 patients treated. FC as a first-line phosphate binder would likely yield substantive savings vs. standard of care under current reimbursement.

    View details for PubMedID 28078600

    View details for PubMedCentralID PMC5318331

  • Consolidation in the Dialysis Industry, Patient Choice, and Local Market Competition CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Erickson, K. F., Zheng, Y., Winkelmayer, W. C., Ho, V., Bhattacharya, J., Chertow, G. M. 2017; 12 (3): 536-545

    Abstract

    The Medicare program insures >80% of patients with ESRD in the United States. An emphasis on reducing outpatient dialysis costs has motivated consolidation among dialysis providers, with two for-profit corporations now providing dialysis for >70% of patients. It is unknown whether industry consolidation has affected patients' ability to choose among competing dialysis providers. We identified patients receiving in-center hemodialysis at the start of 2001 and 2011 from the national ESRD registry and ascertained dialysis facility ownership. For each hospital service area, we determined the maximum distance within which 90% of patients traveled to receive dialysis in 2001. We compared the numbers of competing dialysis providers within that same distance between 2001 and 2011. Additionally, we examined the Herfindahl-Hirschman Index, a metric of market concentration ranging from near zero (perfect competition) to one (monopoly) for each hospital service area. Between 2001 and 2011, the number of different uniquely owned competing providers decreased 8%. However, increased facility entry into markets to meet rising demand for care offset the effect of provider consolidation on the number of choices available to patients. The number of dialysis facilities in the United States increased by 54%, and patients experienced an average 10% increase in the number of competing proximate facilities from which they could choose to receive dialysis (P<0.001). Local markets were highly concentrated in both 2001 and 2011 (mean Herfindahl-Hirschman Index =0.46; SD=0.2 for both years), but overall market concentration did not materially change. In summary, a decade of consolidation in the United States dialysis industry did not (on average) limit patient choice or result in more concentrated local markets. However, because dialysis markets remained highly concentrated, it will be important to understand whether market competition affects prices paid by private insurers, access to dialysis care, quality of care, and associated health outcomes.

    View details for DOI 10.2215/CJN.06340616

    View details for PubMedID 27831510

  • 30-Day Readmissions After an Acute Kidney Injury Hospitalization AMERICAN JOURNAL OF MEDICINE Silver, S. A., Harel, Z., McArthur, E., Nash, D. M., Acedillo, R., Kitchlu, A., Garg, A. X., Chertow, G. M., Bell, C. M., Wald, R. 2017; 130 (2): 163-?

    Abstract

    The risk of hospital readmission in acute kidney injury survivors is not well understood. We estimated the proportion of acute kidney injury patients who were rehospitalized within 30 days and identified characteristics associated with hospital readmission.We conducted a population-based study of patients who survived a hospitalization complicated by acute kidney injury from 2003-2013 in Ontario, Canada. The primary outcome was 30-day hospital readmission. We used a propensity score model to match patients with and without acute kidney injury, and a Cox proportional hazards model with death as a competing risk to identify predictors of 30-day readmission.We identified 156,690 patients who were discharged from 197 hospitals after an episode of acute kidney injury. In the subsequent 30 days, 27,457 (18%) patients were readmitted; 15,988 (10%) visited the emergency department and 7480 (5%) died. We successfully matched 111,778 patients with acute kidney injury 1:1 to patients without acute kidney injury. The likelihood of 30-day readmission was higher in acute kidney injury patients than those without acute kidney injury (hazard ratio [HR] 1.53; 95% confidence interval [CI], 1.50-1.57). Factors most strongly associated with 30-day rehospitalization were the number of hospitalizations in the preceding year (adjusted HR 1.45 for ≥2 hospitalizations; 95% CI, 1.40-1.51) and receipt of inpatient chemotherapy (adjusted HR 1.44; 95% CI, 1.32-1.58).One in 5 patients who survive a hospitalization complicated by acute kidney injury is readmitted in the next 30 days. Better strategies are needed to identify and care for acute kidney injury survivors in the community.

    View details for DOI 10.1016/j.amjmed.2016.09.016

    View details for Web of Science ID 000392623200029

  • Sarcopenia among patients receiving hemodialysis: weighing the evidence. Journal of cachexia, sarcopenia and muscle Kittiskulnam, P., Carrero, J. J., Chertow, G. M., Kaysen, G. A., Delgado, C., Johansen, K. L. 2017; 8 (1): 57-68

    Abstract

    There is no consensus on how best to define low muscle mass in patients with end-stage renal disease. Use of muscle mass normalized to height-squared has been suggested by geriatric societies but may underestimate sarcopenia, particularly in the setting of excess adiposity. We compared four definitions of low muscle mass in a prevalent hemodialysis cohort.ACTIVE/ADIPOSE enrolled prevalent patients receiving hemodialysis from the San Francisco and Atlanta areas from June 2009 to August 2011. Whole-body muscle mass was estimated using bioelectrical impedance spectroscopy, performed before a midweek dialysis session (n = 645; age 56.7 ± 14.5 years, 41% women). We defined low muscle mass as muscle mass of 2SD or more below sex-specific bioelectrical impedance spectroscopy-derived means for young adults (18-49 years) from National Health and Nutrition Examination Survey and indexed to height(2) , body weight (percentage), body surface area (BSA) by the DuBois formula, or Quételet's body mass index (BMI). We compared prevalence of low muscle mass among the four methods and assessed their correlation with strength and physical performance.The prevalence of low muscle mass ranged from 8 to 32%. Muscle mass indexed to height(2) classified the smallest percentage of patients as having low muscle mass, particularly among women, whereas indexing by BSA classified the largest percentage. Low muscle mass/height(2) was present almost exclusively among normal or underweight patients, whereas indexing to body weight and BMI classified more overweight and obese patients as having low muscle mass. Handgrip strength was lower among those with low muscle mass by all methods except height(2) . Handgrip strength was directly and modestly correlated with muscle mass normalized by percentage of body weight, BSA, and BMI (ρ = 0.43, 0.56, and, 0.64, respectively) and less so with muscle/height(2) (ρ = 0.31, P < 0.001). The difference in grip strength among patients with low vs. normal muscle mass was largest according to muscle/BMI (-6.84 kg, 95% CI -8.66 to -5.02, P < 0.001). There were significant direct correlations of gait speed with muscle mass indexed to percentage of body weight, BSA, and BMI but not with muscle mass indexed to height(2) .Skeletal muscle mass normalized to height(2) may underestimate the prevalence of low muscle mass, particularly among overweight and obese patients on hemodialysis. Valid detection of sarcopenia among obese patients receiving hemodialysis requires adjustment for body size.

    View details for DOI 10.1002/jcsm.12130

    View details for PubMedID 27897415

  • Cost of Acute Kidney Injury in Hospitalized Patients. Journal of hospital medicine Silver, S. A., Long, J., Zheng, Y., Chertow, G. M. 2017; 12 (2): 70-76

    Abstract

    The economic burden of acute kidney injury (AKI) is not well understood.To estimate the effects of AKI on hospitalization costs and length of stay (LOS).Using data from the 2012 National Inpatient Sample, we compared hospitalization costs and LOS with and without AKI. We used a generalized linear model with a gamma distribution and a log link fitted to AKI to adjust for demographics, hospital differences, and comorbidities.United States.29,763,649 adult hospitalizations without endstage renal disease.AKI determined using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) diagnosis codes..Hospitalization costs and LOS.AKI was associated with an increase in hospitalization costs of $7933 (95% confidence interval [CI], $7608-$8258) and an increase in LOS of 3.2 (95% CI, 3.2-3.3) days compared to patients without AKI. When adjusted for patient and hospital characteristics, the associated increase in costs was $1795 (95% CI, $1692-$1899) and in LOS, it was 1.1 (95% CI, 1.1-1.1) days. Corresponding results among patients hospitalized with AKI requiring dialysis were $42,077 (95% CI, $39,820-$44,335) and 11.5 (95% CI, 11.2-11.8) days and $11,016 (95% CI, $10,468-$11,564) and 3.9 (95% CI, 3.8-4.1) days. AKI was associated with higher hospitalization costs than myocardial infarction and gastrointestinal bleeding, and costs were comparable to those for stroke, pancreatitis, and pneumonia..In the United States, AKI is associated with excess hospitalization costs and prolonged LOS. The economic burden of AKI warrants further attention from hospitals and policymakers to enhance processes of care and develop novel treatment strategies. Journal of Hospital Medicine 2017;12:70-76.

    View details for DOI 10.12788/jhm.2683

    View details for PubMedID 28182800

  • Estimating the Risk of Radiocontrast-Associated Nephropathy JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Wilhelm-Leen, E., Montez-Rath, M. E., Chertow, G. 2017; 28 (2): 653-659

    Abstract

    Estimates of the incidence of radiocontrast-associated nephropathy vary widely and suffer from misclassification of the cause of AKI and confounding. Using the Nationwide Inpatient Sample, we created multiple estimates of the risk of radiocontrast-associated nephropathy among adult patients hospitalized in the United States in 2009. First, we stratified patients according to the presence or absence of 12 relatively common diagnoses associated with AKI and evaluated the rate of AKI between strata. Next, we created a logistic regression model, controlling for comorbidity and acuity of illness, to estimate the risk of AKI associated with radiocontrast administration within each stratum. Finally, we performed an analysis stratified by the degree of preexisting comorbidity. In general, patients who received radiocontrast did not develop AKI at a clinically significant higher rate. Adjusted only for the complex survey design, patients to whom radiocontrast was and was not administered developed AKI at rates of 5.5% and 5.6%, respectively. After controlling for comorbidity and acuity of illness, radiocontrast administration associated with an odds ratio for AKI of 0.93 (95% confidence interval, 0.88 to 0.97). In conclusion, the risk of radiocontrast-associated nephropathy may be overstated in the literature and overestimated by clinicians. More accurate AKI risk estimates may improve clinical decision-making when attempting to balance the potential benefits of radiocontrast-enhanced imaging and the risk of AKI.

    View details for DOI 10.1681/ASN.2016010021

    View details for PubMedID 27688297

  • Contemporary Use of Partial Nephrectomy: Are Older Patients With Impaired Kidney Function Being Left Behind? UROLOGY Leppert, J. T., Mittakanti, H. R., Thomas, I., Lamberts, R. W., Sonn, G. A., Chung, B. I., Skinner, E. C., Wagner, T. H., Chertow, G. M., Brooks, J. D. 2017; 100: 65-71
  • Hemodialysis Hospitalizations and Readmissions: The Effects of Payment Reform AMERICAN JOURNAL OF KIDNEY DISEASES Erickson, K. F., Winkelmayer, W. C., Chertow, G. M., Bhattacharya, J. 2017; 69 (2): 237-246

    Abstract

    In 2004, the Centers for Medicare & Medicaid Services changed reimbursement for physicians and advanced practitioners caring for patients receiving hemodialysis from a capitated to a tiered fee-for-service system, encouraging increased face-to-face visits. This early version of a pay-for-performance initiative targeted a care process: more frequent provider visits in hemodialysis. Although more frequent provider visits in hemodialysis are associated with fewer hospitalizations and rehospitalizations, it is unknown whether encouraging more frequent visits through reimbursement policy also yielded these benefits.We used a retrospective cohort interrupted time-series study design to examine whether the 2004 nephrologist reimbursement reform led to reduced hospitalizations and rehospitalizations. We also used published data to estimate a range of annual economic costs associated with more frequent visits.Medicare beneficiaries in the United States receiving hemodialysis in the 2 years prior to and following reimbursement reform.The 2 years following nephrologist reimbursement reform.Odds of hospitalization and 30-day hospital readmission for all causes and fluid overload; US dollars.We found no significant change in all-cause hospitalization or rehospitalization and slight reductions in fluid overload hospitalization and rehospitalization following reimbursement reform; the estimated economic cost associated with additional visits ranged from $13 to $87 million per year, depending on who (physicians or advanced practitioners) spent additional time visiting patients and how much additional effort was involved.Due to limited information about how much additional time providers spent seeing patients after reimbursement reform, we could only examine a range of potential economic costs associated with the reform.A Medicare reimbursement policy designed to encourage more frequent visits during outpatient hemodialysis may have been costly. The policy was associated with fewer hospitalizations and rehospitalizations for fluid overload, but had no effect on all-cause hospitalizations or rehospitalizations.

    View details for DOI 10.1053/j.ajkd.2016.08.033

    View details for PubMedID 27856087

  • Blood Calcification Propensity, Cardiovascular Events, and Survival in Patients Receiving Hemodialysis in the EVOLVE Trial CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Pasch, A., Block, G. A., Bachtler, M., Smith, E. R., Jahnen-Dechent, W., Arampatzis, S., Chertow, G. M., Parfrey, P., Ma, X., Floege, J. 2017; 12 (2): 315-322

    Abstract

    Patients receiving hemodialysis are at risk of cardiovascular events. A novel blood test (T50 test) determines the individual calcification propensity of blood.T50 was determined in 2785 baseline serum samples of patients receiving hemodialysis enrolled in the Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events (EVOLVE) trial and the T50 results were related to patient outcomes.Serum albumin, bicarbonate, HDL cholesterol, and creatinine were the main factors positively/directly and phosphate was the main factor negatively/inversely associated with T50. The primary composite end point (all-cause mortality, myocardial infarction [MI], hospitalization for unstable angina, heart failure, or peripheral vascular event [PVE]) was reached in 1350 patients after a median follow-up time of 619 days. After adjustments for confounding, a lower T50 was independently associated with a higher risk of the primary composite end point as a continuous measure (hazard ratio [HR] per 1 SD lower T50, 1.15; 95% confidence interval [95% CI], 1.08 to 1.22; P<0.001). Furthermore, lower T50 was associated with a higher risk in all-cause mortality (HR per 1 SD lower T50, 1.10; 95% CI, 1.02 to 1.17; P=0.001), MI (HR per 1 SD lower T50, 1.38; 95% CI, 1.19 to 1.60; P<0.001), and PVE (HR per 1 SD lower T50, 1.22; 95% CI, 1.05 to 1.42; P=0.01). T50 improved risk prediction (integrated discrimination improvement and net reclassification improvement, P<0.001 and P=0.001) of the primary composite end point.Blood calcification propensity was independently associated with the primary composite end point, all-cause mortality, MI, and PVE in the EVOLVE study and improved risk prediction. Prospective trials should clarify whether T50-guided therapies improve outcomes.

    View details for DOI 10.2215/CJN.04720416

    View details for PubMedID 27940458

  • Limited reduction in uremic solute concentrations with increased dialysis frequency and time in the Frequent Hemodialysis Network Daily Trial. Kidney international Sirich, T. L., Fong, K., Larive, B., Beck, G. J., Chertow, G. M., Levin, N. W., Kliger, A. S., Plummer, N. S., Meyer, T. W. 2017

    Abstract

    The Frequent Hemodialysis Network Daily Trial compared conventional three-times weekly treatment to more frequent treatment with a longer weekly treatment time in patients receiving in-center hemodialysis. Evaluation at one year showed favorable effects of more intensive treatment on left ventricular mass, blood pressure, and phosphate control, but modest or no effects on physical or cognitive performance. The current study compared plasma concentrations of uremic solutes in stored samples from 53 trial patients who received three-times weekly in-center hemodialysis for an average weekly time of 10.9 hours and 30 trial patients who received six-times weekly in-center hemodialysis for an average of 14.6 hours. Metabolomic analysis revealed that increased treatment frequency and time resulted in an average reduction of only 15 percent in the levels of 107 uremic solutes. Quantitative assays confirmed that increased treatment did not significantly reduce levels of the putative uremic toxins p-cresol sulfate or indoxyl sulfate. Kinetic modeling suggested that our ability to lower solute concentrations by increasing hemodialysis frequency and duration may be limited by the presence of non-dialytic solute clearances and/or changes in solute production. Thus, failure to achieve larger reductions in uremic solute concentrations may account, in part, for the limited benefits observed with increasing frequency and weekly treatment time in Frequent Hemodialysis Daily Trial participants.

    View details for DOI 10.1016/j.kint.2016.11.002

    View details for PubMedID 28089366

  • Effect of Etelcalcetide vs Placebo on Serum Parathyroid Hormone in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism Two Randomized Clinical Trials JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Block, G. A., Bushinsky, D. A., Cunningham, J., Drueke, T. B., Ketteler, M., Kewalramani, R., Martin, K. J., Mix, T. C., Moe, S. M., Patel, U. D., Silver, J., Spiegel, D. M., Sterling, L., Walsh, L., Chertow, G. M. 2017; 317 (2): 146-155

    Abstract

    Secondary hyperparathyroidism contributes to extraskeletal complications in chronic kidney disease.To evaluate the effect of the intravenous calcimimetic etelcalcetide on serum parathyroid hormone (PTH) concentrations in patients receiving hemodialysis.Two parallel, phase 3, randomized, placebo-controlled treatment trials were conducted in 1023 patients receiving hemodialysis with moderate to severe secondary hyperparathyroidism. Trial A was conducted in 508 patients at 111 sites in the United States, Canada, Europe, Israel, Russia, and Australia from March 12, 2013, to June 12, 2014; trial B was conducted in 515 patients at 97 sites in the same countries from March 12, 2013, to May 12, 2014.Intravenous administration of etelcalcetide (n = 503) or placebo (n = 513) after each hemodialysis session for 26 weeks.The primary efficacy end point was the proportion of patients achieving greater than 30% reduction from baseline in mean PTH during weeks 20-27. A secondary efficacy end point was the proportion of patients achieving mean PTH of 300 pg/mL or lower.The mean age of the 1023 patients was 58.2 (SD, 14.4) years and 60.4% were men. Mean PTH concentrations at baseline and during weeks 20-27 were 849 and 384 pg/mL vs 820 and 897 pg/mL in the etelcalcetide and placebo groups, respectively, in trial A; corresponding values were 845 and 363 pg/mL vs 852 and 960 pg/mL in trial B. Patients randomized to etelcalcetide were significantly more likely to achieve the primary efficacy end point: in trial A, 188 of 254 (74.0%) vs 21 of 254 (8.3%; P < .001), for a difference in proportions of 65.7% (95% CI, 59.4%-72.1%) and in trial B, 192 of 255 (75.3%) vs 25 of 260 (9.6%; P < .001), for a difference in proportions of 65.7% (95% CI, 59.3%-72.1%). Patients randomized to etelcalcetide were significantly more likely to achieve a PTH level of 300 pg/mL or lower: in trial A, 126 of 254 (49.6%) vs 13 of 254 (5.1%; P < .001), for a difference in proportions of 44.5% (95% CI, 37.8%-51.2%) and in trial B, 136 of 255 (53.3%) vs 12 of 260 (4.6%; P < .001), for a difference in proportions of 48.7% (95% CI, 42.1%-55.4%). In trials A and B, respectively, patients receiving etelcalcetide had more muscle spasms (12.0% and 11.1% vs 7.1% and 6.2% with placebo), nausea (12.4% and 9.1% vs 5.1% and 7.3%), and vomiting (10.4% and 7.5% vs 7.1% and 3.1%).Among patients receiving hemodialysis with moderate to severe secondary hyperparathyroidism, use of etelcalcetide compared with placebo resulted in greater reduction in serum PTH over 26 weeks. Further studies are needed to assess clinical outcomes as well as longer-term efficacy and safety.clinicaltrials.gov Identifiers: NCT01788046.

    View details for DOI 10.1001/jama.2016.19456

    View details for PubMedID 28097355

  • Effect of Etelcalcetide vs Cinacalcet on Serum Parathyroid Hormone in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism A Randomized Clinical Trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Block, G. A., Bushinsky, D. A., Cheng, S., Cunningham, J., Dehmel, B., Drueke, T. B., Ketteler, M., Kewalramani, R., Martin, K. J., Moe, S. M., Patel, U. D., Silver, J., Sun, Y., Wang, H., Chertow, G. M. 2017; 317 (2): 156-164

    Abstract

    Secondary hyperparathyroidism contributes to extraskeletal calcification and is associated with all-cause and cardiovascular mortality. Control is suboptimal in the majority of patients receiving hemodialysis. An intravenously (IV) administered calcimimetic could improve adherence and reduce adverse gastrointestinal effects.To evaluate the relative efficacy and safety of the IV calcimimetic etelcalcetide and the oral calcimimetic cinacalcet.A randomized, double-blind, double-dummy active clinical trial was conducted comparing IV etelcalcetide vs oral placebo and oral cinacalcet vs IV placebo in 683 patients receiving hemodialysis with serum parathyroid hormone (PTH) concentrations higher than 500 pg/mL on active therapy at 164 sites in the United States, Canada, Europe, Russia, and New Zealand. Patients were enrolled from August 2013 to May 2014, with end of follow-up in January 2015.Etelcalcetide intravenously and oral placebo (n = 340) or oral cinacalcet and IV placebo (n = 343) for 26 weeks. The IV study drug was administered 3 times weekly with hemodialysis; the oral study drug was administered daily.The primary efficacy end point was noninferiority of etelcalcetide at achieving more than a 30% reduction from baseline in mean predialysis PTH concentrations during weeks 20-27 (noninferiority margin, 12.0%). Secondary end points included superiority in achieving biochemical end points (>50% and >30% reduction in PTH) and self-reported nausea or vomiting.The mean (SD) age of the trial participants was 54.7 (14.1) years and 56.2% were men. Etelcalcetide was noninferior to cinacalcet on the primary end point. The estimated difference in proportions of patients achieving reduction in PTH concentrations of more than 30% between the 198 of 343 patients (57.7%) randomized to receive cinacalcet and the 232 of 340 patients (68.2%) randomized to receive etelcalcetide was -10.5% (95% CI, -17.5% to -3.5%, P for noninferiority, <.001; P for superiority, .004). One hundred seventy-eight patients (52.4%) randomized to etelcalcetide achieved more than 50% reduction in PTH concentrations compared with 138 patients (40.2%) randomized to cinacalcet (P = .001; difference in proportions, 12.2%; 95% CI, 4.7% to 19.5%). The most common adverse effect was decreased blood calcium (68.9% vs 59.8%).Among patients receiving hemodialysis with moderate to severe secondary hyperparathyroidism, the use of etelcalcetide was not inferior to cinacalcet in reducing serum PTH concentrations over 26 weeks; it also met superiority criteria. Further studies are needed to assess clinical outcomes as well as longer-term efficacy and safety.clinicaltrials.gov Identifier: NCT1896232.

    View details for DOI 10.1001/jama.2016.19468

    View details for PubMedID 28097356

  • Predialysis volume overload and patient-reported sleep duration and quality in patients receiving hemodialysis. Hemodialysis international. International Symposium on Home Hemodialysis Abreo, A. P., Dalrymple, L. S., Chertow, G. M., Kaysen, G. A., Herzog, C. A., Johansen, K. L. 2017; 21 (1): 133-141

    Abstract

    Previous studies of patients with end-stage renal disease have examined the role of fluid shifts on apnea-hypopnea episodes, but the association between volume overload and patient-reported sleep quality or duration has not been well-established.We studied the association between predialysis bioimpedance spectroscopy-derived volume estimates and self-reported sleep quality and duration in 638 patients in the United States Renal Data System ACTIVE/ADIPOSE study receiving hemodialysis from 2009 to 2011. We used questionnaires to assess self-reported sleep duration and quality. We used relative hydration status (fluid overload/extracellular water; FO/ECW) as the primary predictor and examined associations with hours of sleep duration using linear regression. We used multivariable ordinal logistic regression to determine the association between categories of relative hydration status (normal hydration [FO/ECW < 6.8%], mild overhydration [FO/ECW 6.8%-15%], and hyperhydration [FO/ECW > 15%]) and four levels of difficulty with falling asleep, waking, and returning to sleep.Higher relative hydration status was associated with fewer hours of sleep (-0.31 hours per 10%, 95% confidence interval (CI) -0.49 to -0.13). Compared to the normal hydration group, there was a statistically significant association between higher relative hydration status category and more frequent nighttime waking (OR: mild overhydration 1.92 [95% CI 1.23-2.99], hyperhydration 1.87 [95% CI 1.16-2.99]), a trend toward more difficulty returning to sleep (OR: mild overhydration 1.46 [95% CI 0.94-2.27], hyperhydration 1.52 [95% CI 0.95-2.43]), and no association between relative hydration category and difficulty falling asleep.Hydration status was associated with self-reported sleep duration in patients on dialysis. Future studies should prospectively examine the effects of optimizing fluid status on sleep duration and quality.

    View details for DOI 10.1111/hdi.12446

    View details for PubMedID 27346666

  • Donation, Not Disease! A Multiple-Hit Hypothesis on Development of Post-Donation Kidney Disease. Current transplantation reports Cheng, X. S., Glassock, R. J., Lentine, K. L., Chertow, G. M., Tan, J. C. 2017; 4 (4): 320–26

    Abstract

    The risks following living kidney donation has been the subject of rigorous investigation in the past several decades. How to utilize the burgeoning new knowledge base to better the risk assessment, education, and health maintenance of donors is unclear. We review the physiologic and epidemiologic evidences on the post-donation state and submit a multiple-hit hypothesis to reconcile the finite elevation in risk of kidney disease after donation with the benign course of most kidney donors.The risk of end-stage kidney disease is higher in kidney donors compared to similarly healthy non-kidney donors. Nonetheless, post-donation kidney disease is uncommon and arises mostly in the setting of other "hits"-either a "first hit" present at birth or a "second hit" acquired later in life.The transplant community's focus should be directed toward (1) personalized risk assessment to inform consent before donation and (2) preventing and treating development of "second hits" following kidney donation.

    View details for PubMedID 29201600

  • The Economic Consequences of Acute Kidney Injury NEPHRON Silver, S. A., Chertow, G. M. 2017; 137 (4): 297–301

    Abstract

    Acute kidney injury (AKI) is an increasingly common condition associated with poor health outcomes. Combined with its rising incidence, AKI has emerged as a major public health concern with high human and financial costs. In England, the estimated inpatient costs related to AKI consume 1% of the National Health Service budget. In the United States, AKI is associated with an increase in hospitalization costs that range from $5.4 to $24.0 billion. The most expensive patients are those with AKI of sufficient severity to require dialysis, where cost increases relative to patients without AKI range from $11,016 to $42,077 per hospitalization. Even with these high costs, significant hospital-level variation still exists in the cost of AKI care. In this article, we review the economic consequences of AKI for both the general and critically ill AKI population. Our primary objective is to shed light on an opportunity for hospitals and policymakers to develop new care processes for patients with AKI that have the potential to yield substantial cost savings. By exposing the high rates of death and disability experienced by affected patients and the immense financial burden attributable to AKI, we also hope to motivate scientists and entrepreneurs to pursue a variety of innovative therapeutic strategies to combat AKI in the near term.

    View details for PubMedID 28595193

    View details for PubMedCentralID PMC5743773

  • Incident CKD after Radical or Partial Nephrectomy. Journal of the American Society of Nephrology : JASN Leppert, J. T., Lamberts, R. W., Thomas, I. C., Chung, B. I., Sonn, G. A., Skinner, E. C., Wagner, T. H., Chertow, G. M., Brooks, J. D. 2017

    Abstract

    The comparative effectiveness of partial nephrectomy versus radical nephrectomy to preserve kidney function has not been well established. We determined the risk of clinically significant (stage 4 and higher) CKD after radical or partial nephrectomy among veterans treated for kidney cancer in the Veterans Health Administration (2001-2013). Among patients with preoperative eGFR≥30 ml/min per 1.73 m(2), the incidence of CKD stage 4 or higher after radical (n=9759) or partial nephrectomy (n=4370) was 7.9% overall. The median time to stage 4 or higher CKD after surgery was 5 months, after which few patients progressed. In propensity score-matched cohorts, partial nephrectomy associated with a significantly lower relative risk of incident CKD stage 4 or higher (hazard ratio, 0.34; 95% confidence interval [95% CI], 0.26 to 0.43, versus radical nephrectomy). In a parallel analysis of patients with normal or near-normal preoperative kidney function (eGFR≥60 ml/min per 1.73 m(2)), partial nephrectomy was also associated with a significantly lower relative risk of incident CKD stage 3b or higher (hazard ratio, 0.15; 95% CI, 0.11 to 0.19, versus radical nephrectomy) in propensity score-matched cohorts. Competing risk regression models produced consistent results. Finally, patients treated with a partial nephrectomy had reduced risk of mortality (hazard ratio, 0.55; 95% CI, 0.49 to 0.62). In conclusion, compared with radical nephrectomy, partial nephrectomy was associated with a marked reduction in the incidence of clinically significant CKD and with enhanced survival. Postoperative decline in kidney function occurred mainly in the first year after surgery and appeared stable over time.

    View details for PubMedID 29018140

  • The Pathogenesis of Ebola Virus Disease ANNUAL REVIEW OF PATHOLOGY: MECHANISMS OF DISEASE, VOL 12 Baseler, L., Chertow, D. S., Johnson, K. M., Feldmann, H., Morens, D. M. 2017; 12: 387-418

    Abstract

    For almost 50 years, ebolaviruses and related filoviruses have been repeatedly reemerging across the vast equatorial belt of the African continent to cause epidemics of highly fatal hemorrhagic fever. The 2013-2015 West African epidemic, by far the most geographically extensive, most fatal, and longest lasting epidemic in Ebola's history, presented an enormous international public health challenge, but it also provided insights into Ebola's pathogenesis and natural history, clinical expression, treatment, prevention, and control. Growing understanding of ebolavirus pathogenetic mechanisms and important new clinical observations of the disease course provide fresh clues about prevention and treatment approaches. Although viral cytopathology and immune-mediated cell damage in ebolavirus disease often result in severe compromise of multiple organs, tissue repair and organ function recovery can be expected if patients receive supportive care with fluids and electrolytes; maintenance of oxygenation and tissue perfusion; and respiratory, renal, and cardiovascular support. Major challenges for managing future Ebola epidemics include establishment of early and aggressive epidemic control and earlier and better patient care and treatment in remote, resource-poor areas where Ebola typically reemerges. In addition, it will be important to further develop Ebola vaccines and to adopt policies for their use in epidemic and pre-epidemic situations.

    View details for DOI 10.1146/annurev-pathol-052016-100506

    View details for PubMedID 27959626

  • Can twice weekly hemodialysis expand patient access under resource constraints? Hemodialysis international. International Symposium on Home Hemodialysis Savla, D., Chertow, G. M., Meyer, T., Anand, S. 2016

    Abstract

    The convention of prescribing hemodialysis on a thrice weekly schedule began empirically when it seemed that this frequency was convenient and likely to treat symptoms for a majority of patients. Later, when urea was identified as the main target and marker of clearance, studies supported the prevailing notion that thrice weekly dialysis provided appropriate clearance of urea. Today, national guidelines on hemodialysis from most countries recommend patients receive at least thrice weekly therapy. However, resource constraints in low- and middle-income countries (LMIC) have resulted in a substantial proportion of patients using less frequent hemodialysis in these settings. Observational studies of patients on twice weekly dialysis show that twice weekly therapy has noninferior survival rates compared with thrice weekly therapy. In fact, models of urea clearance also show that twice weekly therapy can meet urea clearance "targets" if patients have significant residual function or if they follow a protein-restricted diet, as may be common in LMIC. Greater reliance on twice weekly therapy, at least at the start of hemodialysis, therefore has potential to reduce health care costs and increase access to renal replacement therapy in low-resource settings; however, randomized control trials are needed to better understand long-term outcomes of twice versus thrice weekly therapy.

    View details for DOI 10.1111/hdi.12501

    View details for PubMedID 27966247

  • Introduction of Biosimilar Therapeutics Into Nephrology Practice in the United States: Report of a Scientific Workshop Sponsored by the National Kidney Foundation AMERICAN JOURNAL OF KIDNEY DISEASES Wish, J. B., Charytan, C., Chertow, G. M., Kalantar-Zadeh, K., Kliger, A. S., Rubin, R. J., Yee, J., Fishbane, S. 2016; 68 (6): 843-852

    Abstract

    Biosimilars are biologic medicines highly similar to the reference product with no meaningful clinical differences in terms of safety, purity, and potency. All biologic medicines are produced by living cells, resulting in an inherent heterogeneity in their higher order structures and post-translational modifications. In 2010, the US Congress enacted legislation to streamline the approval process for biosimilars of products losing patent protection, with the goal of decreasing costs and improving patient access to therapeutically important but expensive biologic agents. In 2015, the US Food and Drug Administration approved the first biosimilar agent through this pathway. Approval of additional biosimilar agents in the United States, including those used by nephrologists, is anticipated. Given the relative lack of knowledge regarding biosimilars and their approval process and a lack of trust by the nephrology community regarding their safety and efficacy, the National Kidney Foundation conducted a symposium, Introduction of Biosimilar Therapeutics Into Nephrology Practice in the U.S., September 17 to 18, 2015. Issues related to manufacturing, the regulatory approval process, interchangeability, substitution/switching, nomenclature, and clinician and patient awareness and acceptance were examined. This report summarizes the main discussions at the symposium, highlights several controversies, and makes recommendations related to public policy, professional and patient education, and research needs.

    View details for DOI 10.1053/j.ajkd.2016.06.022

    View details for PubMedID 27599628

  • Metabolic Profiling of Impaired Cognitive Function in Patients Receiving Dialysis JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Tamura, M. K., Chertow, G. M., Depner, T. A., Nissenson, A. R., Schiller, B., Mehta, R. L., Liu, S., Sirich, T. L. 2016; 27 (12): 3780-3787

    Abstract

    Retention of uremic metabolites is a proposed cause of cognitive impairment in patients with ESRD. We used metabolic profiling to identify and validate uremic metabolites associated with impairment in executive function in two cohorts of patients receiving maintenance dialysis. We performed metabolic profiling using liquid chromatography/mass spectrometry applied to predialysis plasma samples from a discovery cohort of 141 patients and an independent replication cohort of 180 patients participating in a trial of frequent hemodialysis. We assessed executive function with the Trail Making Test Part B and the Digit Symbol Substitution test. Impaired executive function was defined as a score ≥2 SDs below normative values. Four metabolites-4-hydroxyphenylacetate, phenylacetylglutamine, hippurate, and prolyl-hydroxyproline-were associated with impaired executive function at the false-detection rate significance threshold. After adjustment for demographic and clinical characteristics, the associations remained statistically significant: relative risk 1.16 (95% confidence interval [95% CI], 1.03 to 1.32), 1.39 (95% CI, 1.13 to 1.71), 1.24 (95% CI, 1.03 to 1.50), and 1.20 (95% CI, 1.05 to 1.38) for each SD increase in 4-hydroxyphenylacetate, phenylacetylglutamine, hippurate, and prolyl-hydroxyproline, respectively. The association between 4-hydroxyphenylacetate and impaired executive function was replicated in the second cohort (relative risk 1.12; 95% CI, 1.02 to 1.23), whereas the associations for phenylacetylglutamine, hippurate, and prolyl-hydroxyproline did not reach statistical significance in this cohort. In summary, four metabolites related to phenylalanine, benzoate, and glutamate metabolism may be markers of cognitive impairment in patients receiving maintenance dialysis.

    View details for DOI 10.1681/ASN.2016010039

    View details for PubMedID 27444566

  • Analyzing Health-Related Quality of Life in the EVOLVE Trial: The Joint Impact of Treatment and Clinical Events. Medical decision making Briggs, A. H., Parfrey, P. S., Khan, N., Tseng, S., Dehmel, B., Kubo, Y., Chertow, G. M., Belozeroff, V. 2016; 36 (8): 965-972

    Abstract

    The Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) clinical trial evaluated the effects of cinacalcet on clinical events in patients with secondary hyperparathyroidism (sHPT) who were on hemodialysis. Health-related quality of life (HRQoL) was assessed by a generic, preference-based health outcome measure (EQ-5D) at scheduled visits and after a study event. Here, we report the HRQoL analysis from EVOLVE.We assessed changes in HRQoL from baseline to scheduled visits, and estimated the acute (3 mo) and chronic (beyond 3 mo) effects of sHPT-related events on HRQoL using generalized estimating equation analysis controlling for baseline HRQoL and randomized assignment.Data on HRQoL were available for 3547 of 3883 subjects, with 1650 events in the placebo and 1502 in the cinacalcet arm. At the study end, no difference in change from baseline HRQoL was observed in the direct comparison of EQ-5D by treatment arms. The regression analysis showed significant effects of events on HRQoL and a modest positive effect of cinacalcet. Estimated quality-adjusted life-year gains were of similar magnitude based on the observed data or the predictions from the model, with only a small gain in precision from the predicted analysis.By contrast with a conventional comparison, a regression analysis demonstrated large decrements in HRQoL after events and a modest improvement in HRQoL with cinacalcet. As randomized controlled trials are rarely powered to detect differences in HRQoL, a prespecified regression analysis may be acceptable to improve precision of the effects and understand their origin.

    View details for DOI 10.1177/0272989X16638312

    View details for PubMedID 26987347

  • Hyperprolactinemia in end-stage renal disease and effects of frequent hemodialysis. Hemodialysis international. International Symposium on Home Hemodialysis Lo, J. C., Beck, G. J., Kaysen, G. A., Chan, C. T., Kliger, A. S., Rocco, M. V., Chertow, G. M. 2016

    Abstract

    Introduction End-stage renal disease is associated with elevations in circulating prolactin concentrations, but the association of prolactin concentrations with intermediate health outcomes and the effects of hemodialysis frequency on changes in serum prolactin have not been examined. Methods The FHN Daily and Nocturnal Dialysis Trials compared the effects of conventional thrice weekly hemodialysis with in-center daily hemodialysis (6 days/week) and nocturnal home hemodialysis (6 nights/week) over 12 months and obtained measures of health-related quality of life, self-reported physical function, mental health and cognition. Serum prolactin concentrations were measured at baseline and 12-month follow-up in 70% of the FHN Trial cohort to examine the associations among serum prolactin concentrations and physical, mental and cognitive function and the effects of hemodialysis frequency on serum prolactin. Findings Among 177 Daily Trial and 60 Nocturnal Trial participants with baseline serum prolactin measurements, the median serum prolactin concentration was 65 ng/mL (25th-75th percentile 48-195 ng/mL) and 81% had serum prolactin concentrations >30 ng/mL. While serum prolactin was associated with sex (higher in women), we observed no association between baseline serum prolactin and age, dialysis vintage, and baseline measures of physical, mental and cognitive function. Furthermore, there was no significant effect of hemodialysis frequency on serum prolactin in either of the two trials. Discussion Serum prolactin concentrations were elevated in the large majority of patients with ESRD, but were not associated with several measures of health status. Circulating prolactin levels also do not appear to decrease in response to more frequent hemodialysis over a one-year period.

    View details for DOI 10.1111/hdi.12489

    View details for PubMedID 27774730

  • Re-evaluation of re-hospitalization and rehabilitation in renal research. Hemodialysis international. International Symposium on Home Hemodialysis Lin, E., Kurella Tamura, M., Montez-Rath, M. E., Chertow, G. M. 2016

    Abstract

    Introduction The use of administrative data to capture 30-day readmission rates in end-stage renal disease is challenging since Medicare combines claims from acute care, inpatient rehabilitation (IRF), and long-term care hospital stays into a single "Inpatient" file. For data prior to 2012, the United States Renal Data System does not contain the variables necessary to easily identify different facility types, making it likely that prior studies have inaccurately estimated 30-day readmission rates. Methods For this report, we developed two methods (a "simple method" and a "rehabilitation-adjusted method") to identify acute care, IRF, and long-term care hospital stays from United States Renal Data System claims data, and compared them to methods used in previously published reports. Findings We found that prior methods overestimated 30-day readmission rates by up to 12.3% and overestimated average 30-day readmission costs by up to 11%. In contrast, the simple and rehabilitation-adjusted methods overestimated 30-day readmission rates by 0.1% and average 30-day readmission costs by 1.8%. The rehabilitation-adjusted method also accurately identified 96.8% of IRF stays. Discussion Prior research has likely provided inaccurate estimates of 30-day readmissions in patients undergoing dialysis. In the absence of data on specific facility types particularly when using data prior to 2012, future researchers could employ our method to more accurately characterize 30-day readmission rates and associated outcomes in patients with end-stage renal disease.

    View details for DOI 10.1111/hdi.12497

    View details for PubMedID 27766736

  • Waste Informatics: Establishing Characteristics of Contemporary US Landfill Quantities and Practices ENVIRONMENTAL SCIENCE & TECHNOLOGY Powell, J. T., Pons, J. C., Chertow, M. 2016; 50 (20): 10877-10884

    Abstract

    Waste generation is expected to increase in most countries for many decades with landfill disposal still the dominant solid waste management method(1-3). Yet, operational characteristics of landfills are often poorly understood with comparative statistics substantially lacking. Here, we call for a more formal waste informatics to organize and standardize waste management knowledge at multiple spatial scales through analysis of recently reported data from 1232 U.S. landfills and other high resolution data sets. We create the first known estimate of available U.S. municipal waste stocks (8.5 billion tonnes) and go on to resolve these stocks at the county level, reflecting prospective urban mining opportunities. Our analysis of disposal rates and landfill capacities reveals that more than half of U.S. states have more than 25 years of life remaining. We also estimate the gross energy potential of landfill gas in the U.S. (338 billion MJ/yr) by examining 922 operational methane collection systems and demonstrate that the greatest energy recovery opportunities lie at landfills with existing collection systems and energy conversion infrastructure. Finally, we found that the number of landfills reaching the federally defined 30-year postclosure care period will more than triple in the coming two decades, with 264 sites expected by the year 2044, highlighting the need to develop and standardize metrics carefully to define and standardize when it is appropriate to end or scale back long-term landfill monitoring.

    View details for DOI 10.1021/acs.est.6b02848

    View details for Web of Science ID 000385907200013

    View details for PubMedID 27651028

  • 30-Day Readmissions after an Acute Kidney Injury Hospitalization. American journal of medicine Silver, S. A., Harel, Z., McArthur, E., Nash, D. M., Acedillo, R., Kitchlu, A., Garg, A. X., Chertow, G. M., Bell, C. M., Wald, R. 2016

    Abstract

    The risk of hospital readmission in acute kidney injury survivors is not well understood. We estimated the proportion of acute kidney injury patients who were rehospitalized within 30 days and identified characteristics associated with hospital readmission.We conducted a population-based study of patients who survived a hospitalization complicated by acute kidney injury from 2003-2013 in Ontario, Canada. The primary outcome was 30-day hospital readmission. We used a propensity score model to match patients with and without acute kidney injury, and a Cox proportional hazards model with death as a competing risk to identify predictors of 30-day readmission.We identified 156,690 patients who were discharged from 197 hospitals after an episode of acute kidney injury. In the subsequent 30 days, 27,457 (18%) patients were readmitted; 15,988 (10%) visited the emergency department and 7480 (5%) died. We successfully matched 111,778 patients with acute kidney injury 1:1 to patients without acute kidney injury. The likelihood of 30-day readmission was higher in acute kidney injury patients than those without acute kidney injury (hazard ratio [HR] 1.53; 95% confidence interval [CI], 1.50-1.57). Factors most strongly associated with 30-day rehospitalization were the number of hospitalizations in the preceding year (adjusted HR 1.45 for ≥2 hospitalizations; 95% CI, 1.40-1.51) and receipt of inpatient chemotherapy (adjusted HR 1.44; 95% CI, 1.32-1.58).One in 5 patients who survive a hospitalization complicated by acute kidney injury is readmitted in the next 30 days. Better strategies are needed to identify and care for acute kidney injury survivors in the community.

    View details for DOI 10.1016/j.amjmed.2016.09.016

    View details for PubMedID 27751901

  • Results of human factors testing in a novel Hemodialysis system designed for ease of patient use HEMODIALYSIS INTERNATIONAL Wilcox, S. B., Carver, M., Yau, M., Sneeringer, P., Prichard, S., Alvarez, L., Chertow, G. M. 2016; 20 (4): 643-649

    Abstract

    Introduction Home hemodialysis has not been widely adopted despite superior outcomes relative to conventional in-center hemodialysis. Patients receiving home hemodialysis experience high rates of technique failure owing to machine complexity, training burden, and the inability to master treatments independently. Methods We conducted human factors testing on 15 health care professionals (HCPs) and 15 patients upon release of the defined training program on the Tablo™ Hemodialysis System. Each participant completed one training and one testing session conducted in a simulated clinical environment. Training sessions lasted <3 hours for HCPs and <4 hours for patients, with an hour break between sessions for knowledge decay. During the testing session, we recorded participant behavior and data according to standard performance and safety-based criteria. Findings Of 15 HCPs, 10 were registered nurses and five patient care technicians, with a broad range of dialysis work experience and no limitations other than visual correction. Of 15 patients (average age 48 years), 13 reported no limitations and two reported modest limitations-partial deafness and blindness in one eye, respectively. The average error rate was 4.4 per session for HCPs and 2.9 per session for patients out of a total possible 1,710 opportunities for errors. Despite having received minimal training, neither HCPs nor patients committed safety-related errors that required mitigation; rather, we noted only minor errors and operational difficulties. Discussion The Tablo™ Hemodialysis System is easy to use, and may help to enable self-care and home hemodialysis in settings heretofore associated with high rates of technique failure.

    View details for DOI 10.1111/hdi.12430

    View details for PubMedID 27194590

  • Epoetin Alfa and Outcomes in Dialysis amid Regulatory and Payment Reform JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Chertow, G. M., Liu, J., Monde, K. L., Gilbertson, D. T., Brookhart, M. A., Beaubrun, A. C., Winkelmayer, W. C., Pollock, A., Herzog, C. A., Ashfaq, A., Sturmer, T., Rothman, K. J., Bradbury, B. D., Collins, A. J. 2016; 27 (10): 3129-3138

    Abstract

    Erythropoiesis-stimulating agents (ESAs) are commonly used to treat anemia in patients with CKD, including those receiving dialysis, although clinical trials have identified risks associated with ESA use. We evaluated the effects of changes in dialysis payment policies and product labeling instituted in 2011 on mortality and major cardiovascular events across the United States dialysis population in an open cohort study of patients on dialysis from January 1, 2005, through December 31, 2012, with Medicare as primary payer. We compared observed rates of death and major cardiovascular events in 2011 and 2012 with expected rates calculated on the basis of rates in 2005-2010, accounting for differences in patient characteristics and influenza virulence. An abrupt decline in erythropoietin dosing and hemoglobin concentration began in late 2010. Observed rates of all-cause mortality, cardiovascular mortality, and myocardial infarction in 2011 and 2012 were consistent with expected rates. During 2012, observed rates of stroke, venous thromboembolic disease (VTE), and heart failure were lower than expected (absolute deviation from trend per 100 patient-years [95% confidence interval]: -0.24 [-0.08 to -0.37] for stroke, -2.43 [-1.35 to -3.70] for VTE, and -0.77 [-0.28 to -1.27] for heart failure), although non-ESA-related changes in practice and Medicare payment penalties for rehospitalization may have confounded the results. This initial evidence suggests that action taken to mitigate risks associated with ESA use and changes in payment policy did not result in a relative increase in death or major cardiovascular events and may reflect improvements in stroke, VTE, and heart failure.

    View details for DOI 10.1681/ASN.2015111232

    View details for PubMedID 26917691

  • Hip Fracture in Patients With Non-Dialysis-Requiring Chronic Kidney Disease. Journal of bone and mineral research Kim, S. M., Long, J., Montez-Rath, M., Leonard, M., Chertow, G. M. 2016; 31 (10): 1803-1809

    Abstract

    Patients with end-stage renal disease (ESRD) are at a high risk for hip fracture. Little is known about the risk for, and consequences of, hip fracture among patients with non-dialysis-requiring chronic kidney disease (CKD). We examined the incidence of hip fracture, in-hospital mortality, length of stay, and costs among patients with ESRD, non-dialysis-requiring CKD, and normal or near normal kidney function. Using the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample, a nationally representative database, we identified hospitalizations for hip fracture in 2010. We incorporated data from the United States Renal Data System (USRDS) and the US census to calculate population-specific rates. Age-standardized incidence of hip fracture was highest among patients with ESRD (3.89/1000 person-years), followed by non-dialysis-requiring CKD (1.81/1000 persons) and patients with normal or near normal kidney function (1.18/1000 persons). In-hospital mo rtality (odds ratio [OR] = 1.69, 95% confidence interval [CI] 1.46 to 1.96), lengths of stay (median [10th, 90th percentiles] 5 [3 to 11] versus 5 [3 to 10] days) and costs (median $14,807 versus $13,314) were significantly higher in patients with non-dialysis-requiring CKD relative to patients with normal or near normal kidney function. In summary, non-dialysis-requiring CKD is associated with higher age-standardized rates of hip fracture and post-hip fracture mortality and higher resource utilization. © 2016 American Society for Bone and Mineral Research.

    View details for DOI 10.1002/jbmr.2862

    View details for PubMedID 27145189

  • Contemporary Use of Partial Nephrectomy: Are Older Patients With Impaired Kidney Function Being Left Behind? Urology Leppert, J. T., Mittakanti, H. R., Thomas, I., Lamberts, R. W., Sonn, G. A., Chung, B. I., Skinner, E. C., Wagner, T. H., Chertow, G. M., Brooks, J. D. 2016

    Abstract

    To assess whether patient factors, such as age and preoperative kidney function, were associated with receipt of partial nephrectomy in a national integrated healthcare system.We identified patients treated with a radical or partial nephrectomy from 2002 to 2014 in the Veterans Health Administration. We examined associations among patient age, sex, race or ethnicity, multimorbidity, baseline kidney function, tumor characteristics, and receipt of partial nephrectomy. We estimated the odds of receiving a partial nephrectomy and assessed interactions between covariates and the year of surgery to explore whether patient factors associated with partial nephrectomy changed over time.In our cohort of 14,186 patients, 4508 (31.2%) received a partial nephrectomy. Use of partial nephrectomy increased from 17% in 2002 to 32% in 2008 and to 38% in 2014. Patient race or ethnicity, age, tumor stage, and year of surgery were independently associated with receipt of partial nephrectomy. Black veterans had significantly increased odds of receipt of partial nephrectomy, whereas older patients had significantly reduced odds. Partial nephrectomy utilization increased for all groups over time, but older patients and patients with worse baseline kidney function showed the least increase in odds of partial nephrectomy.Although the utilization of partial nephrectomy increased for all groups, the greatest increase occurred in the youngest patients and those with the highest baseline kidney function. These trends warrant further investigation to ensure that patients at the highest risk of impaired kidney function are considered for partial nephrectomy whenever possible.

    View details for DOI 10.1016/j.urology.2016.08.044

    View details for PubMedID 27634733

  • Clinical trials of intensive versus less intensive control of hypertension: HOPE or HYPE? KIDNEY INTERNATIONAL Wyatt, C. M., Chertow, G. M. 2016; 90 (3): 460–65

    Abstract

    The recently published Heart Outcomes Prevention Evaluation trial (HOPE-3) demonstrated no benefit of lowering blood pressure with candesartan and hydrochlorothiazide in persons at intermediate cardiovascular risk and with adequate blood pressure control as determined by the enrolling physician. The results of Systolic Blood Pressure Intervention Trial (SPRINT) and HOPE-3 highlight the importance of considering differences in study design and patient population when interpreting the results of clinical trials.

    View details for DOI 10.1016/j.kint.2016.06.021

    View details for Web of Science ID 000382415300001

    View details for PubMedID 27521103

  • Overall Survival in Patients with Localized Prostate Cancer in the US Veterans Health Administration: Is PIVOT Generalizable? EUROPEAN UROLOGY Barbosa, P. V., Thomas, I., Srinivas, S., Buyyounouski, M. K., Chung, B. I., Chertow, G. M., Asch, S. M., Wagner, T. H., Brooks, J. D., Leppert, J. T. 2016; 70 (2): 227-230

    Abstract

    A better understanding of overall survival among patients with clinically localized prostate cancer (PCa) in the US Veterans Health Administration (VHA) is critical to inform PCa treatment decisions, especially in light of data from the Prostate Intervention Versus Observation Trial (PIVOT). We sought to describe patterns of survival for all patients with clinically localized PCa treated by the VHA. We created an analytic cohort of 35 954 patients with clinically localized PCa diagnosed from 1995 to 2001, approximating the PIVOT inclusion criteria (age of diagnosis ≤75 yr and clinical stage T2 or lower). Mean patient age was 65.9 yr, and median follow-up was 161 mo. Overall, 22.5% of patients were treated with surgery, 16.6% were treated with radiotherapy, and 23.1% were treated with androgen deprivation. Median survival of the entire cohort was 14 yr (25th, 75th percentiles, range: 7.9-20 yr). Among patients who received treatment with curative intent, median survival was 17.9 yr following surgery and 12.9 yr following radiotherapy. One-third of patients died within 10 yr of diagnosis compared with nearly half of the participants in PIVOT. This finding sounds a note of caution when generalizing the mortality data from PIVOT to VHA patients and those in the community.More than one-third of patients diagnosed with clinically localized prostate cancer treated through the US Veterans Health Administration from 1995 to 2001 died within 10 yr of their diagnosis. Caution should be used when generalizing the estimates of competing mortality data from PIVOT.

    View details for DOI 10.1016/j.eururo.2016.02.037

    View details for PubMedID 26948397

  • New Policies, New Sources of Error: Impact of Recent Medicare Policies on Database Research Gilbertson, D. T., Liu, J., Beaubrun, A. C., Chertow, G. M., Rothman, K. J., Winkelmayer, W. C., Monda, K. L., Ashfaq, A., Brookhart, A., Collins, A. J., Bradbury, B. D. WILEY-BLACKWELL. 2016: 144
  • Potential Effects of Medicare Payment Policy Changes on Hospitalization-Based Outcomes Research Beaubrun, A. C., Gilbertson, D. T., Chertow, G. M., Rothman, K. J., Winkelmayer, W. C., Monda, K. L., Liu, J., Ashfaq, A., Brookhart, M., Collins, A. J., Bradbury, B. D. WILEY-BLACKWELL. 2016: 143–44
  • Sex differences in obesity, dietary habits, and physical activity among urban middle-class Bangladeshis. International journal of health sciences Saquib, J., Saquib, N., Stefanick, M. L., Khanam, M. A., Anand, S., Rahman, M., Chertow, G. M., Barry, M., Ahmed, T., Cullen, M. R. 2016; 10 (3): 363-372

    Abstract

    The sustained economic growth in Bangladesh during the previous decade has created a substantial middle-class population, who have adequate income to spend on food, clothing, and lifestyle management. Along with the improvements in living standards, has also come negative impact on health for the middle class. The study objective was to assess sex differences in obesity prevalence, diet, and physical activity among urban middle-class Bangladeshi.In this cross-sectional study, conducted in 2012, we randomly selected 402 adults from Mohammedpur, Dhaka. The sampling technique was multi-stage random sampling. We used standardized questionnaires for data collection and measured height, weight, and waist circumference.Mean age (standard deviation) was 49.4 (12.7) years. The prevalence of both generalized (79% vs. 53%) and central obesity (85% vs. 42%) were significantly higher in women than men. Women reported spending more time watching TV and spending less time walking than men (p<.05); however, men reported a higher intake of unhealthy foods such as fast food and soft drinks.We conclude that the prevalence of obesity is significantly higher in urban middle-class Bangladeshis than previous urban estimates, and the burden of obesity disproportionately affects women. Future research and public health efforts are needed to address this severe obesity problem and to promote active lifestyles.

    View details for PubMedID 27610059

  • Rates and Outcomes of Parathyroidectomy for Secondary Hyperparathyroidism in the United States CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Kim, S. M., Long, J., Montez-Rath, M. E., Leonard, M. B., Norton, J. A., Chertow, G. M. 2016; 11 (7): 1260-1267

    Abstract

    Secondary hyperparathyroidism is common among patients with ESRD. Although medical therapy for secondary hyperparathyroidism has changed dramatically over the last decade, rates of parathyroidectomy for secondary hyperparathyroidism across the United States population are unknown. We examined temporal trends in rates of parathyroidectomy, in-hospital mortality, length of hospital stay, and costs of hospitalization.Using the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample, a representative national database on hospital stay regardless of age and payer in the United States, we identified parathyroidectomies for secondary hyperparathyroidism from 2002 to 2011. Data from the US Renal Data System reports were used to calculate the rate of parathyroidectomy.We identified 32,971 parathyroidectomies for secondary hyperparathyroidism between 2002 and 2011. The overall rate of parathyroidectomy was approximately 5.4/1000 patients (95% confidence interval [95% CI], 5.0/1000 to 6.0/1000). The rate decreased from 2003 (7.9/1000 patients; 95% CI, 6.2/1000 to 9.6/1000), reached a nadir in 2005 (3.3/1000 patients; 95% CI, 2.6/1000 to 4.0/1000), increased again through 2006 (5.4/1000 patients; 95% CI, 4.4/1000 to 6.4/1000), and remained stable since that time. Rates of in-hospital mortality decreased from 1.7% (95% CI, 0.8% to 2.6%) in 2002 to 0.8% (95% CI, 0.1% to 1.6%) in 2011 (P for trend <0.001). In-hospital mortality rates were significantly higher in patients with heart failure (odds ratio [OR], 4.23; 95% CI, 2.59 to 6.91) and peripheral vascular disease (OR, 4.59; 95% CI, 2.75 to 7.65) and lower among patients with prior kidney transplantation (OR, 0.20; 95% CI, 0.06 to 0.65).Despite the use of multiple medical therapies, rates of parathyroidectomy of secondary hyperparathyroidism have not declined in recent years.

    View details for DOI 10.2215/CJN.10370915

    View details for PubMedID 27269300

  • Cinacalcet, dialysate calcium concentration, and cardiovascular events in the EVOLVE trial HEMODIALYSIS INTERNATIONAL Pun, P. H., Abdalla, S., Block, G. A., Chertow, G. M., Correa-Rotter, R., Dehmel, B., Drueke, T. B., Floege, J., Goodman, W. G., Herzog, C. A., London, G. M., Mahaffey, K. W., Moe, S. M., Parfrey, P. S., Wheeler, D. C., Middleton, J. P. 2016; 20 (3): 421-431

    Abstract

    Among patients receiving hemodialysis, abnormalities in calcium regulation have been linked to an increased risk of cardiovascular events. Cinacalcet lowers serum calcium concentrations through its effect on parathyroid hormone secretion and has been hypothesized to reduce the risk of cardiovascular events. In observational cohort studies, prescriptions of low dialysate calcium concentration and larger observed serum-dialysate calcium gradients have been associated with higher risks of in-dialysis facility or peri-dialytic sudden cardiac arrest. We performed this study to examine the risks associated with dialysate calcium and serum-dialysate gradients among participants in the Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events (EVOLVE) trial. In EVOLVE, 3883 hemodialysis patients were randomized 1:1 to cinacalcet or placebo. Dialysate calcium was administered at the discretion of treating physicians. We examined whether baseline dialysate calcium concentration or the serum-dialysate calcium gradient modified the effect of cinacalcet on the following adjudicated endpoints: (1) primary composite endpoint (death or first non-fatal myocardial infarction, hospitalization for unstable angina, heart failure, or peripheral vascular event); (2) cardiovascular death; and (3) sudden death. In EVOLVE, use of higher dialysate calcium concentrations was more prevalent in Europe and Latin America compared with North America. There was a significant fall in serum calcium concentration in the cinacalcet group; dialysate calcium concentrations were changed infrequently in both groups. There was no association between baseline dialysate calcium concentration or serum-dialysate calcium gradient and the endpoints examined. Neither the baseline dialysate calcium nor the serum-dialysate calcium gradient significantly modified the effects of cinacalcet on the outcomes examined. The effects of cinacalcet on cardiovascular death and major cardiovascular events are not altered by the dialysate calcium prescription and serum-dialysate calcium gradient.

    View details for DOI 10.1111/hdi.12382

    View details for PubMedID 26564024

  • Intensive vs Standard Blood Pressure Control and Cardiovascular Disease Outcomes in Adults Aged >= 75 Years A Randomized Clinical Trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Williamson, J. D., Supiano, M. A., Applegate, W. B., Berlowitz, D. R., Campbell, R. C., Chertow, G. M., Fine, L. J., Haley, W. E., Hawfield, A. T., Ix, J. H., Kitzman, D., Kostis, J. B., Krousel-Wood, M. A., Launer, L. J., Oparil, S., Rodriguez, C. J., Roumie, C. L., Shorr, R. I., Sink, K. M., Wadley, V. G., Whelton, P. K., Whittle, J., Woolard, N. F., Wright, J. T., Pajewski, N. M. 2016; 315 (24): 2673-2682

    Abstract

    The appropriate treatment target for systolic blood pressure (SBP) in older patients with hypertension remains uncertain.To evaluate the effects of intensive (<120 mm Hg) compared with standard (<140 mm Hg) SBP targets in persons aged 75 years or older with hypertension but without diabetes.A multicenter, randomized clinical trial of patients aged 75 years or older who participated in the Systolic Blood Pressure Intervention Trial (SPRINT). Recruitment began on October 20, 2010, and follow-up ended on August 20, 2015.Participants were randomized to an SBP target of less than 120 mm Hg (intensive treatment group, n = 1317) or an SBP target of less than 140 mm Hg (standard treatment group, n = 1319).The primary cardiovascular disease outcome was a composite of nonfatal myocardial infarction, acute coronary syndrome not resulting in a myocardial infarction, nonfatal stroke, nonfatal acute decompensated heart failure, and death from cardiovascular causes. All-cause mortality was a secondary outcome.Among 2636 participants (mean age, 79.9 years; 37.9% women), 2510 (95.2%) provided complete follow-up data. At a median follow-up of 3.14 years, there was a significantly lower rate of the primary composite outcome (102 events in the intensive treatment group vs 148 events in the standard treatment group; hazard ratio [HR], 0.66 [95% CI, 0.51-0.85]) and all-cause mortality (73 deaths vs 107 deaths, respectively; HR, 0.67 [95% CI, 0.49-0.91]). The overall rate of serious adverse events was not different between treatment groups (48.4% in the intensive treatment group vs 48.3% in the standard treatment group; HR, 0.99 [95% CI, 0.89-1.11]). Absolute rates of hypotension were 2.4% in the intensive treatment group vs 1.4% in the standard treatment group (HR, 1.71 [95% CI, 0.97-3.09]), 3.0% vs 2.4%, respectively, for syncope (HR, 1.23 [95% CI, 0.76-2.00]), 4.0% vs 2.7% for electrolyte abnormalities (HR, 1.51 [95% CI, 0.99-2.33]), 5.5% vs 4.0% for acute kidney injury (HR, 1.41 [95% CI, 0.98-2.04]), and 4.9% vs 5.5% for injurious falls (HR, 0.91 [95% CI, 0.65-1.29]).Among ambulatory adults aged 75 years or older, treating to an SBP target of less than 120 mm Hg compared with an SBP target of less than 140 mm Hg resulted in significantly lower rates of fatal and nonfatal major cardiovascular events and death from any cause.clinicaltrials.gov Identifier: NCT01206062.

    View details for DOI 10.1001/jama.2016.7050

    View details for PubMedID 27195814

  • Risk prediction to inform surveillance of chronic kidney disease in the US Healthcare Safety Net: a cohort study BMC NEPHROLOGY Xie, Y., Maziarz, M., Tuot, D. S., Chertow, G. M., Himmelfarb, J., Hall, Y. N. 2016; 17

    Abstract

    The capacity of electronic health record (EHR) data to guide targeted surveillance in chronic kidney disease (CKD) is unclear. We sought to leverage EHR data for predicting risk of progressing from CKD to end-stage renal disease (ESRD) to help inform surveillance of CKD among vulnerable patients from the healthcare safety-net.We conducted a retrospective cohort study of adults (n = 28,779) with CKD who received care within 2 regional safety-net health systems during 1996-2009 in the Western United States. The primary outcomes were progression to ESRD and death as ascertained by linkage with United States Renal Data System and Social Security Administration Death Master files, respectively, through September 29, 2011. We evaluated the performance of 3 models which included demographic, comorbidity and laboratory data to predict progression of CKD to ESRD in conditions commonly targeted for disease management (hypertension, diabetes, chronic viral diseases and severe CKD) using traditional discriminatory criteria (AUC) and recent criteria intended to guide population health management strategies.Overall, 1730 persons progressed to end-stage renal disease and 7628 died during median follow-up of 6.6 years. Performance of risk models incorporating common EHR variables was highest in hypertension, intermediate in diabetes and chronic viral diseases, and lowest in severe CKD. Surveillance of persons who were in the highest quintile of ESRD risk yielded 83-94 %, 74-95 %, and 75-82 % of cases who progressed to ESRD among patients with hypertension, diabetes and chronic viral diseases, respectively. Similar surveillance yielded 42-71 % of ESRD cases among those with severe CKD. Discrimination in all conditions was universally high (AUC ≥0.80) when evaluated using traditional criteria.Recently proposed discriminatory criteria account for varying risk distribution and when applied to common clinical conditions may help to inform surveillance of CKD in diverse populations.

    View details for DOI 10.1186/s12882-016-0272-0

    View details for PubMedID 27276913

  • The effect of frequent hemodialysis on self-reported sleep quality: Frequent Hemodialysis Network Trials. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association Unruh, M. L., Larive, B., Eggers, P. W., Garg, A. X., Gassman, J. J., Finkelstein, F. O., Kimmel, P. L., Chertow, G. M. 2016; 31 (6): 984-991

    Abstract

    Many patients who receive maintenance hemodialysis experience poor sleep. Uncontrolled studies suggest frequent hemodialysis improves sleep quality, which is a strong motivation for some patients to undertake the treatment. We studied the effects of frequent in-center ('daily') and nocturnal home hemodialysis on self-reported sleep quality in two randomized trials.Participants were randomly assigned to frequent (six times per week) or conventional (three times per week) hemodialysis in the Frequent Hemodialysis Network Daily (n = 245) and Nocturnal (n = 87) Trials. We used the Medical Outcomes Study Sleep Problems Index II (SPI II), a validated and reliable instrument in patients with end-stage renal disease, to measure self-reported sleep quality. The SPI II is scored from 0-100, with a higher value indicating poorer quality of sleep. A mean relative decline in SPI II would suggest improved sleep quality. The primary sleep outcome was the change in the SPI II score over 12 months.In the Daily Trial, after adjustment for baseline SPI II, subjects randomized to frequent as compared with conventional in-center hemodialysis experienced a 4.2 [95% confidence interval (CI) 0.4-8.0] point adjusted mean relative decline in SPI II at 4 months and a 2.6 (95% CI -2.3-7.5) point adjusted mean relative decline at 12 months. In the Nocturnal Trial, subjects randomized to frequent nocturnal as compared with conventional home hemodialysis experienced 2.9 (95% CI -3.4-9.3) and 4.5 (95% CI -3.2-12.2) point mean relative declines at Months 4 and 12, respectively.Although a possible benefit of frequent in-center hemodialysis was observed at 4 months, neither frequent in-center hemodialysis nor home nocturnal hemodialysis demonstrated significant improvements in self-reported sleep quality compared with conventional hemodialysis at 12 months.

    View details for DOI 10.1093/ndt/gfw062

    View details for PubMedID 27190356

  • ISCHEMIA in chronic kidney disease: improving the representation of patients with chronic kidney disease in cardiovascular trials KIDNEY INTERNATIONAL Wyatt, C. M., Shineski, M., Chertow, G. M., Bangalore, S. 2016; 89 (6): 1178–79

    Abstract

    Despite the high cardiovascular risk associated with chronic kidney disease, a recent systematic review confirmed that patients with kidney disease remain underrepresented in cardiovascular trials. Two ongoing trials are assessing the risk:benefit of aggressive evaluation and intervention for ischemic heart disease in patients with advanced chronic kidney disease.

    View details for DOI 10.1016/j.kint.2016.03.012

    View details for Web of Science ID 000375693100002

    View details for PubMedID 27181770

  • Effects of Physician Payment Reform on Provision of Home Dialysis AMERICAN JOURNAL OF MANAGED CARE Erickson, K. F., Winkelmayer, W. C., Chertow, G. M., Bhattacharya, J. 2016; 22 (6): E215-?

    Abstract

    Patients with end-stage renal disease can receive dialysis at home or in-center. In 2004, CMS reformed physician payment for in-center hemodialysis care from a capitated to a tiered fee-for-service model, augmenting physician payment for frequent in-center visits. We evaluated whether payment reform influenced dialysis modality assignment.Cohort study of patients starting dialysis in the United States in the 3 years before and the 3 years after payment reform.We conducted difference-in-difference analyses comparing patients with traditional Medicare coverage (who were affected by the policy) to others with Medicare Advantage (who were unaffected by the policy). We also examined whether the policy had a more pronounced influence on dialysis modality assignment in areas with lower costs of traveling to dialysis facilities.Patients with traditional Medicare coverage experienced a 0.7% (95% CI, 0.2%-1.1%; P = .003) reduction in the absolute probability of home dialysis use following payment reform compared with patients with Medicare Advantage. Patients living in areas with larger dialysis facilities (where payment reform made in-center hemodialysis comparatively more lucrative for physicians) experienced a 0.9% (95% CI, 0.5%-1.4%; P < .001) reduction in home dialysis use following payment reform compared with patients living in areas with smaller facilities (where payment reform made in-center hemodialysis comparatively less lucrative for physicians).The transition from a capitated to a tiered fee-for-service payment model for in-center hemodialysis care resulted in fewer patients receiving home dialysis. This area of policy failure highlights the importance of considering unintended consequences of future physician payment reform efforts.

    View details for Web of Science ID 000380245300005

    View details for PubMedID 27355909

    View details for PubMedCentralID PMC5055389

  • Long-Term Effects of Frequent In-Center Hemodialysis JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Chertow, G. M., Levin, N. W., Beck, G. J., Daugirdas, J. T., Eggers, P. W., Kliger, A. S., Larive, B., Rocco, M. V., Greene, T. 2016; 27 (6): 1830-1836

    Abstract

    The Frequent Hemodialysis Network Daily Trial randomized 245 patients to receive six (frequent) or three (conventional) in-center hemodialysis sessions per week for 12 months. As reported previously, frequent in-center hemodialysis yielded favorable effects on the coprimary composite outcomes of death or change in left ventricular mass and death or change in self-reported physical health. Here, we determined the long-term effects of the 12-month frequent in-center hemodialysis intervention. We determined the vital status of patients over a median of 3.6 years (10%-90% range, 1.5-5.3 years) after randomization. Using an intention to treat analysis, we compared the mortality hazard in randomized groups. In a subset of patients from both groups, we reassessed left ventricular mass and self-reported physical health a year or more after completion of the intervention; 20 of 125 patients (16%) randomized to frequent hemodialysis died during the combined trial and post-trial observation periods in contrast to 34 of 120 patients (28%) randomized to conventional hemodialysis. The relative mortality hazard for frequent versus conventional hemodialysis was 0.54 (95% confidence interval, 0.31 to 0.93); with censoring of time after kidney transplantation, the relative hazard was 0.56 (95% confidence interval, 0.32 to 0.99). Bayesian analysis suggested a relatively high probability of clinically significant benefit and a very low probability of harm with frequent hemodialysis. In conclusion, a 12-month frequent in-center hemodialysis intervention significantly reduced long-term mortality, suggesting that frequent hemodialysis may benefit selected patients with ESRD.

    View details for DOI 10.1681/ASN.2015040426

    View details for PubMedID 26467779

  • Antihypertensive medications and sexual function in women: baseline data from the SBP intervention trial (SPRINT) JOURNAL OF HYPERTENSION Thomas, H. N., Evans, G. W., Berlowitz, D. R., Chertow, G. M., Conroy, M. B., Foy, C. G., Glasser, S. P., Lewis, C. E., Riley, W. T., Russell, L., Williams, O., Hess, R. 2016; 34 (6): 1224-1231

    Abstract

    Hypertension is a risk factor for the development of cardiovascular and kidney disease, but treatment can substantially reduce risks. Many patients avoid antihypertensive medications because of fear of side-effects. Although associations between antihypertensives and sexual dysfunction in men have been documented, it remains unclear whether antihypertensives are associated with sexual dysfunction in women. We conducted a cross-sectional analysis of baseline data from women in the Systolic Blood Pressure Intervention Trial (SPRINT) to evaluate the relations among class of antihypertensive medication and the outcomes: sexual activity and sexual function.SPRINT enrolled individuals 50 and older with hypertension at high risk for cardiovascular disease. A subset of participants completed questionnaires regarding quality of life, including sexual function. Antihypertensive class was determined by medications taken at baseline.Of 690 women in the quality of life subset of SPRINT, 183 (26.5%) were sexually active. There were no significant differences in sexual activity among women taking one or more antihypertensives and women not taking any. Women taking an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker had higher odds of sexual activity [odds ratio 1.66 (1.12-4.27), P = 0.011]. Among sexually active women, the prevalence of sexual dysfunction was high (52.5%). No class of medication was associated with sexual dysfunction in the multivariable model.Angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use was associated with higher odds of sexual activity. Although prevalence of sexual dysfunction was high, no single class of antihypertensive medication was associated with sexual dysfunction.

    View details for DOI 10.1097/HJH.0000000000000911

    View details for Web of Science ID 000375146000029

    View details for PubMedID 27032074

    View details for PubMedCentralID PMC4859426

  • Early to Dialyze Healthy and Wise? JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Chertow, G. M., Winkelmayer, W. C. 2016; 315 (20): 2171–72

    View details for PubMedID 27209075

  • How to Diagnose Solutions to a Quality of Care Problem CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Harel, Z., Silver, S. A., McQuillan, R. F., Weizman, A. V., Thomas, A., Chertow, G. M., Nesrallah, G., Chan, C. T., Bell, C. M. 2016; 11 (5): 901-907

    Abstract

    To change a particular quality of care outcome within a system, quality improvement initiatives must first understand the causes contributing to the outcome. After the causes of a particular outcome are known, changes can be made to address these causes and change the outcome. Using the example of home dialysis (home hemodialysis and peritoneal dialysis), this article within this Moving Points feature on quality improvement will provide health care professionals with the tools necessary to analyze the steps contributing to certain outcomes in health care quality and develop ideas that will ultimately lead to their resolution. The tools used to identify the main contributors to a quality of care outcome will be described, including cause and effect diagrams, Pareto analysis, and process mapping. We will also review common change concepts and brainstorming activities to identify effective change ideas. These methods will be applied to our home dialysis quality improvement project, providing a practical example that other kidney health care professionals can replicate at their local centers.

    View details for DOI 10.2215/CJN.11481015

    View details for PubMedID 27016495

  • How to Use Quality Improvement Tools in Clinical Practice: A Primer for Nephrologists CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Chan, C. T., Chertow, G. M., Nesrallah, G., Bell, C. M. 2016; 11 (5): 891–92

    View details for PubMedID 27016499

    View details for PubMedCentralID PMC4858493

  • How to Sustain Change and Support Continuous Quality Improvement CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Silver, S. A., McQuillan, R., Harel, Z., Weizman, A. V., Thomas, A., Nesrallah, G., Bell, C. M., Chan, C. T., Chertow, G. M. 2016; 11 (5): 916-924

    Abstract

    To achieve sustainable change, quality improvement initiatives must become the new way of working rather than something added on to routine clinical care. However, most organizational change is not maintained. In this next article in this Moving Points in Nephrology feature on quality improvement, we provide health care professionals with strategies to sustain and support quality improvement. Threats to sustainability may be identified both at the beginning of a project and when it is ready for implementation. The National Health Service Sustainability Model is reviewed as one example to help identify issues that affect long-term success of quality improvement projects. Tools to help sustain improvement include process control boards, performance boards, standard work, and improvement huddles. Process control and performance boards are methods to communicate improvement results to staff and leadership. Standard work is a written or visual outline of current best practices for a task and provides a framework to ensure that changes that have improved patient care are consistently and reliably applied to every patient encounter. Improvement huddles are short, regular meetings among staff to anticipate problems, review performance, and support a culture of improvement. Many of these tools rely on principles of visual management, which are systems transparent and simple so that every staff member can rapidly distinguish normal from abnormal working conditions. Even when quality improvement methods are properly applied, the success of a project still depends on contextual factors. Context refers to aspects of the local setting in which the project operates. Context affects resources, leadership support, data infrastructure, team motivation, and team performance. For these reasons, the same project may thrive in a supportive context and fail in a different context. To demonstrate the practical applications of these quality improvement principles, these principles are applied to a hypothetical quality improvement initiative that aims to promote home dialysis (home hemodialysis and peritoneal dialysis).

    View details for DOI 10.2215/CJN.11501015

    View details for PubMedID 27016498

  • How to Measure and Interpret Quality Improvement Data CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY McQuillan, R. F., Silver, S. A., Harel, Z., Weizman, A., Thomas, A., Bell, C., Chertow, G. M., Chan, C. T., Nesrallah, G. 2016; 11 (5): 908-914

    Abstract

    This article will demonstrate how to conduct a quality improvement project using the change idea generated in "How To Use Quality Improvement Tools in Clinical Practice: How To Diagnose Solutions to a Quality of Care Problem" by Dr. Ziv Harel and colleagues in this Moving Points feature. This change idea involves the introduction of a nurse educator into a CKD clinic with a goal of increasing rates of patients performing dialysis independently at home (home hemodialysis or peritoneal dialysis). Using this example, we will illustrate a Plan-Do-Study-Act (PDSA) cycle in action and highlight the principles of rapid cycle change methodology. We will then discuss the selection of outcome, process, and balancing measures, and the practicalities of collecting these data in the clinic environment. We will also introduce the PDSA worksheet as a practical way to oversee the progress of a quality improvement project. Finally, we will demonstrate how run charts are used to visually illustrate improvement in real time, and how this information can be used to validate achievement, respond appropriately to challenges the project may encounter, and prove the significance of results. This article aims to provide readers with a clear and practical framework upon which to trial their own ideas for quality improvement in the clinical setting.

    View details for DOI 10.2215/CJN.11511015

    View details for PubMedID 27016496

  • How to Begin a Quality Improvement Project CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Silver, S. A., Harel, Z., McQuillan, R., Weizman, A. V., Thomas, A., Chertow, G. M., Nesrallah, G., Bell, C. M., Chan, C. T. 2016; 11 (5): 893-900

    Abstract

    Quality improvement involves a combined effort among health care staff and stakeholders to diagnose and treat problems in the health care system. However, health care professionals often lack training in quality improvement methods, which makes it challenging to participate in improvement efforts. This article familiarizes health care professionals with how to begin a quality improvement project. The initial steps involve forming an improvement team that possesses expertise in the quality of care problem, leadership, and change management. Stakeholder mapping and analysis are useful tools at this stage, and these are reviewed to help identify individuals who might have a vested interest in the project. Physician engagement is a particularly important component of project success, and the knowledge that patients/caregivers can offer as members of a quality improvement team should not be overlooked. After a team is formed, an improvement framework helps to organize the scientific process of system change. Common quality improvement frameworks include Six Sigma, Lean, and the Model for Improvement. These models are contrasted, with a focus on the Model for Improvement, because it is widely used and applicable to a variety of quality of care problems without advanced training. It involves three steps: setting aims to focus improvement, choosing a balanced set of measures to determine if improvement occurs, and testing new ideas to change the current process. These new ideas are evaluated using Plan-Do-Study-Act cycles, where knowledge is gained by testing changes and reflecting on their effect. To show the real world utility of the quality improvement methods discussed, they are applied to a hypothetical quality improvement initiative that aims to promote home dialysis (home hemodialysis and peritoneal dialysis). This provides an example that kidney health care professionals can use to begin their own quality improvement projects.

    View details for DOI 10.2215/CJN.11491015

    View details for PubMedID 27016497

  • Characterizing Frailty Status in the Systolic Blood Pressure Intervention Trial JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Pajewski, N. M., Williamson, J. D., Applegate, W. B., Berlowitz, D. R., Bolin, L. P., Chertow, G. M., Krousel-Wood, M. A., Lopez-Barrera, N., Powell, J. R., Roumie, C. L., Still, C., Sink, K. M., Tang, R., Wright, C. B., Supiano, M. A. 2016; 71 (5): 649-655

    Abstract

    The Systolic Blood Pressure Intervention Trial (SPRINT) is testing whether a lower systolic blood pressure (BP) target of 120 mm Hg leads to a reduction in cardiovascular morbidity and mortality among hypertensive, nondiabetic adults. Because there may be detrimental effects of intensive BP control, particularly in older, frail adults, we sought to characterize frailty within SPRINT to address ongoing questions about the ability of large-scale trials to enroll representative samples of noninstitutionalized, community-dwelling, older adults.We constructed a 36-item frailty index (FI) in 9,306 SPRINT participants, classifying participants as fit (FI ≤ 0.10), less fit (0.10 < FI ≤ 0.21), or frail (FI > 0.21). Recurrent event models were used to evaluate the association of the FI with the incidence of self-reported falls, injurious falls, and all-cause hospitalizations.The distribution of the FI was comparable with what has been observed in population studies, with 2,570 (27.6%) participants classified as frail. The median FI was 0.18 (interquartile range = 0.14 to 0.24) in participants aged 80 years and older (N = 1,159), similar to the median FI of 0.17 reported for participants in the Hypertension in the Very Elderly Trial. In multivariable analyses, a 1% increase in the FI was associated with increased risk for self-reported falls (hazard ratio [HR] = 1.030), injurious falls (HR = 1.035), and all-cause hospitalizations (HR = 1.038) (all p values < .0001).Large clinical trials assessing treatments to reduce cardiovascular disease risk, such as SPRINT, can enroll heterogeneous populations of older adults, including the frail elderly, comparable with general population cohorts.

    View details for DOI 10.1093/gerona/glv228

    View details for PubMedID 26755682

  • ONE YEAR EFFICACY AND SAFETY OF INTRAVENOUS (IV) ETELCALCETIDE (AMG 416) IN PATIENTS ON HEMODIALYSIS (HD) WITH SECONDARY HYPERPARATHYROIDISM (SHPT) Bushinsky, D. A., Block, G. A., Cheng, S., Deng, H., Torres, P., Vervloet, M., Chertow, G. M. OXFORD UNIV PRESS. 2016: 13–14
  • The win ratio approach to analyzing composite outcomes: An application to the EVOLVE trial CONTEMPORARY CLINICAL TRIALS Abdalla, S., Montez-Rath, M. E., Parfrey, P. S., Chertow, G. M. 2016; 48: 119-124

    Abstract

    Unlike conventional time-to-event analysis of composite endpoints in clinical trials, the "win ratio" method allows for flexibility in prioritizing their components. Here, we compare the EVOLVE trial findings using the win ratio with those from time-to-event analysis.Randomization to cinacalcet or placebo.The primary composite endpoint combining all-cause mortality and non-fatal myocardial infarction, hospitalization for unstable angina, heart failure, and peripheral vascular events.In an unadjusted analysis, we paired each participant from the cinacalcet arm with every participant from the placebo arm within randomization strata. Pairs were classified as "winners" or "losers," according to which participant died first during the shared follow-up time, or experienced the next ranked event first. We ranked non-fatal events in two ways: 1) all ranked evenly; and 2) prioritized by their effect on health-related quality of life. The win ratio equaled the total winners divided by total losers. Further analyses were conducted where the win ratio was stratified by, or adjusted for, age.The unadjusted win ratio for the primary composite endpoint was 1.09 (95% CI 0.97 to 1.21), a statistically non-significant result which supports the primary trial result - unadjusted hazard ratio 0.93 (95% CI 0.85 to 1.02). Age-stratified analyses showed a nominally significant benefit of cinacalcet (win ratio 1.14, 95% CI 1.04 to 1.26). Ranking of non-fatal outcomes by their relative effects on quality of life did not materially alter the results.The win ratio method corroborated the findings of EVOLVE based on conventional time-to-event analysis. EVOLVE ClinicalTrials.gov number: NCT00345839.

    View details for DOI 10.1016/j.cct.2016.04.001

    View details for PubMedID 27080930

  • Understanding barriers to home-based and self-care in-center hemodialysis. Hemodialysis international. International Symposium on Home Hemodialysis Yau, M., Carver, M., Alvarez, L., Block, G. A., Chertow, G. M. 2016; 20 (2): 235-241

    Abstract

    Despite superior outcomes and lower associated costs, relatively few patients with end-stage renal disease undergo self-care or home hemodialysis. Few studies have examined patient- and physician-specific barriers to self-care and home hemodialysis in the modern era. The degree to which innovative technology might facilitate the adoption of these modalities is unknown. We surveyed 250 patients receiving in-center hemodialysis and 51 board-certified nephrologists to identify key barriers to adoption of self-care and home hemodialysis. Overall, 172 (69%) patients reported that they were "likely" or "very likely" to consider self-care hemodialysis if they were properly trained on a new hemodialysis system designed for self-care or home use. Nephrologists believed that patients were capable of performing many dialysis-relevant tasks, including: weighing themselves (98%), wiping down the chair and machine (84%), clearing alarms during treatment (53%), taking vital signs (46%), and cannulating vascular access (41%), but thought that patients would be willing to do the same in only 69%, 34%, 31%, 29%, and 16%, respectively. Reasons that nephrologists believe patients are hesitant to pursue self-care or home hemodialysis do not correspond in parallel or by priority to reasons reported by patients. Self-care and home hemodialysis offer several advantages to patients and dialysis providers. Overcoming real and perceived barriers with new technology, education and coordinated care will be required for these modalities to gain traction in the coming years.

    View details for DOI 10.1111/hdi.12357

    View details for PubMedID 26415746

  • Misclassification of Obesity by Body Mass Index Among Patients Receiving Hemodialysis AMERICAN JOURNAL OF KIDNEY DISEASES Kittiskulnam, P., Chertow, G. M., Kaysen, G. A., Delgado, C., Dalrymple, L. S., Johansen, K. L. 2016; 67 (4): 709–11

    View details for PubMedID 26612278

    View details for PubMedCentralID PMC5657149

  • Association of Performance-Based and Self-Reported Function-Based Definitions of Frailty with Mortality among Patients Receiving Hemodialysis CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Johansen, K. L., Dalrymple, L. S., Glidden, D., Delgado, C., Kaysen, G. A., Grimes, B., Chertow, G. M. 2016; 11 (4): 626-632

    Abstract

    Frailty is common among patients on dialysis and increases vulnerability to dependency and death.We examined the predictive ability of frailty on the basis of physical performance and self-reported function in participants of a US Renal Data System special study that enrolled a convenience sample of 771 prevalent patients on hemodialysis from 14 facilities in the Atlanta and northern California areas from 2009 to 2011. Performance-based frailty was assessed using direct measures of grip strength (weakness) and gait speed along with weight loss, exhaustion, and low physical activity; poor self-reported function was substituted for weakness and slow gait speed in the self-reported function-based definition. For both definitions, patients meeting three or more criteria were considered frail.The mean age of 762 patients included in analyses was 57.1±14.2 years old; 240 patients (31%) met the physical performance-based definition of frailty, and 396 (52%) met the self-reported function-based definition. There were 106 deaths during 1.7 (interquartile range, 1.4-2.4) years of follow-up. After adjusting for demographic and clinical characteristics, the hazard ratio (HR) for mortality for the performance-based definition (2.16; 95% confidence interval [95% CI], 1.41 to 3.29) was slightly higher than that of the self-reported function-based definition (HR, 1.93; 95% CI, 1.24 to 3.00). Patients who met the self-report-based definition but not the physical performance definition of frailty (n=192) were not at statistically significantly higher risk of mortality than those who were not frail by either definition (n=330; HR, 1.41; 95% CI, 0.81 to 2.45), but those who met both definitions of frailty (n=204) were at significantly higher risk (HR, 2.46; 95% CI, 1.51 to 4.01).Frailty, defined using either direct tests of physical performance or self-reported physical function, was associated with higher mortality among patients receiving hemodialysis. Future studies are needed to determine the utility of assessing frailty in clinical practice.

    View details for DOI 10.2215/CJN.03710415

    View details for PubMedID 26792529

  • Chronic kidney disease, cerebral blood flow, and white matter volume in hypertensive adults NEUROLOGY Tamura, M. K., Pajewski, N. M., Bryan, R. N., Weiner, D. E., Diamond, M., Van Buren, P., Taylor, A., Beddhu, S., Rosendorff, C., Jahanian, H., Zaharchuk, G. 2016; 86 (13): 1208-1216

    Abstract

    To determine the relation between markers of kidney disease-estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR)-with cerebral blood flow (CBF) and white matter volume (WMV) in hypertensive adults.We used baseline data collected from 665 nondiabetic hypertensive adults aged ≥50 years participating in the Systolic Blood Pressure Intervention Trial (SPRINT). We used arterial spin labeling to measure CBF and structural 3T images to segment tissue into normal and abnormal WMV. We used quantile regression to estimate the association between eGFR and UACR with CBF and abnormal WMV, adjusting for sociodemographic and clinical characteristics.There were 218 participants (33%) with eGFR <60 mL/min/1.73 m(2) and 146 participants (22%) with UACR ≥30 mg/g. Reduced eGFR was independently associated with higher adjusted median CBF, but not with abnormal WMV. Conversely, in adjusted analyses, there was a linear independent association between UACR and larger abnormal WMV, but not with CBF. Compared to participants with neither marker of CKD (eGFR ≥60 mL/min/1.73 m(2) and UACR <30 mg/g), median CBF was 5.03 mL/100 g/min higher (95% confidence interval [CI] 0.78, 9.29) and abnormal WMV was 0.63 cm(3) larger (95% CI 0.08, 1.17) among participants with both markers of CKD (eGFR <60 mL/min/1.73 m(2) and UACR ≥30 mg/g).Among nondiabetic hypertensive adults, reduced eGFR was associated with higher CBF and higher UACR was associated with larger abnormal WMV.

    View details for DOI 10.1212/WNL.0000000000002527

    View details for Web of Science ID 000372853000007

    View details for PubMedCentralID PMC4818564

  • Patterns and Correlates of Baseline Thiazide-Type Diuretic Prescription in the Systolic Blood Pressure Intervention Trial HYPERTENSION Chang, T. I., Evans, G., Cheung, A. K., Cushman, W. C., Diamond, M. J., Dwyer, J. P., Huan, Y., Kitzman, D., Kostis, J. B., Oparil, S., Rastogi, A., Roumie, C. L., Sahay, R., Stafford, R. S., Taylor, A. A., Wright, J. T., Chertow, G. M. 2016; 67 (3): 550-555

    Abstract

    Thiazides and thiazide-type diuretics are recommended as first-line agents for the treatment of hypertension, but contemporary information on their use in clinical practice is lacking. We examined patterns and correlates of thiazide prescription in a cross-sectional analysis of baseline data from participants enrolled in the Systolic Blood Pressure Intervention Trial (SPRINT). We examined baseline prescription of thiazides in 7582 participants receiving at least 1 antihypertensive medication by subgroup, and used log-binomial regression to calculate adjusted prevalence ratios for thiazide prescription (versus no thiazide). Forty-three percent of all participants were prescribed a thiazide at baseline, but among participants prescribed a single agent, the proportion was only 16%. The prevalence of thiazide prescription differed significantly by demographic factors, with younger participants, women, and blacks all having higher adjusted prevalence of thiazide prescription than other corresponding subgroups. Participants in the lowest category of kidney function (estimated glomerular filtration rate <30 mL/min per 1.73 m2) were half as likely to be prescribed a thiazide as participants with preserved kidney function. In conclusion, among persons with hypertension and heightened cardiovascular risk, we found that thiazide prescription varied significantly by demographics and kidney disease status, despite limited evidence about relative differences in effectiveness.

    View details for DOI 10.1161/HYPERTENSIONAHA.115.06851

    View details for PubMedID 26865200

  • Validating Appetite Assessment Tools Among Patients Receiving Hemodialysis JOURNAL OF RENAL NUTRITION Molfino, A., Kaysen, G. A., Chertow, G. M., Doyle, J., Delgado, C., Dwyer, T., Laviano, A., Fanelli, F. R., Johansen, K. L. 2016; 26 (2): 103-110

    Abstract

    To test the performance of appetite assessment tools among patients receiving hemodialysis (HD).Cross-sectional.Two hundred twenty-one patients receiving HD enrolled in seven dialysis facilities in Northern California.We assessed 5 appetite assessment tools (self-assessment of appetite, subjective assessment of appetite, visual analog scale [VAS], Functional Assessment of Anorexia/Cachexia Therapy [FAACT] score, and the Anorexia Questionnaire [AQ]).Reported food intake, normalized protein catabolic rate, and change in body weight were used as criterion measures, and we assessed associations among the appetite tools and biomarkers associated with nutrition and inflammation. Patients were asked to report their appetite and the percentage of food eaten (from 0% to 100%) during the last meal compared to usual intake.Fifty-eight (26%) patients reported food intake ≤ 50% (defined as poor appetite). The prevalence of anorexia was 12% by self-assessment of appetite, 6% by subjective assessment of appetite, 24% by VAS, 17% by FAACT score, and 12% by AQ. All the tools were significantly associated with food intake ≤ 50% (P < .001), except self-assessment of appetite. The FAACT score and the VAS had the strongest association with food intake ≤ 50% (C-statistic 0.80 and 0.76). Patients with food intake ≤ 50% reported weight loss more frequently than patients without low intake (36% vs 22%) and weight gain less frequently (19% vs 35%; P = .03). Normalized protein catabolic rate was lower among anorexic patients based on the VAS (1.1 ± 0.3 vs 1.2 ± 0.3, P = .03). Ln interleukin-6 correlated inversely with food intake (P = .03), but neither interleukin-6 nor C-reactive protein correlated with any of the appetite tools. Furthermore, only the self-assessment of appetite was significantly associated with serum albumin (P = .02), prealbumin (P = .02) and adiponectin concentrations (P = .03).Alternative appetite assessment tools yielded widely different estimates of the prevalence of anorexia in HD. When considering self-reported food intake as the criterion standard for anorexia, the FAACT score and VAS discriminated patients reasonably well.

    View details for DOI 10.1053/j.jrn.2015.09.002

    View details for PubMedID 26522141

  • Lessons Learned from EVOLVE for Planning of Future Randomized Trials in Patients on Dialysis CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Parfrey, P. S., Block, G. A., Correa-Rotter, R., Drueeke, T. B., Floege, J., Herzog, C. A., London, G. M., Mahaffey, K. W., Moe, S. M., Wheeler, D. C., Chertow, G. M. 2016; 11 (3): 539-546

    Abstract

    The effect of the calcimimetic cinacalcet on cardiovascular disease in patients undergoing hemodialysis with secondary hyperparathyroidism was assessed in the Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events trial. This was the largest (in size) and longest (in duration) randomized controlled clinical trial undertaken in this population. During planning, execution, analysis, and reporting of the trial, many lessons were learned, including those related to the use of a composite cardiovascular primary endpoint, definition of endpoints (particularly heart failure and severe unremitting hyperparathyroidism), importance of age for optimal stratification at randomization, use of unadjusted and adjusted intention-to-treat analysis for the primary outcome, how to respond to a lower-than-predicted event rate during the trial, development of a prespecified analytic plan that accounted for nonadherence and for cointerventions that diminished the power of the trial to observe a treatment effect, determination of the credibility of a subgroup effect, use of adverse effects database to investigate rare diseases, collection of blood for biomarker measurement not designated before trial initiation, and interpretation of the benefits-to-harms ratio for individual patients. It is likely that many of these issues will arise in the planning of future trials in CKD.

    View details for DOI 10.2215/CJN.06370615

    View details for Web of Science ID 000371453100023

    View details for PubMedID 26614406

  • The effects of cinacalcet on blood pressure, mortality and cardiovascular endpoints in the EVOLVE trial JOURNAL OF HUMAN HYPERTENSION Chang, T. I., AbdAlla, S., London, G. M., Block, G. A., Correa-Rotter, R., Drueeke, T. B., Floege, J., Herzog, C. A., Mahaffey, K. W., Moe, S. M., Parfrey, P. S., Wheeler, D. C., Dehmel, B., Goodman, W. G., Chertow, G. M. 2016; 30 (3): 204-209

    Abstract

    Patients with end-stage renal disease often have derangements in calcium and phosphorus homeostasis and resultant secondary hyperparathyroidism (sHPT), which may contribute to the high prevalence of arterial stiffness and hypertension. We conducted a secondary analysis of the Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events (EVOLVE) trial, in which patients receiving hemodialysis with sHPT were randomly assigned to receive cinacalcet or placebo. We sought to examine whether the effect of cinacalcet on death and major cardiovascular events was modified by baseline pulse pressure as a marker of arterial stiffness, and whether cinacalcet yielded any effects on blood pressure. As reported previously, an unadjusted intention-to-treat analysis failed to conclude that randomization to cinacalcet reduces the risk of the primary composite end point (all-cause mortality or non-fatal myocardial infarction, heart failure, hospitalization for unstable angina or peripheral vascular event). However, after prespecified adjustment for baseline characteristics, patients randomized to cinacalcet experienced a nominally significant 13% lower adjusted risk (95% confidence limit 4-20%) of the primary composite end point. The effect of cinacalcet was not modified by baseline pulse pressure (Pinteraction=0.44). In adjusted models, at 20 weeks cinacalcet resulted in a 2.2 mm Hg larger average decrease in systolic blood pressure (P=0.002) and a 1.3 mm Hg larger average decrease in diastolic blood pressure (P=0.002) compared with placebo. In summary, in the EVOLVE trial, the effect of cinacalcet on death and major cardiovascular events was independent of baseline pulse pressure.

    View details for DOI 10.1038/jhh.2015.56

    View details for PubMedID 26040438

  • Managing Hypertension in Patients with CKD: A Marathon, Not a SPRINT JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Chertow, G. M., Beddhu, S., Lewis, J. B., Toto, R. D., Cheung, A. K. 2016; 27 (1): 40-43

    Abstract

    In this manuscript, nephrologist-investigators from one of five Clinical Center Networks of the Systolic Blood Pressure Intervention Trial (SPRINT) provide background information and context on the intensity of anti-hypertensive therapy in conjunction with the release of detailed results from SPRINT's primary analysis. The authors highlight published evidence on the safety and efficacy of differing intensities of anti-hypertensive therapy in mild to moderate CKD, where SPRINT will help to inform practice, as well as where gaps in evidence will remain. The authors also challenge the nephrology community to renew its attention and efforts on hypertension clinical care and research.

    View details for DOI 10.1681/ASN.2015101125

    View details for Web of Science ID 000367632400007

    View details for PubMedCentralID PMC4696594

  • Managing Hypertension in Patients with CKD: A Marathon, Not a SPRINT. Journal of the American Society of Nephrology : JASN Chertow, G. M., Beddhu, S., Lewis, J. B., Toto, R. D., Cheung, A. K. 2016; 27 (1): 40–43

    Abstract

    In this manuscript, nephrologist-investigators from one of five Clinical Center Networks of the Systolic Blood Pressure Intervention Trial (SPRINT) provide background information and context on the intensity of anti-hypertensive therapy in conjunction with the release of detailed results from SPRINT's primary analysis. The authors highlight published evidence on the safety and efficacy of differing intensities of anti-hypertensive therapy in mild to moderate CKD, where SPRINT will help to inform practice, as well as where gaps in evidence will remain. The authors also challenge the nephrology community to renew its attention and efforts on hypertension clinical care and research.

    View details for PubMedID 26553785

  • Iron management in chronic kidney disease: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies Conference KIDNEY INTERNATIONAL Macdougall, I. C., Bircher, A. J., Eckardt, K., Obrador, G. T., Pollock, C. A., Stenvinkel, P., Swinkels, D. W., Wanner, C., Weiss, G., Chertow, G. M. 2016; 89 (1): 28-39

    Abstract

    Before the introduction of erythropoiesis-stimulating agents (ESAs) in 1989, repeated transfusions given to patients with end-stage renal disease caused iron overload, and the need for supplemental iron was rare. However, with the widespread introduction of ESAs, it was recognized that supplemental iron was necessary to optimize hemoglobin response and allow reduction of the ESA dose for economic reasons and recent concerns about ESA safety. Iron supplementation was also found to be more efficacious via intravenous compared to oral administration, and the use of intravenous iron has escalated in recent years. The safety of various iron compounds has been of theoretical concern due to their potential to induce iron overload, oxidative stress, hypersensitivity reactions, and a permissive environment for infectious processes. Therefore, an expert group was convened to assess the benefits and risks of parenteral iron, and to provide strategies for its optimal use while mitigating the risk for acute reactions and other adverse effects.

    View details for DOI 10.1016/j.kint.2015.10.002

    View details for Web of Science ID 000368321300012

  • Chronic Kidney Disease Classification in Systolic Blood Pressure Intervention Trial: Comparison Using Modification of Diet in Renal Disease and CKD-Epidemiology Collaboration Definitions AMERICAN JOURNAL OF NEPHROLOGY Rocco, M. V., Chapman, A., Chertow, G. M., Cohen, D., Chen, J., Cutler, J. A., Diamond, M. J., Freedman, B. I., Hawfield, A., Judd, E., Killeen, A. A., Kirchner, K., Lewis, C. E., Pajewski, N. M., Wall, B. M., Yee, J. 2016; 44 (2): 130-140

    Abstract

    Interventional trials have used either the Modification of Diet in Renal Disease (MDRD) or chronic kidney disease (CKD)-Epidemiology Collaboration (CKD-EPI) equation for determination of estimated glomerular filtration rate (eGFR) to define whether participants have stages 3-5 CKD. The equation used to calculate eGFR may influence the number and characteristics of participants designated as having CKD.We examined the classification of CKD at baseline using both equations in the Systolic Blood Pressure Intervention Trial (SPRINT). eGFR was calculated at baseline using fasting serum creatinine values from a central laboratory.Among 9,308 participants with baseline CKD classification using the 4-variable MDRD equation specified in the SPRINT protocol, 681 (7.3%) participants were reclassified to a less advanced CKD stage (higher eGFR) and 346 (3.7%) were reclassified to a more advanced CKD stage (lower eGFR) when the CKD-EPI equation was used to calculate eGFR. For eGFRs <90 ml/min/1.73 m2, participants <75 years were more likely to be reclassified to a less advanced CKD stage; this reclassification was more likely to occur in non-blacks rather than blacks. Participants aged ≥75 years were more likely to be reclassified to a more advanced than a less advanced CKD stage, regardless of baseline CKD stage. Reclassification of baseline CKD status (eGFR <60 ml/min/1.73 m2) occurred in 3% of participants.Use of the MDRD equation led to a higher percentage of participants being classified as having CKD stages 3-4. Younger and non-black participants were more likely to be reclassified as not having CKD using the CKD-EPI equation.

    View details for DOI 10.1159/000448722

    View details for Web of Science ID 000383216200006

    View details for PubMedID 27513312

    View details for PubMedCentralID PMC5096787

  • Declining Rates of Inpatient Parathyroidectomy for Primary Hyperparathyroidism in the US. PloS one Kim, S. M., Shu, A. D., Long, J., Montez-Rath, M. E., Leonard, M. B., Norton, J. A., Chertow, G. M. 2016; 11 (8)

    Abstract

    Parathyroidectomy is the only curative therapy for patients with primary hyperparathyroidism. However, the incidence, correlates and consequences of parathyroidectomy for primary hyperparathyroidism across the entire US population are unknown. We evaluated temporal trends in rates of inpatient parathyroidectomy for primary hyperparathyroidism, and associated in-hospital mortality, length of stay, and costs. We used the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (NIS) from 2002-2011. Parathyroidectomies for primary hyperparathyroidism were identified using International Classification of Diseases, Ninth Revision codes. Unadjusted and age- and sex- adjusted rates of inpatient parathyroidectomy for primary hyperparathyroidism were derived from the NIS and the annual US Census. We estimated 109,583 parathyroidectomies for primary hyperparathyroidism between 2002 and 2011. More than half (55.4%) of patients were younger than age 65, and more than three-quarters (76.8%) were female. The overall rate of inpatient parathyroidectomy was 32.3 cases per million person-years. The adjusted rate decreased from 2004 (48.3 cases/million person-years) to 2007 (31.7 cases/million person-years) and was sustained thereafter. Although inpatient parathyroidectomy rates declined over time across all geographic regions, a steeper decline was observed in the South compared to other regions. Overall in-hospital mortality rates were 0.08%: 0.02% in patients younger than 65 years and 0.14% in patients 65 years and older. Inpatient parathyroidectomy rates for primary hyperparathyroidism have declined in recent years.

    View details for DOI 10.1371/journal.pone.0161192

    View details for PubMedID 27529699

  • The Effect of Increased Frequency of Hemodialysis on Volume-Related Outcomes: A Secondary Analysis of the Frequent Hemodialysis Network Trials. Blood purification Raimann, J. G., Chan, C. T., Daugirdas, J. T., Depner, T., Gotch, F. A., Greene, T., Kaysen, G. A., Kliger, A. S., Kotanko, P., Larive, B., Lindsay, R., Rocco, M. V., Chertow, G. M., Levin, N. W. 2016; 41 (4): 277-286

    Abstract

    In previous reports of the Frequent Hemodialysis Network trials, frequent hemodialysis (HD) reduced extracellular fluid (ECF) and left ventricular mass (LVM), with more pronounced effects observed among patients with low urine volume (UVol). We analyzed the effect of frequent HD on interdialytic weight gain (IDWG) and a time-integrated estimate of ECF load (TIFL). We also explored whether volume and sodium loading contributed to the change in LVM over the study period. Treatment effects on volume parameters were analyzed for modification by UVol and the dialysate-to-serum sodium gradient. Predictors of change in LVM were determined using linear regression. Frequent HD reduced IDWG and TIFL in the Daily Trial. Among patients with UVol <100 ml/day, reduction in TIFL was associated with LVM reduction. This suggests that achievement of better volume control could attenuate changes in LVM associated with mortality and cardiovascular morbidity. TIFL may prove more useful than IDWG alone in guiding HD practice. Video Journal Club 'Cappuccino with Claudio Ronco' at http://www.karger.com/?doi=441966.

    View details for DOI 10.1159/000441966

    View details for PubMedID 26795100

  • Iron management in chronic kidney disease: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies Conference. Kidney international Macdougall, I. C., Bircher, A. J., Eckardt, K. U., Obrador, G. T., Pollock, C. A., Stenvinkel, P., Swinkels, D. W., Wanner, C., Weiss, G., Chertow, G. M. 2016; 89 (1): 28–39

    Abstract

    Before the introduction of erythropoiesis-stimulating agents (ESAs) in 1989, repeated transfusions given to patients with end-stage renal disease caused iron overload, and the need for supplemental iron was rare. However, with the widespread introduction of ESAs, it was recognized that supplemental iron was necessary to optimize hemoglobin response and allow reduction of the ESA dose for economic reasons and recent concerns about ESA safety. Iron supplementation was also found to be more efficacious via intravenous compared to oral administration, and the use of intravenous iron has escalated in recent years. The safety of various iron compounds has been of theoretical concern due to their potential to induce iron overload, oxidative stress, hypersensitivity reactions, and a permissive environment for infectious processes. Therefore, an expert group was convened to assess the benefits and risks of parenteral iron, and to provide strategies for its optimal use while mitigating the risk for acute reactions and other adverse effects.

    View details for PubMedID 26759045

  • Rehospitalizations and Emergency Department Visits after Hospital Discharge in Patients Receiving Maintenance Hemodialysis. Journal of the American Society of Nephrology Harel, Z., Wald, R., McArthur, E., Chertow, G. M., Harel, S., Gruneir, A., Fischer, H. D., Garg, A. X., Perl, J., Nash, D. M., Silver, S., Bell, C. M. 2015; 26 (12): 3141-3150

    Abstract

    Clinical outcomes after a hospital discharge are poorly defined for patients receiving maintenance in-center (outpatient) hemodialysis. To describe the proportion and characteristics of these patients who are rehospitalized, visit an emergency department, or die within 30 days after discharge from an acute hospitalization, we conducted a population-based study of all adult patients receiving maintenance in-center hemodialysis who were discharged between January 1, 2003, and December 31, 2011, from 157 acute care hospitals in Ontario, Canada. For patients with more than one hospitalization, we randomly selected a single hospitalization as the index hospitalization. Of the 11,177 patients included in the final cohort, 1926 (17%) were rehospitalized, 2971 (27%) were treated in the emergency department, and 840 (7.5%) died within 30 days of discharge. Complications of type 2 diabetes mellitus were the most common reason for rehospitalization, whereas heart failure was the most common reason for an emergency department visit. In multivariable analysis using a cause-specific Cox proportional hazards model, the following characteristics were associated with 30-day rehospitalization: older age, the number of hospital admissions in the preceding 6 months, the number of emergency department visits in the preceding 6 months, higher Charlson comorbidity index score, and the receipt of mechanical ventilation during the index hospitalization. Thus, a large proportion of patients receiving maintenance in-center hemodialysis will be readmitted or visit an emergency room within 30 days of an acute hospitalization. A focus on improving care transitions from the inpatient setting to the outpatient dialysis unit may improve outcomes and reduce healthcare costs.

    View details for DOI 10.1681/ASN.2014060614

    View details for PubMedID 25855772

  • Risk Factors for Infection-Related Hospitalization in In-Center Hemodialysis CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Dalrymple, L. S., Mu, Y., Nguyen, D. V., Romano, P. S., Chertow, G. M., Grimes, B., Kaysen, G. A., Johansen, K. L. 2015; 10 (12): 2170-2180

    Abstract

    Infection-related hospitalizations have increased dramatically over the last 10 years in patients receiving in-center hemodialysis. Patient and dialysis facility characteristics associated with the rate of infection-related hospitalization were examined, with consideration of the region of care, rural-urban residence, and socioeconomic status.The US Renal Data System linked to the American Community Survey and Rural-Urban Commuting Area codes was used to examine factors associated with hospitalization for infection among Medicare beneficiaries starting in-center hemodialysis between 2005 and 2008. A Poisson mixed effects model was used to examine the associations among patient and dialysis facility characteristics and the rate of infection-related hospitalization.Among 135,545 Medicare beneficiaries, 38,475 (28%) had at least one infection-related hospitalization. The overall rate of infection-related hospitalization was 40.2 per 100 person-years. Age ≥ 85 years old, cancer, chronic obstructive pulmonary disease, inability to ambulate or transfer, drug dependence, residence in a care facility, serum albumin <3.5 g/dl at dialysis initiation, and dialysis initiation with an access other than a fistula were associated with a ≥ 20% increase in the rate of infection-related hospitalization. Patients residing in isolated small rural compared with urban areas had lower rates of hospitalization for infection (rate ratio, 0.91; 95% confidence interval, 0.86 to 0.97), and rates of hospitalization for infection varied across the ESRD networks. Measures of socioeconomic status (at the zip code level), total facility staffing, and the composition of staff (percentage of nurses) were not associated with the rate of hospitalization for infection.Patient and facility factors associated with higher rates of infection-related hospitalization were identified. The findings from this study can be used to identify patients at higher risk for infection and inform the design of infection prevention strategies.

    View details for DOI 10.2215/CJN.03050315

    View details for PubMedID 26567370

  • Economic Evaluation of Cinacalcet in the United States: The EVOLVE Trial VALUE IN HEALTH Belozeroff, V., Chertow, G. M., Graham, C. N., Dehmel, B., Parfrey, P. S., Briggs, A. H. 2015; 18 (8): 1079-1087

    Abstract

    Previous economic evaluations of cinacalcet in patients with secondary hyperparathyroidism (sHPT) relied on the combination of surrogate end points in clinical trials and epidemiologic studies.The objective was to conduct an economic evaluation of cinacalcet on the basis of the EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) trial from a US payer perspective.We developed a semi-Markov model to assess the cost-effectiveness of cinacalcet in addition to conventional therapy, compared with conventional therapy alone, in patients with moderate-to-severe sHPT receiving hemodialysis. We used treatment effect estimates from the unadjusted intent-to-treat (ITT) analysis and prespecified covariate-adjusted ITT analysis as our main analyses. We assessed model sensitivity to variations in individual inputs and overall decision uncertainty through probabilistic sensitivity analyses.The incremental cost-effectiveness ratio (ICER) for cinacalcet was $61,705 per life-year and $79,562 per quality-adjusted life-year (QALY) gained using the covariate-adjusted ITT analysis. Probabilistic sensitivity analysis suggested a 73.2% chance of the ICER being below a willingness-to-pay threshold of $100,000. Treatment effects from unadjusted ITT analysis yielded an ICER of $115,876 per QALY. The model was most sensitive to the treatment effect on mortality.In the unadjusted ITT analysis, cinacalcet does not represent a cost- effective use of health care resources when applying a willingness-to-pay threshold of $100,000 per QALY. When using the covariate-adjusted ITT treatment effect, which represents the least biased estimate, however, cinacalcet is a cost-effective therapy for patients with moderate-to-severe sHPT on hemodialysis.

    View details for DOI 10.1016/j.jval.2015.08.007

    View details for PubMedID 26686794

  • Effects of daily hemodialysis on heart rate variability: results from the Frequent Hemodialysis Network (FHN) Daily Trial PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES Chan, C. T., Chertow, G. M., Daugirdasl, J. T., Greene', T. H., Kotanko, P., Larive, B., Pierratosi, A., Stokes, J. B. 2015; 282 (1816)

    Abstract

    End-stage renal disease is associated with reduced heart rate variability (HRV), components of which generally are associated with advanced age, diabetes mellitus and left ventricular hypertrophy. We hypothesized that daily in-center hemodialysis (HD) would increase HRV.The Frequent Hemodialysis Network (FHN) Daily Trial randomized 245 patients to receive 12 months of six versus three times per week in-center HD. Two hundred and seven patients had baseline Holter recordings. HRV measures were calculated from 24-h Holter electrocardiograms at both baseline and 12 months in 131 patients and included low-frequency power (LF, a measure of sympathetic modulation), high-frequency power (HF, a measure of parasympathetic modulation) and standard deviation (SD) of the R-R interval (SDNN, a measure of beat-to-beat variation).Baseline to Month 12 change in LF was augmented by 50% [95% confidence interval (95% CI) 6.1-112%, P =0.022] and LF + HF was augmented by 40% (95% CI 3.3-88.4%, P = 0.03) in patients assigned to daily hemodialysis (DHD) compared with conventional HD. Changes in HF and SDNN were similar between the randomized groups. The effects of DHD on LF were attenuated by advanced age and diabetes mellitus (predefined subgroups). Changes in HF (r = -0.20, P = 0.02) and SDNN (r = -0.18, P = 0.04) were inversely associated with changes in left ventricular mass (LVM).DHD increased the LF component of HRV. Reduction of LVM by DHD was associated with increased vagal modulation of heart rate (HF) and with increased beat-to-beat heart rate variation (SDNN), suggesting an important functional correlate to the structural effects of DHD on the heart in uremia.

    View details for DOI 10.1093/ndt/gft212

    View details for Web of Science ID 000363484700016

    View details for PubMedCentralID PMC3888308

  • Association of bioimpedance spectroscopy-based volume estimation with postdialysis hypotension in patients receiving hemodialysis HEMODIALYSIS INTERNATIONAL Abreo, A. P., Chertow, G. M., Dalrymple, L. S., Kaysen, G. A., Johansen, K. L. 2015; 19 (4): 536-542

    Abstract

    Clinical examination to determine the dry weight of patients on hemodialysis (HD) has been problematic, with studies showing discordance between physician assessment and objective measures of volume status.We studied the association between predialysis bioimpedance spectroscopy (BIS)-based estimates of fluid overload and postdialysis hypotension in 635 patients in the United States Renal Data System ACTIVE/ADIPOSE (A Cohort study To Investigate the Value of Exercise/Analyses Designed to Investigate the Paradox of Obesity and Survival in ESRD) study receiving HD in 2009-2011. We recorded predialysis and postdialysis weight and blood pressures over 3 consecutive HD sessions and performed BIS before a single session. Using a previously reported method of estimating normohydration weight, we estimated postdialysis fluid overload (FOpost ) in liters. We used logistic regression with extracellular water/total body water (ECW/TBW) or estimated FOpost as the primary predictor and 1 or more postdialysis systolic blood pressures less than 110 mmHg as the dependent variable. Models were adjusted for age, sex, race, ultrafiltration rate per kilogram of body weight, end-stage renal disease vintage, diabetes mellitus, heart failure, and albumin. Higher ECW/TBW was associated with lower odds of postdialysis hypotension (odds ratio [OR] 0.35, 95% confidence interval [CI] 0.15-0.84 per 0.1, P = 0.02). Every liter of FOpost was associated with lower adjusted odds of postdialysis hypotension (OR 0.86, 95% CI 0.79-0.95, P = 0.003). Prospective studies are needed to determine whether this application of BIS could improve current clinical efforts to minimize episodes of postdialysis hypotension without leading to volume overload.

    View details for DOI 10.1111/hdi.12305

    View details for PubMedID 25881673

  • Cardiovascular and Renal Outcomes Trials-Is There a Difference? AMERICAN JOURNAL OF CARDIOLOGY Raggi, P., Boer, R., Goodman, W. G., Kalantar-Zadeh, K., Chertow, G. M., Belozeroff, V. 2015; 116 (6): 982-988

    Abstract

    There is a general sense that most outcomes trials in patients receiving dialysis failed to yield statistically significant benefits, in contrast to many cardiovascular (CV) trials in the general population. It is unknown whether methodologic reasons caused this discrepancy. We performed a systematic MEDLINE search for randomized trials with mortality end points of the 42 compounds most commonly used for CV indications. In total, 115 trials were selected for review. We further reviewed 9 mortality end point trials in patients receiving dialysis. The CV trials in populations not receiving dialysis enrolled from 66 to 33,357 participants with an average of 4,910; 59% of the trials showed statistically significant results. The average hazard ratio (HR) was 0.77, ranging from 0.10 to 1.65; 10 drugs had ≥5 published trials each. In the population receiving dialysis, most drugs were studied in single trials; the average number of patients was 1,500 with a range of 127 to 3,883. The average HR was 0.77 and ranged from 0.06 to 1.30. Only 22% of the trials showed statistically significant results. The limitations listed in the general population and dialysis studies were similar. In conclusion, no apparent methodologic issues were detected (other than sample size) that could justify the lower frequency of randomized trials with statistically significant results in patients receiving dialysis. The most obvious difference was the paucity of trials with each drug in the dialysis cohorts; this lowers the chances of at least 1 trial being successful.

    View details for DOI 10.1016/j.amjcard.2015.06.024

    View details for PubMedID 26198118

  • Menopausal symptoms in women with chronic kidney disease. Menopause (New York, N.Y.) Cheung, K. L., Stefanick, M. L., Allison, M. A., LeBlanc, E. S., Vitolins, M. Z., Shara, N., Chertow, G. M., Winkelmayer, W. C., Kurella Tamura, M. 2015; 22 (9): 1006-1011

    Abstract

    This study aims to determine whether menopausal symptoms differed between women with chronic kidney disease (CKD) and women without CKD, and whether CKD modified associations of late vasomotor symptoms (VMS) with mortality and/or cardiovascular events.CKD, defined as estimated glomerular filtration rate lower than 60 mL/minute/1.73 m (using the Chronic Kidney Disease Epidemiology Collaboration equation), was determined in 17,891 postmenopausal women, aged 50 to 79 years at baseline, in the multiethnic Women's Health Initiative cohort. Primary outcomes were presence, severity, and timing/duration of VMS (self-reported hot flashes and night sweats) at baseline. We used polytomous logistic regression to test for associations among CKD and four VMS categories (no VMS; early VMS-present before menopause but not at study baseline; late VMS-present only at study baseline; persistent VMS-present before menopause and study baseline) and Cox regression to determine whether CKD modified associations between late VMS and mortality or cardiovascular events.Women with CKD (1,017 of 17,891; mean estimated glomerular filtration rate, 50.7 mL/min/1.73 m) were more likely to have had menopause before age 45 years (26% vs 23%, P = 0.02) but were less likely to experience VMS (38% vs 46%, P < 0.001) than women without CKD. Women with CKD were not more likely than women without CKD to experience late VMS. Late VMS (hazard ratio, 1.16; 95% CI, 1.04-1.29) and CKD (hazard ratio, 1.74; 95% CI, 1.54-1.97) were each independently associated with increased risk for mortality, but CKD did not modify the association of late VMS with mortality (Pinteraction = 0.53), coronary heart disease (Pinteraction = 0.12), or stroke (Pinteraction = 0.68).Women with mild CKD experience earlier menopause and fewer VMS than women without CKD.

    View details for DOI 10.1097/GME.0000000000000416

    View details for PubMedID 25628057

  • Long-term Effects of Frequent Nocturnal Hemodialysis on Mortality: The Frequent Hemodialysis Network (FHN) Nocturnal Trial AMERICAN JOURNAL OF KIDNEY DISEASES Rocco, M. V., Daugirdas, J. T., Greene, T., Lockridge, R. S., Chan, C., Pierratos, A., Lindsay, R., Larive, B., Chertow, G. M., Beck, G. J., Eggers, P. W., Kliger, A. S. 2015; 66 (3): 459-468

    Abstract

    Few data are available regarding the long-term mortality rate for patients receiving nocturnal home hemodialysis.Posttrial observational study.Frequent Hemodialysis Network (FHN) Nocturnal Trial participants who consented to extended follow-up.The FHN Nocturnal Trial randomly assigned 87 individuals to 6-times-weekly home nocturnal hemodialysis or 3-times-weekly hemodialysis for 1 year. Patients were enrolled starting in March 2006 and follow-up was completed by May 2010. After the 1-year trial concluded, FHN Nocturnal participants were free to modify their hemodialysis prescription.We obtained dates of death and kidney transplantation through July 2011 using linkage to the US Renal Data System and queries of study centers. We used log-rank tests and Cox regression to relate mortality to the initial randomization assignment.Median follow-up for the trial and posttrial observational period was 3.7 years. In the nocturnal arm, there were 2 deaths during the 12-month trial period and an additional 12 deaths during the extended follow-up. In the conventional arm, the numbers of deaths were 1 and 4, respectively. In the nocturnal dialysis group, the overall mortality HR was 3.88 (95% CI, 1.27-11.79; P=0.01). Using as-treated analysis with a 12-month running treatment average, the HR for mortality was 3.06 (95% CI, 1.11-8.43; P=0.03). Six-month running treatment data analysis showed an HR of 1.12 (95% CI, 0.44-3.22; P=0.7).These results should be interpreted cautiously due to a surprisingly low (0.03 deaths/patient-year) mortality rate for individuals randomly assigned to conventional home hemodialysis, low statistical power for the mortality comparison due to the small sample size, and the high rate of hemodialysis prescription changes.Patients randomly assigned to nocturnal hemodialysis had a higher mortality rate than those randomly assigned to conventional dialysis. The implications of this result require further investigation.

    View details for DOI 10.1053/j.ajkd.2015.02.331

    View details for Web of Science ID 000360115400019

    View details for PubMedCentralID PMC4549208

  • Long-term Effects of Frequent Nocturnal Hemodialysis on Mortality: The Frequent Hemodialysis Network (FHN) Nocturnal Trial. American journal of kidney diseases Rocco, M. V., Daugirdas, J. T., Greene, T., Lockridge, R. S., Chan, C., Pierratos, A., Lindsay, R., Larive, B., Chertow, G. M., Beck, G. J., Eggers, P. W., Kliger, A. S. 2015; 66 (3): 459-468

    Abstract

    Few data are available regarding the long-term mortality rate for patients receiving nocturnal home hemodialysis.Posttrial observational study.Frequent Hemodialysis Network (FHN) Nocturnal Trial participants who consented to extended follow-up.The FHN Nocturnal Trial randomly assigned 87 individuals to 6-times-weekly home nocturnal hemodialysis or 3-times-weekly hemodialysis for 1 year. Patients were enrolled starting in March 2006 and follow-up was completed by May 2010. After the 1-year trial concluded, FHN Nocturnal participants were free to modify their hemodialysis prescription.We obtained dates of death and kidney transplantation through July 2011 using linkage to the US Renal Data System and queries of study centers. We used log-rank tests and Cox regression to relate mortality to the initial randomization assignment.Median follow-up for the trial and posttrial observational period was 3.7 years. In the nocturnal arm, there were 2 deaths during the 12-month trial period and an additional 12 deaths during the extended follow-up. In the conventional arm, the numbers of deaths were 1 and 4, respectively. In the nocturnal dialysis group, the overall mortality HR was 3.88 (95% CI, 1.27-11.79; P=0.01). Using as-treated analysis with a 12-month running treatment average, the HR for mortality was 3.06 (95% CI, 1.11-8.43; P=0.03). Six-month running treatment data analysis showed an HR of 1.12 (95% CI, 0.44-3.22; P=0.7).These results should be interpreted cautiously due to a surprisingly low (0.03 deaths/patient-year) mortality rate for individuals randomly assigned to conventional home hemodialysis, low statistical power for the mortality comparison due to the small sample size, and the high rate of hemodialysis prescription changes.Patients randomly assigned to nocturnal hemodialysis had a higher mortality rate than those randomly assigned to conventional dialysis. The implications of this result require further investigation.

    View details for DOI 10.1053/j.ajkd.2015.02.331

    View details for PubMedID 25863828

  • Risk prediction models for contrast induced nephropathy: systematic review BMJ-BRITISH MEDICAL JOURNAL Silver, S. A., Shah, P. M., Chertow, G. M., Harel, S., Wald, R., Harel, Z. 2015; 351

    Abstract

    To look at the available literature on validated prediction models for contrast induced nephropathy and describe their characteristics.Systematic review.Medline, Embase, and CINAHL (cumulative index to nursing and allied health literature) databases.Databases searched from inception to 2015, and the retrieved reference lists hand searched. Dual reviews were conducted to identify studies published in the English language of prediction models tested with patients that included derivation and validation cohorts. Data were extracted on baseline patient characteristics, procedural characteristics, modelling methods, metrics of model performance, risk of bias, and clinical usefulness. Eligible studies evaluated characteristics of predictive models that identified patients at risk of contrast induced nephropathy among adults undergoing a diagnostic or interventional procedure using conventional radiocontrast media (media used for computed tomography or angiography, and not gadolinium based contrast).16 studies were identified, describing 12 prediction models. Substantial interstudy heterogeneity was identified, as a result of different clinical settings, cointerventions, and the timing of creatinine measurement to define contrast induced nephropathy. Ten models were validated internally and six were validated externally. Discrimination varied in studies that were validated internally (C statistic 0.61-0.95) and externally (0.57-0.86). Only one study presented reclassification indices. The majority of higher performing models included measures of pre-existing chronic kidney disease, age, diabetes, heart failure or impaired ejection fraction, and hypotension or shock. No prediction model evaluated its effect on clinical decision making or patient outcomes.Most predictive models for contrast induced nephropathy in clinical use have modest ability, and are only relevant to patients receiving contrast for coronary angiography. Further research is needed to develop models that can better inform patient centred decision making, as well as improve the use of prevention strategies for contrast induced nephropathy.

    View details for DOI 10.1136/bmj.h4395

    View details for Web of Science ID 000360438200001

    View details for PubMedCentralID PMC4784870

  • Provider Visits and Early Vascular Access Placement in Maintenance Hemodialysis JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Erickson, K. F., Mell, M., Winkelmayer, W. C., Chertow, G. M., Bhattacharya, J. 2015; 26 (8): 1990-1997

    Abstract

    Medicare reimbursement policy encourages frequent provider visits for patients with ESRD undergoing hemodialysis. We hypothesize that patients seen more frequently by their nephrologist or advanced practitioner within the first 90 days of hemodialysis are more likely to undergo surgery to create an arteriovenous (AV) fistula or place an AV graft. We selected 35,959 patients aged ≥67 years starting hemodialysis in the United States from a national registry. We used multivariable regression to evaluate the associations between mean visit frequency and AV fistula creation or graft placement in the first 90 days of hemodialysis. We conducted an instrumental variable analysis to test the sensitivity of our findings to potential bias from unobserved characteristics. One additional visit per month in the first 90 days of hemodialysis was associated with a 21% increase in the odds of AV fistula creation or graft placement during that period (95% confidence interval, 19% to 24%), corresponding to an average 4.5% increase in absolute probability. An instrumental variable analysis demonstrated similar findings. Excluding visits in months when patients were hospitalized, one additional visit per month was associated with a 10% increase in odds of vascular access surgery (95% confidence interval, 8% to 13%). In conclusion, patients seen more frequently by care providers in the first 90 days of hemodialysis undergo earlier AV fistula creation or graft placement. Payment policies that encourage more frequent visits to patients at key clinical time points may yield more favorable health outcomes than policies that operate irrespective of patients' health status.

    View details for DOI 10.1681/ASN.2014050464

    View details for PubMedID 25452668

  • Cinacalcet, Fibroblast Growth Factor-23, and Cardiovascular Disease in Hemodialysis The Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial CIRCULATION Moe, S. M., Chertow, G. M., Parfrey, P. S., Kubo, Y., Block, G. A., Correa-Rotter, R., Drueeke, T. B., Herzog, C. A., London, G. M., Mahaffey, K. W., Wheeler, D. C., Stolina, M., Dehmel, B., Goodman, W. G., Floege, J. 2015; 132 (1): 27-39

    Abstract

    Patients with kidney disease have disordered bone and mineral metabolism, including elevated serum concentrations of fibroblast growth factor-23 (FGF23). These elevated concentrations are associated with cardiovascular and all-cause mortality. The objective was to determine the effects of the calcimimetic cinacalcet (versus placebo) on reducing serum FGF23 and whether changes in FGF23 are associated with death and cardiovascular events.This was a secondary analysis of a randomized clinical trial comparing cinacalcet to placebo in addition to conventional therapy (phosphate binders/vitamin D) in patients receiving hemodialysis with secondary hyperparathyroidism (intact parathyroid hormone ≥300 pg/mL). The primary study end point was time to death or a first nonfatal cardiovascular event (myocardial infarction, hospitalization for angina, heart failure, or a peripheral vascular event). This analysis included 2985 patients (77% of randomized) with serum samples at baseline and 2602 patients (67%) with samples at both baseline and week 20. The results demonstrated that a significantly larger proportion of patients randomized to cinacalcet had ≥30% (68% versus 28%) reductions in FGF23. Among patients randomized to cinacalcet, a ≥30% reduction in FGF23 between baseline and week 20 was associated with a nominally significant reduction in the primary composite end point (relative hazard, 0.82; 95% confidence interval, 0.69-0.98), cardiovascular mortality (relative hazard, 0.66; 95% confidence interval, 0.50-0.87), sudden cardiac death (relative hazard, 0.57; 95% confidence interval, 0.37-0.86), and heart failure (relative hazard, 0.69; 95% confidence interval, 0.48-0.99).Treatment with cinacalcet significantly lowers serum FGF23. Treatment-induced reductions in serum FGF23 are associated with lower rates of cardiovascular death and major cardiovascular events.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00345839.

    View details for DOI 10.1161/CIRCULATIONAHA.114.013876

    View details for Web of Science ID 000357498100005

  • Cinacalcet, Fibroblast Growth Factor-23, and Cardiovascular Disease in Hemodialysis: The Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial. Circulation Moe, S. M., Chertow, G. M., Parfrey, P. S., Kubo, Y., Block, G. A., Correa-Rotter, R., Drüeke, T. B., Herzog, C. A., London, G. M., Mahaffey, K. W., Wheeler, D. C., Stolina, M., Dehmel, B., Goodman, W. G., Floege, J. 2015; 132 (1): 27-39

    Abstract

    Patients with kidney disease have disordered bone and mineral metabolism, including elevated serum concentrations of fibroblast growth factor-23 (FGF23). These elevated concentrations are associated with cardiovascular and all-cause mortality. The objective was to determine the effects of the calcimimetic cinacalcet (versus placebo) on reducing serum FGF23 and whether changes in FGF23 are associated with death and cardiovascular events.This was a secondary analysis of a randomized clinical trial comparing cinacalcet to placebo in addition to conventional therapy (phosphate binders/vitamin D) in patients receiving hemodialysis with secondary hyperparathyroidism (intact parathyroid hormone ≥300 pg/mL). The primary study end point was time to death or a first nonfatal cardiovascular event (myocardial infarction, hospitalization for angina, heart failure, or a peripheral vascular event). This analysis included 2985 patients (77% of randomized) with serum samples at baseline and 2602 patients (67%) with samples at both baseline and week 20. The results demonstrated that a significantly larger proportion of patients randomized to cinacalcet had ≥30% (68% versus 28%) reductions in FGF23. Among patients randomized to cinacalcet, a ≥30% reduction in FGF23 between baseline and week 20 was associated with a nominally significant reduction in the primary composite end point (relative hazard, 0.82; 95% confidence interval, 0.69-0.98), cardiovascular mortality (relative hazard, 0.66; 95% confidence interval, 0.50-0.87), sudden cardiac death (relative hazard, 0.57; 95% confidence interval, 0.37-0.86), and heart failure (relative hazard, 0.69; 95% confidence interval, 0.48-0.99).Treatment with cinacalcet significantly lowers serum FGF23. Treatment-induced reductions in serum FGF23 are associated with lower rates of cardiovascular death and major cardiovascular events.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00345839.

    View details for DOI 10.1161/CIRCULATIONAHA.114.013876

    View details for PubMedID 26059012

  • Prevalence of chronic kidney disease in two major Indian cities and projections for associated cardiovascular disease KIDNEY INTERNATIONAL Anand, S., Shivashankar, R., Ali, M. K., Kondal, D., Binukumar, B., Montez-Rath, M. E., Ajay, V. S., Pradeepa, R., Deepa, M., Gupta, R., Mohan, V., Narayan, K. M., Tandon, N., Chertow, G. M., Prabhakaran, D. 2015; 88 (1): 178-185

    Abstract

    India is experiencing an alarming rise in the burden of noncommunicable diseases, but data on the incidence of chronic kidney disease (CKD) are sparse. Using the Center for Cardiometabolic Risk Reduction in South Asia surveillance study (a population-based survey of Delhi and Chennai, India) we estimated overall, and age-, sex-, city-, and diabetes-specific prevalence of CKD, and defined the distribution of the study population by the Kidney Disease Improving Global Outcomes (KDIGO) classification scheme. The likelihood of cardiovascular events in participants with and without CKD was estimated by the Framingham and Interheart Modifiable Risk Scores. Of the 12,271 participants, 80% had complete data on serum creatinine and albuminuria. The prevalence of CKD and albuminuria, age standardized to the World Bank 2010 world population, was 8.7% (95% confidence interval: 7.9-9.4%) and 7.1% (6.4-7.7%), respectively. Nearly 80% of patients with CKD had an abnormally high hemoglobin A1c (5.7 and above). Based on KDIGO guidelines, 6.0, 1.0, and 0.5% of study participants are at moderate, high, or very high risk for experiencing CKD-associated adverse outcomes. The cardiovascular risk scores placed a greater proportion of patients with CKD in the high-risk categories for experiencing cardiovascular events when compared with participants without CKD. Thus, 1 in 12 individuals living in two of India's largest cities have evidence of CKD, with features that put them at high risk for adverse outcomes.

    View details for DOI 10.1038/ki.2015.58

    View details for PubMedID 25786102

  • Associations of Trimethylamine N-Oxide With Nutritional and Inflammatory Biomarkers and Cardiovascular Outcomes in Patients New to Dialysis JOURNAL OF RENAL NUTRITION Kaysen, G. A., Johansen, K. L., Chertow, G. M., Dalrymple, L. S., Kornak, J., Grimes, B., Dwyer, T., Chassy, A. W., Fiehn, O. 2015; 25 (4): 351-356

    Abstract

    Trimethylamine N-oxide (TMAO) is a product of metabolism of phosphatidylcholine (lecithin) and carnitine by the intestinal microbiome. Elevated serum concentrations of TMAO have been linked to adverse cardiovascular outcomes in the general population. We examined correlates of serum TMAO and the relations among serum TMAO concentrations, all-cause mortality, and cardiovascular mortality and hospitalizations in a nationally derived cohort of patients new to hemodialysis (HD).We quantified serum TMAO by liquid chromatography and online tandem mass spectrometry and assessed nutritional and cardiovascular risk factors in 235 patients receiving HD and measured TMAO in pooled serum from healthy controls. We analyzed time to death and time to cardiovascular death or hospitalization using Cox proportional hazards regression.Serum TMAO concentrations of patients undergoing HD (median, 43 μM/L; 25th-75th percentile, 28-67 μM/L) were elevated compared with those with normal or near-normal kidney function (1.41 ± 0.49 μM/L). TMAO was directly correlated with serum albumin (Spearman rank correlation, 0.24; 95% CI, 0.12-0.35; P <.001), prealbumin (Spearman rank correlation, 0.19; 95% CI, 0.07-0.31; P = .003), and creatinine (Spearman rank correlation, 0.21; 95% CI, 0.08-0.33; P = .002) and inversely correlated with log C-reactive protein (Spearman rank correlation, -0.18; 95% CI, -0.30 to -0.06; P = .005). Higher serum concentrations of TMAO were not significantly associated with time to death (Spearman rank correlation, 0.84; CI, 0.65-1.09; P = .19) or time to cardiovascular hospitalization or cardiovascular death (Spearman rank correlation, 0.88; CI, 0.57-1.35; P = .55).Serum TMAO concentrations were markedly elevated and correlated directly with biochemical markers of nutritional status and inversely with markers of inflammation in patients receiving HD. There was no significant association between serum TMAO concentrations and all-cause mortality, cardiovascular death, or hospitalizations. In patients receiving dialysis-in contrast with the general population-adverse vascular effects of TMAO may be counterbalanced by associations with nutritional or inflammatory status.

    View details for DOI 10.1053/j.jrn.2015.02.006

    View details for Web of Science ID 000360282800006

    View details for PubMedCentralID PMC4469547

  • Associations of Trimethylamine N-Oxide With Nutritional and Inflammatory Biomarkers and Cardiovascular Outcomes in Patients New to Dialysis. Journal of renal nutrition Kaysen, G. A., Johansen, K. L., Chertow, G. M., Dalrymple, L. S., Kornak, J., Grimes, B., Dwyer, T., Chassy, A. W., Fiehn, O. 2015; 25 (4): 351-356

    Abstract

    Trimethylamine N-oxide (TMAO) is a product of metabolism of phosphatidylcholine (lecithin) and carnitine by the intestinal microbiome. Elevated serum concentrations of TMAO have been linked to adverse cardiovascular outcomes in the general population. We examined correlates of serum TMAO and the relations among serum TMAO concentrations, all-cause mortality, and cardiovascular mortality and hospitalizations in a nationally derived cohort of patients new to hemodialysis (HD).We quantified serum TMAO by liquid chromatography and online tandem mass spectrometry and assessed nutritional and cardiovascular risk factors in 235 patients receiving HD and measured TMAO in pooled serum from healthy controls. We analyzed time to death and time to cardiovascular death or hospitalization using Cox proportional hazards regression.Serum TMAO concentrations of patients undergoing HD (median, 43 μM/L; 25th-75th percentile, 28-67 μM/L) were elevated compared with those with normal or near-normal kidney function (1.41 ± 0.49 μM/L). TMAO was directly correlated with serum albumin (Spearman rank correlation, 0.24; 95% CI, 0.12-0.35; P <.001), prealbumin (Spearman rank correlation, 0.19; 95% CI, 0.07-0.31; P = .003), and creatinine (Spearman rank correlation, 0.21; 95% CI, 0.08-0.33; P = .002) and inversely correlated with log C-reactive protein (Spearman rank correlation, -0.18; 95% CI, -0.30 to -0.06; P = .005). Higher serum concentrations of TMAO were not significantly associated with time to death (Spearman rank correlation, 0.84; CI, 0.65-1.09; P = .19) or time to cardiovascular hospitalization or cardiovascular death (Spearman rank correlation, 0.88; CI, 0.57-1.35; P = .55).Serum TMAO concentrations were markedly elevated and correlated directly with biochemical markers of nutritional status and inversely with markers of inflammation in patients receiving HD. There was no significant association between serum TMAO concentrations and all-cause mortality, cardiovascular death, or hospitalizations. In patients receiving dialysis-in contrast with the general population-adverse vascular effects of TMAO may be counterbalanced by associations with nutritional or inflammatory status.

    View details for DOI 10.1053/j.jrn.2015.02.006

    View details for PubMedID 25802017

  • Longer-term Outcomes of Darbepoetin Alfa Versus Epoetin Alfa in Patients With ESRD Initiating Hemodialysis: A Quasi-experimental Cohort Study AMERICAN JOURNAL OF KIDNEY DISEASES Winkelmayer, W. C., Chang, T. I., Mitani, A. A., Wilhelm-Leen, E. R., Ding, V., Chertow, G. M., Brookhart, M. A., Goldstein, B. A. 2015; 66 (1): 106-113

    Abstract

    Adequately powered studies directly comparing hard clinical outcomes of darbepoetin alfa (DPO) versus epoetin alfa (EPO) in patients undergoing dialysis are lacking.Observational, registry-based, retrospective cohort study; we mimicked a cluster-randomized trial by comparing mortality and cardiovascular events in US patients initiating hemodialysis therapy in facilities (almost) exclusively using DPO versus EPO.Nonchain US hemodialysis facilities; each facility switching from EPO to DPO (2003-2010) was matched for location, profit status, and facility type with one EPO facility. Patients subsequently initiating hemodialysis therapy in these facilities were assigned their facility-level exposure.DPO versus EPO.All-cause mortality, cardiovascular mortality; composite of cardiovascular death, nonfatal myocardial infarction (MI), and nonfatal stroke.Unadjusted and adjusted HRs from Cox proportional hazards regression models.Of 508 dialysis facilities that switched to DPO, 492 were matched with a similar EPO facility; 19,932 (DPO: 9,465 [47.5%]; EPO: 10,467 [52.5%]) incident hemodialysis patients were followed up for 21,918 person-years during which 5,550 deaths occurred. Almost all baseline characteristics were tightly balanced. The demographics-adjusted mortality HR for DPO (vs EPO) was 1.06 (95% CI, 1.00-1.13) and was materially unchanged after adjustment for all other baseline characteristics (HR, 1.05; 95% CI, 0.99-1.12). Cardiovascular mortality did not differ between groups (HR, 1.05; 95% CI, 0.94-1.16). Nonfatal outcomes were evaluated among 9,455 patients with fee-for-service Medicare: 4,542 (48.0%) in DPO and 4,913 (52.0%) in EPO facilities. During 10,457 and 10,363 person-years, 248 and 372 events were recorded, respectively, for strokes and MIs. We found no differences in adjusted stroke or MI rates or their composite with cardiovascular death (HR, 1.10; 95% CI, 0.96-1.25).Nonrandom treatment assignment, potential residual confounding.In incident hemodialysis patients, mortality and cardiovascular event rates did not differ between patients treated at facilities predominantly using DPO versus EPO.

    View details for DOI 10.1053/j.ajkd.2015.02.339

    View details for PubMedID 25943715

  • Assessing the treatment effect in a randomized controlled trial with extensive non-adherence: the EVOLVE trial. Pharmaceutical statistics Kubo, Y., Sterling, L. R., Parfrey, P. S., Gill, K., Mahaffey, K. W., Gioni, I., Trotman, M., Dehmel, B., Chertow, G. M. 2015; 14 (4): 368-?

    View details for DOI 10.1002/pst.1694

    View details for PubMedID 26096896

  • Dialysis plus do not resuscitate--not a contradiction. JAMA internal medicine Wilhelm-Leen, E. R., Chertow, G. M. 2015; 175 (6): 1035-1036

    View details for DOI 10.1001/jamainternmed.2015.0413

    View details for PubMedID 25915153

  • Effects of Cinacalcet on Fracture Events in Patients Receiving Hemodialysis: The EVOLVE Trial JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Moe, S. M., Abdalla, S., Chertow, G. M., Parfrey, P. S., Block, G. A., Correa-Rotter, R., Floege, J., Herzog, C. A., London, G. M., Mahaffey, K. W., Wheeler, D. C., Dehmel, B., Goodman, W. G., Drueeke, T. B. 2015; 26 (6): 1466-1475

    Abstract

    Fractures are frequent in patients receiving hemodialysis. We tested the hypothesis that cinacalcet would reduce the rate of clinical fractures in patients receiving hemodialysis using data from the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events trial, a placebo-controlled trial that randomized 3883 hemodialysis patients with secondary hyperparathyroidism to receive cinacalcet or placebo for ≤64 months. This study was a prespecified secondary analysis of the trial whose primary end point was all-cause mortality and non-fatal cardiovascular events, and one of the secondary end points was first clinical fracture event. Clinical fractures were observed in 255 of 1935 (13.2%) patients randomized to placebo and 238 of 1948 (12.2%) patients randomized to cinacalcet. In an unadjusted intention-to-treat analysis, the relative hazard for fracture (cinacalcet versus placebo) was 0.89 (95% confidence interval [95% CI], 0.75 to 1.07). After adjustment for baseline characteristics and multiple fractures, the relative hazard was 0.83 (95% CI, 0.72 to 0.98). Using a prespecified lag-censoring analysis (a measure of actual drug exposure), the relative hazard for fracture was 0.72 (95% CI, 0.58 to 0.90). When participants were censored at the time of cointerventions (parathyroidectomy, transplant, or provision of commercial cinacalcet), the relative hazard was 0.71 (95% CI, 0.58 to 0.87). Fracture rates were higher in older compared with younger patients and the effect of cinacalcet appeared more pronounced in older patients. In conclusion, using an unadjusted intention-to-treat analysis, cinacalcet did not reduce the rate of clinical fracture. However, when accounting for differences in baseline characteristics, multiple fractures, and/or events prompting discontinuation of study drug, cinacalcet reduced the rate of clinical fracture by 16%-29%.

    View details for DOI 10.1681/ASN.2014040414

    View details for Web of Science ID 000355386100024

    View details for PubMedCentralID PMC4446874

  • Evaluating Risk of ESRD in the Urban Poor JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Maziarz, M., Black, R. A., Fong, C. T., Himmelfarb, J., Chertow, G. M., Hall, Y. N. 2015; 26 (6): 1434-1442

    Abstract

    The capacity of risk prediction to guide management of CKD in underserved health settings is unknown. We conducted a retrospective cohort study of 28,779 adults with nondialysis-requiring CKD who received health care in two large safety net health systems during 1996-2009 and were followed for ESRD through September of 2011. We developed and evaluated the performance of ESRD risk prediction models using recently proposed criteria designed to inform population health approaches to disease management: proportion of cases followed and proportion that needs to be followed. Overall, 1730 persons progressed to ESRD during follow-up (median follow-up=6.6 years). ESRD risk for time frames up to 5 years was highly concentrated among relatively few individuals. A predictive model using five common variables (age, sex, race, eGFR, and dipstick proteinuria) performed similarly to more complex models incorporating extensive sociodemographic and clinical data. Using this model, 80% of individuals who eventually developed ESRD were among the 5% of cohort members at the highest estimated risk for ESRD at 1 year. Similarly, a program that followed 8% and 13% of individuals at the highest ESRD risk would have included 80% of those who eventually progressed to ESRD at 3 and 5 years, respectively. In this underserved health setting, a simple five-variable model accurately predicts most cases of ESRD that develop within 5 years. Applying risk prediction using a population health approach may improve CKD surveillance and management of vulnerable groups by directing resources to a small subpopulation at highest risk for progressing to ESRD.

    View details for DOI 10.1681/ASN.2014060546

    View details for PubMedID 25475746

  • Red blood cell transfusion, hyperkalemia, and heart failure in advanced chronic kidney disease PHARMACOEPIDEMIOLOGY AND DRUG SAFETY Gill, K., Fink, J. C., Gilbertson, D. T., Monda, K. L., Muntner, P., Lafayette, R. A., Petersen, J., Chertow, G. M., Bradbury, B. D. 2015; 24 (6): 654-662

    Abstract

    In recent years, the use of red blood cell (RBC) transfusion for the treatment of chronic kidney disease (CKD)-related anemia has increased. We used the OptumInsight medical claims database to study the association between receiving a transfusion and hyperkalemia and heart failure events.Persons 18-64 years of age with diagnosed stage 4 or 5 CKD (not requiring dialysis) between 2006 and 2010 were followed until their first hospitalization or emergency room visit with a diagnosis of hyperkalemia or heart failure, termination of insurance coverage, or death. We used a case-only design and conditional logistic regression to estimate rate ratios (RR) and 95% confidence intervals (CIs) describing associations between RBC transfusion and the risks of hyperkalemia or heart failure. We used single (1:1) and variable (1:m) self-control matching intervals, with adjustment for time-varying confounders.Seven thousand eight hundred twenty-nine individuals met our inclusion criteria; two-thirds were age 50 years or older; 43% were women and 51% had diabetes. Rates of hyperkalemia and heart failure were 7.9/100 person-years (95%CI: 7.3, 8.5) and 16.3/100 person-years (95%CI: 15.5, 17.2), respectively. RBC transfusion was associated with an increased risk of both hyperkalemia (single interval matched RR = 12.0, 95%CI: 1.3, 109; multiple interval matched RR = 6.1, 95%CI: 2.5, 15.1) and heart failure (single interval matched RR = 1.7, 95%CI: 0.3, 9.2; multiple interval matched RR = 3.8, 95%CI: 1.4, 10.3).In patients with advanced CKD, RBC transfusion appears to be associated with an elevated risk of hyperkalemia and heart failure; further investigation into these risks is warranted. Copyright © 2015 John Wiley & Sons, Ltd.

    View details for DOI 10.1002/pds.3779

    View details for PubMedID 25903095

  • Effects of Cinacalcet on Fracture Events in Patients Receiving Hemodialysis: The EVOLVE Trial. Journal of the American Society of Nephrology Moe, S. M., Abdalla, S., Chertow, G. M., Parfrey, P. S., Block, G. A., Correa-Rotter, R., Floege, J., Herzog, C. A., London, G. M., Mahaffey, K. W., Wheeler, D. C., Dehmel, B., Goodman, W. G., Drüeke, T. B. 2015; 26 (6): 1466-1475

    Abstract

    Fractures are frequent in patients receiving hemodialysis. We tested the hypothesis that cinacalcet would reduce the rate of clinical fractures in patients receiving hemodialysis using data from the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events trial, a placebo-controlled trial that randomized 3883 hemodialysis patients with secondary hyperparathyroidism to receive cinacalcet or placebo for ≤64 months. This study was a prespecified secondary analysis of the trial whose primary end point was all-cause mortality and non-fatal cardiovascular events, and one of the secondary end points was first clinical fracture event. Clinical fractures were observed in 255 of 1935 (13.2%) patients randomized to placebo and 238 of 1948 (12.2%) patients randomized to cinacalcet. In an unadjusted intention-to-treat analysis, the relative hazard for fracture (cinacalcet versus placebo) was 0.89 (95% confidence interval [95% CI], 0.75 to 1.07). After adjustment for baseline characteristics and multiple fractures, the relative hazard was 0.83 (95% CI, 0.72 to 0.98). Using a prespecified lag-censoring analysis (a measure of actual drug exposure), the relative hazard for fracture was 0.72 (95% CI, 0.58 to 0.90). When participants were censored at the time of cointerventions (parathyroidectomy, transplant, or provision of commercial cinacalcet), the relative hazard was 0.71 (95% CI, 0.58 to 0.87). Fracture rates were higher in older compared with younger patients and the effect of cinacalcet appeared more pronounced in older patients. In conclusion, using an unadjusted intention-to-treat analysis, cinacalcet did not reduce the rate of clinical fracture. However, when accounting for differences in baseline characteristics, multiple fractures, and/or events prompting discontinuation of study drug, cinacalcet reduced the rate of clinical fracture by 16%-29%.

    View details for DOI 10.1681/ASN.2014040414

    View details for PubMedID 25505257

    View details for PubMedCentralID PMC4446874

  • The Effects of Cinacalcet in Older and Younger Patients on Hemodialysis: The Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial. Clinical journal of the American Society of Nephrology Parfrey, P. S., Drüeke, T. B., Block, G. A., Correa-Rotter, R., Floege, J., Herzog, C. A., London, G. M., Mahaffey, K. W., Moe, S. M., Wheeler, D. C., Kubo, Y., Dehmel, B., Goodman, W. G., Chertow, G. M. 2015; 10 (5): 791-799

    Abstract

    The calcimimetic cinacalcet reduced the risk of death or cardiovascular (CV) events in older, but not younger, patients with moderate to severe secondary hyperparathyroidism (HPT) who were receiving hemodialysis. To determine whether the lower risk in younger patients might be due to lower baseline CV risk and more frequent use of cointerventions that reduce parathyroid hormone (kidney transplantation, parathyroidectomy, and commercial cinacalcet use), this study examined the effects of cinacalcet in older (≥65 years, n=1005) and younger (<65 years, n=2878) patients.Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) was a global, multicenter, randomized placebo-controlled trial in 3883 prevalent patients on hemodialysis, whose outcomes included death, major CV events, and development of severe unremitting HPT. The age subgroup analysis was prespecified.Older patients had higher baseline prevalence of diabetes mellitus and CV comorbidity. Annualized rates of kidney transplantation and parathyroidectomy were >3-fold higher in younger relative to older patients and were more frequent in patients randomized to placebo. In older patients, the adjusted relative hazard (95% confidence interval) for the primary composite (CV) end point (cinacalcet versus placebo) was 0.70 (0.60 to 0.81); in younger patients, the relative hazard was 0.97 (0.86 to 1.09). Corresponding adjusted relative hazards for mortality were 0.68 (0.51 to 0.81) and 0.99 (0.86 to 1.13). Reduction in the risk of severe unremitting HPT was similar in both groups.In the EVOLVE trial, cinacalcet decreased the risk of death and of major CV events in older, but not younger, patients with moderate to severe HPT who were receiving hemodialysis. Effect modification by age may be partly explained by differences in underlying CV risk and differential application of cointerventions that reduce parathyroid hormone.

    View details for DOI 10.2215/CJN.07730814

    View details for PubMedID 25710802

  • The Effects of Cinacalcet in Older and Younger Patients on Hemodialysis: The Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Parfrey, P. S., Drueeke, T. B., Block, G. A., Correa-Rotter, R., Floege, J., Herzog, C. A., London, G. M., Mahaffey, K. W., Moe, S. M., Wheeler, D. C., Kubo, Y., Dehmel, B., Goodman, W. G., Chertow, G. M. 2015; 10 (5): 791-799

    Abstract

    The calcimimetic cinacalcet reduced the risk of death or cardiovascular (CV) events in older, but not younger, patients with moderate to severe secondary hyperparathyroidism (HPT) who were receiving hemodialysis. To determine whether the lower risk in younger patients might be due to lower baseline CV risk and more frequent use of cointerventions that reduce parathyroid hormone (kidney transplantation, parathyroidectomy, and commercial cinacalcet use), this study examined the effects of cinacalcet in older (≥65 years, n=1005) and younger (<65 years, n=2878) patients.Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) was a global, multicenter, randomized placebo-controlled trial in 3883 prevalent patients on hemodialysis, whose outcomes included death, major CV events, and development of severe unremitting HPT. The age subgroup analysis was prespecified.Older patients had higher baseline prevalence of diabetes mellitus and CV comorbidity. Annualized rates of kidney transplantation and parathyroidectomy were >3-fold higher in younger relative to older patients and were more frequent in patients randomized to placebo. In older patients, the adjusted relative hazard (95% confidence interval) for the primary composite (CV) end point (cinacalcet versus placebo) was 0.70 (0.60 to 0.81); in younger patients, the relative hazard was 0.97 (0.86 to 1.09). Corresponding adjusted relative hazards for mortality were 0.68 (0.51 to 0.81) and 0.99 (0.86 to 1.13). Reduction in the risk of severe unremitting HPT was similar in both groups.In the EVOLVE trial, cinacalcet decreased the risk of death and of major CV events in older, but not younger, patients with moderate to severe HPT who were receiving hemodialysis. Effect modification by age may be partly explained by differences in underlying CV risk and differential application of cointerventions that reduce parathyroid hormone.

    View details for DOI 10.2215/CJN.07730814

    View details for Web of Science ID 000354144900011

    View details for PubMedCentralID PMC4422239

  • Assessing the treatment effect in a randomized controlled trial with extensive non-adherence: the EVOLVE trial PHARMACEUTICAL STATISTICS Kubo, Y., Sterling, L. R., Parfrey, P. S., Gill, K., Mahaffey, K. W., Gioni, I., Trotman, M., Dehmel, B., Chertow, G. M. 2015; 14 (3): 242-251

    Abstract

    Intention-to-treat (ITT) analysis is widely used to establish efficacy in randomized clinical trials. However, in a long-term outcomes study where non-adherence to study drug is substantial, the on-treatment effect of the study drug may be underestimated using the ITT analysis. The analyses presented herein are from the EVOLVE trial, a double-blind, placebo-controlled, event-driven cardiovascular outcomes study conducted to assess whether a treatment regimen including cinacalcet compared with placebo in addition to other conventional therapies reduces the risk of mortality and major cardiovascular events in patients receiving hemodialysis with secondary hyperparathyroidism. Pre-specified sensitivity analyses were performed to assess the impact of non-adherence on the estimated effect of cinacalcet. These analyses included lag-censoring, inverse probability of censoring weights (IPCW), rank preserving structural failure time model (RPSFTM) and iterative parameter estimation (IPE). The relative hazard (cinacalcet versus placebo) of mortality and major cardiovascular events was 0.93 (95% confidence interval 0.85, 1.02) using the ITT analysis; 0.85 (0.76, 0.95) using lag-censoring analysis; 0.81 (0.70, 0.92) using IPCW; 0.85 (0.66, 1.04) using RPSFTM and 0.85 (0.75, 0.96) using IPE. These analyses, while not providing definitive evidence, suggest that the intervention may have an effect while subjects are receiving treatment. The ITT method remains the established method to evaluate efficacy of a new treatment; however, additional analyses should be considered to assess the on-treatment effect when substantial non-adherence to study drug is expected or observed.

    View details for DOI 10.1002/pst.1680

    View details for PubMedID 25851955

  • A 12-Week, Double-Blind, Placebo-Controlled Trial of Ferric Citrate for the Treatment of Iron Deficiency Anemia and Reduction of Serum Phosphate in Patients With CKD Stages 3-5 AMERICAN JOURNAL OF KIDNEY DISEASES Block, G. A., Fishbane, S., Rodriguez, M., Smits, G., Shemesh, S., Pergola, P. E., Wolf, M., Chertow, G. M. 2015; 65 (5): 728-736

    Abstract

    Iron deficiency anemia and serum phosphate levels > 4.0mg/dL are relatively common in chronic kidney disease stages 3 to 5 and are associated with higher risks of progressive loss of kidney function, cardiovascular events, and mortality.Double-blind, placebo-controlled, randomized trial.149 patients with estimated glomerular filtration rates < 60 mL/min/1.73 m(2), iron deficiency anemia (hemoglobin, 9.0-12.0 g/dL; transferrin saturation [TSAT]≤ 30%, serum ferritin ≤ 300 ng/mL), and serum phosphate levels ≥ 4.0 to 6.0mg/dL. Use of intravenous iron or erythropoiesis-stimulating agents was prohibited.Randomization to treatment for 12 weeks with ferric citrate coordination complex (ferric citrate) or placebo.Coprimary end points were change in TSAT and serum phosphate level from baseline to end of study. Secondary outcomes included change from baseline to end of treatment in values for ferritin, hemoglobin, intact fibroblast growth factor 23 (FGF-23), urinary phosphate excretion, and estimated glomerular filtration rate.Ferric citrate treatment increased mean TSAT from 22% ± 7% (SD) to 32% ± 14% and reduced serum phosphate levels from 4.5 ± 0.6 to 3.9 ± 0.6 mg/dL, while placebo exerted no effect on TSAT (21% ± 8% to 20% ± 8%) and less effect on serum phosphate level (4.7 ± 0.6 to 4.4 ± 0.8 mg/dL; between-group P<0.001 for each). Ferric citrate increased hemoglobin levels (from 10.5 ± 0.8 to 11.0 ± 1.0 g/dL; P<0.001 vs placebo), reduced urinary phosphate excretion 39% (P<0.001 vs placebo), and reduced serum intact FGF-23 levels from a median of 159 (IQR, 102-289) to 105 (IQR, 65-187) pg/mL (P=0.02 vs placebo). The incidence and severity of adverse effects were similar between treatment arms.The study is limited by relatively small sample size and short duration and by having biochemical rather than clinical outcomes.Short-term use of ferric citrate repletes iron stores, increases hemoglobin levels, and reduces levels of serum phosphate, urinary phosphate excretion, and FGF-23 in patients with chronic kidney disease stages 3 to 5.

    View details for DOI 10.1053/j.ajkd.2014.10.014

    View details for PubMedID 25468387

  • The Effect of Cinacalcet on Calcific Uremic Arteriolopathy Events in Patients Receiving Hemodialysis: The EVOLVE Trial CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Floege, J., Kubo, Y., Floege, A., Chertow, G. M., Parfrey, P. S. 2015; 10 (5): 800-807

    Abstract

    Uncontrolled secondary hyperparathyroidism (sHPT) in patients with ESRD is a risk factor for calcific uremic arteriolopathy (CUA; calciphylaxis).Adverse event reports collected during the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events trial were used to determine the frequency of CUA in patients receiving hemodialysis who had moderate to severe sHPT, as well as the effects of cinacalcet versus placebo. CUA events were collected while patients were receiving the study drug.Among the 3861 trial patients who received at least one dose of the study drug, 18 patients randomly assigned to placebo and six assigned to cinacalcet developed CUA (unadjusted relative hazard, 0.31; 95% confidence interval [95% CI], 0.13 to 0.79; P=0.014). Corresponding cumulative event rates (95% CI) at year 4 were 0.011% (0.006% to 0.018%) and 0.005% (0.002% to 0.010%). By multivariable analysis, other factors associated with CUA included female sex, higher body mass index, higher diastolic BP, and history of dyslipidemia or parathyroidectomy. Median (10%, 90% percentile) plasma parathyroid hormone concentrations proximal to the report of CUA were 796 (225, 2093) pg/ml and 410 (71, 4957) pg/ml in patients randomly assigned to placebo and cinacalcet, respectively. Active use of vitamin K antagonists was recorded in 11 of 24 patients with CUA, nine randomly assigned to placebo, and two to cinacalcet, in contrast to 5%-7% at any one time point in patients in whom CUA was not reported.Cinacalcet appeared to reduce the incidence of CUA in hemodialysis recipients who have moderate to severe sHPT.

    View details for DOI 10.2215/CJN.10221014

    View details for PubMedID 25887067

  • Outcomes of Infection-Related Hospitalization in Medicare Beneficiaries Receiving In-Center Hemodialysis AMERICAN JOURNAL OF KIDNEY DISEASES Dalrymple, L. S., Mu, Y., Romano, P. S., Nguyen, D. V., Chertow, G. M., Delgado, C., Grimes, B., Kaysen, G. A., Johansen, K. L. 2015; 65 (5): 754-762

    Abstract

    Infection is a common cause of hospitalization in adults receiving hemodialysis. Limited data are available about downstream events resulting from or following these hospitalizations.Retrospective cohort study using the US Renal Data System.Medicare beneficiaries initiating in-center hemodialysis therapy in 2005 to 2008.Demographics, dual Medicare/Medicaid eligibility, body mass index, comorbid conditions, initial vascular access type, nephrology care prior to dialysis therapy initiation, residence in a care facility, tobacco use, biochemical measures, and type of infection.30-day hospital readmission or death following first infection-related hospitalization.60,270 Medicare beneficiaries had at least one hospitalization for infection. Of those who survived the initial hospitalization, 15,113 (27%) were readmitted and survived the 30 days following hospital discharge, 1,624 (3%) were readmitted to the hospital and then died within 30 days of discharge, and 2,425 (4%) died without hospital readmission. Complications related to dialysis access, sepsis, and heart failure accounted for 12%, 9%, and 7% of hospital readmissions, respectively. Factors associated with higher odds of 30-day readmission or death without readmission included non-Hispanic ethnicity, lower serum albumin level, inability to ambulate or transfer, limited nephrology care prior to dialysis therapy, and specific types of infection. In comparison, older age, select comorbid conditions, and institutionalization had stronger associations with death without readmission than with readmission.Findings limited to Medicare beneficiaries receiving in-center hemodialysis.Hospitalizations for infection among patients receiving in-center hemodialysis are associated with exceptionally high rates of 30-day hospital readmission and death without readmission.

    View details for DOI 10.1053/j.ajkd.2014.11.030

    View details for PubMedID 25641061

  • AURYXIA (FERRIC CITRATE), AN ORAL IRON-BASED PHOSPHATE BINDER SIGNIFICANTLY IMPROVES SERUM IRON MEASURES IN PATIENTS WITH STAGE 3, 4 AND 5 CHRONIC KIDNEY DISEASE (CKD) Fishbane, S., Block, G. A., Loram, L. C., Chertow, G. M. W B SAUNDERS CO-ELSEVIER INC. 2015: A35
  • AURYXIA (FERRIC CITRATE) EFFECTIVELY REDUCES SERUM PHOSPHATE AND FIBROBLAST GROWTH FACTOR 23 (FGF23) LEVELS IN PATIENTS WITH STAGES 3-5 CHRONIC KIDNEY DISEASE (CKD) Block, G. A., Chertow, G. M., Fishbane, S., Loram, L. C., Wolf, M. W B SAUNDERS CO-ELSEVIER INC. 2015: A23
  • Navigating toward research success in times of uncertainty: funding opportunities for early career investigators in nephrology. American journal of kidney diseases Ikizler, T. A., Lovett, D. H., Chertow, G. M., Mitch, W. E., Schiller, B. 2015; 65 (3): 381-383

    Abstract

    There is considerable concern within the nephrology community about recent federal budget cuts and the decreasing availability of funds for research. This is especially difficult for junior investigators who are about to start a career as physician-scientists. Accordingly, it is imperative that resources other than federal funds be made available to these individuals during this most delicate yet crucial transition period. This commentary aims to provide an overview of nonfederal funding resources, focusing on the Norman S. Coplon Extramural Grant Program. This program emphasizes support of investigators at the most fragile period in their development of an academic career; it has provided >$11 million of research funds to more than 80 individuals since 2000. The outcome has been stellar, with more than 130 publications originating from these projects and >90% of awardees staying in academia. We hope these accomplishments will encourage similar activities by other entities and scientific programs in addition to ones that are ongoing. Ultimately, these collective efforts will inspire young researchers to use their knowledge, passion, and dedication to advance research into kidney diseases.

    View details for DOI 10.1053/j.ajkd.2014.11.008

    View details for PubMedID 25542413

  • Time-Updated Systolic Blood Pressure and the Progression of Chronic Kidney Disease A Cohort Study ANNALS OF INTERNAL MEDICINE Anderson, A. H., Yang, W., Townsend, R. R., Pan, Q., Chertow, G. M., Kusek, J. W., Charleston, J., He, J., Kallem, R., Lash, J. P., Miller, E. R., Rahman, M., Steigerwalt, S., Weir, M., Wright, J. T., Feldman, H. I. 2015; 162 (4): 258-?

    Abstract

    Previous reports of the longitudinal association between achieved blood pressure (BP) and end-stage renal disease (ESRD) among patients with chronic kidney disease (CKD) have not incorporated time-updated BP with appropriate covariate adjustment.To assess the association between baseline and time-updated systolic blood pressure (SBP) with CKD progression.Observational, prospective cohort study. (ClinicalTrials.gov: NCT00304148).7 U.S. clinical centers.Patients in the Chronic Renal Insufficiency Cohort Study (n = 3708) followed for a median of 5.7 years (25th to 75th percentile, 4.6 to 6.7 years).The mean of 3 seated SBP measurements made up the visit-specific SBP. Time-updated SBP was the mean of that and all previous visits. Outcomes were ESRD and the composite end point of ESRD or halving of the estimated glomerular filtration rate. Analyses investigating baseline and time-updated SBP used Cox proportional hazards models and marginal structural models, respectively.Systolic blood pressure was 130 mm Hg or greater at all visits in 19.2% of patients. The hazard ratio for ESRD among patients with SBP of 130 to 139 mm Hg, compared with SBP less than 120 mm Hg, was 1.46 (95% CI, 1.13 to 1.88) using only baseline data and 2.37 (CI, 1.48 to 3.80) using time-updated data. Among patients with SBP of 140 mm Hg or greater, corresponding hazard ratios were 1.46 (CI, 1.18 to 1.88) and 3.37 (CI, 2.26 to 5.03) for models using only baseline data and those using time-updated data, respectively.Blood pressure was measured once annually, and the cohort was not a random sample.Time-updated SBP greater than 130 mm Hg was more strongly associated with CKD progression than analyses based on baseline SBP.National Institute of Diabetes and Digestive and Kidney Diseases.

    View details for DOI 10.7326/M14-0488

    View details for Web of Science ID 000350232500015

    View details for PubMedID 25686166

    View details for PubMedCentralID PMC4404622

  • Provider visit frequency and vascular access interventions in hemodialysis. Clinical journal of the American Society of Nephrology Erickson, K. F., Mell, M. W., Winkelmayer, W. C., Chertow, G. M., Bhattacharya, J. 2015; 10 (2): 269-277

    Abstract

    Medicare reimbursement policy encourages frequent provider visits to patients with ESRD undergoing hemodialysis. This study sought to determine whether more frequent face-to-face provider (physician and advanced practitioner) visits lead to more procedures and therapeutic interventions aimed at preserving arteriovenous fistulas and grafts, improved vascular access outcomes, and fewer related hospitalizations.Multivariable regression was used to evaluate the association between provider (physician and advanced practitioner) visit frequency and interventions aimed at preserving vascular access, vascular access survival, hospitalization for vascular access infection, and outpatient antibiotic use in a cohort of 63,488 Medicare beneficiaries receiving hemodialysis in the United States. Medicare claims were used to identify the type of vascular access used, access-related events, and vascular access failure.One additional provider (physician and advanced practitioner) visit per month was associated with a 13% higher odds of receiving an intervention to preserve vascular access (95% confidence interval [95% CI], 12% to 14%) but was not associated with vascular access survival (hazard ratio, 1.01; 95% CI, 0.99 to 1.03). One additional provider visit was associated with a 9% (95% CI, 5% to 14%) lower odds of hospitalization for vascular access infection and a corresponding 9% (95% CI, 5% to 14%) higher odds of outpatient intravenous antibiotic administration. However, the associated changes in absolute probabilities of hospitalization and antibiotic administration were small.More frequent face-to-face provider (physician and advanced practitioner) visits were associated with more procedures and therapeutic interventions aimed at preserving vascular accesses, but not with prolonged vascular access survival and only a small decrease in hospitalization for vascular access.

    View details for DOI 10.2215/CJN.05540614

    View details for PubMedID 25587105

  • Effects of Cinacalcet on Atherosclerotic and Nonatherosclerotic Cardiovascular Events in Patients Receiving Hemodialysis: The EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) Trial JOURNAL OF THE AMERICAN HEART ASSOCIATION Wheeler, D. C., London, G. M., Parfrey, P. S., Block, G. A., Correa-Rotter, R., Dehmel, B., Drueeke, T. B., Floege, J., Kubo, Y., Mahaffey, K. W., Goodman, W. G., Moe, S. M., Trotman, M., Abdalla, S., Chertow, G. M., Herzog, C. A. 2015; 4 (1)
  • Use of novel oral anticoagulants in patients with end-stage renal disease HEMODIALYSIS INTERNATIONAL Winkelmayer, W. C., Herzog, C. A., Montez-Rath, M. E., Chang, T. I., Chertow, G. M. 2015; 19 (1): 150–53

    View details for PubMedID 25495752

  • Ambulatory care after acute kidney injury: an opportunity to improve patient outcomes. Canadian journal of kidney health and disease Silver, S. A., Goldstein, S. L., Harel, Z., Harvey, A., Rompies, E. J., Adhikari, N. K., Acedillo, R., Jain, A. K., Richardson, R., Chan, C. T., Chertow, G. M., Bell, C. M., Wald, R. 2015; 2: 36

    Abstract

    PURPOSE OF REVIEW: Acute kidney injury (AKI) is an increasingly common problem among hospitalized patients. Patients who survive an AKI-associated hospitalization are at higher risk of de novo and worsening chronic kidney disease, end-stage kidney disease, cardiovascular disease, and death. For hospitalized patients with dialysis-requiring AKI, outpatient follow-up with a nephrologist within 90days of hospital discharge has been associated with enhanced survival. However, most patients who survive an AKI episode do not receive any follow-up nephrology care. This narrative review describes the experience of two new clinical programs to care for AKI patients after hospital discharge: the Acute Kidney Injury Follow-up Clinic for adults (St. Michael's Hospital and University Health Network, Toronto, Canada) and the AKI Survivor Clinic for children (Cincinnati Children's Hospital, USA).SOURCES OF INFORMATION: MEDLINE, PubMed, ISI Web of Science.FINDINGS: These two ambulatory clinics have been in existence for close to two (adult) and four (pediatric) years, and were developed separately and independently in different populations and health systems. The components of both clinics are described, including the target population, referral process, medical interventions, patient education activities, and follow-up schedule. Common elements include targeting patients with KDIGO stage 2 or 3 AKI, regular audits of the inpatient nephrology census to track eligible patients, medication reconciliation, and education on the long-term consequences of AKI.LIMITATIONS: Despite the theoretical benefits of post-AKI follow-up and the clinic components described, there is no high quality evidence to prove that the interventions implemented in these clinics will reduce morbidity or mortality. Therefore, we also present a plan to evaluate the adult AKI Follow-up Clinic in order to determine if it can improve clinical outcomes compared to patients with AKI who do not receive follow-up care.IMPLICATIONS: Follow-up of AKI survivors is low, and this review describes two different clinics that care for patients who survive an AKI episode. We believe that sharing the experiences of the AKI Follow-up Clinic and AKI Survivor Clinic provide physicians with a feasible framework to implement their own clinics, which may help AKI patients receive outpatient care commensurate with their high risk status.

    View details for PubMedID 26445676

  • Risk prediction models for contrast induced nephropathy: systematic review. BMJ (Clinical research ed.) Silver, S. A., Shah, P. M., Chertow, G. M., Harel, S., Wald, R., Harel, Z. 2015; 351: h4395

    Abstract

    To look at the available literature on validated prediction models for contrast induced nephropathy and describe their characteristics.Systematic review.Medline, Embase, and CINAHL (cumulative index to nursing and allied health literature) databases.Databases searched from inception to 2015, and the retrieved reference lists hand searched. Dual reviews were conducted to identify studies published in the English language of prediction models tested with patients that included derivation and validation cohorts. Data were extracted on baseline patient characteristics, procedural characteristics, modelling methods, metrics of model performance, risk of bias, and clinical usefulness. Eligible studies evaluated characteristics of predictive models that identified patients at risk of contrast induced nephropathy among adults undergoing a diagnostic or interventional procedure using conventional radiocontrast media (media used for computed tomography or angiography, and not gadolinium based contrast).16 studies were identified, describing 12 prediction models. Substantial interstudy heterogeneity was identified, as a result of different clinical settings, cointerventions, and the timing of creatinine measurement to define contrast induced nephropathy. Ten models were validated internally and six were validated externally. Discrimination varied in studies that were validated internally (C statistic 0.61-0.95) and externally (0.57-0.86). Only one study presented reclassification indices. The majority of higher performing models included measures of pre-existing chronic kidney disease, age, diabetes, heart failure or impaired ejection fraction, and hypotension or shock. No prediction model evaluated its effect on clinical decision making or patient outcomes.Most predictive models for contrast induced nephropathy in clinical use have modest ability, and are only relevant to patients receiving contrast for coronary angiography. Further research is needed to develop models that can better inform patient centred decision making, as well as improve the use of prevention strategies for contrast induced nephropathy.

    View details for PubMedID 26316642

  • Planning for Hemodialysis CHRONIC RENAL DISEASE Isom, R. T., Chertow, G. M., Kimmel, P. L., Rosenberg, M. E. 2015: 751–64
  • Improving Care after Acute Kidney Injury: A Prospective Time Series Study NEPHRON Silver, S. A., Harel, Z., Harvey, A., Adhikari, N. K., Slack, A., Acedillo, R., Jain, A. K., Richardson, R. M., Chan, C. T., Chertow, G. M., Bell, C. M., Wald, R. 2015; 131 (1): 43-50

    Abstract

    Acute kidney injury (AKI) complicates 15-20% of hospitalizations, and AKI survivors are at increased risk of chronic kidney disease and death. However, less than 20% of patients see a nephrologist within 3 months of discharge, even though a nephrologist visit within 90 days of discharge is associated with enhanced survival. To address this, we established an AKI Follow-Up Clinic and characterized the patterns of care delivered.We conducted a prospective time series study. All hospitalized patients who developed Kidney Disease Improving Global Outcomes (KDIGO) stage 2 or 3 AKI were eligible. The pre-intervention period consisted of electronic reminders to the nephrology consults and cardiovascular surgery services to refer to the AKI Follow-Up Clinic. In the post-intervention period, eligible patients were automatically scheduled into the AKI Follow-Up Clinic at discharge. The primary outcome was the percentage of KDIGO stages 2-3 AKI survivors assessed by a nephrologist within 30 days of discharge.In the pre-intervention period, 8 of 46 patients (17%) were seen by a nephrologist within 30 days after discharge, and no additional patients were seen for 90 days. In the post-intervention period, 17 of 69 patients (25%) were seen by a nephrologist within 30 days after discharge (p = 0.36), with an additional 30 patients seen in 90 days (47 of 69, 68%, p < 0.001). The mean serum creatinine was 99 (SD 35) µmol/l prior to hospitalization and 133 (58) µmol/l at 3 months. Fifty-five of 79 patients (70%) received at least 1 medical intervention at their first AKI Follow-Up Clinic visit.An AKI Follow-Up Clinic with an automatic referral process increased the proportion of patients seen at 90 days, but not 30 days post discharge. Being seen in the AKI Follow-Up Clinic was associated with interventions in most patients. Future research is needed to evaluate the effect of the AKI Follow-Up Clinic on patient-centered outcomes, but physicians should be aware that AKI survivors may benefit from close outpatient follow-up and a multipronged approach to care similarly for other high-risk populations.

    View details for DOI 10.1159/000438871

    View details for Web of Science ID 000362148500007

    View details for PubMedID 26329832

  • Association of Self-Reported Frailty with Falls and Fractures among Patients New to Dialysis AMERICAN JOURNAL OF NEPHROLOGY Delgado, C., Shieh, S., Grimes, B., Chertow, G. M., Dalrymple, L. S., Kaysen, G. A., Kornak, J., Johansen, K. L. 2015; 42 (2): 134-140

    Abstract

    Although frailty has been linked to higher risk of falls and fracture in the general population, only few studies have examined the extent to which frailty is associated with these outcomes among patients with end-stage renal disease, who are at particularly high risk for these events.A total of 1,646 patients who were beginning maintenance hemodialysis in 297 dialysis units throughout the United States from September 2005 to June 2007 were enrolled in the Comprehensive Dialysis Study, and 1,053 Medicare beneficiaries were included in this study. Self-reported frailty was defined by the patients endorsing 2 or more of the following: poor physical functioning, exhaustion or low physical activity. Falls and fractures requiring medical attention were identified through Medicare claims data. We examined the association between frailty and the time to first fall or fracture using the Fine-Gray modification of Cox proportional hazards regression, adjusted for demographics, Quételet's body mass index, diabetes mellitus, heart failure and atherosclerosis.Seventy-seven percent of patients were frail by self-report. The median length of follow-up was 2.5 (1.0-3.9) years. Crude rates of first medically urgent falls or fractures were 66 and 126 per 1,000 person-years in non-frail and self-reported frail participants, respectively. After accounting for demographic factors, comorbidities and the competing risk of death, self-reported frailty was associated with a higher risk of falls or fractures requiring medical attention (hazards ratio 1.60, 95% CI 1.16-2.20).Participants reporting frailty experienced nearly twice the risk of medically urgent falls or fractures compared to those who did not report frailty.

    View details for DOI 10.1159/000439000

    View details for Web of Science ID 000363937800007

    View details for PubMedID 26381744

    View details for PubMedCentralID PMC4596065

  • Design of a Phase 2 Clinical Trial of an ASK1 Inhibitor, GS-4997, in Patients with Diabetic Kidney Disease NEPHRON Lin, J. H., Zhang, J. J., Lin, S., Chertow, G. M. 2015; 129 (1): 29-33

    Abstract

    Most patients with diabetic kidney disease (DKD) experience disease progression despite receiving standard care therapy. Oxidative stress is associated with DKD severity and risk of progression, but currently approved therapies do not directly attenuate the pathologic consequences of oxidative stress. GS-4997 is a once daily, oral molecule that inhibits Apoptosis Signal-regulating Kinase 1 (ASK1), which is a key mediator of the deleterious effects of oxidative stress.We describe the rationale and design of a Phase 2 placebo-controlled clinical trial investigating the effects of GS-4997 in patients with T2DM and stage 3/4 DKD receiving standard of care therapy. Approximately, 300 subjects will be randomized in a stratified manner, based on the estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio, to one of four arms in this dose-ranging study. The primary endpoint is change in eGFR at 48 weeks, and the key secondary endpoint is change in albuminuria.Guided by the biology of oxidative stress signaling through ASK1, the biology of DKD pathogenesis, and solid statistical methods, the decisions made for this Phase 2 study regarding delineating study population, efficacy outcomes, treatment period and statistical methods represent innovative attempts to resolve challenges specific to DKD study design.

    View details for DOI 10.1159/000369152

    View details for Web of Science ID 000350758500006

    View details for PubMedID 25531162

  • Effects of Cinacalcet on Atherosclerotic and Nonatherosclerotic Cardiovascular Events in Patients Receiving Hemodialysis: The EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) Trial JOURNAL OF THE AMERICAN HEART ASSOCIATION Wheeler, D. C., London, G. M., Parfrey, P. S., Block, G. A., Correa-Rotter, R., Dehmel, B., Drueeke, T. B., Floege, J., Kubo, Y., Mahaffey, K. W., Goodman, W. G., Moe, S. M., Trotman, M., Abdalla, S., Chertow, G. M., Herzog, C. A. 2014; 3 (6)

    Abstract

    Premature cardiovascular disease limits the duration and quality of life on long-term hemodialysis. The objective of this study was to define the frequency of fatal and nonfatal cardiovascular events attributable to atherosclerotic and nonatherosclerotic mechanisms, risk factors for these events, and the effects of cinacalcet, using adjudicated data collected during the EValuation of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) Trial.EVOLVE was a randomized, double-blind, placebo-controlled clinical trial that randomized 3883 hemodialysis patients with moderate to severe secondary hyperparathyroidism to cinacalcet or matched placebo for up to 64 months. For this post hoc analysis, the outcome measure was fatal and nonfatal cardiovascular events reflecting atherosclerotic and nonatherosclerotic cardiovascular diseases. During the trial, 1518 patients experienced an adjudicated cardiovascular event, including 958 attributable to nonatherosclerotic disease. Of 1421 deaths during the trial, 768 (54%) were due to cardiovascular disease. Sudden death was the most frequent fatal cardiovascular event, accounting for 24.5% of overall mortality. Combining fatal and nonfatal cardiovascular events, randomization to cinacalcet reduced the rates of sudden death and heart failure. Patients randomized to cinacalcet experienced fewer nonatherosclerotic cardiovascular events (adjusted relative hazard 0.84, 95% CI 0.74 to 0.96), while the effect of cinacalcet on atherosclerotic events did not reach statistical significance.Accepting the limitations of post hoc analysis, any benefits of cinacalcet on cardiovascular disease in the context of hemodialysis may result from attenuation of nonatherosclerotic processes.Unique identifier: NCT00345839. URL: ClinicalTrials.gov.

    View details for DOI 10.1161/JAHA.114.001363

    View details for Web of Science ID 000345067600025

  • Reforming Medicare's Dialysis Payment Policies: Implications for Patients with Secondary Hyperparathyroidism HEALTH SERVICES RESEARCH Gupta, C., Chertow, G. M., Linthicum, M. T., Van Nuys, K., Belozeroff, V., Quarles, D., Lakdawalla, D. N. 2014; 49 (6): 1925-1943

    Abstract

    To demonstrate how expanding services covered by a "bundled payment" can also expand variation in the costs of treating patients under the bundle, using the Medicare dialysis program as an example.Observational claims-based study of 197,332 Medicare hemodialysis beneficiaries enrolled for at least one quarter during 2006-2008.We estimated how resource utilization (all health services, dialysis-related services, and medications) changes with intensity of secondary hyperparathyroidism (sHPT) treatment.Using Medicare claims, a patient-quarter level dataset was constructed, including a measure of sHPT treatment intensity.Under the existing, narrow dialysis bundle, utilization of covered services is relatively constant across treatment intensity groups; under a broader bundle, it rises more rapidly with treatment intensity.The broader Medicare dialysis bundle reimburses providers uniformly, even though patients treated more intensively for sHPT cost more to treat. Absent any payment adjustments or efforts to ensure quality, this flat payment schedule may encourage providers to avoid high-intensity patients or reduce their treatment intensity. The first incentive harms efficiency. The second may improve or worsen efficiency, depending on whether it reduces appropriate or inappropriate treatment.

    View details for DOI 10.1111/1475-6773.12202

    View details for Web of Science ID 000345346300013

    View details for PubMedID 25040130

    View details for PubMedCentralID PMC4254132

  • Risk Factors for Heart Failure in Patients With Type 2 Diabetes Mellitus and Stage 4 Chronic Kidney Disease Treated With Bardoxolone Methyl JOURNAL OF CARDIAC FAILURE Chin, M. P., Wrolstad, D., Bakris, G. L., Chertow, G. M., de Zeeuw, D., Goldsberry, A., Linde, P. G., McCullough, P. A., McMurray, J. J., Wittes, J., Meyer, C. J. 2014; 20 (12): 953-958

    Abstract

    A phase 3 randomized clinical trial was designed to test whether bardoxolone methyl, a nuclear factor erythroid-2-related factor 2 (Nrf2) activator, slows progression to end-stage renal disease in patients with stage 4 chronic kidney disease and type 2 diabetes mellitus. The trial was terminated because of an increase in heart failure in the bardoxolone methyl group; many of the events were clinically associated with fluid retention.We randomized 2,185 patients with type 2 diabetes mellitus (T2DM) and stage 4 chronic kidney disease (CKD) (estimated glomerular filtration rate 15 to <30 mL min(-1) 1.73 m(-2)) to once-daily bardoxolone methyl (20 mg) or placebo. We used classification and regression tree analysis to identify baseline factors predictive of heart failure or fluid overload events. Elevated baseline B-type natriuretic peptide and previous hospitalization for heart failure were identified as predictors of heart failure events; bardoxolone methyl increased the risk of heart failure by 60% in patients with these risk factors. For patients without these baseline characteristics, the risk for heart failure events among bardoxolone methyl- and placebo-treated patients was similar (2%). The same risk factors were also identified as predictors of fluid overload and appeared to be related to other serious adverse events.Bardoxolone methyl contributed to events related to heart failure and/or fluid overload in a subpopulation of susceptible patients with an increased risk for heart failure at baseline. Careful selection of participants and vigilant monitoring of the study drug will be required in any future trials of bardoxolone methyl to mitigate the risk of heart failure and other serious adverse events.

    View details for DOI 10.1016/j.cardfail.2014.10.001

    View details for PubMedID 25307295

  • Effects of cinacalcet on atherosclerotic and nonatherosclerotic cardiovascular events in patients receiving hemodialysis: the EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) trial. Journal of the American Heart Association Wheeler, D. C., London, G. M., Parfrey, P. S., Block, G. A., Correa-Rotter, R., Dehmel, B., Drüeke, T. B., Floege, J., Kubo, Y., Mahaffey, K. W., Goodman, W. G., Moe, S. M., Trotman, M., Abdalla, S., Chertow, G. M., Herzog, C. A. 2014; 3 (6)

    Abstract

    Premature cardiovascular disease limits the duration and quality of life on long-term hemodialysis. The objective of this study was to define the frequency of fatal and nonfatal cardiovascular events attributable to atherosclerotic and nonatherosclerotic mechanisms, risk factors for these events, and the effects of cinacalcet, using adjudicated data collected during the EValuation of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) Trial.EVOLVE was a randomized, double-blind, placebo-controlled clinical trial that randomized 3883 hemodialysis patients with moderate to severe secondary hyperparathyroidism to cinacalcet or matched placebo for up to 64 months. For this post hoc analysis, the outcome measure was fatal and nonfatal cardiovascular events reflecting atherosclerotic and nonatherosclerotic cardiovascular diseases. During the trial, 1518 patients experienced an adjudicated cardiovascular event, including 958 attributable to nonatherosclerotic disease. Of 1421 deaths during the trial, 768 (54%) were due to cardiovascular disease. Sudden death was the most frequent fatal cardiovascular event, accounting for 24.5% of overall mortality. Combining fatal and nonfatal cardiovascular events, randomization to cinacalcet reduced the rates of sudden death and heart failure. Patients randomized to cinacalcet experienced fewer nonatherosclerotic cardiovascular events (adjusted relative hazard 0.84, 95% CI 0.74 to 0.96), while the effect of cinacalcet on atherosclerotic events did not reach statistical significance.Accepting the limitations of post hoc analysis, any benefits of cinacalcet on cardiovascular disease in the context of hemodialysis may result from attenuation of nonatherosclerotic processes.Unique identifier: NCT00345839. URL: ClinicalTrials.gov.

    View details for DOI 10.1161/JAHA.114.001363

    View details for PubMedID 25404192

  • Comparison of Self-report-Based and Physical Performance-Based Frailty Definitions Among Patients Receiving Maintenance Hemodialysis AMERICAN JOURNAL OF KIDNEY DISEASES Johansen, K. L., Dalrymple, L. S., Delgado, C., Kaysen, G. A., Kornak, J., Grimes, B., Chertow, G. M. 2014; 64 (4): 600-607

    Abstract

    A well-accepted definition of frailty includes measurements of physical performance, which may limit its clinical utility.In a cross-sectional study, we compared prevalence and patient characteristics based on a frailty definition that uses self-reported function to the classic performance-based definition and developed a modified self-report-based definition.Prevalent adult patients receiving hemodialysis in 14 centers around San Francisco and Atlanta in 2009-2011.Self-report-based frailty definition in which a score lower than 75 on the Physical Function scale of the 36-Item Short Form Health Survey (SF-36) was substituted for gait speed and grip strength in the classic definition; modified self-report definition with optimized Physical Function score cutoff points derived in a development (one-half) cohort and validated in the other half.Performance-based frailty defined as 3 of the following: weight loss, weakness, exhaustion, low physical activity, and slow gait speed.387 (53%) patients were frail based on self-reported function, of whom 209 (29% of the cohort) met the performance-based definition. Only 23 (3%) met the performance-based definition of frailty only. The self-report definition had 90% sensitivity, 64% specificity, 54% positive predictive value, 93% negative predictive value, and 72.5% overall accuracy. Intracellular water per kilogram of body weight and serum albumin, prealbumin, and creatinine levels were highest among nonfrail individuals, intermediate among those who were frail by self-report, and lowest among those who also were frail by performance. Age, percentage of body fat, and C-reactive protein level followed an opposite pattern. The modified self-report definition had better accuracy (84%; 95% CI, 79%-89%) and superior specificity (88%) and positive predictive value (67%).Our study did not address prediction of outcomes.Patients who meet the self-report-based but not the performance-based definition of frailty may represent an intermediate phenotype. A modified self-report definition can improve the accuracy of a questionnaire-based method of defining frailty.

    View details for DOI 10.1053/j.ajkd.2014.03.016

    View details for Web of Science ID 000342739900020

    View details for PubMedCentralID PMC4177262

  • Thienopyridine use after coronary stenting in low income patients enrolled in medicare part D receiving maintenance dialysis. Journal of the American Heart Association Chang, T. I., Montez-Rath, M. E., Shen, J. I., Solomon, M. D., Chertow, G. M., Winkelmayer, W. C. 2014; 3 (5)

    View details for DOI 10.1161/JAHA.114.001356

    View details for PubMedID 25336465

  • Comparison of self-report-based and physical performance-based frailty definitions among patients receiving maintenance hemodialysis. American journal of kidney diseases Johansen, K. L., Dalrymple, L. S., Delgado, C., Kaysen, G. A., Kornak, J., Grimes, B., Chertow, G. M. 2014; 64 (4): 600-607

    Abstract

    A well-accepted definition of frailty includes measurements of physical performance, which may limit its clinical utility.In a cross-sectional study, we compared prevalence and patient characteristics based on a frailty definition that uses self-reported function to the classic performance-based definition and developed a modified self-report-based definition.Prevalent adult patients receiving hemodialysis in 14 centers around San Francisco and Atlanta in 2009-2011.Self-report-based frailty definition in which a score lower than 75 on the Physical Function scale of the 36-Item Short Form Health Survey (SF-36) was substituted for gait speed and grip strength in the classic definition; modified self-report definition with optimized Physical Function score cutoff points derived in a development (one-half) cohort and validated in the other half.Performance-based frailty defined as 3 of the following: weight loss, weakness, exhaustion, low physical activity, and slow gait speed.387 (53%) patients were frail based on self-reported function, of whom 209 (29% of the cohort) met the performance-based definition. Only 23 (3%) met the performance-based definition of frailty only. The self-report definition had 90% sensitivity, 64% specificity, 54% positive predictive value, 93% negative predictive value, and 72.5% overall accuracy. Intracellular water per kilogram of body weight and serum albumin, prealbumin, and creatinine levels were highest among nonfrail individuals, intermediate among those who were frail by self-report, and lowest among those who also were frail by performance. Age, percentage of body fat, and C-reactive protein level followed an opposite pattern. The modified self-report definition had better accuracy (84%; 95% CI, 79%-89%) and superior specificity (88%) and positive predictive value (67%).Our study did not address prediction of outcomes.Patients who meet the self-report-based but not the performance-based definition of frailty may represent an intermediate phenotype. A modified self-report definition can improve the accuracy of a questionnaire-based method of defining frailty.

    View details for DOI 10.1053/j.ajkd.2014.03.016

    View details for PubMedID 24793033

  • Thienopyridine use after coronary stenting in low income patients enrolled in medicare part D receiving maintenance dialysis. Journal of the American Heart Association Chang, T. I., Montez-Rath, M. E., Shen, J. I., Solomon, M. D., Chertow, G. M., Winkelmayer, W. C. 2014; 3 (5)

    Abstract

    Coronary stenting in patients on dialysis has increased by nearly 50% over the past decade, despite heightened risks of associated stent thrombosis and bleeding relative to the general population. We examined clopidogrel, prasugrel or ticlopidine use after percutaneous coronary intervention (PCI) with stenting in patients on dialysis. We conducted 3-, 6-, and 12-month landmark analyses to test the hypothesis that thienopyridine discontinuation prior to those time points would be associated with higher risks of death, myocardial infarction, or repeat revascularization, and a lower risk of major bleeding episodes compared with continued thienopyridine use.Using the US Renal Data System, we identified 8458 patients on dialysis with Medicare Parts A+B+D undergoing PCI with stenting between July 2007 and December 2010. Ninety-nine percent of all thienopyridine prescriptions were for clopidogrel. At 3 months, 82% of patients who received drug-eluting stents (DES) had evidence of thienopyridine use. These proportions fell to 62% and 40% at 6 and 12 months, respectively. In patients who received a bare-metal stent (BMS), 70%, 34%, and 26% of patients had evidence of thienopyridine use at 3, 6, and 12 months, respectively. In patients who received a DES, there was a suggestion of higher risks of death or myocardial infarction associated with thienopyridine discontinuation in the 3-, 6-, and 12-months landmark analyses, but no higher risk of major bleeding episodes. In patients who received a BMS, there were no differences in death or cardiovascular events, and possibly lower risk of major bleeding with thienopyridine discontinuation in the 3- and 6-month landmark analyses.The majority of patients on dialysis who undergo PCI discontinue thienopyridines before 1 year regardless of stent type. While not definitive, these data suggest that longer-term thienopyridine use may be of benefit to patients on dialysis who undergo PCI with DES.

    View details for DOI 10.1161/JAHA.114.001356

    View details for PubMedID 25336465

  • Physician visits and 30-day hospital readmissions in patients receiving hemodialysis. Journal of the American Society of Nephrology Erickson, K. F., Winkelmayer, W. C., Chertow, G. M., Bhattacharya, J. 2014; 25 (9): 2079-2087

    Abstract

    A focus of health care reform has been on reducing 30-day hospital readmissions. Patients with ESRD are at high risk for hospital readmission. It is unknown whether more monitoring by outpatient providers can reduce hospital readmissions in patients receiving hemodialysis. In nationally representative cohorts of patients in the United States receiving in-center hemodialysis between 2004 and 2009, we used a quasi-experimental (instrumental variable) approach to assess the relationship between frequency of visits to patients receiving hemodialysis following hospital discharge and the probability of rehospitalization. We then used a multivariable regression model and published hospitalization data to estimate the cost savings and number of hospitalizations that could be prevented annually with additional provider visits to patients in the month following hospitalization. In the main cohort (n=26,613), one additional provider visit in the month following hospital discharge was estimated to reduce the absolute probability of 30-day hospital readmission by 3.5% (95% confidence interval, 1.6% to 5.3%). The reduction in 30-day hospital readmission ranged from 0.5% to 4.9% in an additional four cohorts tested, depending on population density around facilities, facility profit status, and patient Medicaid eligibility. At current Medicare reimbursement rates, the effort to visit patients one additional time in the month following hospital discharge could lead to 31,370 fewer hospitalizations per year, and $240 million per year saved. In conclusion, more frequent physician visits following hospital discharge are estimated to reduce rehospitalizations in patients undergoing hemodialysis. Incentives for closer outpatient monitoring following hospital discharge could lead to substantial cost savings.

    View details for DOI 10.1681/ASN.2013080879

    View details for PubMedID 24812168

  • Urine electrolyte composition and diuretic therapy in heart failure: back to the future? Circulation. Heart failure Pao, A. C., Chertow, G. M. 2014; 7 (5): 697-698
  • Prognostic stratification in older adults commencing dialysis. journals of gerontology. Series A, Biological sciences and medical sciences Cheung, K. L., Montez-Rath, M. E., Chertow, G. M., Winkelmayer, W. C., Periyakoil, V. S., Kurella Tamura, M. 2014; 69 (8): 1033-1039

    Abstract

    Accurate prognostic models could inform treatment decisions for older adults with end-stage renal disease who are considering dialysis and might identify patients more appropriate for conservative care or hospice.In a cohort of patients aged ≥67 years commencing dialysis in the United States between January 1, 2008 and June 30, 2009, we compared the discrimination of three existing instruments (the Liu index; the French Renal Epidemiology and Information Network score; and hospice eligibility criteria) for the prediction of 6-month mortality. We estimated the odds of death associated with each prognostic index using logistic regression with and without adjustment for age. Predictive indices were compared using the concordance ("c")-statistic.Of 44,109 eligible patients, 10,289 (23.3%) died within 6 months of dialysis initiation. The c-statistic for the Liu, Renal Epidemiology and Information Network, hospice eligibility criteria, and combined Liu/hospice eligibility criteria scores without and with age were 0.62/0.65, 0.63/0.66, 0.65/0.68, and 0.68/0.70, respectively. Discrimination was poorer at older ages, especially for the Liu and Renal Epidemiology and Information Network scores. Although sensitivity was poor, a Renal Epidemiology and Information Network score ≥9 or an hospice eligibility criteria ≥3 had relatively high specificity.Existing prognostic indices based on administrative data perform poorly with respect to prediction of 6-month mortality in older patients with end-stage renal disease commencing dialysis.

    View details for DOI 10.1093/gerona/glt289

    View details for PubMedID 24482541

  • Homelessness and Risk of End-stage Renal Disease JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED Maziarz, M., Chertow, G. M., Himmeffarb, J., Hall, Y. N. 2014; 25 (3): 1231-1244

    Abstract

    To identify homeless people with chronic kidney disease (CKD) who were at highest risk for end-stage renal disease (ESRD), we studied 982 homeless and 15,674 domiciled people with CKD receiving public health care. We developed four risk prediction models for the primary outcome of ESRD. Overall, 71 homeless and 888 domiciled people progressed to ESRD during follow-up (median: 6.6 years). Homeless people with CKD experienced significantly higher incidence rates of ESRD than poor but domiciled peers. Most homeless people who developed progressive CKD were readily identifiable well before ESRD using a prediction model with five common variables. We estimated that program following homeless people in the highest decile of ESRD risk would have captured 64-85% of those who eventually progressed to ESRD within five years. Thus, an approach targeting homeless people at high risk for ESRD appears feasible and could reduce substantial morbidity and costs incurred by this highly vulnerable group.

    View details for Web of Science ID 000340306300021

    View details for PubMedID 25130236

    View details for PubMedCentralID PMC4285149

  • Anticoagulation, delivered dose and outcomes in CRRT: The program to improve care in acute renal disease (PICARD). Hemodialysis international. International Symposium on Home Hemodialysis Claure-Del Granado, R., Macedo, E., Soroko, S., Kim, Y., Chertow, G. M., Himmelfarb, J., Ikizler, T. A., Paganini, E. P., Mehta, R. L. 2014; 18 (3): 641-649

    Abstract

    Delivered dialysis dose by continuous renal replacement therapies (CRRT) depends on circuit efficacy, which is influenced in part by the anticoagulation strategy. We evaluated the association of anticoagulation strategy used on solute clearance efficacy, circuit longevity, bleeding complications, and mortality. We analyzed data from 1740 sessions 24 h in length among 244 critically ill patients, with at least 48 h on CRRT. Regional citrate, heparin, or saline flushes was variably used to prevent or attenuate filter clotting. We calculated delivered dose using the standardized Kt/Vurea . We monitored filter efficacy by calculating effluent urea nitrogen/blood urea nitrogen ratios. Filter longevity was significantly higher with citrate (median 48, interquartile range [IQR] 20.3-75.0 hours) than with heparin (5.9, IQR 8.5-27.0 hours) or no anticoagulation (17.5, IQR 9.5-32 hours, P < 0.0001). Delivered dose was highest in treatments where citrate was employed. Bleeding complications were similar across the three groups (P = 0.25). Compared with no anticoagulation, odds of death was higher with the heparin use (odds ratio [OR] 1.82, 95% confidence interval [CI] 1.02-3.32; P = 0.033), but not with citrate (OR 1.02 95% CI 0.54-1.96; P = 0.53). Relative to heparin or no anticoagulation, the use of regional citrate for anticoagulation in CRRT was associated with significantly prolonged filter life and increased filter efficacy with respect to delivered dialysis dose. Rates of bleeding complications, transfusions, and mortality were similar across the three groups. While these and other data suggest that citrate anticoagulation may offer superior technical performance than heparin or no anticoagulation, adequately powered clinical trials comparing alternative anticoagulation strategies should be performed to evaluate overall safety and efficacy.

    View details for DOI 10.1111/hdi.12157

    View details for PubMedID 24620987

  • Long-Term Safety and Efficacy of a Novel Iron-Containing Phosphate Binder, JTT-751, in Patients Receiving Hemodialysis JOURNAL OF RENAL NUTRITION Yokoyama, K., Akiba, T., Fukagawa, M., Nakayama, M., Sawada, K., Kumagai, Y., Chertow, G. M., Hirakata, H. 2014; 24 (4): 261–67

    Abstract

    JTT-751 is a novel phosphate binder containing ferric citrate as the active ingredient. This study investigated long-term safety and efficacy of JTT-751 for hyperphosphatemia in patients receiving hemodialysis.This was 52-week, phase 3, multicenter, open-label, dose titration, long-term study. All patients were receiving thrice-weekly hemodialysis for ≥3 months before the initiation of the study. JTT-751 was given at titrated doses between 1.5 and 6.0 g/day.Safety endpoints were adverse events and adverse drug reactions. Efficacy outcomes were the change in serum phosphate, corrected serum calcium, and intact parathyroid hormone. Changes in ferritin, transferrin saturation, and doses of erythropoiesis-stimulating agents (ESAs) and intravenous iron formulations were additional outcomes.One hundred and eighty patients were included in the trial. Dose-titrated JTT-751 decreased mean serum phosphate after administration and satisfactorily maintained serum phosphate concentrations throughout the entire duration of the 52-week trial. Mean serum phosphate concentrations were kept lower than 5.5 mg/dL from weeks 5 to 52. The most common adverse events were gastrointestinal disorders, which were mild to moderate in intensity. Serum ferritin concentrations rose to a peak around week 28 and stabilized thereafter. The mean intravenous iron dose decreased from 57.3 mg/4 weeks (weeks 0-12) to 3.6 mg/4 weeks (weeks 28-52); weekly ESA dose declined by 25% over the same time frame, while mean hemoglobin concentrations remained stable.JTT-751 1.5-6.0 g/day controls serum phosphorus concentrations and reduces the need for ESAs and intravenous iron in patients receiving hemodialysis.

    View details for PubMedID 24836401

  • Characteristics and performance of minority-serving dialysis facilities. Health services research Hall, Y. N., Xu, P., Chertow, G. M., Himmelfarb, J. 2014; 49 (3): 971-991

    Abstract

    To examine the structure, processes, and outcomes of American dialysis facilities that predominantly treat racial-ethnic minority patients.Secondary analysis of data from all patients who initiated dialysis during 2005-2008 in the United States.In this retrospective cohort study, we examined the associations of the racial-ethnic composition of the dialysis facility with facility-level survival and achievement of performance targets for anemia and dialysis adequacy.We obtained dialysis facility- and patient-level data from the national data registry of patients with end-stage renal disease. We linked these data with clinical performance measures from the Centers for Medicare and Medicaid Services.Overall, minority-serving facilities were markedly larger, more often community based, and less likely to offer home dialysis than facilities serving predominantly white patients. A significantly higher proportion of minority-serving dialysis facilities exhibited worse than expected survival as compared with facilities serving predominantly white patients (p < .001 for each). However, clinical performance measures for anemia and dialysis adequacy were similar across minority-serving status.While minority-serving facilities generally met dialysis performance targets mandated by Medicare, they exhibited worse than expected patient survival.

    View details for DOI 10.1111/1475-6773.12144

    View details for PubMedID 24354718

  • Lowering Blood Pressure to Lower the Risk of Cardiovascular Events in CKD AMERICAN JOURNAL OF KIDNEY DISEASES Chang, T. I., Owens, D. K., Chertow, G. M. 2014; 63 (6): 900–902

    View details for PubMedID 24685064

  • Characteristics and Performance of Minority-Serving Dialysis Facilities HEALTH SERVICES RESEARCH Hall, Y. N., Xu, P., Chertow, G. M., Himmelfarb, J. 2014; 49 (3): 971-991

    Abstract

    To examine the structure, processes, and outcomes of American dialysis facilities that predominantly treat racial-ethnic minority patients.Secondary analysis of data from all patients who initiated dialysis during 2005-2008 in the United States.In this retrospective cohort study, we examined the associations of the racial-ethnic composition of the dialysis facility with facility-level survival and achievement of performance targets for anemia and dialysis adequacy.We obtained dialysis facility- and patient-level data from the national data registry of patients with end-stage renal disease. We linked these data with clinical performance measures from the Centers for Medicare and Medicaid Services.Overall, minority-serving facilities were markedly larger, more often community based, and less likely to offer home dialysis than facilities serving predominantly white patients. A significantly higher proportion of minority-serving dialysis facilities exhibited worse than expected survival as compared with facilities serving predominantly white patients (p < .001 for each). However, clinical performance measures for anemia and dialysis adequacy were similar across minority-serving status.While minority-serving facilities generally met dialysis performance targets mandated by Medicare, they exhibited worse than expected patient survival.

    View details for DOI 10.1111/1475-6773.12144

    View details for Web of Science ID 000335975000012

    View details for PubMedCentralID PMC4024357

  • Effects of Frequent Hemodialysis on Perceived Caregiver Burden in the Frequent Hemodialysis Network Trials CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Suri, R. S., Larive, B., Hall, Y., Kimmel, P. L., Kliger, A. S., Levin, N., Tamura, M. K., Chertow, G. M. 2014; 9 (5): 936-942

    Abstract

    Patients receiving hemodialysis often perceive their caregivers are overburdened. We hypothesize that increasing hemodialysis frequency would result in higher patient perceptions of burden on their unpaid caregivers.In two separate trials, 245 patients were randomized to receive in-center daily hemodialysis (6 days/week) or conventional hemodialysis (3 days/week) while 87 patients were randomized to receive home nocturnal hemodialysis (6 nights/week) or home conventional hemodialysis for 12 months. Changes in overall mean scores over time in the 10-question Cousineau perceived burden scale were compared.In total, 173 of 245 (70%) and 80 of 87 (92%) randomized patients in the Daily and Nocturnal Trials, respectively, reported having an unpaid caregiver at baseline or during follow-up. Relative to in-center conventional dialysis, the 12-month change in mean perceived burden score with in-center daily hemodialysis was -2.1 (95% confidence interval, -9.4 to +5.3; P=0.58). Relative to home conventional dialysis, the 12-month change in mean perceived burden score with home nocturnal dialysis was +6.1 (95% confidence interval, -0.8 to +13.1; P=0.08). After multiple imputation for missing data in the Nocturnal Trial, the relative difference between home nocturnal and home conventional hemodialysis was +9.4 (95% confidence interval, +0.55 to +18.3; P=0.04). In the Nocturnal Trial, changes in perceived burden were inversely correlated with adherence to dialysis treatments (Pearson r=-0.35; P=0.02).Relative to conventional hemodialysis, in-center daily hemodialysis did not result in higher perceptions of caregiver burden. There was a trend to higher perceived caregiver burden among patients randomized to home nocturnal hemodialysis. These findings may have implications for the adoption of and adherence to frequent nocturnal hemodialysis.

    View details for DOI 10.2215/CJN.07170713

    View details for Web of Science ID 000335519300017

    View details for PubMedID 24721892

  • Utilization of cytoreductive nephrectomy and patient survival in the targeted therapy era. International journal of cancer. Journal international du cancer Conti, S. L., Thomas, I., Hagedorn, J. C., Chung, B. I., Chertow, G. M., Wagner, T. H., Brooks, J. D., Srinivas, S., Leppert, J. T. 2014; 134 (9): 2245-2252

    Abstract

    We sought to analyze utilization and survival outcomes of cytoreductive nephrectomy in patients with metastatic renal cell carcinoma (RCC) before and after introduction of targeted therapy. We identified patients with metastatic RCC between 1993 and 2010 in the SEER registry and examined temporal trends in utilization. We performed a joinpoint regression to determine when changes in utilization of cytoreductive nephrectomy occurred. We fitted multivariable proportional hazard models in full and propensity score-matched cohorts. We performed a difference-in-difference analysis to compare survival outcomes before and after introduction of targeted therapy. The proportion of patients undergoing cytoreductive nephrectomy increased from 1993 to 2004, from 29% to 39%. We identified a primary joinpoint of 2004, just prior to the introduction of targeted therapy. Beginning in 2005, there was a modest decrease in utilization of cytoreductive nephrectomy. Cytoreductive nephrectomy was associated with a lower adjusted relative hazard (0.41, 95% confidence interval 0.34 to 0.43). Median survival among patients receiving cytoreductive nephrectomy increased in the targeted therapy era (19 versus 13 months), while median survival among patients not receiving cytoreductive nephrectomy increased only slightly (4 versus 3 months). Difference-in-difference analysis showed a significant decrease in hazard of death among patients who received cytoreductive nephrectomy in the targeted therapy era. Despite decreased utilization in the targeted therapy era, cytoreductive nephrectomy remains associated with improved survival. Prospective randomized trials are needed to confirm the benefit of cytoreductive nephrectomy among patients with metastatic RCC treated with novel targeted therapies. © 2013 Wiley Periodicals, Inc.

    View details for PubMedID 24135850

  • FERRIC CITRATE REDUCES FIBROBLAST GROWTH FACTOR 23 LEVELS IN PATIENTS WITH MODERATE CHRONIC KIDNEY DISEASE Block, G., Chertow, G., Fishbane, S., Rodriguez, M., Chen, M., Shemesh, S., Sharma, A., Wolf, M. OXFORD UNIV PRESS. 2014: 156
  • Bardoxolone Methyl in Type 2 Diabetes and Advanced Chronic Kidney Disease REPLY NEW ENGLAND JOURNAL OF MEDICINE Chertow, G. M., de Zeeuw, D., BEACON Steering Comm 2014; 370 (18): 1768

    View details for Web of Science ID 000335405200030

    View details for PubMedID 24785223

  • A randomized trial of JTT-751 versus sevelamer hydrochloride in patients on hemodialysis NEPHROLOGY DIALYSIS TRANSPLANTATION Yokoyama, K., Akiba, T., Fukagawa, M., Nakayama, M., Sawada, K., Kumagai, Y., Chertow, G. M., Hirakata, H. 2014; 29 (5): 1053–60

    Abstract

    JTT-751 is a novel phosphate binder containing ferric citrate as the active ingredient.In this Phase 3, multicenter, randomized, open-label, parallel-group study, we compared the efficacy and safety of JTT-751 and sevelamer hydrochloride in patients undergoing hemodialysis. A total of 230 patients with a serum phosphate ≥1.97 and <3.23 mmol/L were randomized to JTT-751 (dose adjusted between 1.5 and 6.0 g/day) or sevelamer hydrochloride (dose adjusted between 3.0 and 9.0 g/day) for 12 weeks. The primary outcome was change in serum phosphate from baseline to end of treatment. Secondary outcomes included the changes in corrected serum calcium and intact parathyroid hormone (PTH). The changes in ferritin, transferrin saturation and erythropoiesis-stimulating agent dose were additional outcomes.Changes in serum phosphate at the end of treatment were -0.82 mmol/L in the JTT-751 group and -0.78 mmol/L in the sevelamer group, establishing non-inferiority of JTT-751 compared with sevelamer (least squares mean, -0.03 mmol/L; 95% confidence interval, -0.13 to 0.07 mmol/L). Corrected serum calcium increased and PTH decreased from baseline within both groups; changes between groups were similar. Gastrointestinal disorders were the most common adverse events in both groups; the incidence of diarrhea was higher in the JTT-751 group, while constipation occurred frequently in the sevelamer group. Treatment with JTT-751 resulted in significant relative increases in serum ferritin and transferrin saturation.Efficacy and safety of JTT-751 was comparable to sevelamer in patients on hemodialysis with hyperphosphatemia. Differential adverse effects were observed; biochemical markers of iron status increased in patients treated with JTT-751.CTI-111433 (The Japan Pharmaceutical Information Center at: http//www.clinicaltrials.jp). Date of registration: 7 March 2011.

    View details for DOI 10.1093/ndt/gft483

    View details for Web of Science ID 000336093900019

    View details for PubMedID 24376274

  • ZERENEX (TM) (FERRIC CITRATE) FOR THE TREATMENT OF IRON-DEFICIENCY ANEMIA AND REDUCTION OF SERUM PHOSHATE IN NON-DIALYSIS DEPENDENT CKD Block, G. A., Fishbane, S., Shemesh, S., Sharma, A., Chertow, G. M. W B SAUNDERS CO-ELSEVIER INC. 2014: A118
  • MORTALITY DURING EXTENDED FOLLOW-UP IN THE FREQUENT HEMODIALYSIS NETWORK NOCTURNAL TRIAL Rocco, M., Daugirdas, J., Greene, T., Lockridge, R., Chan, C., Pierratos, A., Lindsay, R., Larive, B., Chertow, G., Beck, G., Eggers, P., Kliger, A., Grp, F. OXFORD UNIV PRESS. 2014: 37
  • LONG-TERM EFFECTS OF FREQUENT IN-CENTER HEMODIALYSIS: FHN DAILY TRIAL Kliger, A. S., Chertow, G. M., Levin, N. W., Beck, G. J., Daugirdas, J. T., Eggers, P. W., Larive, B., Rocco, M. V., Greene, T. OXFORD UNIV PRESS. 2014: 37–38
  • EFFECTS OF CINACALCET ON FRACTURE EVENTS IN PATIENTS RECEIVING HEMODIALYSIS: THE EVOLVE TRIAL Drueke, T. B., Moe, S. M., Abdalla, S., Parfrey, P. S., Chertow, G. M. OXFORD UNIV PRESS. 2014: 41
  • THE EFFECTS OF CINACALCET IN OLDER AND YOUNGER PATIENTS ON HEMODIALYSIS: THE EVOLVE TRIAL Parfrey, P. S., Drueke, T., Block, G. A., Kubo, Y., Chertow, G. M. OXFORD UNIV PRESS. 2014: 47
  • A DOUBLE-BLIND PLACEBO CONTROLLED RANDOMIZED TRIAL OF FERRIC CITRATE COORDINATION COMPLEX FOR THE TREATMENT OF IRON-DEFICIENCY ANEMIA AND REDUCTION OF SERUM PHOSPHATE IN PATIENTS WITH NON-DIALYSIS DEPENDENT CHRONIC KIDNEY DISEASE Block, G., Fishbane, S., Shemesh, S., Sharma, A., Wolf, M., Chertow, G. OXFORD UNIV PRESS. 2014: 151
  • THE EFFECT OF CINACALCET ON ATHEROSCLEROTIC AND NON-ATHEROSCLEROTIC EVENTS IN HAEMODIALYSIS PATIENTS IN THE EVOLVE CLINICAL TRIAL Wheeler, D. C., Abdalla, S., Chertow, G., Parfrey, P., Herzog, C. OXFORD UNIV PRESS. 2014: 233
  • Bardoxolone Methyl in Type 2 Diabetes and Advanced Chronic Kidney Disease REPLY NEW ENGLAND JOURNAL OF MEDICINE Himmelfarb, J., Tuttle, K. R. 2014; 370 (18): 1768–69

    View details for Web of Science ID 000335405200031

    View details for PubMedID 24785221

  • Bardoxolone Methyl in Type 2 Diabetes and Advanced Chronic Kidney Disease NEW ENGLAND JOURNAL OF MEDICINE Chartoumpekis, D. V., Sykiotis, G. P. 2014; 370 (18): 1767
  • Calibration of the Brief Food Frequency Questionnaire Among Patients on Dialysis JOURNAL OF RENAL NUTRITION Delgado, C., Ward, P., Chertow, G. M., Storer, L., Dalrymple, L., Block, T., Kaysen, G. A., Kornak, J., Grimes, B., Kutner, N. G., Johansen, K. L. 2014; 24 (3): 151-U30

    Abstract

    Estimating dietary intake is challenging in patients with chronic diseases. The aim of this study was to calibrate the Block Brief 2000 food frequency questionnaire (BFFQ) using 3-day food diary records among patients on dialysis.Data from 3-day food diary records from 146 patients new to dialysis were reviewed and entered into National Cancer Institute self-administered 24-hour dietary recall (ASA24), a web-based dietary interview system. The information was then re-entered omitting foods reported in the diaries that were not in the BFFQ to generate a "BFFQ-restricted" set of intakes. We modeled each major dietary component (i.e., energy [total calories], protein, carbohydrate, fat) separately using linear regression. The main independent variables were BFFQ-restricted food diary estimates computed as the average of the 3 days of diaries, restricted to items included in the BFFQ, with the unrestricted 3-day food diary averages as dependent variables.The BFFQ-restricted diary energy estimate of 1,325 ± 545 kcal was 87% of the energy intake in the full food diary (1,510.3 ± 510.4, P < .0001). The BFFQ-restricted diary carbohydrate intake was 83% of the full food diary (156.7 ± 78.7 g vs. 190.4 ± 72.7, P < .0001). The BFFQ-restricted fat intake was 90% of the full-diary-reported fat intake (50.1 ± 24.1 g vs. 56.4 ± 21.6 g, P < .0001). Daily protein intake assessments were not statistically different by BFFQ-restricted diary and full diary assessment (63.1 ± 28.5 vs. 64.1 ± 21.4 g, P = .60). The associations between BFFQ-restricted diary intake and unrestricted intake were linear. Three-day diary-reported intake could be estimated from BFFQ-restricted intake with r2 ranging from 0.36 to 0.56 (P < .0001 for energy [total calories], protein, carbohydrate, and fat). Final equations did not include adjustments for age, sex, or race because the patterns of associations were not significantly different.Energy and macronutrient estimates by BFFQ are lower than estimates from 3-day food diaries, but simple calibration equations can be used to approximate total intake from BFFQ responses.

    View details for DOI 10.1053/j.jrn.2013.12.004

    View details for Web of Science ID 000335313500004

  • Estimation of 24-hour urine phosphate excretion from spot urine collection: development of a predictive equation. Journal of renal nutrition Robinson-Cohen, C., Ix, J. H., Smits, G., Persky, M., Chertow, G. M., Block, G. A., Kestenbaum, B. R. 2014; 24 (3): 194-199

    Abstract

    The management of hyperphosphatemia in patients with moderate to severe chronic kidney disease (CKD) includes dietary phosphate restriction and/or prescription of phosphate binders. Measuring phosphate intake in CKD is important for monitoring dietary adherence and for the effectiveness of therapeutic interventions. The 24-hour urine collection is the gold standard method for determining phosphate intake; however, timed urine collections are cumbersome and prone to error. We investigated the precision and accuracy of spot urine phosphate measurements, compared to 24-hour urine phosphate (24hUrP) collection.We evaluated simultaneous spot and 24hUrP measurements, collected on multiple occasions, from 143 participants in the Phosphate Normalization Trial, a randomized trial of phosphate binders versus placebo among persons with an estimated glomerular filtration rate between 20-45 mL/minute per 1.73 m2. We used residual analyses and graphical methods to model the functional relationship of spot urine phosphate and creatinine measurements with 24hUrP. We used multiple linear regression to test whether additional covariates improved model prediction, including treatment assignment, age, sex, height, weight, urine collection time, and last meal time. We internally validated results using leave-one-out cross-validation, and externally validated in an independent replication cohort.A log-log relation between the spot urine phosphate-to-creatinine ratio and 24hUrP excretion yielded the best model fit. In addition to spot urine phosphate and creatinine concentrations, inclusion of age, sex, and weight significantly improved prediction of 24hUrP. Compared with a spot urine phosphate-to-creatinine ratio alone (r2 = 0.12, P < .001), the new equation more accurately predicted 24hUrP (leave-one-out validation r2 = 0.43, P < .001, independent validation r2 = 0.39, P < .001).We describe a novel equation to predict 24hUrP excretion using spot urine phosphate and creatinine, age, sex, and weight. The equation is more accurate and precise than the urine phosphate-to-creatinine ratio alone, and it provides a simple method for estimating 24hUrP excretion in patients with nondialysis-requiring CKD.

    View details for DOI 10.1053/j.jrn.2014.02.001

    View details for PubMedID 24759300

  • KRAS mutation confers resistance to antibody-dependent cellular cytotoxicity of cetuximab against human colorectal cancer cells INTERNATIONAL JOURNAL OF CANCER Conti, S. L., Thomas, I., Hagedorn, J. C., Chung, B. I., Chertow, G. M., Wagner, T. H., Brooks, J. D., Srinivas, S., Leppert, J. T. 2014; 134 (9): 2245-2252

    Abstract

    We sought to analyze utilization and survival outcomes of cytoreductive nephrectomy in patients with metastatic renal cell carcinoma (RCC) before and after introduction of targeted therapy. We identified patients with metastatic RCC between 1993 and 2010 in the SEER registry and examined temporal trends in utilization. We performed a joinpoint regression to determine when changes in utilization of cytoreductive nephrectomy occurred. We fitted multivariable proportional hazard models in full and propensity score-matched cohorts. We performed a difference-in-difference analysis to compare survival outcomes before and after introduction of targeted therapy. The proportion of patients undergoing cytoreductive nephrectomy increased from 1993 to 2004, from 29% to 39%. We identified a primary joinpoint of 2004, just prior to the introduction of targeted therapy. Beginning in 2005, there was a modest decrease in utilization of cytoreductive nephrectomy. Cytoreductive nephrectomy was associated with a lower adjusted relative hazard (0.41, 95% confidence interval 0.34 to 0.43). Median survival among patients receiving cytoreductive nephrectomy increased in the targeted therapy era (19 versus 13 months), while median survival among patients not receiving cytoreductive nephrectomy increased only slightly (4 versus 3 months). Difference-in-difference analysis showed a significant decrease in hazard of death among patients who received cytoreductive nephrectomy in the targeted therapy era. Despite decreased utilization in the targeted therapy era, cytoreductive nephrectomy remains associated with improved survival. Prospective randomized trials are needed to confirm the benefit of cytoreductive nephrectomy among patients with metastatic RCC treated with novel targeted therapies. © 2013 Wiley Periodicals, Inc.

    View details for DOI 10.1002/ijc.28550

    View details for Web of Science ID 000331006600013

  • Trends in anemia care in older patients approaching end-stage renal disease in the United States (1995-2010). JAMA internal medicine Winkelmayer, W. C., Mitani, A. A., Goldstein, B. A., Brookhart, M. A., Chertow, G. M. 2014; 174 (5): 699-707

    Abstract

    IMPORTANCE Anemia is common in patients with advanced chronic kidney disease. Whereas the treatment of anemia in patients with end-stage renal disease (ESRD) has attracted considerable attention, relatively little is known about patterns and trends in the anemia care received by patients before they start maintenance dialysis or undergo preemptive kidney transplantation. OBJECTIVE To determine the trends in anemia treatment received by Medicare beneficiaries approaching ESRD. DESIGN, SETTING, AND PARTICIPANTS Closed cohort study in the United States using national ESRD registry data (US Renal Data System) of patients 67 years or older who initiated maintenance dialysis or underwent preemptive kidney transplantation between 1995 and 2010. All eligible patients had uninterrupted Medicare (A+B) coverage for at least 2 years before ESRD. EXPOSURE Time, defined as calendar year of incident ESRD. MAIN OUTCOMES AND MEASURES Use of erythropoiesis-stimulating agents (ESA), intravenous iron supplements, and blood transfusions in the 2 years prior to ESRD; hemoglobin concentration at the time of ESRD. We used multivariable modified Poisson regression to estimate utilization prevalence ratios (PRs). RESULTS Records of 466 803 patients were analyzed. The proportion of patients with incident ESRD receiving any ESA in the 2 years before increased from 3.2% in 1995 to a peak of 40.8% in 2007; thereafter, ESA use decreased modestly to 35.0% in 2010 (compared with 1995; PR, 9.85 [95% CI, 9.04-10.74]). Among patients who received an ESA, median time from first recorded ESA use to ESRD increased from 120 days in 1995 to 337 days in 2010. Intravenous iron administration increased from 1.2% (1995) to 12.3% (2010; PR, 9.20 [95% CI, 7.97-10.61]). The proportion of patients receiving any blood transfusions increased monotonically from 20.6% (1995) to 40.3% (2010; PR, 1.88 [95% CI, 1.82-1.95]). Mean hemoglobin concentrations were 9.5 g/dL in 1995, increased to a peak of 10.3 g/dL in 2006, and then decreased moderately to 9.9 g/dL in 2010. CONCLUSIONS AND RELEVANCE Between 1995 and 2010, older adults approaching ESRD were increasingly more likely to be treated with ESAs and to receive intravenous iron supplementation, but also more likely to receive blood transfusions.

    View details for PubMedID 24589911

  • Bardoxolone methyl in type 2 diabetes and advanced chronic kidney disease. New England journal of medicine Chertow, G. M., de Zeeuw, D. 2014; 370 (18): 1768-?

    View details for DOI 10.1056/NEJMc1400872

    View details for PubMedID 24785220

  • Calibration of the brief food frequency questionnaire among patients on dialysis. Journal of renal nutrition Delgado, C., Ward, P., Chertow, G. M., Storer, L., Dalrymple, L., Block, T., Kaysen, G. A., Kornak, J., Grimes, B., Kutner, N. G., Johansen, K. L. 2014; 24 (3): 151-156 e1

    Abstract

    Estimating dietary intake is challenging in patients with chronic diseases. The aim of this study was to calibrate the Block Brief 2000 food frequency questionnaire (BFFQ) using 3-day food diary records among patients on dialysis.Data from 3-day food diary records from 146 patients new to dialysis were reviewed and entered into National Cancer Institute self-administered 24-hour dietary recall (ASA24), a web-based dietary interview system. The information was then re-entered omitting foods reported in the diaries that were not in the BFFQ to generate a "BFFQ-restricted" set of intakes. We modeled each major dietary component (i.e., energy [total calories], protein, carbohydrate, fat) separately using linear regression. The main independent variables were BFFQ-restricted food diary estimates computed as the average of the 3 days of diaries, restricted to items included in the BFFQ, with the unrestricted 3-day food diary averages as dependent variables.The BFFQ-restricted diary energy estimate of 1,325 ± 545 kcal was 87% of the energy intake in the full food diary (1,510.3 ± 510.4, P < .0001). The BFFQ-restricted diary carbohydrate intake was 83% of the full food diary (156.7 ± 78.7 g vs. 190.4 ± 72.7, P < .0001). The BFFQ-restricted fat intake was 90% of the full-diary-reported fat intake (50.1 ± 24.1 g vs. 56.4 ± 21.6 g, P < .0001). Daily protein intake assessments were not statistically different by BFFQ-restricted diary and full diary assessment (63.1 ± 28.5 vs. 64.1 ± 21.4 g, P = .60). The associations between BFFQ-restricted diary intake and unrestricted intake were linear. Three-day diary-reported intake could be estimated from BFFQ-restricted intake with r2 ranging from 0.36 to 0.56 (P < .0001 for energy [total calories], protein, carbohydrate, and fat). Final equations did not include adjustments for age, sex, or race because the patterns of associations were not significantly different.Energy and macronutrient estimates by BFFQ are lower than estimates from 3-day food diaries, but simple calibration equations can be used to approximate total intake from BFFQ responses.

    View details for DOI 10.1053/j.jrn.2013.12.004

    View details for PubMedID 24613023

  • Estimation of 24-Hour Urine Phosphate Excretion From Spot Urine Collection: Development of a Predictive Equation JOURNAL OF RENAL NUTRITION Robinson-Cohen, C., Ix, J. H., Smits, G., Persky, M., Chertow, G. M., Block, G. A., Kestenbaum, B. R. 2014; 24 (3): 194-199

    Abstract

    The management of hyperphosphatemia in patients with moderate to severe chronic kidney disease (CKD) includes dietary phosphate restriction and/or prescription of phosphate binders. Measuring phosphate intake in CKD is important for monitoring dietary adherence and for the effectiveness of therapeutic interventions. The 24-hour urine collection is the gold standard method for determining phosphate intake; however, timed urine collections are cumbersome and prone to error. We investigated the precision and accuracy of spot urine phosphate measurements, compared to 24-hour urine phosphate (24hUrP) collection.We evaluated simultaneous spot and 24hUrP measurements, collected on multiple occasions, from 143 participants in the Phosphate Normalization Trial, a randomized trial of phosphate binders versus placebo among persons with an estimated glomerular filtration rate between 20-45 mL/minute per 1.73 m2. We used residual analyses and graphical methods to model the functional relationship of spot urine phosphate and creatinine measurements with 24hUrP. We used multiple linear regression to test whether additional covariates improved model prediction, including treatment assignment, age, sex, height, weight, urine collection time, and last meal time. We internally validated results using leave-one-out cross-validation, and externally validated in an independent replication cohort.A log-log relation between the spot urine phosphate-to-creatinine ratio and 24hUrP excretion yielded the best model fit. In addition to spot urine phosphate and creatinine concentrations, inclusion of age, sex, and weight significantly improved prediction of 24hUrP. Compared with a spot urine phosphate-to-creatinine ratio alone (r2 = 0.12, P < .001), the new equation more accurately predicted 24hUrP (leave-one-out validation r2 = 0.43, P < .001, independent validation r2 = 0.39, P < .001).We describe a novel equation to predict 24hUrP excretion using spot urine phosphate and creatinine, age, sex, and weight. The equation is more accurate and precise than the urine phosphate-to-creatinine ratio alone, and it provides a simple method for estimating 24hUrP excretion in patients with nondialysis-requiring CKD.

    View details for DOI 10.1053/j.jrn.2014.02.001

    View details for Web of Science ID 000335313500010

  • Temporal trends in the incidence, treatment and outcomes of hip fracture after first kidney transplantation in the United States. American journal of transplantation Sukumaran Nair, S., Lenihan, C. R., Montez-Rath, M. E., Lowenberg, D. W., Chertow, G. M., Winkelmayer, W. C. 2014; 14 (4): 943-951

    Abstract

    It is currently unknown whether any secular trends exist in the incidence and outcomes of hip fracture in kidney transplant recipients (KTR). We identified first-time KTR (1997-2010) who had >1 year of Medicare coverage and no recorded history of hip fracture. New hip fractures were identified from corresponding diagnosis and surgical procedure codes. Outcomes studied included time to hip fracture, type of surgery received and 30-day mortality. Of 69 740 KTR transplanted in 1997-2010, 597 experienced a hip fracture event during 155 341 person-years of follow-up for an incidence rate of 3.8 per 1000 person-years. While unadjusted hip fracture incidence did not change, strong confounding by case mix was present. Using year of transplantation as a continuous variable, the hazard ratio (HR) for hip fracture in 2010 compared with 1997, adjusted for demographic, dialysis, comorbid and most transplant-related factors, was 0.56 (95% confidence interval [CI]: 0.41-0.77). Adjusting for baseline immunosuppression modestly attenuated the HR (0.68; 95% CI: 0.47-0.99). The 30-day mortality was 2.2 (95% CI: 1.3-3.7) per 100 events. In summary, hip fractures remain an important complication after kidney transplantation. Since 1997, case-mix adjusted posttransplant hip fracture rates have declined substantially. Changes in immunosuppressive therapy appear to be partly responsible for these favorable findings.

    View details for DOI 10.1111/ajt.12652

    View details for PubMedID 24712332

  • THE RELATION BETWEEN ANTIHYPERTENSIVE MEDICATION AND SEXUAL FUNCTION IN WOMEN: BASELINE DATA FROM THE SPRINT STUDY Thomas, H. N., Evans, G. W., Berlowitz, D., Bonds, D. E., Chertow, G. M., Conroy, M. B., Foy, C., Glasser, S., Lewis, C. E., Riley, W. T., Russell, L., Williams, O., Hess, R. SPRINGER. 2014: S231
  • Utilization of Renal Mass Biopsy in Patients With Renal Cell Carcinoma Reply UROLOGY Leppert, J. T., Hanley, J., Wagner, T. H., Chung, B. I., Brooks, J. D., Srinivas, S., Chertow, G. M., Saigal, C. S. 2014; 83 (4): 779-780
  • Utilization of renal mass biopsy in patients with renal cell carcinoma. Urology Leppert, J. T., Hanley, J., Wagner, T. H., Chung, B. I., Srinivas, S., Chertow, G. M., Brooks, J. D., Saigal, C. S. 2014; 83 (4): 774-780

    Abstract

    To examine the patient, tumor, and temporal factors associated with receipt of renal mass biopsy (RMB) in a contemporary nationally representative sample.We queried the Surveillance, Epidemiology, and End Results-Medicare data set for incident cases of renal cell carcinoma diagnosed between 1992 and 2007. We tested for associations among receipt of RMB and patient and tumor characteristics, type of therapy, and procedure type. Temporal trends in receipt of RMB were characterized over the study period.Approximately 1 in 5 (20.7%) patients diagnosed with renal cell carcinoma (n = 24,702) underwent RMB before instituting therapy. There was a steady and modest increase in RMB utilization, with the highest utilization (30%) occurring in the final study year. Of patients who underwent radical (n = 15,666) or partial (n = 2211) nephrectomy, 17% and 20%, respectively, underwent RMB in advance of surgery. Sixty-five percent of patients who underwent ablation (n = 314) underwent RMB before or in conjunction with the procedure. Roughly half of patients (50.4%) treated with systemic therapy alone underwent RMB. Factors independently associated with use of RMB included younger age, black race, Hispanic ethnicity, tumor size <7 cm, and metastatic disease at presentation.At present, most patients who eventually undergo radical or partial nephrectomy do not undergo RMB, whereas most patients who eventually undergo ablation or systemic therapy do. The optimal use of RMB in the evaluation of kidney tumors has yet to be determined.

    View details for DOI 10.1016/j.urology.2013.10.073

    View details for PubMedID 24529579

  • Reply. Urology Leppert, J. T., Hanley, J., Wagner, T. H., Chung, B. I., Brooks, J. D., Srinivas, S., Chertow, G. M., Saigal, C. S. 2014; 83 (4): 779-780

    View details for DOI 10.1016/j.urology.2013.10.077

    View details for PubMedID 24529590

  • A Pint of Sweat Will Save a Gallon of Blood A Call for Randomized Trials of Anticoagulation in End- Stage Renal Disease CIRCULATION Granger, C. B., Chertow, G. M. 2014; 129 (11): 1190–92

    View details for PubMedID 24452751

  • Association between body composition and frailty among prevalent hemodialysis patients: a US Renal Data System special study. Journal of the American Society of Nephrology Johansen, K. L., Dalrymple, L. S., Delgado, C., Kaysen, G. A., Kornak, J., Grimes, B., Chertow, G. M. 2014; 25 (2): 381-389

    Abstract

    Studies of frailty among patients on hemodialysis have relied on definitions that substitute self-reported functioning for measures of physical performance and omit weight loss or substitute alternate criteria. We examined the association between body composition and a definition of frailty that includes measured physical performance and weight loss in a cross-sectional analysis of 638 adult patients receiving maintenance hemodialysis at 14 centers. Frailty was defined as having three of following characteristics: weight loss, weakness, exhaustion, low physical activity, and slow gait speed. We performed logistic regression with body mass index (BMI) and bioelectrical impedance spectroscopy (BIS)-derived estimates of intracellular water (ICW), fat mass, and extracellular water (ECW) as the main predictors, and age, sex, race, and comorbidity as covariates. Overall, 30% of participants were frail. Older age (odds ratio [OR], 1.31 per 10 years; 95% confidence interval [95% CI], 1.14 to 1.50), diabetes (OR, 1.65; 95% CI, 1.13 to 2.40), higher fat mass (OR, 1.18; 95% CI, 1.02 to 1.37), and higher ECW (OR, 1.33; 95% CI, 1.20 to 1.47) associated with higher odds of frailty. Higher ICW associated with lower odds of frailty (OR, 0.80 per kg; 95% CI, 0.73 to 0.87). The addition of BMI data did not change the area under the receiver operating characteristics curve (AUC; AUC=0.66 versus 0.66; P=0.71), but the addition of BIS data did change the AUC (AUC=0.72; P<0.001). Thus, individual components of body composition but not BMI associate strongly with frailty in this cohort of patients receiving hemodialysis.

    View details for DOI 10.1681/ASN.2013040431

    View details for PubMedID 24158987

  • Changes in serum inflammatory markers are associated with changes in apolipoprotein A1 but not B after the initiation of dialysis. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association Kaysen, G. A., Dalrymple, L. S., Grimes, B., Chertow, G. M., Kornak, J., Johansen, K. L. 2014; 29 (2): 430-437

    Abstract

    Few studies have examined the changes in lipoproteins over time and how inflammation is associated with lipoprotein concentrations among patients with end-stage renal disease on dialysis. One possible explanation for the association of low LDL cholesterol concentration and adverse outcomes is that inflammation reduces selected apolipoprotein concentrations.Serum samples were collected from a subsample of patients enrolled into the Comprehensive Dialysis Study every 3 months for up to 1 year. We examined the relation between temporal patterns in levels of inflammatory markers and changes in apolipoproteins (apo) A1 and B and the apo B/A1 ratio using linear mixed effects modeling and adjusting for potential confounders.We enrolled 266 participants from 56 dialysis facilities. The mean age was 62 years, 45% were women and 26% were black. Apo A1 was lower among patients with higher Quetelet's (body mass) index (BMI), diabetes mellitus and atherosclerosis. Apo B was lower among older patients, patients with higher serum creatinine and patients with lower BMI. Over the course of a year, apo A1 changed inversely with serum concentrations of the acute phase proteins C-reactive protein (CRP) and α1 acid glycoprotein (α1AG), while apo B did not. Changes in α1AG were more strongly associated with changes in apolipoprotein concentrations than were changes in CRP; increases in α1AG were associated with decreases in apo A1 and increases in the apo B/A1 ratio.Changes in inflammatory markers were associated with changes in apo A1, but not apo B over 1 year, suggesting that reductions in high-density lipoprotein cholesterol are associated with inflammation, either of which could mediate cardiovascular risk, but not supporting a hypothesis linking increased risk of low levels of apo B containing lipoproteins to the risk associated with inflammation.

    View details for DOI 10.1093/ndt/gft370

    View details for PubMedID 24009290

  • Changes in serum inflammatory markers are associated with changes in apolipoprotein A1 but not B after the initiation of dialysis NEPHROLOGY DIALYSIS TRANSPLANTATION Kaysen, G. A., Dalrymple, L. S., Grimes, B., Chertow, G. M., Kornak, J., Johansen, K. L. 2014; 29 (2): 430-437

    Abstract

    Few studies have examined the changes in lipoproteins over time and how inflammation is associated with lipoprotein concentrations among patients with end-stage renal disease on dialysis. One possible explanation for the association of low LDL cholesterol concentration and adverse outcomes is that inflammation reduces selected apolipoprotein concentrations.Serum samples were collected from a subsample of patients enrolled into the Comprehensive Dialysis Study every 3 months for up to 1 year. We examined the relation between temporal patterns in levels of inflammatory markers and changes in apolipoproteins (apo) A1 and B and the apo B/A1 ratio using linear mixed effects modeling and adjusting for potential confounders.We enrolled 266 participants from 56 dialysis facilities. The mean age was 62 years, 45% were women and 26% were black. Apo A1 was lower among patients with higher Quetelet's (body mass) index (BMI), diabetes mellitus and atherosclerosis. Apo B was lower among older patients, patients with higher serum creatinine and patients with lower BMI. Over the course of a year, apo A1 changed inversely with serum concentrations of the acute phase proteins C-reactive protein (CRP) and α1 acid glycoprotein (α1AG), while apo B did not. Changes in α1AG were more strongly associated with changes in apolipoprotein concentrations than were changes in CRP; increases in α1AG were associated with decreases in apo A1 and increases in the apo B/A1 ratio.Changes in inflammatory markers were associated with changes in apo A1, but not apo B over 1 year, suggesting that reductions in high-density lipoprotein cholesterol are associated with inflammation, either of which could mediate cardiovascular risk, but not supporting a hypothesis linking increased risk of low levels of apo B containing lipoproteins to the risk associated with inflammation.

    View details for DOI 10.1093/ndt/gft370

    View details for Web of Science ID 000331404100028

    View details for PubMedCentralID PMC3910339

  • Association between Body Composition and Frailty among Prevalent Hemodialysis Patients: A US Renal Data System Special Study JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Johansen, K. L., Dalrymple, L. S., Delgado, C., Kaysen, G. A., Kornak, J., Grimes, B., Chertow, G. M. 2014; 25 (2): 381-389

    Abstract

    Studies of frailty among patients on hemodialysis have relied on definitions that substitute self-reported functioning for measures of physical performance and omit weight loss or substitute alternate criteria. We examined the association between body composition and a definition of frailty that includes measured physical performance and weight loss in a cross-sectional analysis of 638 adult patients receiving maintenance hemodialysis at 14 centers. Frailty was defined as having three of following characteristics: weight loss, weakness, exhaustion, low physical activity, and slow gait speed. We performed logistic regression with body mass index (BMI) and bioelectrical impedance spectroscopy (BIS)-derived estimates of intracellular water (ICW), fat mass, and extracellular water (ECW) as the main predictors, and age, sex, race, and comorbidity as covariates. Overall, 30% of participants were frail. Older age (odds ratio [OR], 1.31 per 10 years; 95% confidence interval [95% CI], 1.14 to 1.50), diabetes (OR, 1.65; 95% CI, 1.13 to 2.40), higher fat mass (OR, 1.18; 95% CI, 1.02 to 1.37), and higher ECW (OR, 1.33; 95% CI, 1.20 to 1.47) associated with higher odds of frailty. Higher ICW associated with lower odds of frailty (OR, 0.80 per kg; 95% CI, 0.73 to 0.87). The addition of BMI data did not change the area under the receiver operating characteristics curve (AUC; AUC=0.66 versus 0.66; P=0.71), but the addition of BIS data did change the AUC (AUC=0.72; P<0.001). Thus, individual components of body composition but not BMI associate strongly with frailty in this cohort of patients receiving hemodialysis.

    View details for DOI 10.1681/ASN.2013040431

    View details for Web of Science ID 000337971700020

    View details for PubMedCentralID PMC3904567

  • Cost-effectiveness of tolvaptan in autosomal dominant polycystic kidney disease. Annals of internal medicine Erickson, K. F., Chertow, G. M., Goldhaber-Fiebert, J. D. 2014; 160 (2): 143-?

    View details for DOI 10.7326/L14-5001-7

    View details for PubMedID 24445704

    View details for PubMedCentralID PMC4096316

  • Comparison of Hospitalization Rates among For-Profit and Nonprofit Dialysis Facilities CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Dalrymple, L. S., Johansen, K. L., Romano, P. S., Chertow, G. M., Mu, Y., Ishida, J. H., Grimes, B., Kaysen, G. A., Nguyen, D. V. 2014; 9 (1): 73-81

    Abstract

    The vast majority of US dialysis facilities are for-profit and profit status has been associated with processes of care and outcomes in patients on dialysis. This study examined whether dialysis facility profit status was associated with the rate of hospitalization in patients starting dialysis.This was a retrospective cohort study of Medicare beneficiaries starting dialysis between 2005 and 2008 using data from the US Renal Data System. All-cause hospitalization was examined and compared between for-profit and nonprofit dialysis facilities through 2009 using Poisson regression. Companion analyses of cause-specific hospitalization that are likely to be influenced by dialysis facility practices including hospitalizations for heart failure and volume overload, access complications, or hyperkalemia were conducted.The cohort included 150,642 patients. Of these, 12,985 (9%) were receiving care in nonprofit dialysis facilities. In adjusted models, patients receiving hemodialysis in for-profit facilities had a 15% (95% confidence interval [95% CI], 13% to 18%) higher relative rate of hospitalization compared with those in nonprofit facilities. Among patients receiving peritoneal dialysis, the rate of hospitalization in for-profit versus nonprofit facilities was not significantly different (relative rate, 1.07; 95% CI, 0.97 to 1.17). Patients on hemodialysis receiving care in for-profit dialysis facilities had a 37% (95% CI, 31% to 44%) higher rate of hospitalization for heart failure or volume overload and a 15% (95% CI, 11% to 20%) higher rate of hospitalization for vascular access complications.Hospitalization rates were significantly higher for patients receiving hemodialysis in for-profit compared with nonprofit dialysis facilities.

    View details for DOI 10.2215/CJN.04200413

    View details for Web of Science ID 000329364700012

    View details for PubMedCentralID PMC3878699

  • Visit-to-visit systolic blood pressure variability and outcomes in hemodialysis JOURNAL OF HUMAN HYPERTENSION Chang, T. I., Flythe, J. E., Brunelli, S. M., Muntner, P., Greene, T., Cheung, A. K., Chertow, G. M. 2014; 28 (1): 18-24

    Abstract

    Visit-to-visit blood pressure variability (VTV-BPV) is an independent risk factor for cardiovascular events and death in the general population. We sought to determine the association of VTV-BPV with outcomes in patients on hemodialysis, using data from a National Institutes of Health-sponsored randomized trial (the HEMO study). We used the coefficient of variation (CV) and the average real variability in systolic blood pressure (SBP) as metrics of VTV-BPV. In all, 1844 out of 1846 randomized subjects had at least three visits with SBP measurements and were included in the analysis. Median follow-up was 2.5 years (interquartile range 1.3-4.3 years), during which time there were 869 deaths from any cause and 408 (adjudicated) cardiovascular deaths. The mean pre-dialysis SBP CV was 9.9±4.6%. In unadjusted models, we found a 31% higher risk of death from any cause per 10% increase in VTV-BPV. This association was attenuated after multivariable adjustment but remained statistically significant. Similarly, we found a 28% higher risk of cardiovascular death per 10% increase in VTV-BPV, which was attenuated and no longer statistically significant in fully adjusted models. The associations among VTV-BPV, death and cardiovascular death were modified by baseline SBP. In a diverse, well-dialyzed cohort of patients on maintenance hemodialysis, VTV-BPV, assessed using metrics of variability in pre-dialysis SBP, was associated with a higher risk of all-cause mortality and a trend toward higher risk of cardiovascular mortality, particularly in patients with a lower baseline SBP.Journal of Human Hypertension advance online publication, 27 June 2013; doi:10.1038/jhh.2013.49.

    View details for DOI 10.1038/jhh.2013.49

    View details for Web of Science ID 000327940600005

  • Nutrition in Kidney Disease Preface NUTRITION IN KIDNEY DISEASE, 2ND EDITION Byham-Gray, L. D., Burrowes, J. D., Chertow, G. M., ByhamGray, L. D., Burrowes, J. D., Chertow, G. M. 2014: IX-X
  • Medicare Reimbursement Reform for Provider Visits and Health Outcomes in Patients on Hemodialysis. Forum for health economics & policy Erickson, K. F., Winkelmayer, W. C., Chertow, G. M., Bhattacharya, J. 2014; 17 (1): 53-77

    Abstract

    The relation between the quantity of many healthcare services delivered and health outcomes is uncertain. In January 2004, the Centers for Medicare and Medicaid Services introduced a tiered fee-for-service system for patients on hemodialysis, creating an incentive for providers to see patients more frequently. We analyzed the effect of this change on patient mortality, transplant wait-listing, and costs. While mortality rates for Medicare beneficiaries on hemodialysis declined after reimbursement reform, mortality declined more - or was no different - among patients whose providers were not affected by the economic incentive. Similarly, improved placement of patients on the kidney transplant waitlist was no different among patients whose providers were not affected by the economic incentive; payments for dialysis visits increased 13.7% in the year following reform. The payment system designed to increase provider visits to hemodialysis patients increased Medicare costs with no evidence of a benefit on survival or kidney transplant listing.

    View details for PubMedID 26180520

  • High prevalence of chronic kidney disease in a community survey of urban Bangladeshis: a cross-sectional study. Globalization and health Anand, S., Khanam, M. A., Saquib, J., Saquib, N., Ahmed, T., Alam, D. S., Cullen, M. R., Barry, M., Chertow, G. M. 2014; 10 (1): 9-?

    Abstract

    The burden of chronic kidney disease (CKD) will rise in parallel with the growing prevalence of type two diabetes mellitus in South Asia but is understudied. Using a cross-sectional survey of adults living in a middle-income neighborhood of Dhaka, Bangladesh, we tested the hypothesis that the prevalence of CKD in this group would approach that of the U.S. and would be strongly associated with insulin resistance.We enrolled 402 eligible adults (>30 years old) after performing a multi-stage random selection procedure. We administered a questionnaire, and collected fasting serum samples and urine samples. We used the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation to estimate glomerular filtration rate, and sex-specific cut offs for albuminuria: > 1.9 mg/mmol (17 mg/g) for men, and >2.8 mg/mmol (25 mg/g) for women. We assessed health-related quality of life using the Medical Outcomes Study Short Form-12 (SF-12).A total of 357 (89%) participants with serum samples comprised the analytic cohort. Mean age of was 49.5 (± 12.7) years. Chronic kidney disease was evident in 94 (26%). Of the participants with CKD, 58 (62%) had albuminuria only. A participant with insulin resistance had a 3.6-fold increase in odds of CKD (95% confidence interval 2.1 to 6.4). Participants with stage three or more advanced CKD reported a decrement in the Physical Health Composite score of the SF-12, compared with participants without CKD.We found an alarmingly high prevalence of CKD-particularly CKD associated with insulin resistance-in middle-income, urban Bangladeshis.

    View details for DOI 10.1186/1744-8603-10-9

    View details for PubMedID 24555767

    View details for PubMedCentralID PMC3944963

  • Phase Angle, Frailty and Mortality in Older Adults JOURNAL OF GENERAL INTERNAL MEDICINE Wilhelm-Leen, E. R., Hall, Y. N., Horwitz, R. I., Chertow, G. M. 2014; 29 (1): 147-154

    Abstract

    Frailty is a multidimensional phenotype that describes declining physical function and a vulnerability to adverse outcomes in the setting of physical stress such as illness or hospitalization. Phase angle is a composite measure of tissue resistance and reactance measured via bioelectrical impedance analysis (BIA). Whether phase angle is associated with frailty and mortality in the general population is unknown.To evaluate associations among phase angle, frailty and mortality.Population-based survey.Third National Health and Nutritional Examination Survey (1988-1994).In all, 4,667 persons aged 60 and older.Frailty was defined according to a set of criteria derived from a definition previously described and validated.Narrow phase angle (the lowest quintile) was associated with a four-fold higher odds of frailty among women and a three-fold higher odds of frailty among men, adjusted for age, sex, race-ethnicity and comorbidity. Over a 12-year follow-up period, the adjusted relative hazard for mortality associated with narrow phase angle was 2.4 (95 % confidence interval [95 % CI] 1.8 to 3.1) in women and 2.2 (95 % CI 1.7 to 2.9) in men. Narrow phase angle was significantly associated with mortality even among participants with little or no comorbidity.Analyses of BIA and frailty were cross-sectional; BIA was not measured serially and incident frailty during follow-up was not assessed. Participants examined at home were excluded from analysis because they did not undergo BIA.Narrow phase angle is associated with frailty and mortality independent of age and comorbidity.

    View details for DOI 10.1007/s11606-013-2585-z

    View details for PubMedID 24002625

  • High prevalence of chronic kidney disease in a community survey of urban Bangladeshis: a cross-sectional study. Globalization and health Anand, S., Khanam, M. A., Saquib, J., Saquib, N., Ahmed, T., Alam, D. S., Cullen, M. R., Barry, M., Chertow, G. M. 2014; 10: 9-?

    Abstract

    The burden of chronic kidney disease (CKD) will rise in parallel with the growing prevalence of type two diabetes mellitus in South Asia but is understudied. Using a cross-sectional survey of adults living in a middle-income neighborhood of Dhaka, Bangladesh, we tested the hypothesis that the prevalence of CKD in this group would approach that of the U.S. and would be strongly associated with insulin resistance.We enrolled 402 eligible adults (>30 years old) after performing a multi-stage random selection procedure. We administered a questionnaire, and collected fasting serum samples and urine samples. We used the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation to estimate glomerular filtration rate, and sex-specific cut offs for albuminuria: > 1.9 mg/mmol (17 mg/g) for men, and >2.8 mg/mmol (25 mg/g) for women. We assessed health-related quality of life using the Medical Outcomes Study Short Form-12 (SF-12).A total of 357 (89%) participants with serum samples comprised the analytic cohort. Mean age of was 49.5 (± 12.7) years. Chronic kidney disease was evident in 94 (26%). Of the participants with CKD, 58 (62%) had albuminuria only. A participant with insulin resistance had a 3.6-fold increase in odds of CKD (95% confidence interval 2.1 to 6.4). Participants with stage three or more advanced CKD reported a decrement in the Physical Health Composite score of the SF-12, compared with participants without CKD.We found an alarmingly high prevalence of CKD-particularly CKD associated with insulin resistance-in middle-income, urban Bangladeshis.

    View details for DOI 10.1186/1744-8603-10-9

    View details for PubMedID 24555767

    View details for PubMedCentralID PMC3944963

  • Comparison of hospitalization rates among for-profit and nonprofit dialysis facilities. Clinical journal of the American Society of Nephrology Dalrymple, L. S., Johansen, K. L., Romano, P. S., Chertow, G. M., Mu, Y., Ishida, J. H., Grimes, B., Kaysen, G. A., Nguyen, D. V. 2014; 9 (1): 73-81

    Abstract

    The vast majority of US dialysis facilities are for-profit and profit status has been associated with processes of care and outcomes in patients on dialysis. This study examined whether dialysis facility profit status was associated with the rate of hospitalization in patients starting dialysis.This was a retrospective cohort study of Medicare beneficiaries starting dialysis between 2005 and 2008 using data from the US Renal Data System. All-cause hospitalization was examined and compared between for-profit and nonprofit dialysis facilities through 2009 using Poisson regression. Companion analyses of cause-specific hospitalization that are likely to be influenced by dialysis facility practices including hospitalizations for heart failure and volume overload, access complications, or hyperkalemia were conducted.The cohort included 150,642 patients. Of these, 12,985 (9%) were receiving care in nonprofit dialysis facilities. In adjusted models, patients receiving hemodialysis in for-profit facilities had a 15% (95% confidence interval [95% CI], 13% to 18%) higher relative rate of hospitalization compared with those in nonprofit facilities. Among patients receiving peritoneal dialysis, the rate of hospitalization in for-profit versus nonprofit facilities was not significantly different (relative rate, 1.07; 95% CI, 0.97 to 1.17). Patients on hemodialysis receiving care in for-profit dialysis facilities had a 37% (95% CI, 31% to 44%) higher rate of hospitalization for heart failure or volume overload and a 15% (95% CI, 11% to 20%) higher rate of hospitalization for vascular access complications.Hospitalization rates were significantly higher for patients receiving hemodialysis in for-profit compared with nonprofit dialysis facilities.

    View details for DOI 10.2215/CJN.04200413

    View details for PubMedID 24370770

  • Effects of daily hemodialysis on heart rate variability: results from the Frequent Hemodialysis Network (FHN) Daily Trial. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association Chan, C. T., Chertow, G. M., Daugirdas, J. T., Greene, T. H., Kotanko, P., Larive, B., Pierratos, A., Stokes, J. B. 2014; 29 (1): 168-178

    Abstract

    End-stage renal disease is associated with reduced heart rate variability (HRV), components of which generally are associated with advanced age, diabetes mellitus and left ventricular hypertrophy. We hypothesized that daily in-center hemodialysis (HD) would increase HRV.The Frequent Hemodialysis Network (FHN) Daily Trial randomized 245 patients to receive 12 months of six versus three times per week in-center HD. Two hundred and seven patients had baseline Holter recordings. HRV measures were calculated from 24-h Holter electrocardiograms at both baseline and 12 months in 131 patients and included low-frequency power (LF, a measure of sympathetic modulation), high-frequency power (HF, a measure of parasympathetic modulation) and standard deviation (SD) of the R-R interval (SDNN, a measure of beat-to-beat variation).Baseline to Month 12 change in LF was augmented by 50% [95% confidence interval (95% CI) 6.1-112%, P =0.022] and LF + HF was augmented by 40% (95% CI 3.3-88.4%, P = 0.03) in patients assigned to daily hemodialysis (DHD) compared with conventional HD. Changes in HF and SDNN were similar between the randomized groups. The effects of DHD on LF were attenuated by advanced age and diabetes mellitus (predefined subgroups). Changes in HF (r = -0.20, P = 0.02) and SDNN (r = -0.18, P = 0.04) were inversely associated with changes in left ventricular mass (LVM).DHD increased the LF component of HRV. Reduction of LVM by DHD was associated with increased vagal modulation of heart rate (HF) and with increased beat-to-beat heart rate variation (SDNN), suggesting an important functional correlate to the structural effects of DHD on the heart in uremia.

    View details for DOI 10.1093/ndt/gft212

    View details for PubMedID 24078335

  • Diabetic Severity and Risk of Kidney Stone Disease EUROPEAN UROLOGY Weinberg, A. E., Patel, C. J., Chertow, G. M., Leppert, J. T. 2014; 65 (1): 242-247

    Abstract

    BACKGROUND: The prevalence of kidney stone disease is rising along with increasing rates of obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome. OBJECTIVE: To investigate the associations among the presence and severity of T2DM, glycemic control, and insulin resistance with kidney stone disease. DESIGN, SETTING, AND PARTICIPANTS: We performed a cross-sectional analysis of all adult participants in the 2007-2010 National Health and Nutrition Examination Survey (NHANES). A history of kidney stone disease was obtained by self-report. T2DM was defined by self-reported history, T2DM-related medication usage, and reported diabetic comorbidity. Insulin resistance was estimated using fasting plasma insulin (FPI) levels and the homeostasis model assessment of insulin resistance (HOMA-IR) definition. We classified glycemic control using glycosylated hemoglobin A1c (HbA1c) and fasting plasma-glucose levels (FPG). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Odds ratios (OR) for having kidney stone disease were calculated for each individual measure of T2DM severity. Logistic regression models were fitted adjusting for age, sex, race/ethnicity, smoking history, and the Quételet index (body mass index), as well as laboratory values and components of metabolic syndrome. RESULTS AND LIMITATIONS: Correlates of kidney stone disease included a self-reported history of T2DM (OR: 2.44; 95% confidence interval [CI], 1.84-3.25) and history of insulin use (OR: 3.31; 95% CI, 2.02-5.45). Persons with FPG levels 100-126mg/dl and >126mg/dl had increased odds of having kidney stone disease (OR 1.28; 95% CI, 0.95-1.72; and OR 2.29; 95% CI, 1.68-3.12, respectively). Corresponding results for persons with HbA1c 5.7-6.4% and =6.5% were OR 1.68 (95% CI, 1.17-2.42) and OR 2.82 (95% CI, 1.98-4.02), respectively. When adjusting for patient factors, a history of T2DM, the use of insulin, FPI, and HbA1c remained significantly associated with kidney stone disease. The cross-sectional design limits causal inference. CONCLUSIONS: Among persons with T2DM, more-severe disease is associated with a heightened risk of kidney stones.

    View details for DOI 10.1016/j.eururo.2013.03.026

    View details for PubMedID 23523538

  • Bardoxolone Methyl in Type 2 Diabetes and Stage 4 Chronic Kidney Disease NEW ENGLAND JOURNAL OF MEDICINE de Zeeuw, D., Akizawa, T., Audhya, P., Bakris, G. L., Chin, M., Christ-Schmidt, H., Goldsberry, A., Houser, M., Krauth, M., Heerspink, H. J., McMurray, J. J., Meyer, C. J., Parving, H., Remuzzi, G., Toto, R. D., Vaziri, N. D., Wanner, C., Wittes, J., Wrolstad, D., Chertow, G. M. 2013; 369 (26): 2492-2503

    Abstract

    Although inhibitors of the renin-angiotensin-aldosterone system can slow the progression of diabetic kidney disease, the residual risk is high. Whether nuclear 1 factor (erythroid-derived 2)-related factor 2 activators further reduce this risk is unknown.We randomly assigned 2185 patients with type 2 diabetes mellitus and stage 4 chronic kidney disease (estimated glomerular filtration rate [GFR], 15 to <30 ml per minute per 1.73 m(2) of body-surface area) to bardoxolone methyl, at a daily dose of 20 mg, or placebo. The primary composite outcome was end-stage renal disease (ESRD) or death from cardiovascular causes.The sponsor and the steering committee terminated the trial on the recommendation of the independent data and safety monitoring committee; the median follow-up was 9 months. A total of 69 of 1088 patients (6%) randomly assigned to bardoxolone methyl and 69 of 1097 (6%) randomly assigned to placebo had a primary composite outcome (hazard ratio in the bardoxolone methyl group vs. the placebo group, 0.98; 95% confidence interval [CI], 0.70 to 1.37; P=0.92). In the bardoxolone methyl group, ESRD developed in 43 patients, and 27 patients died from cardiovascular causes; in the placebo group, ESRD developed in 51 patients, and 19 patients died from cardiovascular causes. A total of 96 patients in the bardoxolone methyl group were hospitalized for heart failure or died from heart failure, as compared with 55 in the placebo group (hazard ratio, 1.83; 95% CI, 1.32 to 2.55; P<0.001). Estimated GFR, blood pressure, and the urinary albumin-to-creatinine ratio increased significantly and body weight decreased significantly in the bardoxolone methyl group, as compared with the placebo group.Among patients with type 2 diabetes mellitus and stage 4 chronic kidney disease, bardoxolone methyl did not reduce the risk of ESRD or death from cardiovascular causes. A higher rate of cardiovascular events with bardoxolone methyl than with placebo prompted termination of the trial. (Funded by Reata Pharmaceuticals; BEACON ClinicalTrials.gov number, NCT01351675.).

    View details for DOI 10.1056/NEJMoa1306033

    View details for PubMedID 24206459

  • Effects of Frequent Hemodialysis on Ventricular Volumes and Left Ventricular Remodeling CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Chan, C. T., Greene, T., Chertow, G. M., Kliger, A. S., Stokes, J. B., Beck, G. J., Daugirdas, J. T., Kotanko, P., Larive, B., Levin, N. W., Mehta, R. L., Rocco, M., Sanz, J., Yang, P. C., Rajagopalan, S. 2013; 8 (12): 2106-2116

    Abstract

    Higher left ventricular volume is associated with death in patients with ESRD. This work investigated the effects of frequent hemodialysis on ventricular volumes and left ventricular remodeling.The Frequent Hemodialysis Network daily trial randomized 245 patients to 12 months of six times per week versus three times per week in-center hemodialysis; the Frequent Hemodialysis Network nocturnal trial randomized 87 patients to 12 months of six times per week nocturnal hemodialysis versus three times per week predominantly home-based hemodialysis. Left and right ventricular end systolic and diastolic volumes, left ventricular mass, and ejection fraction at baseline and end of the study were ascertained by cardiac magnetic resonance imaging. The ratio of left ventricular mass/left ventricular end diastolic volume was used as a surrogate marker of left ventricular remodeling. In each trial, the effect of frequent dialysis on left or right ventricular end diastolic volume was tested between predefined subgroups.In the daily trial, frequent hemodialysis resulted in significant reductions in left ventricular end diastolic volume (-11.0% [95% confidence interval, -16.1% to -5.5%]), left ventricular end systolic volume (-14.8% [-22.7% to -6.2%]), right ventricular end diastolic volume (-11.6% [-19.0% to -3.6%]), and a trend for right ventricular end systolic volume (-11.3% [-21.4% to 0.1%]) compared with conventional therapy. The magnitude of reduction in left and right ventricular end diastolic volumes with frequent hemodialysis was accentuated among patients with residual urine output<100 ml/d (P value [interaction]=0.02). In the nocturnal trial, there were no significant changes in left or right ventricular volumes. The frequent dialysis interventions had no substantial effect on the ratio of left ventricular mass/left ventricular end diastolic volume in either trial.Frequent in-center hemodialysis reduces left and right ventricular end systolic and diastolic ventricular volumes as well as left ventricular mass, but it does not affect left ventricular remodeling.

    View details for DOI 10.2215/CJN.03280313

    View details for Web of Science ID 000327951100012

    View details for PubMedID 23970131

    View details for PubMedCentralID PMC3848394

  • The Clinical Course of Treated Hyperparathyroidism Among Patients Receiving Hemodialysis and the Effect of Cinacalcet: The EVOLVE Trial JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Parfrey, P. S., Chertow, G. M., Block, G. A., Correa-Rotter, R., Drueeke, T. B., Floege, J., Herzog, C. A., London, G. M., Mahaffey, K. W., Moe, S. M., Wheeler, D. C., Dehmel, B., Trotman, M., Modafferi, D. M., Goodman, W. G. 2013; 98 (12): 4834-4844

    Abstract

    The clinical course of secondary hyperparathyroidism (sHPT) in patients on hemodialysis is not well described, and the effect of the calcimimetic cinacalcet on disease progression is uncertain.Our objective was to describe 1) the clinical course of sHPT in patients treated with phosphate binders and/or vitamin D sterols and 2) the impact of cinacalcet on the occurrence of severe unremitting HPT, defined by the persistence of markedly elevated PTH concentrations together with hypercalcemia or parathyroidectomy (PTX).This was a randomized, double-blind, placebo-controlled, global, multicenter clinical trial.Of 5755 patients screened with moderate to severe sHPT, 3883 patients on hemodialysis were included in the trial.Outcomes included PTX; severe, unremitting HPT; and use of commercial cinacalcet (a protocol violation). Intervention: Intervention was cinacalcet (30-180 mg daily) or placebo for up to 64 months.In the 1935 patients randomized to placebo, 278 patients (14%) underwent PTX (median PTH 1872 pg/mL within the previous 12 weeks from surgery). Age, sex, geographic region, co-morbidity, calcium-containing phosphate binder use, and baseline serum calcium, phosphorus, and PTH concentrations were associated with PTX. Commercial cinacalcet was started in 443 (23%) patients (median PTH 1108 pg/mL before treatment began). Severe unremitting HPT developed in 470 patients (24%). In a multivariable Cox model, the relative hazard (comparing patients randomized to cinacalcet versus placebo) of severe unremitting HPT was 0.31 (95% confidence interval = 0.26-0.37). The relative hazard differed little when adjusted by baseline clinical characteristics.Severe unremitting HPT develops frequently in patients on hemodialysis despite conventional therapy, and cinacalcet substantially reduces its occurrence.

    View details for DOI 10.1210/jc.2013-2975

    View details for Web of Science ID 000328477200057

    View details for PubMedID 24108314

  • Diabetes Severity, Metabolic Syndrome, and the Risk of Erectile Dysfunction JOURNAL OF SEXUAL MEDICINE Weinberg, A. E., Eisenberg, M., Patel, C. J., Chertow, G. M., Leppert, J. T. 2013; 10 (12): 3102-3109

    Abstract

    Erectile dysfunction (ED) is more common in men with type 2 diabetes mellitus (T2DM), obesity, and/or the metabolic syndrome (MetS).The aim of this study is to investigate the associations among proxy measures of diabetic severity and the presence of MetS with ED in a nationally representative U.S. data sample.We performed a cross-sectional analysis of adult participants in the 2001-2004 National Health and Nutrition Examination Survey.ED was ascertained by self-report. T2DM severity was defined by calculated measures of glycemic control and insulin resistance (IR). IR was estimated using fasting plasma insulin (FPI) levels and the homeostasis model assessment of IR (HOMA-IR) definition. We classified glycemic control using hemoglobin-A1c (HbA1c) and fasting plasma glucose (FPG) levels. MetS was defined by the American Heart Association and National Heart, Lung, and Blood Institute criteria. Logistic regression models, adjusted for sociodemographics, risk factors, and comorbidities, were fitted for each measure of T2DM severity, MetS, and the presence of ED.Proxy measures of glycemic control and IR were associated with ED. Participants with FPG between 100-126 mg/dL (5.6-7 mmol/L) and ≥ 126 mg/dL (>7 mmol/L) had higher odds of ED, odds ratio (OR) 1.22 (confidence interval or CI, 0.83-1.80), and OR 2.68 (CI, 1.48-4.86), respectively. Participants with HbA1c 5.7-6.4% (38.8-46.4 mmol/mol) and ≥ 6.5% (47.5 mmol/mol) had higher odds of ED (OR 1.73 [CI, 1.08-2.76] and 3.70 [CI, 2.19-6.27], respectively). When FPI and HOMA-IR were evaluated by tertiles, there was a graded relation among participants in the top tertile. In multivariable models, a strong association remained between HbA1c and ED (OR 3.19 [CI,1.13-9.01]). MetS was associated with >2.5-fold increased odds of self reported ED (OR 2.55 [CI, 1.85-3.52]).Poor glycemic control, impaired insulin sensitivity, and the MetS are associated with a heightened risk of ED.

    View details for DOI 10.1111/jsm.12318

    View details for PubMedID 24010555

  • Systematic evaluation of environmental and behavioural factors associated with all-cause mortality in the United States National Health and Nutrition Examination Survey. International journal of epidemiology Patel, C. J., Rehkopf, D. H., Leppert, J. T., Bortz, W. M., Cullen, M. R., Chertow, G. M., Ioannidis, J. P. 2013; 42 (6): 1795-1810

    Abstract

    Environmental and behavioural factors are thought to contribute to all-cause mortality. Here, we develop a method to systematically screen and validate the potential independent contributions to all-cause mortality of 249 environmental and behavioural factors in the National Health and Nutrition Examination Survey (NHANES).We used Cox proportional hazards regression to associate 249 factors with all-cause mortality while adjusting for sociodemographic factors on data in the 1999-2000 and 2001-02 surveys (median 5.5 follow-up years). We controlled for multiple comparisons with the false discovery rate (FDR) and validated significant findings in the 2003-04 survey (median 2.8 follow-up years). We selected 249 factors from a set of all possible factors based on their presence in both the 1999-2002 and 2003-04 surveys and linkage with at least 20 deceased participants. We evaluated the correlation pattern of validated factors and built a multivariable model to identify their independent contribution to mortality.We identified seven environmental and behavioural factors associated with all-cause mortality, including serum and urinary cadmium, serum lycopene levels, smoking (3-level factor) and physical activity. In a multivariable model, only physical activity, past smoking, smoking in participant's home and lycopene were independently associated with mortality. These three factors explained 2.1% of the variance of all-cause mortality after adjusting for demographic and socio-economic factors.Our association study suggests that, of the set of 249 factors in NHANES, physical activity, smoking, serum lycopene and serum/urinary cadmium are associated with all-cause mortality as identified in previous studies and after controlling for multiple hypotheses and validation in an independent survey. Whereas other NHANES factors may be associated with mortality, they may require larger cohorts with longer time of follow-up to detect. It is possible to use a systematic association study to prioritize risk factors for further investigation.

    View details for DOI 10.1093/ije/dyt208

    View details for PubMedID 24345851

  • Vitamin d deficiency and mortality in patients receiving dialysis: the comprehensive dialysis study. Journal of renal nutrition Anand, S., Chertow, G. M., Johansen, K. L., Grimes, B., Dalrymple, L. S., Kaysen, G. A., Kurella Tamura, M. 2013; 23 (6): 422-427

    Abstract

    Although several studies have shown poorer survival among individuals with 25-hydroxy (OH) vitamin D deficiency, data on patients receiving dialysis are limited. Using data from the Comprehensive Dialysis Study (CDS), we tested the hypothesis that patients new to dialysis with low serum concentrations of 25-OH vitamin D would experience higher mortality and hospitalizations.The CDS is a prospective cohort study.We recruited participants from 56 dialysis units located throughout the United States.We obtained data on demographics, comorbidites, and laboratory values from the CDS Patient Questionnaire as well as the Medical Evidence Form (CMS form 2728). Participants provided baseline serum samples for 25-OH vitamin D measurements.We ascertained time to death and first hospitalization as well as number of first-year hospitalizations via the U.S. Renal Data System standard analysis files. We used Cox proportional hazards to determine the association between 25-OH vitamin D tertiles and survival and hospitalization. For number of hospitalizations in the first year, we used negative binomial regression.The analytic cohort was composed of 256 patients with Patient Questionnaire data and 25-OH vitamin D concentrations. The mean age of participants was 62 (±14.0) years, and mean follow-up was 3.8 years. Patients with 25-OH vitamin D concentrations in the lowest tertile (<10.6 ng/mL) at the start of dialysis experienced higher mortality (adjusted hazard ratio 1.75, 95% confidence interval [CI] 1.03-2.97) as well as hospitalization (adjusted hazard ratio 1.76, 95% CI 1.24-2.49). Patients in the lower 2 tertiles (<15.5 ng/mL) experienced a higher rate of hospitalizations in the first year (incidence rate ratio 1.70 [95% CI 1.06-2.72] for middle tertile, 1.66 [95% CI 1.10-2.51] for lowest tertile).We found a sizeable increase in mortality and hospitalization for patients on dialysis with severe 25-OH vitamin D deficiency.

    View details for DOI 10.1053/j.jrn.2013.05.003

    View details for PubMedID 23876600

  • Vitamin D Deficiency and Mortality in Patients Receiving Dialysis: The Comprehensive Dialysis Study JOURNAL OF RENAL NUTRITION Anand, S., Chertow, G. M., Johansen, K. L., Grimes, B., Dalrymple, L. S., Kaysen, G. A., Tamura, M. K. 2013; 23 (6): 422-427

    Abstract

    Although several studies have shown poorer survival among individuals with 25-hydroxy (OH) vitamin D deficiency, data on patients receiving dialysis are limited. Using data from the Comprehensive Dialysis Study (CDS), we tested the hypothesis that patients new to dialysis with low serum concentrations of 25-OH vitamin D would experience higher mortality and hospitalizations.The CDS is a prospective cohort study.We recruited participants from 56 dialysis units located throughout the United States.We obtained data on demographics, comorbidites, and laboratory values from the CDS Patient Questionnaire as well as the Medical Evidence Form (CMS form 2728). Participants provided baseline serum samples for 25-OH vitamin D measurements.We ascertained time to death and first hospitalization as well as number of first-year hospitalizations via the U.S. Renal Data System standard analysis files. We used Cox proportional hazards to determine the association between 25-OH vitamin D tertiles and survival and hospitalization. For number of hospitalizations in the first year, we used negative binomial regression.The analytic cohort was composed of 256 patients with Patient Questionnaire data and 25-OH vitamin D concentrations. The mean age of participants was 62 (±14.0) years, and mean follow-up was 3.8 years. Patients with 25-OH vitamin D concentrations in the lowest tertile (<10.6 ng/mL) at the start of dialysis experienced higher mortality (adjusted hazard ratio 1.75, 95% confidence interval [CI] 1.03-2.97) as well as hospitalization (adjusted hazard ratio 1.76, 95% CI 1.24-2.49). Patients in the lower 2 tertiles (<15.5 ng/mL) experienced a higher rate of hospitalizations in the first year (incidence rate ratio 1.70 [95% CI 1.06-2.72] for middle tertile, 1.66 [95% CI 1.10-2.51] for lowest tertile).We found a sizeable increase in mortality and hospitalization for patients on dialysis with severe 25-OH vitamin D deficiency.

    View details for DOI 10.1053/j.jrn.2013.05.003

    View details for Web of Science ID 000327007600007

  • Sensitization from transfusion in patients awaiting primary kidney transplant. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association Yabu, J. M., Anderson, M. W., Kim, D., Bradbury, B. D., Lou, C. D., Petersen, J., Rossert, J., Chertow, G. M., Tyan, D. B. 2013; 28 (11): 2908-2918

    Abstract

    Sensitization to human leukocyte antigen (HLA) from red blood cell (RBC) transfusion is poorly quantified and is based on outdated, insensitive methods. The objective was to evaluate the effect of transfusion on the breadth, magnitude and specificity of HLA antibody formation using sensitive and specific methods.Transfusion, demographic and clinical data from the US Renal Data System were obtained for patients on dialysis awaiting primary kidney transplant who had ≥2 HLA antibody measurements using the Luminex single-antigen bead assay. One cohort included patients with a transfusion (n = 50) between two antibody measurements matched with up to four nontransfused patients (n = 155) by age, sex, race and vintage (time on dialysis). A second crossover cohort (n = 25) included patients with multiple antibody measurements before and after transfusion. We studied changes in HLA antibody mean fluorescence intensity (MFI) and calculated panel reactive antibody (cPRA).In the matched cohort, 10 of 50 (20%) transfused versus 6 of 155 (4%) nontransfused patients had a ≥10 HLA antibodies increase of >3000 MFI (P = 0.0006); 6 of 50 (12%) transfused patients had a ≥30 antibodies increase (P = 0.0007). In the crossover cohort, the number of HLA antibodies increasing >1000 and >3000 MFI was higher in the transfused versus the control period, P = 0.03 and P = 0.008, respectively. Using a ≥3000 MFI threshold, cPRA significantly increased in both matched (P = 0.01) and crossover (P = 0.002) transfused patients.Among prospective primary kidney transplant recipients, RBC transfusion results in clinically significant increases in HLA antibody strength and breadth, which adversely affect the opportunity for future transplant.

    View details for DOI 10.1093/ndt/gft362

    View details for PubMedID 24009295

  • Utilization of cytoreductive nephrectomy and patient survival in the targeted therapy era 12th International Kidney Cancer Symposium Conti, S. L., Thomas, I., Hagedorn, J. C., Chung, B. I., Chertow, G. M., Wagner, T. H., Brooks, J. D., Srinivas, S., Leppert, J. T. WILEY-BLACKWELL. 2013: 14–16
  • Utilization of renal mass biopsy in patients with renal cell carcinoma 12th International Kidney Cancer Symposium Leppert, J. T., Hanley, J., Wagner, T. H., Chung, B. I., Srinivas, S., Chertow, G. M., Brooks, J. D., Saigal, C. S. WILEY-BLACKWELL. 2013: 14–14
  • Baseline characteristics in the Bardoxolone methyl EvAluation in patients with Chronic kidney disease and type 2 diabetes mellitus: the Occurrence of renal eveNts (BEACON) trial. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association Lambers Heerspink, H. J., Chertow, G. M., Akizawa, T., Audhya, P., Bakris, G. L., Goldsberry, A., Krauth, M., Linde, P., McMurray, J. J., Meyer, C. J., Parving, H., Remuzzi, G., Christ-Schmidt, H., Toto, R. D., Vaziri, N. D., Wanner, C., Wittes, J., Wrolstad, D., de Zeeuw, D. 2013; 28 (11): 2841-2850

    Abstract

    Type 2 diabetes mellitus (T2DM) is the most important contributing cause of end-stage renal disease (ESRD) worldwide. Bardoxolone methyl, a nuclear factor-erythroid-2-related factor 2 activator, augments estimated glomerular filtration. The Bardoxolone methyl EvAluation in patients with Chronic kidney disease and type 2 diabetes mellitus: the Occurrence of renal eveNts (BEACON) trial was designed to establish whether bardoxolone methyl slows or prevents progression to ESRD. Herein, we describe baseline characteristics of the BEACON population.BEACON is a randomized double-blind placebo-controlled clinical trial in 2185 patients with T2DM and chronic kidney disease stage 4 (eGFR between 15 and 30 mL/min/1.73 m(2)) designed to test the hypothesis that bardoxolone methyl added to guideline-recommended treatment including inhibitors of the renin-angiotensin-aldosterone system slows or prevents progression to ESRD or cardiovascular death compared with placebo.Baseline characteristics (mean or percentage) of the population include age 68.5 years, female 43%, Caucasian 78%, eGFR 22.5 mL/min/1.73 m(2) and systolic/diastolic blood pressure 140/70 mmHg. The median urinary albumin:creatinine ratio was 320 mg/g and the frequency of micro- and macroalbuminuria was 30 and 51%, respectively. Anemia, abnormalities in markers of bone metabolism and elevations in cardiovascular biomarkers were frequently observed. A history of cardiovascular disease was present in 56%, neuropathy in 47% and retinopathy in 41% of patients.The BEACON trial enrolled a population heretofore unstudied in an international randomized controlled trial. Enrolled patients suffered with numerous co-morbid conditions and exhibited multiple laboratory abnormalities, highlighting the critical need for new therapies to optimize management of these conditions.

    View details for DOI 10.1093/ndt/gft445

    View details for PubMedID 24169612

  • High prevalence of type 2 diabetes among the urban middle class in Bangladesh BMC PUBLIC HEALTH Saquib, N., Khanam, M. A., Saquib, J., Anand, S., Chertow, G. M., Barry, M., Ahmed, T., Cullen, M. R. 2013; 13

    Abstract

    The prevalence of type-2 diabetes and metabolic syndrome are increasing in the developing world; we assessed their prevalence among the urban middle class in Bangladesh.In this cross-sectional survey (n = 402), we randomly selected consenting adults (≥ 30 years) from a middle-income neighborhood in Dhaka. We assessed demography, lifestyle, and health status, measured physical indices and blood pressure and obtained blood samples. We evaluated two primary outcomes: (1) type-2 diabetes (fasting blood glucose ≥ 7.0 mmol/L or hemoglobin A1C ≥ 6.5% (48 mmol/mol) or diabetes medication use) and (2) insulin resistance (type-2 diabetes or metabolic syndrome using International Diabetes Federation criteria).Mean age and Quételet's (body mass) index were 49.4 ± 12.6 years and 27.0 ± 5.1 kg/m²; 83% were married, 41% had ≥12 years of education, 47% were employed, 47% had a family history of diabetes. Thirty-five percent had type-2 diabetes and 45% had metabolic syndrome. In multivariate models older age and family history of diabetes were significantly associated with type-2 diabetes. Older age, female sex, overweight or obese, high wealth index and positive family history of diabetes were significantly associated with insulin resistance. Participants with type-2 diabetes or insulin resistance had significantly poorer physical health only if they had associated cardiovascular disease.The prevalence of type-2 diabetes and metabolic syndrome among the middle class in Dhaka is alarmingly high. Screening services should be implemented while researchers focus on strategies to lessen the incidence and morbidity associated with these conditions.

    View details for DOI 10.1186/1471-2458-13-1032

    View details for Web of Science ID 000329293000002

    View details for PubMedID 24172217

    View details for PubMedCentralID PMC3924340

  • Pre-ESRD Changes in Body Weight and Survival in Nursing Home Residents Starting Dialysis CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Stack, S., Chertow, G. M., Johansen, K. L., Si, Y., Tamura, M. K. 2013; 8 (10): 1734-1740

    Abstract

    Among patients receiving maintenance dialysis, weight loss at any body mass index is associated with mortality. However, it is not known whether weight changes before dialysis initiation are associated with mortality and if so, what risks are associated with weight gain or loss.Linking data from the US Renal Data System to a national registry of nursing home residents, this study identified 11,090 patients who started dialysis between January of 2000 and December of 2006. Patients were categorized according to weight measured between 3 and 6 months before dialysis initiation and the percentage change in body weight before dialysis initiation (divided into quintiles). The outcome was mortality within 1 year of starting dialysis.There were 361 patients (3.3%) who were underweight (Quételet's [body mass] index<18.5 kg/m(2)) and 4046 patients (36.5%) who were obese (body mass index ≥ 30 kg/m(2)) before dialysis initiation. The median percentage change in body weight before dialysis initiation was -6% (interquartile range=-13% to 1%). There were 6063 deaths (54.7%) over 1 year of follow-up. Compared with patients with minimal weight changes (-3% to 3%, quintile 4), patients with weight loss ≥ 15% (quintile 1) had 35% higher risk for mortality (95% confidence interval, 1.25 to 1.47), whereas those patients with weight gain ≥ 4% (quintile 5) had a 24% higher risk for mortality (95% confidence interval, 1.14 to 1.35) adjusted for baseline body mass index and other confounders.Among nursing home residents, changes in body weight in advance of dialysis initiation are associated with significantly higher 1-year mortality.

    View details for DOI 10.2215/CJN.01410213

    View details for PubMedID 24009221

  • Piecewise Analysis of Patient Survival after Onset of AKI CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Zhang, J. H., Palevsky, P. M., Chertow, G. M., Hartigan, J., O'Connor, T. Z., Guarino, P., Zhou, B. 2013; 8 (10): 1679-1684

    Abstract

    AKI affects approximately 2%-7% of hospitalized patients and >35% of critically ill patients. Survival after AKI may be described as having an acute phase (including an initial hyperacute component) followed by a convalescent phase, which may itself have early and late components.Data from the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network (ATN) study was used to model mortality risk among patients with dialysis-requiring AKI. This study assumed that the mortality hazard can be described by a piecewise log-linear function with change points. Using an average likelihood method, the authors tested for the number of change points in a piecewise log-linear hazard model. The maximum likelihood approach to locate the change point(s) was then adopted, and associated parameters and standard errors were estimated.There were 1124 ATN participants with follow-up to 1 year. The mortality hazard of AKI decreased over time with inflections in the rate of decrease at days 4, 42, and 148, with the sharpest change at day 42. The daily rate of decline in the log of the hazard for death was 0.220 over the first 4 days, 0.046 between day 4 and day 42, 0.017 between day 42 and day 148, and 0.003 between day 148 and day 365.There appear to be two major phases of mortality risk after AKI: an early phase extending over the first 6 weeks and a late phase from 6 weeks to 1 year. Within the first 42 days, this can be further divided into hyperacute (days 1-4) and acute (days 4-42) phases. After 42 days, there appear to be early (days 42-148) and late (after day 148) convalescent phases. These findings may help to inform the design of AKI clinical trials and assist critical care physicians in prognostic stratification.

    View details for DOI 10.2215/CJN.07250712

    View details for Web of Science ID 000325268200008

  • Piecewise analysis of patient survival after onset of AKI. Clinical journal of the American Society of Nephrology Zhang, J. H., Palevsky, P. M., Chertow, G. M., Hartigan, J., O'Connor, T. Z., Guarino, P., Zhou, B. 2013; 8 (10): 1679-1684

    Abstract

    AKI affects approximately 2%-7% of hospitalized patients and >35% of critically ill patients. Survival after AKI may be described as having an acute phase (including an initial hyperacute component) followed by a convalescent phase, which may itself have early and late components.Data from the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network (ATN) study was used to model mortality risk among patients with dialysis-requiring AKI. This study assumed that the mortality hazard can be described by a piecewise log-linear function with change points. Using an average likelihood method, the authors tested for the number of change points in a piecewise log-linear hazard model. The maximum likelihood approach to locate the change point(s) was then adopted, and associated parameters and standard errors were estimated.There were 1124 ATN participants with follow-up to 1 year. The mortality hazard of AKI decreased over time with inflections in the rate of decrease at days 4, 42, and 148, with the sharpest change at day 42. The daily rate of decline in the log of the hazard for death was 0.220 over the first 4 days, 0.046 between day 4 and day 42, 0.017 between day 42 and day 148, and 0.003 between day 148 and day 365.There appear to be two major phases of mortality risk after AKI: an early phase extending over the first 6 weeks and a late phase from 6 weeks to 1 year. Within the first 42 days, this can be further divided into hyperacute (days 1-4) and acute (days 4-42) phases. After 42 days, there appear to be early (days 42-148) and late (after day 148) convalescent phases. These findings may help to inform the design of AKI clinical trials and assist critical care physicians in prognostic stratification.

    View details for DOI 10.2215/CJN.07250712

    View details for PubMedID 23813558

  • Cost-effectiveness of tolvaptan in autosomal dominant polycystic kidney disease. Annals of internal medicine Erickson, K. F., Chertow, G. M., Goldhaber-Fiebert, J. D. 2013; 159 (6): 382-389

    Abstract

    Chinese translationIn the TEMPO (Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes) trial, tolvaptan significantly reduced expansion of kidney volume and loss of kidney function.To determine how the benefits of tolvaptan seen in TEMPO may relate to longer-term health outcomes, such as progression to end-stage renal disease (ESRD) and death, and cost-effectiveness.A decision-analytic model.Published literature from 1993 to 2012.Persons with early autosomal dominant polycystic kidney disease.Lifetime.Societal.Patients received tolvaptan therapy until death, development of ESRD, or liver complications or no tolvaptan therapy.Median age at ESRD onset, life expectancy, discounted quality-adjusted life-years and lifetime costs (in 2010 U.S. dollars), and incremental cost-effectiveness ratios.Tolvaptan prolonged the median age at ESRD onset by 6.5 years and increased life expectancy by 2.6 years. At $5760 per month, tolvaptan cost $744 100 per quality-adjusted life-year gained compared with standard care.For patients with autosomal dominant polycystic kidney disease that progressed more slowly, the cost per quality-adjusted life-year gained was even greater for tolvaptan.Although TEMPO followed patients for 3 years, the main analysis assumed that clinical benefits persisted over patients' lifetimes.Assuming that the benefits of tolvaptan persist in the longer term, the drug may slow progression to ESRD and reduce mortality rates. However, barring an approximately 95% reduction in price, cost-effectiveness does not compare favorably with many other commonly accepted medical interventions.National Institutes of Health and Agency for Healthcare Research and Quality.

    View details for DOI 10.7326/0003-4819-159-6-201309170-00004

    View details for PubMedID 24042366

  • Cost-effectiveness of tolvaptan in autosomal dominant polycystic kidney disease. Annals of internal medicine Erickson, K. F., Chertow, G. M., Goldhaber-Fiebert, J. D. 2013; 159 (6): 382-389

    Abstract

    Chinese translationIn the TEMPO (Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes) trial, tolvaptan significantly reduced expansion of kidney volume and loss of kidney function.To determine how the benefits of tolvaptan seen in TEMPO may relate to longer-term health outcomes, such as progression to end-stage renal disease (ESRD) and death, and cost-effectiveness.A decision-analytic model.Published literature from 1993 to 2012.Persons with early autosomal dominant polycystic kidney disease.Lifetime.Societal.Patients received tolvaptan therapy until death, development of ESRD, or liver complications or no tolvaptan therapy.Median age at ESRD onset, life expectancy, discounted quality-adjusted life-years and lifetime costs (in 2010 U.S. dollars), and incremental cost-effectiveness ratios.Tolvaptan prolonged the median age at ESRD onset by 6.5 years and increased life expectancy by 2.6 years. At $5760 per month, tolvaptan cost $744 100 per quality-adjusted life-year gained compared with standard care.For patients with autosomal dominant polycystic kidney disease that progressed more slowly, the cost per quality-adjusted life-year gained was even greater for tolvaptan.Although TEMPO followed patients for 3 years, the main analysis assumed that clinical benefits persisted over patients' lifetimes.Assuming that the benefits of tolvaptan persist in the longer term, the drug may slow progression to ESRD and reduce mortality rates. However, barring an approximately 95% reduction in price, cost-effectiveness does not compare favorably with many other commonly accepted medical interventions.National Institutes of Health and Agency for Healthcare Research and Quality.

    View details for DOI 10.7326/0003-4819-159-6-201309170-00004

    View details for PubMedID 24042366

  • Prevention of Contrast-Induced AKI: A Review of Published Trials and the Design of the Prevention of Serious Adverse Events following Angiography (PRESERVE) Trial CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Weisbord, S. D., Gallagher, M., Kaufman, J., Cass, A., Parikh, C. R., Chertow, G. M., Shunk, K. A., McCullough, P. A., Fine, M. J., Mor, M. K., Lew, R. A., Huang, G. D., Conner, T. A., Brophy, M. T., Lee, J., Soliva, S., Palevsky, P. M. 2013; 8 (9): 1618-1631
  • Prevention of contrast-induced AKI: a review of published trials and the design of the prevention of serious adverse events following angiography (PRESERVE) trial. Clinical journal of the American Society of Nephrology Weisbord, S. D., Gallagher, M., Kaufman, J., Cass, A., Parikh, C. R., Chertow, G. M., Shunk, K. A., McCullough, P. A., Fine, M. J., Mor, M. K., Lew, R. A., Huang, G. D., Conner, T. A., Brophy, M. T., Lee, J., Soliva, S., Palevsky, P. M. 2013; 8 (9): 1618-1631

    Abstract

    Contrast-induced AKI (CI-AKI) is a common condition associated with serious, adverse outcomes. CI-AKI may be preventable because its risk factors are well characterized and the timing of renal insult is commonly known in advance. Intravenous (IV) fluids and N-acetylcysteine (NAC) are two of the most widely studied preventive measures for CI-AKI. Despite a multitude of clinical trials and meta-analyses, the most effective type of IV fluid (sodium bicarbonate versus sodium chloride) and the benefit of NAC remain unclear. Careful review of published trials of these interventions reveals design limitations that contributed to their inconclusive findings. Such design limitations include the enrollment of small numbers of patients, increasing the risk for type I and type II statistical errors; the use of surrogate primary endpoints defined by small increments in serum creatinine, which are associated with, but not necessarily causally related to serious, adverse, patient-centered outcomes; and the inclusion of low-risk patients with intact baseline kidney function, yielding low event rates and reduced generalizability to a higher-risk population. The Prevention of Serious Adverse Events following Angiography (PRESERVE) trial is a randomized, double-blind, multicenter trial that will enroll 8680 high-risk patients undergoing coronary or noncoronary angiography to compare the effectiveness of IV isotonic sodium bicarbonate versus IV isotonic sodium chloride and oral NAC versus oral placebo for the prevention of serious, adverse outcomes associated with CI-AKI. This article discusses key methodological issues of past trials investigating IV fluids and NAC and how they informed the design of the PRESERVE trial.

    View details for DOI 10.2215/CJN.11161012

    View details for PubMedID 23660180

  • Temporal Trends in the Incidence, Treatment, and Outcomes of Hip Fracture in Older Patients Initiating Dialysis in the United States CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Nair, S. S., Mitani, A. A., Goldstein, B. A., Chertow, G. M., Lowenberg, D. W., Winkelmayer, W. C. 2013; 8 (8): 1336-1342

    Abstract

    BACKGROUND AND OBJECTIVES: Patients with ESRD experience a fivefold higher incidence of hip fracture than the age- and sex-matched general population. Despite multiple changes in the treatment of CKD mineral bone disorder, little is known about long-term trends in hip fracture incidence, treatment patterns, and outcomes in patients on dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Fourteen annual cohorts (1996-2009) of older patients (≥67 years) initiating dialysis in the United States were studied. Eligible patients had Medicare fee-for-service coverage for ≥2 years before dialysis initiation and were followed for ≤3 years for a first hip fracture. Type of treatment (internal fixation or partial or total hip replacement) was ascertained along with 30-day mortality. Cox and modified Poisson regressions were used to describe trends in study outcomes. RESULTS: This study followed 409,040 patients over 607,059 person-years, during which time 17,887 hip fracture events were recorded (29.3 events/1000 person-years). Compared with patients incident for ESRD in 1996, adjusted hip fracture rates increased until the 2004 cohort (+41%) and declined thereafter. Surgical treatment included internal fixation in 56%, partial hip replacement in 29%, and total hip replacement in 2%, which remained essentially unchanged over time; 30-day mortality after hip fracture declined from 20% (1996) to 16% (2009). CONCLUSIONS: Hip fracture incidence rates remain higher today than in patients reaching ESRD in 1996, despite multiple purported improvements in the management of CKD mineral bone disorder. Although recent declines in incidence and steady declines in associated short-term mortality are encouraging, hip fractures remain among the most common and consequential noncardiovascular complications of ESRD.

    View details for DOI 10.2215/CJN.10901012

    View details for PubMedID 23660182

  • Oh! What a tangled web we weave. Clinical journal of the American Society of Nephrology Arora, N., Chertow, G. M. 2013; 8 (7): 1066-1067

    View details for DOI 10.2215/CJN.05420513

    View details for PubMedID 23766364

  • Variation in Nephrologist Visits to Patients on Hemodialysis across Dialysis Facilities and Geographic Locations. Clinical journal of the American Society of Nephrology Erickson, K. F., Tan, K. B., Winkelmayer, W. C., Chertow, G. M., Bhattacharya, J. 2013; 8 (6): 987-994

    Abstract

    BACKGROUND AND OBJECTIVES: Geographic and other variations in medical practices lead to differences in medical costs, often without a clear link to health outcomes. This work examined variation in the frequency of physician visits to patients receiving hemodialysis to measure the relative importance of provider practice patterns (including those patterns linked to geographic region) and patient health in determining visit frequency. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This work analyzed a nationally representative 2006 database of patients receiving hemodialysis in the United States. A variation decomposition analysis of the relative importance of facility, geographic region, and patient characteristics-including demographics, socioeconomic status, and indicators of health status-in explaining physician visit frequency variation was conducted. Finally, the associations between facility, geographic and patient characteristics, and provider visit frequency were measured using multivariable regression. RESULTS: Patient characteristics accounted for only 0.9% of the total visit frequency variation. Accounting for case-mix differences, patients' hemodialysis facilities explained about 24.9% of visit frequency variation, of which 9.3% was explained by geographic region. Visit frequency was more closely associated with many facility and geographic characteristics than indicators of health status. More recent dialysis initiation and recent hospitalization were associated with decreased visit frequency. CONCLUSIONS: In hemodialysis, provider visit frequency depends more on geography and facility location and characteristics than patients' health status or acuity of illness. The magnitude of variation unrelated to patient health suggests that provider visit frequency practices do not reflect optimal management of patients on dialysis.

    View details for DOI 10.2215/CJN.10171012

    View details for PubMedID 23430207

  • Cinacalcet for cardiovascular disease in patients undergoing dialysis. New England journal of medicine Chertow, G. M., Parfrey, P. S. 2013; 368 (19): 1844-1845

    View details for DOI 10.1056/NEJMc1301247

    View details for PubMedID 23656653

  • Cinacalcet for Cardiovascular Disease in Patients Undergoing Dialysis NEW ENGLAND JOURNAL OF MEDICINE Goldsmith, D. J., Lamb, E. J. 2013; 368 (19): 1843

    View details for Web of Science ID 000318540000020

    View details for PubMedID 23656654

  • Cinacalcet for Cardiovascular Disease in Patients Undergoing Dialysis NEW ENGLAND JOURNAL OF MEDICINE Locatelli, F., Pontoriero, G., Tentori, F. 2013; 368 (19): 1843

    View details for Web of Science ID 000318540000019

    View details for PubMedID 23656657

  • Cinacalcet for Cardiovascular Disease in Patients Undergoing Dialysis REPLY NEW ENGLAND JOURNAL OF MEDICINE Chertow, G. M., Parfrey, P. S. 2013; 368 (19): 1844–45

    View details for Web of Science ID 000318540000022

    View details for PubMedID 23656656

  • Effect of frequent hemodialysis on residual kidney function. Kidney international Daugirdas, J. T., Greene, T., Rocco, M. V., Kaysen, G. A., Depner, T. A., Levin, N. W., Chertow, G. M., Ornt, D. B., Raimann, J. G., Larive, B., Kliger, A. S. 2013; 83 (5): 949-958

    Abstract

    Frequent hemodialysis can alter volume status, blood pressure, and the concentration of osmotically active solutes, each of which might affect residual kidney function (RKF). In the Frequent Hemodialysis Network Daily and Nocturnal Trials, we examined the effects of assignment to six compared with three-times-per-week hemodialysis on follow-up RKF. In both trials, baseline RKF was inversely correlated with number of years since onset of ESRD. In the Nocturnal Trial, 63 participants had non-zero RKF at baseline (mean urine volume 0.76 liter/day, urea clearance 2.3 ml/min, and creatinine clearance 4.7 ml/min). In those assigned to frequent nocturnal dialysis, these indices were all significantly lower at month 4 and were mostly so at month 12 compared with controls. In the frequent dialysis group, urine volume had declined to zero in 52% and 67% of patients at months 4 and 12, respectively, compared with 18% and 36% in controls. In the Daily Trial, 83 patients had non-zero RKF at baseline (mean urine volume 0.43 liter/day, urea clearance 1.2 ml/min, and creatinine clearance 2.7 ml/min). Here, treatment assignment did not significantly influence follow-up levels of the measured indices, although the range in baseline RKF was narrower, potentially limiting power to detect differences. Thus, frequent nocturnal hemodialysis appears to promote a more rapid loss of RKF, the mechanism of which remains to be determined. Whether RKF also declines with frequent daily treatment could not be determined.

    View details for DOI 10.1038/ki.2012.457

    View details for PubMedID 23344474

  • Effects of 6-Times-Weekly Versus 3-Times-Weekly Hemodialysis on Depressive Symptoms and Self-reported Mental Health: Frequent Hemodialysis Network (FHN) Trials AMERICAN JOURNAL OF KIDNEY DISEASES Unruh, M. L., Larive, B., Chertow, G. M., Eggers, P. W., Garg, A. X., Gassman, J., Tarallo, M., Finkelstein, F. O., Kimmel, P. L. 2013; 61 (5): 748-758

    Abstract

    Patients undergoing maintenance hemodialysis frequently exhibit poor mental health. We studied the effects of frequent in-center and nocturnal hemodialysis on depressive symptoms and self-reported mental health.1-year randomized controlled clinical trials.Hemodialysis centers in the United States and Canada. 332 patients were randomly assigned to frequent (6-times-weekly) compared with conventional (3-times-weekly) hemodialysis in the Frequent Hemodialysis Network (FHN) Daily (n = 245) and Nocturnal (n = 87) Trials.The Daily Trial was a trial of frequent (6-times-weekly) compared with conventional (3-times-weekly) in-center hemodialysis. The Nocturnal Trial assigned patients to either frequent nocturnal (6-times-weekly) hemodialysis or conventional (3-times-weekly) hemodialysis.Self-reported depressive symptoms and mental health.Beck Depression Inventory and the mental health composite score and emotional subscale of the RAND 36-Item Health Survey at baseline and 4 and 12 months. The mental health composite score is derived by summarizing these domains of the RAND 36-Item Health Survey: emotional, role emotional, energy/fatigue, and social functioning scales.In the Daily Trial, participants randomly assigned to frequent compared with conventional in-center hemodialysis showed no significant change over 12 months in adjusted mean Beck Depression Inventory score (-1.9 ± 0.7 vs -0.6 ± 0.7; P = 0.2), but experienced clinically significant improvements in adjusted mean mental health composite (3.7 ± 0.9 vs 0.2 ± 1.0; P = 0.007) and emotional subscale (5.2 ± 1.6 vs -0.3 ± 1.7; P = 0.01) scores. In the Nocturnal Trial, there were no significant changes in the same metrics in participants randomly assigned to nocturnal compared with conventional hemodialysis.Trial interventions were not blinded.Frequent in-center hemodialysis, as compared with conventional in-center hemodialysis, improved self-reported general mental health. Changes in self-reported depressive symptoms were not statistically significant. We were unable to conclude whether nocturnal hemodialysis yielded similar effects.

    View details for DOI 10.1053/j.ajkd.2012.11.047

    View details for Web of Science ID 000317276600016

    View details for PubMedID 23332990

  • TEMPORAL TRENDS IN THE INCIDENCE, TREATMENT, AND OUTCOMES OF HIP FRACTURE IN OLDER PATIENTS INITIATING DIALYSIS IN THE UNITED STATES. International Conference on Glomerular Diseases Nair, S. S., Mitani, A. A., Goldstein, B. A., Chertow, G. M., Lowenberg, D. W., Winkelmayer, W. C. W B SAUNDERS CO-ELSEVIER INC. 2013: A93–A93
  • DIABETIC SEVERITY AND RISK OF KIDNEY STONE DISEASE Weinberg, A., Patel, C., Chertow, G., Leppert, J. ELSEVIER SCIENCE INC. 2013: E27–E28
  • Cost-Effectiveness of Statins for Primary Cardiovascular Prevention in Chronic Kidney Disease JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Erickson, K. F., Japa, S., Owens, D. K., Chertow, G. M., Garber, A. M., Goldhaber-Fiebert, J. D. 2013; 61 (12): 1250-1258

    Abstract

    The authors sought to evaluate the cost-effectiveness of statins for primary prevention of myocardial infarction (MI) and stroke in patients with chronic kidney disease (CKD).Patients with CKD have an elevated risk of MI and stroke. Although HMG Co-A reductase inhibitors (“statins”) may prevent cardiovascular events in patients with non–dialysis-requiring CKD, adverse drug effects and competing risks could materially influence net effects and clinical decision-making.We developed a decision-analytic model of CKD and cardiovascular disease (CVD) to determine the cost-effectiveness of low-cost generic statins for primary CVD prevention in men and women with hypertension and mild-to-moderate CKD. Outcomes included MI and stroke rates, discounted quality-adjusted life years (QALYs) and lifetime costs (2010 USD), and incremental cost-effectiveness ratios.For 65-year-old men with moderate hypertension and mild-to-moderate CKD, statins reduced the combined rate of MI and stroke, yielded 0.10 QALYs, and increased costs by $1,800 ($18,000 per QALY gained). For patients with lower baseline cardiovascular risks, health and economic benefits were smaller; for 65-year-old women, statins yielded 0.06 QALYs and increased costs by $1,900 ($33,400 per QALY gained). Results were sensitive to rates of rhabdomyolysis and drug costs. Statins are less cost-effective when obtained at average retail prices, particularly in patients at lower CVD risk.Although statins reduce absolute CVD risk in patients with CKD, the increased risk of rhabdomyolysis, and competing risks associated with progressive CKD, partly offset these gains. Low-cost generic statins appear cost-effective for primary prevention of CVD in patients with mild-to-moderate CKD and hypertension.

    View details for DOI 10.1016/j.jacc.2012.12.034

    View details for PubMedID 23500327

  • Obesity Prevalence Soars among Urban Middle-class in Bangladesh Saquib, J., Saquib, N., Anand, S., Khanam, M., Chertow, G., Cullen, M. LIPPINCOTT WILLIAMS & WILKINS. 2013
  • Longitudinal Measures of Serum Albumin and Prealbumin Concentrations in Incident Dialysis Patients: The Comprehensive Dialysis Study JOURNAL OF RENAL NUTRITION Dalrymple, L. S., Johansen, K. L., Chertow, G. M., Grimes, B., Anand, S., McCulloch, C. E., Kaysen, G. A. 2013; 23 (2): 91-97

    Abstract

    Serum albumin and prealbumin concentrations are strongly associated with the risk of death in dialysis patients. Our study examined the association among demographic characteristics, body composition, comorbidities, dialysis modality and access, inflammation, and longitudinal measures of albumin and prealbumin concentrations in incident dialysis patients. DESIGN, SETTING, SUBJECTS, AND OUTCOME MEASURES: The Comprehensive Dialysis Study is a prospective cohort study of incident dialysis patients; in this report, we examined the data from 266 Nutrition substudy participants who donated serum. The independent variables of interest were baseline age, sex, race, Quetélet's (body mass) index, dialysis modality and access, diabetes, heart failure, atherosclerotic vascular disease, serum creatinine level, and longitudinal measures of C-reactive protein. The outcomes of interest (dependent variables) were longitudinal measures of albumin and prealbumin concentrations, recorded at study entry and thereafter every 3 months for 1 year.In multivariable mixed linear models, female sex, peritoneal dialysis, hemodialysis with a catheter, and higher C-reactive protein concentrations were associated with lower serum albumin concentrations, and serum albumin concentrations increased slightly over the year. In comparison, prealbumin concentrations did not significantly change over time; female sex, lower body mass index, diabetes, atherosclerotic vascular disease, and higher C-reactive protein concentrations were associated with lower prealbumin concentrations. Serum creatinine had a curvilinear relation with serum albumin and prealbumin.Serum albumin level increases early in the course of dialysis, whereas prealbumin level does not, and the predictors of serum concentrations differ at any given time. Further understanding of the mechanisms underlying differences between albumin and prealbumin kinetics in dialysis patients may lead to an improved approach to the management of protein-energy wasting.

    View details for DOI 10.1053/j.jrn.2012.03.001

    View details for Web of Science ID 000315198700009

    View details for PubMedID 22633987

    View details for PubMedCentralID PMC3434280

  • Association of Physical Activity with Survival among Ambulatory Patients on Dialysis: The Comprehensive Dialysis Study CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Johansen, K. L., Kaysen, G. A., Dalrymple, L. S., Grimes, B. A., Glidden, D. V., Anand, S., Chertow, G. M. 2013; 8 (2): 248-253

    Abstract

    Despite high mortality and low levels of physical activity (PA) among patients starting dialysis, the link between low PA and mortality has not been carefully evaluated.The Comprehensive Dialysis Study was a prospective cohort study that enrolled patients who started dialysis between June 2005 and June 2007 in a random sample of dialysis facilities in the United States. The Human Activity Profile (HAP) was administered to estimate PA among 1554 ambulatory enrolled patients in the Comprehensive Dialysis Study. Patients were followed until death or September 30, 2009, and the major outcome was all-cause mortality.The average age was 59.8 (14.2) years; 55% of participants were male, 28% were black, and 56% had diabetes mellitus. The majority (57.3%) had low fitness estimated from the HAP score. The median follow-up was 2.6 (interquartile range, 2.2-3.1) years. The association between PA and mortality was linear across the range of scores (1-94). After multivariable adjustment, lower adjusted activity score on the HAP was associated with higher mortality (hazard ratio, 1.30; 95% confidence interval, 1.23-1.39 per 10 points). Patients in the lowest level of fitness experienced a 3.5-fold (95% confidence interval, 2.54-4.89) increase in risk of death compared with those with average or above fitness.Low levels of PA are strongly associated with mortality among patients new to dialysis. Interventions aimed to preserve or enhance PA should be prospectively tested.

    View details for DOI 10.2215/CJN.08560812

    View details for Web of Science ID 000314488800013

    View details for PubMedID 23124787

    View details for PubMedCentralID PMC3562868

  • Rationale and trial design of Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes: the Occurrence of Renal Events (BEACON). American journal of nephrology de Zeeuw, D., Akizawa, T., Agarwal, R., Audhya, P., Bakris, G. L., Chin, M., Krauth, M., Lambers Heerspink, H. J., Meyer, C. J., McMurray, J. J., Parving, H., Pergola, P. E., Remuzzi, G., Toto, R. D., Vaziri, N. D., Wanner, C., Warnock, D. G., Wittes, J., Chertow, G. M. 2013; 37 (3): 212-222

    Abstract

    Chronic kidney disease (CKD) associated with type 2 diabetes mellitus constitutes a global epidemic complicated by considerable renal and cardiovascular morbidity and mortality, despite the provision of inhibitors of the renin-angiotensin-aldosterone system (RAAS). Bardoxolone methyl, a synthetic triterpenoid that reduces oxidative stress and inflammation through Nrf2 activation and inhibition of NF-κB was previously shown to increase estimated glomerular filtration rate (eGFR) in patients with CKD associated with type 2 diabetes mellitus. To date, no antioxidant or anti-inflammatory therapy has proved successful at slowing the progression of CKD.Herein, we describe the design of Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes: the Occurrence of Renal Events (BEACON) trial, a multinational, multicenter, double-blind, randomized, placebo-controlled Phase 3 trial designed to determine whether long-term administration of bardoxolone methyl (on a background of standard therapy, including RAAS inhibitors) safely reduces renal and cardiac morbidity and mortality.The primary composite endpoint is time-to-first occurrence of either end-stage renal disease or cardiovascular death. Secondary endpoints include the change in eGFR and time to occurrence of cardiovascular events.BEACON will be the first event-driven trial to evaluate the effect of an oral antioxidant and anti-inflammatory drug in advanced CKD.

    View details for DOI 10.1159/000346948

    View details for PubMedID 23467003

  • Visit-to-visit systolic blood pressure variability and outcomes in hemodialysis. Journal of human hypertension Chang, T. I., Flythe, J. E., Brunelli, S. M., Muntner, P., Greene, T., Cheung, A. K., Chertow, G. M. 2013

    Abstract

    Visit-to-visit blood pressure variability (VTV-BPV) is an independent risk factor for cardiovascular events and death in the general population. We sought to determine the association of VTV-BPV with outcomes in patients on hemodialysis, using data from a National Institutes of Health-sponsored randomized trial (the HEMO study). We used the coefficient of variation (CV) and the average real variability in systolic blood pressure (SBP) as metrics of VTV-BPV. In all, 1844 out of 1846 randomized subjects had at least three visits with SBP measurements and were included in the analysis. Median follow-up was 2.5 years (interquartile range 1.3-4.3 years), during which time there were 869 deaths from any cause and 408 (adjudicated) cardiovascular deaths. The mean pre-dialysis SBP CV was 9.9±4.6%. In unadjusted models, we found a 31% higher risk of death from any cause per 10% increase in VTV-BPV. This association was attenuated after multivariable adjustment but remained statistically significant. Similarly, we found a 28% higher risk of cardiovascular death per 10% increase in VTV-BPV, which was attenuated and no longer statistically significant in fully adjusted models. The associations among VTV-BPV, death and cardiovascular death were modified by baseline SBP. In a diverse, well-dialyzed cohort of patients on maintenance hemodialysis, VTV-BPV, assessed using metrics of variability in pre-dialysis SBP, was associated with a higher risk of all-cause mortality and a trend toward higher risk of cardiovascular mortality, particularly in patients with a lower baseline SBP.Journal of Human Hypertension advance online publication, 27 June 2013; doi:10.1038/jhh.2013.49.

    View details for PubMedID 23803593

  • High prevalence of type 2 diabetes among the urban middle class in Bangladesh. BMC public health Saquib, N., Khanam, M. A., Saquib, J., Anand, S., Chertow, G. M., Barry, M., Ahmed, T., Cullen, M. R. 2013; 13: 1032-?

    Abstract

    The prevalence of type-2 diabetes and metabolic syndrome are increasing in the developing world; we assessed their prevalence among the urban middle class in Bangladesh.In this cross-sectional survey (n = 402), we randomly selected consenting adults (≥ 30 years) from a middle-income neighborhood in Dhaka. We assessed demography, lifestyle, and health status, measured physical indices and blood pressure and obtained blood samples. We evaluated two primary outcomes: (1) type-2 diabetes (fasting blood glucose ≥ 7.0 mmol/L or hemoglobin A1C ≥ 6.5% (48 mmol/mol) or diabetes medication use) and (2) insulin resistance (type-2 diabetes or metabolic syndrome using International Diabetes Federation criteria).Mean age and Quételet's (body mass) index were 49.4 ± 12.6 years and 27.0 ± 5.1 kg/m²; 83% were married, 41% had ≥12 years of education, 47% were employed, 47% had a family history of diabetes. Thirty-five percent had type-2 diabetes and 45% had metabolic syndrome. In multivariate models older age and family history of diabetes were significantly associated with type-2 diabetes. Older age, female sex, overweight or obese, high wealth index and positive family history of diabetes were significantly associated with insulin resistance. Participants with type-2 diabetes or insulin resistance had significantly poorer physical health only if they had associated cardiovascular disease.The prevalence of type-2 diabetes and metabolic syndrome among the middle class in Dhaka is alarmingly high. Screening services should be implemented while researchers focus on strategies to lessen the incidence and morbidity associated with these conditions.

    View details for DOI 10.1186/1471-2458-13-1032

    View details for PubMedID 24172217

  • Rationale and Trial Design of Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes: The Occurrence of Renal Events (BEACON) AMERICAN JOURNAL OF NEPHROLOGY de Zeeuw, D., Akizawa, T., Agarwal, R., Audhya, P., Bakrise, G. L., Chin, M., Krauth, M., Heerspink, H. J., Meyer, C. J., McMurray, J. J., Parving, H., Pergola, P. E., Remuzzi, G., Toto, R. D., Vaziri, N. D., Wanner, C., Warnock, D. G., Wittes, J., Chertow, G. M. 2013; 37 (3): 212-222

    Abstract

    Chronic kidney disease (CKD) associated with type 2 diabetes mellitus constitutes a global epidemic complicated by considerable renal and cardiovascular morbidity and mortality, despite the provision of inhibitors of the renin-angiotensin-aldosterone system (RAAS). Bardoxolone methyl, a synthetic triterpenoid that reduces oxidative stress and inflammation through Nrf2 activation and inhibition of NF-κB was previously shown to increase estimated glomerular filtration rate (eGFR) in patients with CKD associated with type 2 diabetes mellitus. To date, no antioxidant or anti-inflammatory therapy has proved successful at slowing the progression of CKD.Herein, we describe the design of Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes: the Occurrence of Renal Events (BEACON) trial, a multinational, multicenter, double-blind, randomized, placebo-controlled Phase 3 trial designed to determine whether long-term administration of bardoxolone methyl (on a background of standard therapy, including RAAS inhibitors) safely reduces renal and cardiac morbidity and mortality.The primary composite endpoint is time-to-first occurrence of either end-stage renal disease or cardiovascular death. Secondary endpoints include the change in eGFR and time to occurrence of cardiovascular events.BEACON will be the first event-driven trial to evaluate the effect of an oral antioxidant and anti-inflammatory drug in advanced CKD.

    View details for DOI 10.1159/000346948

    View details for Web of Science ID 000317540300005

  • Trends in Acute Kidney Injury, Associated Use of Dialysis, and Mortality After Cardiac Surgery, 1999 to 2008 ANNALS OF THORACIC SURGERY Lenihan, C. R., Montez-Rath, M. E., Mangano, C. T., Chertow, G. M., Winkelmayer, W. C. 2013; 95 (1): 20-28

    Abstract

    The development of acute kidney injury (AKI) after cardiac surgery is associated with significant mortality, morbidity, and cost. The last decade has seen major changes in the complexity of cardiac surgical candidates and in the number and type of cardiac surgical procedures being performed.Using data from the Nationwide Inpatient Sample, we determined the annual rates of AKI, AKI requiring dialysis (AKI-D), and inpatient mortality after cardiac surgery in the United States in the years 1999 through 2008.Inpatient mortality with AKI and AKI-D decreased from 27.9% and 45.9%, respectively, in 1999 to 12.8% and 35.3%, respectively, in 2008. Compared with 1999, the odds of AKI and AKI-D in 2008, adjusted for demographic and clinical factors, were 3.30 (95% confidence interval [CI]: 2.89 to 3.77) and 2.23 (95% CI: 1.78 to 2.80), respectively. Corresponding adjusted odds of death associated with AKI and AKI-D were 0.31 (95% CI: 0.26 to 0.36) and 0.47 (95% CI: 0.34 to 0.65.) Taken together, the attributable risks for death after cardiac surgery associated with AKI and AKI-D increased from 30% and 5%, respectively, in 1999 to 47% and 14%, respectively, in 2008.In sum, despite improvements in individual patient outcomes over the decade 1999 to 2008, the population contribution of AKI and AKI-D to inpatient mortality after surgery increased over the same period.

    View details for DOI 10.1016/j.athoracsur.2012.05.131

    View details for Web of Science ID 000313343700013

  • Risk factors of short-term mortality after acute nonvariceal upper gastrointestinal bleeding in patients on dialysis: a population-based study. BMC nephrology Yang, J., Lee, T., Montez-Rath, M. E., Chertow, G. M., Winkelmayer, W. C. 2013; 14: 97-?

    View details for DOI 10.1186/1471-2369-14-97

    View details for PubMedID 23621917

  • Trends in acute kidney injury, associated use of dialysis, and mortality after cardiac surgery, 1999 to 2008. Annals of thoracic surgery Lenihan, C. R., Montez-Rath, M. E., Mora Mangano, C. T., Chertow, G. M., Winkelmayer, W. C. 2013; 95 (1): 20-28

    Abstract

    The development of acute kidney injury (AKI) after cardiac surgery is associated with significant mortality, morbidity, and cost. The last decade has seen major changes in the complexity of cardiac surgical candidates and in the number and type of cardiac surgical procedures being performed.Using data from the Nationwide Inpatient Sample, we determined the annual rates of AKI, AKI requiring dialysis (AKI-D), and inpatient mortality after cardiac surgery in the United States in the years 1999 through 2008.Inpatient mortality with AKI and AKI-D decreased from 27.9% and 45.9%, respectively, in 1999 to 12.8% and 35.3%, respectively, in 2008. Compared with 1999, the odds of AKI and AKI-D in 2008, adjusted for demographic and clinical factors, were 3.30 (95% confidence interval [CI]: 2.89 to 3.77) and 2.23 (95% CI: 1.78 to 2.80), respectively. Corresponding adjusted odds of death associated with AKI and AKI-D were 0.31 (95% CI: 0.26 to 0.36) and 0.47 (95% CI: 0.34 to 0.65.) Taken together, the attributable risks for death after cardiac surgery associated with AKI and AKI-D increased from 30% and 5%, respectively, in 1999 to 47% and 14%, respectively, in 2008.In sum, despite improvements in individual patient outcomes over the decade 1999 to 2008, the population contribution of AKI and AKI-D to inpatient mortality after surgery increased over the same period.

    View details for DOI 10.1016/j.athoracsur.2012.05.131

    View details for PubMedID 23272825

  • Physical activity and self-reported symptoms of insomnia, restless legs syndrome, and depression: The comprehensive dialysis study HEMODIALYSIS INTERNATIONAL Anand, S., Johansen, K. L., Grimes, B., Kaysen, G. A., Dalrymple, L. S., Kutner, N. G., Chertow, G. M. 2013; 17 (1): 50-58

    Abstract

    Symptoms of sleep and mood disturbances are common among patients on dialysis and are associated with significant decrements in survival and health-related quality of life. We used data from the Comprehensive Dialysis Study (CDS) to examine the association of self-reported physical activity with self-reported symptoms of insomnia, restless legs syndrome (RLS), and depression in patients new to dialysis. The CDS collected data on physical activity, functional status, and health-related quality of life from 1678 patients on either peritoneal (n = 169) or hemodialysis (n = 1509). The Human Activity Profile was used to measure self-reported physical activity. Symptoms were elicited in the following manner: insomnia using three questions designed to capture difficulty in initiating or maintaining sleep, RLS using three questions based on the National Institutes of Health workshop, and depression using the two-item Patient Health Questionnaire. We obtained data on symptoms of insomnia and depression for 1636, and on symptoms of RLS for 1622 (>98%) patients. Of these, 863 (53%) reported one of three insomnia symptoms as occurring at a persistent frequency. Symptoms of RLS and depression occurred in 477 (29%) and 451 (28%) of patients, respectively. The Adjusted Activity Score of the Human Activity Profile was inversely correlated with all three conditions in models adjusting for demographics, comorbid conditions, and laboratory variables. Sleep and mood disturbances were commonly reported in our large, diverse cohort of patients new to dialysis. Patients who reported lower levels of physical activity were more likely to report symptoms of insomnia, RLS, and depression.

    View details for DOI 10.1111/j.1542-4758.2012.00726.x

    View details for PubMedID 22812496

  • Risk factors of short-term mortality after acute nonvariceal upper gastrointestinal bleeding in patients on dialysis: a population-based study. BMC nephrology Yang, J., Lee, T., Montez-Rath, M. E., Chertow, G. M., Winkelmayer, W. C. 2013; 14: 97-?

    Abstract

    Impaired kidney function is an established predictor of mortality after acute nonvariceal upper gastrointestinal bleeding (ANVUGIB); however, which factors are associated with mortality after ANVUGIB among patients undergoing dialysis is unknown. We examined the associations among demographic characteristics, dialysis-specific features, and comorbid conditions with short-term mortality after ANVUGIB among patients on dialysis.Design: Retrospective cohort study. Setting: United States Renal Data System (USRDS), a nation-wide registry of patients with end-stage renal disease. Participants: All ANVUGIB episodes identified by validated algorithms in Medicare-covered patients between 2003 and 2007. Measurements: Demographic characteristics and comorbid conditions from 1 year of billing claims prior to each bleeding event. We used logistic regression extended with generalized estimating equations methods to model the associations among risk factors and 30-day mortality following ANVUGIB events.From 2003 to 2007, we identified 40,016 eligible patients with 50,497 episodes of ANVUGIB. Overall 30-day mortality was 10.7% (95% CI: 10.4-11.0). Older age, white race, longer dialysis vintage, peritoneal dialysis (vs. hemodialysis), and hospitalized (vs. outpatient) episodes were independently associated with a higher risk of 30-day mortality. Most but not all comorbid conditions were associated with death after ANVUGIB. The joint ability of all factors captured to discriminate mortality was modest (c=0.68).We identified a profile of risk factors for 30-day mortality after ANVUGIB among patients on dialysis that was distinct from what had been reported in non-dialysis populations. Specifically, peritoneal dialysis and more years since initiation of dialysis were independently associated with short-term death after ANVUGIB.

    View details for DOI 10.1186/1471-2369-14-97

    View details for PubMedID 23621917

  • A transcriptional blueprint for human and murine diabetic kidney disease. Diabetes Bhalla, V., Velez, M., Chertow, G. M. 2013; 62 (1): 31-33

    View details for DOI 10.2337/db12-1121

    View details for PubMedID 23258910

  • Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis. New England journal of medicine Chertow, G. M., Block, G. A., Correa-Rotter, R., Drüeke, T. B., Floege, J., Goodman, W. G., Herzog, C. A., Kubo, Y., London, G. M., Mahaffey, K. W., Mix, T. C., Moe, S. M., Trotman, M., Wheeler, D. C., Parfrey, P. S. 2012; 367 (26): 2482-2494

    Abstract

    Disorders of mineral metabolism, including secondary hyperparathyroidism, are thought to contribute to extraskeletal (including vascular) calcification among patients with chronic kidney disease. It has been hypothesized that treatment with the calcimimetic agent cinacalcet might reduce the risk of death or nonfatal cardiovascular events in such patients.In this clinical trial, we randomly assigned 3883 patients with moderate-to-severe secondary hyperparathyroidism (median level of intact parathyroid hormone, 693 pg per milliliter [10th to 90th percentile, 363 to 1694]) who were undergoing hemodialysis to receive either cinacalcet or placebo. All patients were eligible to receive conventional therapy, including phosphate binders, vitamin D sterols, or both. The patients were followed for up to 64 months. The primary composite end point was the time until death, myocardial infarction, hospitalization for unstable angina, heart failure, or a peripheral vascular event. The primary analysis was performed on the basis of the intention-to-treat principle.The median duration of study-drug exposure was 21.2 months in the cinacalcet group, versus 17.5 months in the placebo group. The primary composite end point was reached in 938 of 1948 patients (48.2%) in the cinacalcet group and 952 of 1935 patients (49.2%) in the placebo group (relative hazard in the cinacalcet group vs. the placebo group, 0.93; 95% confidence interval, 0.85 to 1.02; P=0.11). Hypocalcemia and gastrointestinal adverse events were significantly more frequent in patients receiving cinacalcet.In an unadjusted intention-to-treat analysis, cinacalcet did not significantly reduce the risk of death or major cardiovascular events in patients with moderate-to-severe secondary hyperparathyroidism who were undergoing dialysis. (Funded by Amgen; EVOLVE ClinicalTrials.gov number, NCT00345839.).

    View details for DOI 10.1056/NEJMoa1205624

    View details for PubMedID 23121374

  • Effect of Cinacalcet on Cardiovascular Disease in Patients Undergoing Dialysis NEW ENGLAND JOURNAL OF MEDICINE Chertow, G. M., Block, G. A., Correa-Rotter, R., Drueeke, T. B., Floege, J., Goodman, W. G., Herzog, C. A., Kubo, Y., London, G. M., Mahaffey, K. W., Mix, T. C., Moe, S. M., Trotman, M., Wheeler, D. C., Parfrey, P. S. 2012; 367 (26): 2482-2494

    Abstract

    Disorders of mineral metabolism, including secondary hyperparathyroidism, are thought to contribute to extraskeletal (including vascular) calcification among patients with chronic kidney disease. It has been hypothesized that treatment with the calcimimetic agent cinacalcet might reduce the risk of death or nonfatal cardiovascular events in such patients.In this clinical trial, we randomly assigned 3883 patients with moderate-to-severe secondary hyperparathyroidism (median level of intact parathyroid hormone, 693 pg per milliliter [10th to 90th percentile, 363 to 1694]) who were undergoing hemodialysis to receive either cinacalcet or placebo. All patients were eligible to receive conventional therapy, including phosphate binders, vitamin D sterols, or both. The patients were followed for up to 64 months. The primary composite end point was the time until death, myocardial infarction, hospitalization for unstable angina, heart failure, or a peripheral vascular event. The primary analysis was performed on the basis of the intention-to-treat principle.The median duration of study-drug exposure was 21.2 months in the cinacalcet group, versus 17.5 months in the placebo group. The primary composite end point was reached in 938 of 1948 patients (48.2%) in the cinacalcet group and 952 of 1935 patients (49.2%) in the placebo group (relative hazard in the cinacalcet group vs. the placebo group, 0.93; 95% confidence interval, 0.85 to 1.02; P=0.11). Hypocalcemia and gastrointestinal adverse events were significantly more frequent in patients receiving cinacalcet.In an unadjusted intention-to-treat analysis, cinacalcet did not significantly reduce the risk of death or major cardiovascular events in patients with moderate-to-severe secondary hyperparathyroidism who were undergoing dialysis. (Funded by Amgen; EVOLVE ClinicalTrials.gov number, NCT00345839.).

    View details for DOI 10.1056/NEJMoa1205624

    View details for Web of Science ID 000312714200006

  • Venous Thromboembolism Yet Another Cardiovascular Complication of Chronic Kidney Disease? CIRCULATION Chertow, G. M., Mahaffey, K. W. 2012; 126 (16): 1937-1938
  • Bardoxolone Methyl Decreases Megalin and Activates Nrf2 in the Kidney JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Reisman, S. A., Chertow, G. M., Hebbar, S., Vaziri, N. D., Ward, K. W., Meyer, C. J. 2012; 23 (10): 1663-1673

    Abstract

    Inflammation and oxidative stress are hallmarks and mediators of the progression of CKD. Bardoxolone methyl, a potent activator of the nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant and anti-inflammatory response, increases estimated GFR and decreases BUN, serum phosphorus, and uric acid concentrations in patients with moderate to severe CKD. However, it also increases albuminuria, which is associated with inflammation and disease progression. Therefore, we investigated whether this bardoxolone methyl-induced albuminuria may result from the downregulation of megalin, a protein involved in the tubular reabsorption of albumin and lipid-bound proteins. Administration of bardoxolone methyl to cynomolgus monkeys significantly decreased the protein expression of renal tubular megalin, which inversely correlated with the urine albumin-to-creatinine ratio. Moreover, daily oral administration of bardoxolone methyl to monkeys for 1 year did not lead to any adverse effects on renal histopathologic findings but did reduce serum creatinine and BUN, as observed in patients with CKD. Finally, the bardoxolone methyl-induced decrease in megalin corresponded with pharmacologic induction of renal Nrf2 targets, including NAD(P)H:quinone oxidoreductase 1 enzyme activity and glutathione content. This result indicates that Nrf2 may have a role in megalin regulation. In conclusion, these data suggest that the increase in albuminuria that accompanies bardoxolone methyl administration may result, at least in part, from reduced expression of megalin, which seems to occur without adverse effects and with strong induction of Nrf2 targets.

    View details for DOI 10.1681/ASN.2012050457

    View details for Web of Science ID 000309736000012

    View details for PubMedID 22859857

    View details for PubMedCentralID PMC3458470

  • Individualized reduction in dialysate sodium in conventional in-center hemodialysis HEMODIALYSIS INTERNATIONAL Arramreddy, R., Sun, S. J., Mendoza, J. M., Chertow, G. M., Schiller, B. 2012; 16 (4): 473-480

    Abstract

    Recent studies have focused on the association between dialysate sodium (Na(+)) prescriptions and interdialytic weight gain (IDWG). We report on a case series of 13 patients undergoing conventional, thrice-weekly in-center hemodialysis with an individualized dialysate Na(+) prescription. Individualized dialysate Na(+) was achieved in all patients through a stepwise weekly reduction of the standard dialysate Na(+) prescription (140 mEq/L) by 2-3 mEq/L until reaching a Na(+) gradient of -2 mEq/L (dialysate Na(+) minus average plasma Na(+) over the preceding 3 months). Interdialytic weight gain, with and without indexing to dry weight (IDWG%), blood pressure, and the proportion of treatments with cramps, intradialytic hypotension (drop in systolic blood pressure >30 mmHg) and intradialytic hypotension requiring an intervention were reviewed. At the beginning of the observation period, the pre-hemodialysis (HD) plasma Na(+) concentration ranged from 130 to 141 mEq/L. When switched from the standard to the individualized dialysate Na(+) concentration, IDWG% decreased from 3.4% ± 1.6% to 2.5% ± 1.0% (P = 0.003) with no change in pre- or post-HD systolic or diastolic blood pressures (all P > 0.05). We found no significant change in the proportion of treatments with cramps (6% vs. 13%), intradialytic hypotension (62% vs. 65%), or intradialytic hypotension requiring an intervention (29% vs. 33%). Individualized reduction of dialysate Na(+) reduces IDWG% without significantly increasing the frequency of cramps or hypotension.

    View details for DOI 10.1111/j.1542-4758.2012.00701.x

    View details for PubMedID 22554224

  • Donor Recipient Sex Mismatch in Kidney Transplantation GENDER MEDICINE Tan, J. C., Kim, J. P., Chertow, G. M., Grumet, F. C., Desai, M. 2012; 9 (5): 335-347

    Abstract

    The lack of reliable human proxies for minor (ie, non-HLA) histocompatibility loci hampers the ability to leverage these factors toward improving transplant outcomes. Despite conflicting reports of the effect of donor-recipient sex mismatch on renal allografts, the association between acute rejection of renal allografts and the development of human alloantibodies to the male H-Y antigen suggested to us that donor-recipient sex mismatch deserved re-evaluation.To evaluate whether the relationships between donor sex and allograft failure differed by recipient sex.We studied recipients of deceased-donor (n = 125,369) and living-donor (n = 63,139) transplants in the United States Renal Data System. Using Cox proportional hazards models stratified by donor type, we estimated the association between donor-recipient sex mismatch and death-censored allograft failure with adjustment for known risk factors, with and without the use of multiple imputation methods to account for potential bias and/or loss of efficiency due to missing data.The advantage afforded by male donor kidneys was more pronounced among male than among female recipients (8% vs 2% relative risk reduction; interaction P < 0.01). This difference is of the order of magnitude of several other risk factors affecting donor selection decisions.Donor-recipient sex mismatch affects renal allograft survival in a direction consistent with immune responses to sexually determined minor histocompatibility antigens. Our study provides a paradigm for clinical detection of markers for minor histocompatibility loci.

    View details for DOI 10.1016/j.genm.2012.07.004

    View details for PubMedID 22906727

  • Effects of Phosphate Binders in Moderate CKD JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Block, G. A., Wheeler, D. C., Persky, M. S., Kestenbaum, B., Ketteler, M., Spiegel, D. M., Allison, M. A., Asplin, J., Smits, G., Hoofnagle, A. N., Kooienga, L., Thadhani, R., Mannstadt, M., Wolf, M., Chertow, G. M. 2012; 23 (8): 1407-1415

    Abstract

    Some propose using phosphate binders in the CKD population given the association between higher levels of phosphorus and mortality, but their safety and efficacy in this population are not well understood. Here, we aimed to determine the effects of phosphate binders on parameters of mineral metabolism and vascular calcification among patients with moderate to advanced CKD. We randomly assigned 148 patients with estimated GFR=20-45 ml/min per 1.73 m(2) to calcium acetate, lanthanum carbonate, sevelamer carbonate, or placebo. The primary endpoint was change in mean serum phosphorus from baseline to the average of months 3, 6, and 9. Serum phosphorus decreased from a baseline mean of 4.2 mg/dl in both active and placebo arms to 3.9 mg/dl with active therapy and 4.1 mg/dl with placebo (P=0.03). Phosphate binders, but not placebo, decreased mean 24-hour urine phosphorus by 22%. Median serum intact parathyroid hormone remained stable with active therapy and increased with placebo (P=0.002). Active therapy did not significantly affect plasma C-terminal fibroblast growth factor 23 levels. Active therapy did, however, significantly increase calcification of the coronary arteries and abdominal aorta (coronary: median increases of 18.1% versus 0.6%, P=0.05; abdominal aorta: median increases of 15.4% versus 3.4%, P=0.03). In conclusion, phosphate binders significantly lower serum and urinary phosphorus and attenuate progression of secondary hyperparathyroidism among patients with CKD who have normal or near-normal levels of serum phosphorus; however, they also promote the progression of vascular calcification. The safety and efficacy of phosphate binders in CKD remain uncertain.

    View details for DOI 10.1681/ASN.2012030223

    View details for Web of Science ID 000309783500018

    View details for PubMedID 22822075

    View details for PubMedCentralID PMC3402292

  • Frailty, Dialysis Initiation, and Mortality in End-Stage Renal Disease ARCHIVES OF INTERNAL MEDICINE Bao, Y., Dalrymple, L., Chertow, G. M., Kaysen, G. A., Johansen, K. L. 2012; 172 (14): 1071-1077

    Abstract

    In light of the recent trend toward earlier dialysis initiation and its association with mortality among patients with end-stage renal disease, we hypothesized that frailty is associated with higher estimated glomerular filtration rate (eGFR) at dialysis start and may confound the relation between earlier dialysis initiation and mortality.We examined frailty among participants of the Comprehensive Dialysis Study (CDS), a special study of the US Renal Data System, which enrolled incident patients from September 1, 2005, through June 1, 2007. Patients were followed for vital status through September 30, 2009, and for time to first hospitalization through December 31, 2008. We used multivariate logistic regression to model the association of frailty with eGFR at dialysis start and proportional hazards regression to assess the outcomes of death or hospitalization.Among 1576 CDS participants included, the prevalence of frailty was 73%. In multivariate analysis, higher eGFR at dialysis initiation was associated with higher odds of frailty (odds ratio [OR], 1.44 [95% CI, 1.23-1.68] per 5 mL/min/1.73 m(2); P < .001). Frailty was independently associated with mortality (hazard ratio [HR], 1.57 [95% CI, 1.25-1.97]; P < .001) and time to first hospitalization (HR, 1.26 [95% CI, 1.09-1.45]; P < .001). While higher eGFR at dialysis initiation was associated with mortality (HR, 1.12 [95% CI, 1.02-1.23] per 5 mL/min/1.73 m(2); P = .02), the association was no longer statistically significant after frailty was accounted for (HR, 1.08 [95% CI, 0.98-1.19] per 5 mL/min/1.73 m(2); P = .11).Frailty is extremely common among patients starting dialysis in the United States and is associated with higher eGFR at dialysis initiation. Recognition of signs and symptoms of frailty by clinicians may prompt earlier initiation of dialysis and may explain, at least in part, the well-described association between eGFR at dialysis initiation and mortality.

    View details for DOI 10.1001/archinternmed.2012.3020

    View details for Web of Science ID 000306582000005

    View details for PubMedID 22733312

  • Baseline characteristics of subjects enrolled in the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) trial NEPHROLOGY DIALYSIS TRANSPLANTATION Chertow, G. M., Correa-Rotter, R., Block, G. A., Drueke, T. B., Floege, J., Goodman, W. G., Herzog, C. A., Kubo, Y., London, G. M., Mahaffey, K. W., Mix, T., Moe, S. M., Wheeler, D. C., Parfrey, P. S. 2012; 27 (7): 2872-2879

    Abstract

    Secondary hyperparathyroidism (sHPT) and other abnormalities associated with chronic kidney disease-mineral bone disorder can contribute to dystrophic (including vascular) calcification. Dietary modification and variety of medications can be used to attenuate the severity of sHPT. However, it is unknown whether any of these approaches can reduce the high risks of death and cardiovascular disease in patients with end-stage renal disease.The Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) trial was designed to test the hypothesis that treatment with the calcimimetic agent cinacalcet compared with placebo (on a background of conventional therapy including phosphate binders +/- vitamin D sterols) reduces time to death or non-fatal cardiovascular events (specifically myocardial infarction, unstable angina, heart failure and peripheral arterial disease events) among patients on hemodialysis with sHPT. This report describes baseline characteristics of enrolled subjects with a focus on regional variation.There were 3883 subjects randomized from 22 countries, including the USA, Canada, Australia, three Latin American nations, Russia and 15 European nations. The burden of overt cardiovascular disease at baseline was high (e.g. myocardial infarction 12.4%, heart failure 23.3%). The median plasma parathyroid hormone concentration at baseline was 692 pg/mL (10%, 90% range, 363-1694 pg/mL). At baseline, 87.2% of subjects were prescribed phosphate binders and 57.5% were prescribed activated vitamin D derivatives. Demographic data, comorbid conditions and baseline laboratory data varied significantly across regions.EVOLVE enrolled 3883 subjects on hemodialysis with moderate to severe sHPT. Inclusion of subjects from multiple global regions with varying degrees of disease severity will enhance the external validity of the trial results.

    View details for DOI 10.1093/ndt/gfr777

    View details for PubMedID 22529163

  • Factors Associated With Depressive Symptoms and Use of Antidepressant Medications Among Participants in the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC Studies AMERICAN JOURNAL OF KIDNEY DISEASES Fischer, M. J., Xie, D., Jordan, N., Kop, W. J., Krousel-Wood, M., Tamura, M. K., Kusek, J. W., Ford, V., Rosen, L. K., Strauss, L., Teal, V. L., Yaffe, K., Powe, N. R., Lash, J. P. 2012; 60 (1): 27-38

    Abstract

    Depressive symptoms are correlated with poor health outcomes in adults with chronic kidney disease (CKD). The prevalence, severity, and treatment of depressive symptoms and potential risk factors, including level of kidney function, in diverse populations with CKD have not been well studied.Cross-sectional analysis.Participants at enrollment into the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC (H-CRIC) Studies. CRIC enrolled Hispanics and non-Hispanics at 7 centers in 2003-2007, and H-CRIC enrolled Hispanics at the University of Illinois in 2005-2008.Depressive symptoms measured by Beck Depression Inventory (BDI).Demographic and clinical factors.Elevated depressive symptoms (BDI score ≥11) and antidepressant medication use.Of 3,853 participants, 27.4% had evidence of elevated depressive symptoms and 18.2% were using antidepressant medications; 31.0% of persons with elevated depressive symptoms were using antidepressants. The prevalence of elevated depressive symptoms varied by level of kidney function: 23.6% for participants with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m(2) and 33.8% of those with eGFR <30 mL/min/1.73 m(2). Lower eGFR (OR per 10-mL/min/1.73 m(2) decrease, 1.10; 95% CI, 1.04-1.17), and non-Hispanic black race (OR, 1.42; 95% CI, 1.16-1.74) were each associated with increased odds of elevated depressive symptoms after controlling for other factors. In regression analyses incorporating BDI score, whereas female sex was associated with greater odds of antidepressant use, Hispanic ethnicity, non-Hispanic black race, and higher urine albumin levels were associated with decreased odds of antidepressant use (P < 0.05 for each).Absence of clinical diagnosis of depression and use of nonpharmacologic treatments.Although elevated depressive symptoms were common in individuals with CKD, use of antidepressant medications is low. Individuals of racial and ethnic minority background and with more advanced CKD had a greater burden of elevated depressive symptoms and lower use of antidepressant medications.

    View details for DOI 10.1053/j.ajkd.2011.12.033

    View details for Web of Science ID 000305406200007

    View details for PubMedID 22497791

  • Homelessness and CKD: A Cohort Study CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Hall, Y. N., Choi, A. I., Himmelfarb, J., Chertow, G. M., Bindman, A. B. 2012; 7 (7): 1094-1102

    Abstract

    This study examined the associations between homelessness and clinical outcomes of CKD among adults from the urban healthcare safety net.This retrospective cohort study examined 15,343 adults with CKD stages 3-5 who received ambulatory care during 1996-2005 from the Community Health Network of San Francisco. Main outcome measures were time to ESRD or death and frequency of emergency department visits and hospitalizations.Overall, 858 persons (6%) with CKD stages 3-5 were homeless. Homeless adults were younger, were disproportionately male and uninsured, and suffered from far higher rates of depression and substance abuse compared with adults with stable housing (P<0.001 for all comparisons). Over a median follow-up of 2.8 years (interquartile range=1.4-6.1), homeless adults experienced significantly higher crude risk of ESRD or death (hazard ratio=1.82, 95% confidence interval=1.49-2.22) compared with housed adults. This elevated risk was attenuated but remained significantly higher (adjusted hazard ratio=1.28, 95% confidence interval=1.04-1.58) after controlling for differences in sociodemographics, comorbid conditions, and laboratory variables. Homeless adults were also far more likely to use acute care services (median [interquartile range] number of emergency department visits was 9 [4-20] versus 1 [0-4], P<0.001) than housed counterparts.Homeless adults with CKD suffer from increased morbidity and mortality and use costly acute care services far more frequently than peers who are stably housed. These findings warrant additional inquiry into the unmet health needs of the homeless with CKD to provide appropriate and effective care to this disadvantaged group.

    View details for DOI 10.2215/CJN.00060112

    View details for Web of Science ID 000306148500008

    View details for PubMedID 22700883

    View details for PubMedCentralID PMC3386666

  • The effect of frequent hemodialysis on nutrition and body composition: Frequent Hemodialysis Network Trial KIDNEY INTERNATIONAL Kaysen, G. A., Greene, T., Larive, B., Mehta, R. L., Lindsay, R. M., Depner, T. A., Hall, Y. N., Daugirdas, J. T., Chertow, G. M. 2012; 82 (1): 90-99

    Abstract

    We investigated the effects of frequency of hemodialysis on nutritional status by analyzing the data in the Frequent Hemodialysis Network Trial. We compared changes in albumin, body weight, and composition among 245 patients randomized to six or three times per week in-center hemodialysis (Daily Trial) and 87 patients randomized to six times per week nocturnal or three times per week conventional hemodialysis, performed largely at home (Nocturnal Trial). In the Daily Trial, there were no significant differences between groups in changes in serum albumin or the equilibrated protein catabolic rate by 12 months. There was a significant relative decrease in predialysis body weight of 1.5 ± 0.2 kg in the six times per week group at 1 month, but this significantly rebounded by 1.3 ± 0.5 kg over the remaining 11 months. Extracellular water (ECW) decreased in the six times per week compared with the three per week hemodialysis group. There were no significant between-group differences in phase angle, intracellular water, or body cell mass (BCM). In the Nocturnal Trial, there were no significant between-group differences in any study parameter. Any gain in 'dry' body weight corresponded to increased adiposity rather than muscle mass but was not statistically significant. Thus, frequent in-center hemodialysis reduced ECW but did not increase serum albumin or BCM while frequent nocturnal hemodialysis yielded no net effect on parameters of nutritional status or body composition.

    View details for DOI 10.1038/ki.2012.75

    View details for Web of Science ID 000305351300012

    View details for PubMedID 22456602

    View details for PubMedCentralID PMC3328304

  • Validation of Reported Predialysis Nephrology Care of Older Patients Initiating Dialysis JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Kim, J. P., Desai, M., Chertow, G. M., Winkelmayer, W. C. 2012; 23 (6): 1078-1085

    Abstract

    The Centers for Medicare and Medicaid Services (CMS) Medical Evidence Report (form CMS-2728) queries providers about the timing of the patient's first nephrologist consultation before initiation of dialysis. The monitoring of disease-specific goals in the Healthy People 2020 initiative will use information from this question, but the accuracy of the reported information is unknown. We defined a cohort of 80,509 patients aged ≥67 years who initiated dialysis between July 2005 and December 2008 with ≥2 years of uninterrupted Medicare coverage as their primary payer. The primary referent, determined from claims data, was the first observed outpatient nephrologist consultation; secondary analyses used the earliest nephrology consultation, whether inpatient or outpatient. We used linear regression models to assess the associations among the magnitude of discrepant reporting and patient characteristics and we tested for any temporal trends. When using the earliest recorded outpatient nephrology encounter, agreement between the two sources of ascertainment was 48.2%, and the κ statistic was 0.29 when we categorized the timing of the visit into four periods (never, <6, 6-12, and >12 months). When we dichotomized the timing of first predialysis nephrology care at >12 or ≤12 months, accuracy was 70% (κ=0.36), but it differed by patient characteristics and declined over time. In conclusion, we found substantial disagreement between information from the CMS Medical Evidence Report and Medicare physician claims on the timing of first predialysis nephrologist care. More-specific instructions may improve reporting and increase the utility of form CMS-2728 for research and public health surveillance.

    View details for DOI 10.1681/ASN.2011080871

    View details for PubMedID 22518002

  • Toward the optimal dose metric in continuous renal replacement therapy INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS Claure-Del Granado, R., Macedo, E., Chertow, G. M., Soroko, S., Himmelfarb, J., Ikizler, T. A., Paganini, E. P., Mehta, R. L. 2012; 35 (6): 413-424

    Abstract

    There is no consensus on the optimal method to measure delivered dialysis dose in patients with acute kidney injury (AKI). The use of direct dialysate-side quantification of dose in preference to the use of formal blood-based urea kinetic modeling and simplified blood urea nitrogen (BUN) methods has been recommended for dose assessment in critically-ill patients with AKI. We evaluate six different blood-side and dialysate-side methods for dose quantification.We examined data from 52 critically-ill patients with AKI requiring dialysis. All patients were treated with pre-dilution CVVHDF and regional citrate anticoagulation. Delivered dose was calculated using blood-side and dialysis-side kinetics. Filter function was assessed during the entire course of therapy by calculating BUN to dialysis fluid urea nitrogen (FUN) ratios q/12 hours.Median daily treatment time was 1,413 min (1,260-1,440). The median observed effluent volume per treatment was 2,355 mL/h (2,060-2,863) (p<0.001). Urea mass removal rate was 13.0 ± 7.6 mg/min. Both EKR (r²=0.250; p<0.001) and KD (r²=0.409; p<0.001) showed a good correlation with actual solute removal. EKR and KD presented a decline in their values that was related to the decrease in filter function assessed by the FUN/BUN ratio.Effluent rate (mL/kg/h) can only empirically provide an estimated of dose in CRRT. For clinical practice, we recommend that the delivered dose should be measured and expressed as KD. EKR also constitutes a good method for dose comparisons over time and across modalities.

    View details for DOI 10.5301/ijao.5000041

    View details for Web of Science ID 000308904000002

    View details for PubMedID 22466995

  • Design of Clinical Trials in Acute Kidney Injury: A Report from an NIDDK Workshop-Prevention Trials CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Okusa, M. D., Molitoris, B. A., Palevsky, P. M., Chinchilli, V. M., Liu, K. D., Cheung, A. K., Weisbord, S. D., Faubel, S., Kellum, J. A., Wald, R., Chertow, G. M., Levin, A., Waikar, S. S., Murray, P. T., Parikh, C. R., Shaw, A. D., Go, A. S., Chavvla, L. S., Kaufman, J. S., Devarajan, P., Toto, R. M., Hsu, C., Greene, T. H., Mehta, R. L., Stokes, J. B., Thompson, A. M., Thompson, B. T., Westenfelder, C. S., Tumlin, J. A., Warnock, D. G., Shah, S. V., Xie, Y., Duggan, E. G., Kimmel, P. L., Star, R. A. 2012; 7 (5): 851-855

    Abstract

    AKI is an important clinical problem that has become increasingly more common. Mortality rates associated with AKI remain high despite advances in supportive care. Patients surviving AKI have increased long-term mortality and appear to be at increased risk of developing CKD and progressing to ESRD. No proven effective pharmacologic therapies are currently available for the prevention or treatment of AKI. Advances in addressing this unmet need will require the development of novel therapeutic agents based on precise understanding of key pathophysiological events and the implementation of well designed clinical trials. To address this need, the National Institute of Diabetes and Digestive and Kidney Diseases sponsored the "Clinical Trials in Acute Kidney Injury: Current Opportunities and Barriers" workshop in December 2010. The event brought together representatives from academia, industry, the National Institutes of Health, and the US Food and Drug Administration. We report the discussions of workgroups that developed outlines of clinical trials for the prevention of AKI in two patient populations: patients undergoing elective surgery who are at risk for or who develop AKI, and patients who are at risk for contrast-induced AKI. In both of these populations, primary prevention or secondary therapy can be delivered at an optimal time relative to kidney injury. The workgroups detailed primary and secondary endpoints for studies in these groups, and explored the use of adaptive clinical trial designs for trials of novel preventive strategies to improve outcomes of patients with AKI.

    View details for DOI 10.2215/CJN.12811211

    View details for Web of Science ID 000303632700023

    View details for PubMedID 22442188

  • Design of Clinical Trials in AKI: A Report from an NIDDK Workshop. Trials of Patients with Sepsis and in Selected Hospital Settings CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Molitoris, B. A., Okusa, M. D., Palevsky, P. M., Chawla, L. S., Kaufman, J. S., Devarajan, P., Toto, R. M., Hsu, C., Greene, T. H., Faubel, S. G., Kellum, J. A., Wald, R., Chertow, G. M., Levin, A., Waikar, S. S., Murray, P. T., Parikh, C. R., Shaw, A. D., Go, A. S., Chinchilli, V. M., Liu, K. D., Cheung, A. K., Weisbord, S. D., Mehta, R. L., Stokes, J. B., Thompson, A. M., Thompson, B. T., Westenfelder, C. S., Turnin, J. A., Warnock, D. G., Shah, S. V., Xie, Y., Duggan, E. G., Kimmel, P. L., Star, R. A. 2012; 7 (5): 856-860

    Abstract

    AKI remains an important clinical problem, with a high mortality rate, increasing incidence, and no Food and Drug Administration-approved therapeutics. Advances in addressing this clinical need require approaches for rapid diagnosis and stratification of injury, development of therapeutic agents based on precise understanding of key pathophysiological events, and implementation of well designed clinical trials. In the near future, AKI biomarkers may facilitate trial design. To address these issues, the National Institute of Diabetes and Digestive and Kidney Diseases sponsored a meeting, "Clinical Trials in Acute Kidney Injury: Current Opportunities and Barriers," in December of 2010 that brought together academic investigators, industry partners, and representatives from the National Institutes of Health and the Food and Drug Administration. Important issues in the design of clinical trials for interventions in AKI in patients with sepsis or AKI in the setting of critical illness after surgery or trauma were discussed. The sepsis working group discussed use of severity of illness scores and focus on patients with specific etiologies to enhance homogeneity of trial participants. The group also discussed endpoints congruent with those endpoints used in critical care studies. The second workgroup emphasized difficulties in obtaining consent before admission and collaboration among interdisciplinary healthcare groups. Despite the difficult trial design issues, these clinical situations represent a clinical opportunity because of the high event rates, severity of AKI, and poor outcomes. The groups considered trial design issues and discussed advantages and disadvantages of several short- and long-term primary endpoints in these patients.

    View details for DOI 10.2215/CJN.12821211

    View details for Web of Science ID 000303632700024

    View details for PubMedID 22442184

  • Challenges to enrollment and randomization of the frequent hemodialysis network (FHN) daily trial JOURNAL OF NEPHROLOGY Sergeyeva, O., Gorodetskaya, I., Ramos, R., Schiller, B. M., Larive, B., Raimann, J. G., Ting, G. O., Eggers, P. W., Chertow, G. M., Levin, N. W. 2012; 25 (3): 302-309

    Abstract

    The US National Institutes of Health (NIH) and Centers for Medicare and Medicaid Services (CMS) sponsored a randomized clinical trial comparing six versus three times per week in-center hemodialysis (the Frequent Hemodialysis Network [FHN] Daily Trial), to test the effects of frequent hemodialysis on an array of intermediate outcomes. Herein we report challenges to enrollment and randomization into the trial.Screening and enrollment was tracked at all participating dialysis clinics and specific reasons for dropout after baseline assessment were recorded for all enrolled subjects. Reasons for consent refusal were recorded in a subset of (10 out of 65) sites.The trial screened 6276 hemodialysis patients on three times weekly hemodialysis in 65 hemodialysis clinics, 3481 (55%) were considered eligible for enrollment, and 3124 (90%) were approached for consent; 378 (12%) consented and 245 were randomized (65% of those enrolled). Prospective subjects chose not to participate primarily because of the anticipated time required for three extra treatments per week and the difficulties in following the protocol.Recruitment into the FHN Daily Trial proved challenging but the goal of 250 randomized subjects was almost met.

    View details for DOI 10.5301/jn.5000160

    View details for Web of Science ID 000306096600005

    View details for PubMedID 22505248

  • Design of Clinical Trials in Acute Kidney Injury: Report from an NIDDK Workshop on Trial Methodology CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Palevsky, P. M., Molitoris, B. A., Okusa, M. D., Levin, A., Waikar, S. S., Wald, R., Chertow, G. M., Murray, P. T., Parikh, C. R., Shaw, A. D., Go, A. S., Faubel, S. G., Kellum, J. A., Chinchilli, V. M., Liu, K. D., Cheung, A. K., Weisbord, S. D., Chawla, L. S., Kaufman, J. S., Devarajan, P., Toto, R. M., Hsu, C., Greene, T., Mehta, R. L., Stokes, J. B., Thompson, A. M., Thompson, B. T., Westenfelder, C. S., Tumlin, J. A., Warnock, D. G., Shah, S. V., Xie, Y., Duggan, E. G., Kimmel, P. L., Star, R. A. 2012; 7 (5): 844-850

    Abstract

    Acute kidney injury (AKI) remains a complex clinical problem associated with significant short-term morbidity and mortality and lacking effective pharmacologic interventions. Patients with AKI experience longer-term risks for progressive chronic ESRD, which diminish patients' health-related quality of life and create a larger burden on the healthcare system. Although experimental models have yielded numerous promising agents, translation into clinical practice has been unsuccessful, possibly because of issues in clinical trial design, such as delayed drug administration, masking of therapeutic benefit by adverse events, and inadequate sample size. To address issues of clinical trial design, the National Institute of Diabetes and Digestive and Kidney Diseases sponsored a workshop titled "Clinical Trials in Acute Kidney Injury: Current Opportunities and Barriers" in December 2010. Workshop participants included representatives from academia, industry, and government agencies whose areas of expertise spanned basic science, clinical nephrology, critical care medicine, biostatistics, pharmacology, and drug development. This document summarizes the discussions of collaborative workgroups that addressed issues related to patient selection, study endpoints, the role of novel biomarkers, sample size and power calculations, and adverse events and pilot/feasibility studies in prevention and treatment of AKI. Companion articles outline the discussions of workgroups for model trials related to prevention or treatment of established AKI in different clinical settings, such as in patients with sepsis.

    View details for DOI 10.2215/CJN.12791211

    View details for Web of Science ID 000303632700022

    View details for PubMedID 22442182

  • Ongoing Clinical Trials in AKI CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Faubel, S., Chawla, L. S., Chertow, G. M., Goldstein, S. L., Jaber, B. L., Liu, K. D. 2012; 7 (5): 861-873

    Abstract

    AKI is an important public health issue. AKI is a common hospital complication associated with increased in-hospital and long-term mortality, extensive morbidity (including prolonged hospital length of stay), and an estimated annual cost of at least $10 billion in the United States. At present, no specific therapy has been developed to prevent AKI, hasten recovery of kidney function, or abrogate the deleterious systemic effects of AKI. However, recent progress includes establishing a consensus definition of AKI and discovery of novel biomarkers that may allow early detection of AKI. Furthermore, significant insights into the pathophysiology of AKI and its deleterious systemic effects have been gleaned from animal studies. Urgently needed are large, definitive randomized clinical trials testing interventions to prevent and/or treat AKI. This review summarizes and analyzes current ongoing clinical trials registered with clinicaltrials.gov that address prevention or management of AKI. The purpose of this review is to provide a resource for people interested in potential prophylactic and therapeutic approaches to patient care and investigators hoping to plan and execute the next round of randomized clinical trials. Finally, this review discusses research needs that are not addressed by the current clinical trials portfolio and suggests key areas for future research in AKI.

    View details for DOI 10.2215/CJN.12191111

    View details for Web of Science ID 000303632700025

    View details for PubMedID 22442183

  • Effects of Six versus Three Times per Week Hemodialysis on Physical Performance, Health, and Functioning: Frequent Hemodialysis Network (FHN) Randomized Trials CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Hall, Y. N., Larive, B., Painter, P., Kaysen, G. A., Lindsay, R. M., Nissenson, A. R., Unruh, M. L., Rocco, M. V., Chertow, G. M. 2012; 7 (5): 782-794

    Abstract

    Relatively little is known about the effects of hemodialysis frequency on the disability of patients with ESRD.This study examined changes in physical performance and self-reported physical health and functioning among subjects randomized to frequent (six times per week) compared with conventional (three times per week) hemodialysis in both the Frequent Hemodialysis Network daily (n=245) and nocturnal (n=87) trials. The main outcome measures were adjusted change in scores over 12 months on the short physical performance battery (SPPB), RAND 36-item health survey physical health composite (PHC), and physical functioning subscale (PF) based on the intention to treat principle.Overall scores for SPPB, PHC, and PF were poor relative to population norms and in line with other studies in ESRD. In the Daily Trial, subjects randomized to frequent compared with conventional in-center hemodialysis experienced no significant change in SPPB (adjusted mean change of -0.20±0.19 versus -0.41±0.21, P=0.45) but experienced significant improvement in PHC (3.4±0.8 versus 0.4±0.8, P=0.009) and a relatively large change in PF that did not reach statistical significance. In the Nocturnal Trial, there were no significant differences among subjects randomized to frequent compared with conventional hemodialysis in SPPB (adjusted mean change of -0.92±0.44 versus -0.41±0.43, P=0.41), PHC (2.7±1.4 versus 2.1±1.5, P=0.75), or PF (-3.1±3.5 versus 1.1±3.6, P=0.40).Frequent in-center hemodialysis compared with conventional in-center hemodialysis improved self-reported physical health and functioning but had no significant effect on objective physical performance. There were no significant effects of frequent nocturnal hemodialysis on the same physical metrics.

    View details for DOI 10.2215/CJN.10601011

    View details for Web of Science ID 000303632700014

    View details for PubMedID 22422538

  • Effects of Frequent Hemodialysis on Measures of CKD Mineral and Bone Disorder JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Daugirdas, J. T., Chertow, G. M., Larive, B., Pierratos, A., Greene, T., Ayus, J. C., Kendrick, C. A., James, S. H., Miller, B. W., Schulman, G., Salusky, I. B., Kliger, A. S. 2012; 23 (4): 727-738

    Abstract

    More frequent hemodialysis sessions and longer session lengths may offer improved phosphorus control. We analyzed data from the Frequent Hemodialysis Network Daily and Nocturnal Trials to examine the effects of treatment assignment on predialysis serum phosphorus and on prescribed dose of phosphorus binder, expressed relative to calcium carbonate on a weight basis. In the Daily Trial, with prescribed session lengths of 1.5-2.75 hours six times per week, assignment to frequent hemodialysis associated with both a 0.46 mg/dl decrease (95% confidence interval [95% CI], 0.13-0.78 mg/dl) in mean serum phosphorus and a 1.35 g/d reduction (95% CI, 0.20-2.50 g/d) in equivalent phosphorus binder dose at month 12 compared with assignment to conventional hemodialysis. In the Nocturnal Trial, with prescribed session lengths of 6-8 hours six times per week, assignment to frequent hemodialysis associated with a 1.24 mg/dl decrease (95% CI, 0.68-1.79 mg/dl) in mean serum phosphorus compared with assignment to conventional hemodialysis. Among patients assigned to the group receiving six sessions per week, 73% did not require phosphorus binders at month 12 compared with only 8% of patients assigned to sessions three times per week (P<0.001). At month 12, 42% of patients on nocturnal hemodialysis required the addition of phosphorus into the dialysate to prevent hypophosphatemia. Frequent hemodialysis did not have major effects on calcium or parathyroid hormone concentrations in either trial. In conclusion, frequent hemodialysis facilitates control of hyperphosphatemia and extended session lengths could allow more liberal diets and freedom from phosphorus binders.

    View details for DOI 10.1681/ASN.2011070688

    View details for Web of Science ID 000302333300020

    View details for PubMedID 22362907

    View details for PubMedCentralID PMC3312501

  • Self-reported symptoms in patients on hemodialysis with moderate to severe secondary hyperparathyroidism receiving combined therapy with cinacalcet and low-dose vitamin D sterols HEMODIALYSIS INTERNATIONAL Chertow, G. M., Lu, Z. J., Xu, X., Knight, T. G., Goodman, W. G., Bushinsky, D. A., Block, G. A. 2012; 16 (2): 188-197

    Abstract

    Patients with secondary hyperparathyroidism experience a variety of clinical symptoms which may adversely affect physical and mental function. As part of a multicenter, open-label clinical trial, subjects completed a questionnaire that included the Medical Outcomes Study Short Form-36 and 14 kidney disease-related symptoms at multiple time points during the study. Out of the 567 subjects who received at least one dose of cinacalcet, 528 to 535 (93.8-94.4%) completed all or portions of the questionnaire at baseline. The median bioactive parathyroid hormone (PTH) was 294 pg/mL (10%, 90% range, 172-655 pg/mL). Following treatment with cinacalcet and low-dose vitamin D sterols, subjects reported significant improvement in the frequency of pain in muscles, joints and bones, stiff joints, dry skin, itchy skin, excessive thirst, and trouble with memory. At end of the efficacy assessment phase (Weeks 16 to 22), the magnitude of improvement was the greatest in joint pain, bone pain, dry skin, and excessive thirst (>5 on a 0-100 scale; P < 0.001). There were no clinically or statistically significant changes in any of the Short Form-36 subscales or in the physical or mental health composite scores. Among patients on hemodialysis with moderate to severe secondary hyperparathyroidism, treatment with cinacalcet and low-dose vitamin D sterols results in significant improvement in pain in the muscles, joints and bones, joint stiffness, dry and itchy skin, excessive thirst, and trouble with memory.

    View details for DOI 10.1111/j.1542-4758.2011.00642.x

    View details for PubMedID 22118402

  • Trends in Acute Nonvariceal Upper Gastrointestinal Bleeding in Dialysis Patients JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Yang, J., Lee, T., Montez-Rath, M. E., Paik, J., Chertow, G. M., Desai, M., Winkelmayer, W. C. 2012; 23 (3): 495-506

    Abstract

    Impaired kidney function is a risk factor for upper gastrointestinal (GI) bleeding, an event associated with poor outcomes. The burden of upper GI bleeding and its effect on patients with ESRD are not well described. Using data from the US Renal Data System, we quantified the rates of occurrence of and associated 30-day mortality from acute, nonvariceal upper GI bleeding in patients undergoing dialysis; we used medical claims and previously validated algorithms where available. Overall, 948,345 patients contributed 2,296,323 patient-years for study. The occurrence rates for upper GI bleeding were 57 and 328 episodes per 1000 person-years according to stringent and lenient definitions of acute, nonvariceal upper GI bleeding, respectively. Unadjusted occurrence rates remained flat (stringent) or increased (lenient) from 1997 to 2008; after adjustment for sociodemographic characteristics and comorbid conditions, however, we found a significant decline for both definitions (linear approximation, 2.7% and 1.5% per year, respectively; P<0.001). In more recent years, patients had higher hematocrit levels before upper GI bleeding episodes and were more likely to receive blood transfusions during an episode. Overall 30-day mortality was 11.8%, which declined significantly over time (relative declines of 2.3% or 2.8% per year for the stringent and lenient definitions, respectively). In summary, despite declining trends worldwide, crude rates of acute, nonvariceal upper GI bleeding among patients undergoing dialysis have not decreased in the past 10 years. Although 30-day mortality related to upper GI bleeding declined, perhaps reflecting improvements in medical care, the burden on the ESRD population remains substantial.

    View details for DOI 10.1681/ASN.2011070658

    View details for PubMedID 22266666

  • Determinants of Left Ventricular Mass in Patients on Hemodialysis Frequent Hemodialysis Network (FHN) Trials CIRCULATION-CARDIOVASCULAR IMAGING Chan, C. T., Greene, T., Chertow, G. M., Kliger, A. S., Stokes, J. B., Beck, G. J., Daugirdas, J. T., Kotanko, P., Larive, B., Levin, N. W., Mehta, R. L., Rocco, M., Sanz, J., Schiller, B. M., Yang, P. C., Rajagopalan, S. 2012; 5 (2): 251-261

    Abstract

    An increase in left ventricular mass (LVM) is associated with mortality and cardiovascular morbidity in patients with end-stage renal disease.The Frequent Hemodialysis Network (FHN) Daily Trial randomized 245 patients to 12 months of 6 times per week daily in-center hemodialysis or conventional hemodialysis; the FHN Nocturnal Trial randomized 87 patients to 12 months of 6 times per week nocturnal hemodialysis or conventional hemodialysis. The main cardiac secondary outcome was change in LVM. In each trial, we examined whether several predefined baseline demographic or clinical factors as well as change in volume removal, blood pressure, or solute clearance influenced the effect of frequent hemodialysis on LVM. In the Daily Trial, frequent hemodialysis resulted in a significant reduction in LVM (13.1 g; 95% CI, 5.0-21.3 g; P=0.002), LVM index (6.9 g/m(2); 95% CI, 2.4-11.3 g/m(2); P=0.003), and percent change in geometric mean of LVM (7.0%; 95% CI, 1.0%-12.6; P=0.02). Similar trends were noted in the Nocturnal Trial but did not reach statistical significance. In the Daily Trial, a more pronounced effect of frequent hemodialysis on LVM was evident among patients with left ventricular hypertrophy at baseline. Changes in LVM were associated with changes in blood pressure (conventional hemodialysis: R=0.28, P=0.01, daily hemodialysis: R=0.54, P<0.001) and were not significantly associated with changes in other parameters.Frequent in-center hemodialysis reduces LVM. The benefit of frequent hemodialysis on LVM may be mediated by salutary effects on blood pressure. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00264758.

    View details for DOI 10.1161/CIRCIMAGING.111.969923

    View details for Web of Science ID 000302122700014

    View details for PubMedID 22360996

    View details for PubMedCentralID PMC3328963

  • Prospective Safety Study of Bardoxolone Methyl in Patients with Type 2 Diabetes Mellitus, End-Stage Renal Disease and Peritoneal Dialysis International Vicenza Course on Peritoneal Dialysis Warnock, D. G., Hebbar, S., Bargman, J., Burkart, J., Davies, S., Finkelstein, F. O., Mehrotra, R., Ronco, C., Teitelbaum, I., Urakpo, K., Chertow, G. M. KARGER. 2012: 157–163

    Abstract

    Patients on peritoneal dialysis experience inflammation associated with advanced chronic kidney disease and the therapy itself. An important consequence of the inflammation may be acceleration of the rate of decline in residual renal function. The decline in residual renal function has been associated with an increased mortality for patients in this population. Bardoxolone methyl is a synthetic triterpenoid. To date, the effects of bardoxolone methyl on kidney function in humans have been studied in patients with type 2 diabetes mellitus. A large-scale event-driven study of bardoxolone methyl in patients with type 2 diabetes mellitus with stage 4 chronic kidney disease is underway. The safety of bardoxolone methyl has not been evaluated in patients with more advanced (stage 5) chronic kidney disease or patients on dialysis. This report describes a proposed double blind, prospective evaluation of bardoxolone methyl in patients with type 2 diabetes mellitus receiving peritoneal dialysis. In addition to assessing the safety of bardoxolone methyl in this population, the study will evaluate the effect of bardoxolone methyl on residual renal function over 6 months as compared to placebo.

    View details for Web of Science ID 000310253200026

    View details for PubMedID 22652731

  • Acute Kidney Injury and Mortality in Hospitalized Patients AMERICAN JOURNAL OF NEPHROLOGY Wang, H. E., Muntner, P., Chertow, G. M., Warnock, D. G. 2012; 35 (4): 349-355

    Abstract

    The objective of this study was to determine the incidence of acute kidney injury (AKI) and its relation with mortality among hospitalized patients.Analysis of hospital discharge and laboratory data from an urban academic medical center over a 1-year period. We included hospitalized adult patients receiving two or more serum creatinine (sCr) measurements. We excluded prisoners, psychiatry, labor and delivery, and transferred patients, 'bedded outpatients' as well as individuals with a history of kidney transplant or chronic dialysis. We defined AKI as (a) an increase in sCr of ≥0.3 mg/dl; (b) an increase in sCr to ≥150% of baseline, or (c) the initiation of dialysis in a patient with no known history of prior dialysis. We identified factors associated with AKI as well as the relationships between AKI and in-hospital mortality. RESUlTS: Among the 19,249 hospitalizations included in the analysis, the incidence of AKI was 22.7%. Older persons, Blacks, and patients with reduced baseline kidney function were more likely to develop AKI (all p < 0.001). Among AKI cases, the most common primary admitting diagnosis groups were circulatory diseases (25.4%) and infection (16.4%). After adjustment for age, sex, race, admitting sCr concentration, and the severity of illness index, AKI was independently associated with in-hospital mortality (adjusted odds ratio 4.43, 95% confidence interval 3.68-5.35).AKI occurred in over 1 of 5 hospitalizations and was associated with a more than fourfold increased likelihood of death. These observations highlight the importance of AKI recognition as well as the association of AKI with mortality in hospitalized patients.

    View details for DOI 10.1159/000337487

    View details for Web of Science ID 000302896900007

    View details for PubMedID 22473149

    View details for PubMedCentralID PMC3362180

  • Validity of Surrogate Measures for Functional Nephron Mass TRANSPLANTATION Tan, J. C., Paik, J., Chertow, G. M., Grumet, F. C., Busque, S., Lapasia, J., Desai, M. 2011; 92 (12): 1335-1341

    Abstract

    Transplanted nephron mass is an important determinant of long-term allograft survival, but accurate assessment before organ retrieval is challenging. Newer radiologic imaging techniques allow for better determination of total kidney and cortical volumes.Using volume measurements reconstructed from magnetic resonance or computed tomography imaging from living donor candidates, we characterized total kidney (n=312) and cortical volumes (n=236) according to sex, age, weight, height, body mass index (BMI), and body surface area (BSA).The mean cortical volume was 204 mL (range 105-355 mL) with no significant differences between left and right cortical volumes. The degree to which existing anthropomorphic surrogates predict nephron mass was quantified, and a diligent attempt was made to derive a better surrogate model for nephron mass. Cortical volumes were strongly associated with sex and BSA, but not with weight, height, or BMI. Four prediction models for cortical volume constructed using combinations of age, sex, race, weight, and height were compared with models including either BSA or BMI.Among existing surrogate measures, BSA was superior to BMI in predicting renal cortical volume. We were able to construct a statistically superior proxy for cortical volume, but whether relevant improvements in predictive accuracy could be gained needs further evaluation in a larger population.

    View details for DOI 10.1097/TP.0b013e31823705ef

    View details for PubMedID 22011765

  • Vitamin D deficiency, self-reported physical activity and health-related quality of life: the Comprehensive Dialysis Study NEPHROLOGY DIALYSIS TRANSPLANTATION Anand, S., Kaysen, G. A., Chertow, G. M., Johansen, K. L., Grimes, B., Dalrymple, L. S., Tamura, M. K. 2011; 26 (11): 3683-3688

    Abstract

    As research has identified a wide array of biological functions of vitamin D, the consequences of vitamin D deficiency in persons with chronic kidney disease has attracted increased attention. The objective of this study was to determine the extent of 25-hydroxyvitamin D (25-OH vitamin D) deficiency and its associations with self-reported physical activity and health-related quality of life (HRQoL) among participants of the Comprehensive Dialysis Study (CDS).The nutrition substudy of the CDS enrolled patients new to dialysis from 68 dialysis units throughout the USA. Baseline 25-OH vitamin D concentration was measured using the Direct Enzyme Immunoassay (Immunodiagnostic Systems Inc.). Physical activity was measured with the Human Activity Profile (HAP); the Medical Outcomes Study Short Form-12 (SF-12) was employed to measure HRQoL.Mean age of the participants (n = 192) was 62 years. There were 124 participants (65%) with 25-OH vitamin D concentrations < 15 ng/mL, indicating deficiency, and 64 (33%) with 25-OH vitamin D ≥ 15 to <30 ng/mL, indicating insufficiency. After adjusting for age, sex, race/ethnicity, diabetes, season and center, lower 25-OH vitamin D concentrations were independently associated with lower scores on the HAP and on the Mental Component Summary of the SF-12 (P < 0.05 for both), but not with the Physical Component Summary of the SF-12.In a well-characterized cohort of incident dialysis patients, lower 25-OH vitamin D concentrations were associated with lower self-reported physical activity and poorer self-reported mental health.

    View details for DOI 10.1093/ndt/gfr098

    View details for PubMedID 21430182

  • Association of Self-reported Physical Activity With Laboratory Markers of Nutrition and Inflammation: The Comprehensive Dialysis Study JOURNAL OF RENAL NUTRITION Anand, S., Chertow, G. M., Johansen, K. L., Grimes, B., Tamura, M. K., Dalrymple, L. S., Kaysen, G. A. 2011; 21 (6): 429-437

    Abstract

    Patients on dialysis maintain extremely low levels of physical activity. Prior studies have demonstrated a direct correlation between nutrition and physical activity but provide conflicting data on the link between inflammation and physical activity. Using a cohort of patients new to dialysis from the Comprehensive Dialysis Study (CDS), we examined associations of self-reported physical activity with laboratory markers of nutrition and inflammation.Between June 2005 and June 2007, CDS collected data on self-reported physical activity, nutrition, and health-related quality of life from patients starting dialysis in 296 facilities located throughout the United States. Baseline serum samples were collected from participants in a nutrition sub-study of CDS.Serum albumin and prealbumin were measured as markers of nutrition, and C-reactive protein (CRP) and α-1-acid glycoprotein as markers of inflammation. Self-reported physical activity was characterized by the maximum activity score (MAS) and adjusted activity score (AAS) of the Human Activity Profile.The mean age of participants in the analytic cohort (n = 201) was 61 years. The MAS and AAS were below the 10th and first percentile, respectively, in comparison with healthy 60 year-old norms. Both activity scores were directly correlated with albumin (r(2) = 0.3, P < .0001) and prealbumin (r(2) = 0.3, P < .0001), and inversely correlated with CRP (AAS: r(2) = -0.2, P = .01; MAS: r(2) = -0.1, P = .08). In multivariate analyses adjusting for age, gender, race/ethnicity, diabetes status, and center, both activity scores were directly correlated with prealbumin and inversely correlated with CRP.Patients new to dialysis with laboratory-based evidence of malnutrition and/or inflammation are likely to report lower levels of physical activity.

    View details for DOI 10.1053/j.jrn.2010.09.007

    View details for PubMedID 21239185

  • The effects of frequent nocturnal home hemodialysis: the Frequent Hemodialysis Network Nocturnal Trial KIDNEY INTERNATIONAL Rocco, M. V., Lockridge, R. S., Beck, G. J., Eggers, P. W., Gassman, J. J., Greene, T., Larive, B., Chan, C. T., Chertow, G. M., Copland, M., Hoy, C. D., Lindsay, R. M., Levin, N. W., Ornt, D. B., Pierratos, A., Pipkin, M. F., Rajagopalan, S., Stokes, J. B., Unruh, M. L., Star, R. A., Kliger, A. S. 2011; 80 (10): 1080-1091

    Abstract

    Prior small studies have shown multiple benefits of frequent nocturnal hemodialysis compared to conventional three times per week treatments. To study this further, we randomized 87 patients to three times per week conventional hemodialysis or to nocturnal hemodialysis six times per week, all with single-use high-flux dialyzers. The 45 patients in the frequent nocturnal arm had a 1.82-fold higher mean weekly stdKt/V(urea), a 1.74-fold higher average number of treatments per week, and a 2.45-fold higher average weekly treatment time than the 42 patients in the conventional arm. We did not find a significant effect of nocturnal hemodialysis for either of the two coprimary outcomes (death or left ventricular mass (measured by MRI) with a hazard ratio of 0.68, or of death or RAND Physical Health Composite with a hazard ratio of 0.91). Possible explanations for the left ventricular mass result include limited sample size and patient characteristics. Secondary outcomes included cognitive performance, self-reported depression, laboratory markers of nutrition, mineral metabolism and anemia, blood pressure and rates of hospitalization, and vascular access interventions. Patients in the nocturnal arm had improved control of hyperphosphatemia and hypertension, but no significant benefit among the other main secondary outcomes. There was a trend for increased vascular access events in the nocturnal arm. Thus, we were unable to demonstrate a definitive benefit of more frequent nocturnal hemodialysis for either coprimary outcome.

    View details for DOI 10.1038/ki.2011.213

    View details for Web of Science ID 000296609800012

    View details for PubMedCentralID PMC3569086

  • Chronic Kidney Disease and Cardiovascular Therapeutics Time to Close the Evidence Gaps JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Chang, T. I., Chertow, G. M. 2011; 58 (11): 1162-1164

    View details for DOI 10.1016/j.jacc.2011.06.010

    View details for Web of Science ID 000294449200013

    View details for PubMedID 21884955

  • Living donor evaluation and exclusion: the Stanford experience CLINICAL TRANSPLANTATION Lapasia, J. B., Kong, S., Busque, S., Scandling, J. D., Chertow, G. M., Tan, J. C. 2011; 25 (5): 697-704

    Abstract

    The proportion of prospective living donors disqualified for medical reasons is unknown. The objective of this study is to delineate and quantify specific reasons for exclusion of prospective living donors from kidney donation.All adult prospective kidney donors who contacted our transplant program between October 1, 2007 and April 1, 2009 were included in our analysis (n = 484). Data were collected by review of an electronic transplant database.Of the 484 prospective donors, 39 (8%) successfully donated, 229 (47%) were excluded, 104 (22%) were actively undergoing evaluation, and 112 (23%) were withdrawn before evaluation was complete. Criteria for exclusion were medical (n = 150), psychosocial (n = 22), or histocompatibility (n = 57) reasons. Of the 150 prospective donors excluded for medical reasons, 79% were excluded because of obesity, hypertension, nephrolithiasis, and/or abnormal glucose tolerance. One hundred and forty-seven (61%) intended recipients had only one prospective living donor, of whom 63 (42%) were excluded.A significant proportion of prospective living kidney donors were excluded for medical reasons such as obesity (body mass index >30), hypertension, nephrolithiasis, and abnormal glucose tolerance. Longer-term studies are needed to characterize the risks to medically complex kidney donors and the potential risks and benefits afforded to recipients.

    View details for DOI 10.1111/j.1399-0012.2010.01336.x

    View details for PubMedID 21044160

  • Model to Predict Mortality in Critically Ill Adults with Acute Kidney Injury CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Demirjian, S., Chertow, G. M., Zhang, J. H., O'Connor, T. Z., Vitale, J., Paganini, E. P., Palevsky, P. M. 2011; 6 (9): 2114-2120

    Abstract

    Acute kidney injury (AKI) requiring dialysis is associated with high mortality. Most prognostic tools used to describe case complexity and to project patient outcome lack predictive accuracy when applied in patients with AKI. In this study, we developed an AKI-specific predictive model for 60-day mortality and compared the model to the performance of two generic (Sequential Organ Failure Assessment [SOFA] and Acute Physiology and Chronic Health Evaluation II [APACHE II]) scores, and a disease specific (Cleveland Clinic [CCF]) score.Data from 1122 subjects enrolled in the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network study; a multicenter randomized trial of intensive versus less intensive renal support in critically ill patients with AKI conducted between November 2003 and July 2007 at 27 VA- and university-affiliated centers.The 60-day mortality was 53%. Twenty-one independent predictors of 60-day mortality were identified. The logistic regression model exhibited good discrimination, with an area under the receiver operating characteristic (ROC) curve of 0.85 (0.83 to 0.88), and a derived integer risk score yielded a value of 0.80 (0.77 to 0.83). Existing scoring systems, including APACHE II, SOFA, and CCF, when applied to our cohort, showed relatively poor discrimination, reflected by areas under the ROC curve of 0.68 (0.64 to 0.71), 0.69 (0.66 to 0.73), and 0.65 (0.62 to 0.69), respectively.Our new risk model outperformed existing generic and disease-specific scoring systems in predicting 60-day mortality in critically ill patients with AKI. The current model requires external validation before it can be applied to other patient populations.

    View details for DOI 10.2215/CJN.02900311

    View details for Web of Science ID 000294654200005

    View details for PubMedID 21896828

    View details for PubMedCentralID PMC3359007

  • Predialysis Nephrology Care of Older Patients Approaching End-stage Renal Disease ARCHIVES OF INTERNAL MEDICINE Winkelmayer, W. C., Liu, J., Chertow, G. M., Tamura, M. K. 2011; 171 (15): 1371-1378

    Abstract

    Little is known about trends in the timing of first nephrology consultation and associated outcomes among older patients initiating dialysis.Data from patients aged 67 years or older who initiated dialysis in the United States between January 1, 1996, and December 31, 2006, were stratified by timing of the earliest identifiable nephrology visit. Trends of earlier nephrology consultation were formally examined in light of concurrently changing case mix and juxtaposed with trends in 1-year mortality rates after initiation of dialysis.Among 323,977 older patients initiating dialysis, the proportion of patients receiving nephrology care less than 3 months before initiation of dialysis decreased from 49.6% (in 1996) to 34.7% (in 2006). Patients initiated dialysis with increasingly preserved kidney function, from a mean estimated glomerular filtration rate of 8 mL/min/1.73 m(2) in 1996 to 12 mL/min/1.73 m(2) in 2006. Patients were less anemic in later years, which was partly attributable to increased use of erythropoiesis-stimulating agents, and fewer used peritoneal dialysis as the initial modality. During the same period, crude 1-year mortality rates remained unchanged (annual change in mortality rate, +0.2%; 95% confidence interval, 0% to +0.4%). Adjustment for changes in demographic and comorbidity patterns yielded estimated annual reductions in 1-year mortality rates of 0.9% (95% confidence interval, 0.7% to 1.1%), which were explained only partly by concurrent trends toward earlier nephrology consultation (annual mortality reduction after accounting for timing of nephrology care was attenuated to 0.4% [0.2% to 0.6%]).Despite significant trends toward earlier use of nephrology consultation among older patients approaching maintenance dialysis, we observed no material improvement in 1-year survival rates after dialysis initiation during the same time period.

    View details for Web of Science ID 000293642800013

    View details for PubMedID 21824952

    View details for PubMedCentralID PMC4123329

  • Assessment and management of vascular disease risk in patients with chronic kidney disease JOURNAL OF CLINICAL LIPIDOLOGY Brown, W. V., Bakris, G., Lerma, E., Chertow, G. 2011; 5 (4): 251-260

    View details for DOI 10.1016/j.jacl.2011.05.001

    View details for Web of Science ID 000293939300002

    View details for PubMedID 21784369

  • Angiotensin Converting Enzyme Inhibitors in Hemodialysis Chang, T. I., Shilane, D., Brunelli, S. M., Cheung, A. K., Chertow, G. M., Winkelmayer, W. C. WILEY PERIODICALS, INC. 2011: S15–S15
  • Intradialytic Hypotension and Vascular Access Thrombosis JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Chang, T. I., Paik, J., Greene, T., Desai, M., Bech, F., Cheung, A. K., Chertow, G. M. 2011; 22 (8): 1526-1533

    Abstract

    Identifying potential modifiable risk factors to reduce the incidence of vascular access thrombosis in hemodialysis could reduce considerable morbidity and health care costs. We analyzed data from a subset of 1426 HEMO study subjects to determine whether more frequent intradialytic hypotension and/or lower predialysis systolic BP were associated with higher rates of vascular access thrombosis. Our primary outcome measure was episodes of vascular access thrombosis occurring within a given 6-month period during HEMO study follow-up. There were 2005 total episodes of vascular access thrombosis during a median 3.1 years of follow-up. The relative rate of thrombosis of native arteriovenous fistulas for the highest quartile of intradialytic hypotension was approximately twice that of the lowest quartile, independent of predialysis systolic BP and other covariates. There was no significant association of intradialytic hypotension with prosthetic arteriovenous graft thrombosis after multivariable adjustment. Higher predialysis systolic BP was associated with a lower rate of fistula and graft thrombosis, independent of intradialytic hypotension and other covariates. In conclusion, more frequent episodes of intradialytic hypotension and lower predialysis systolic BP associate with increased rates of vascular access thrombosis. These results underscore the importance of including vascular access patency in future studies of BP management in hemodialysis.

    View details for DOI 10.1681/ASN.2010101119

    View details for PubMedID 21803971

  • Angiotensin-converting enzyme inhibitors and cardiovascular outcomes in patients on maintenance hemodialysis AMERICAN HEART JOURNAL Chang, T. I., Shilane, D., Brunelli, S. M., Cheung, A. K., Chertow, G. M., Winkelmayer, W. C. 2011; 162 (2): 324-330

    Abstract

    Persons with end-stage renal disease (ESRD) on hemodialysis carry an exceptionally high burden of cardiovascular disease. Angiotensin-converting enzyme inhibitors (ACEIs) are recommended for patients on dialysis, but there are few data regarding their effectiveness in ESRD.We conducted a secondary analysis of results of the HEMO study, a randomized trial of dialysis dose and membrane flux in patients on maintenance hemodialysis. We focused on the nonrandomized exposure of ACEI use, using proportional hazards regression and a propensity score analysis. The primary outcome was all-cause mortality. Secondary outcomes examined in the present analysis were cardiovascular hospitalization, heart failure hospitalization, and the composite outcomes of death or cardiovascular hospitalization and death or heart failure hospitalization.In multivariable-adjusted analyses, there were no significant associations among ACEI use and mortality (hazard ratio 0.97, 95% CI 0.82-1.14), cardiovascular hospitalization, and either composite outcome. Angiotensin-converting enzyme inhibitor use was associated with a higher risk of heart failure hospitalization (hazard ratio 1.41, 95% CI 1.11-1.80). In the propensity score-matched cohort, ACEI use was not significantly associated with any outcomes, including heart failure hospitalization.In a well-characterized cohort of patients on maintenance hemodialysis, ACEI use was not significantly associated with mortality or cardiovascular morbidity. The higher risk of heart failure hospitalization associated with ACEI use may not only reflect residual confounding but also highlights gaps in evidence when applying treatments proven effective in the general population to patients with ESRD. Our results underscore the need for definitive trials in ESRD to inform the treatment of cardiovascular disease.

    View details for DOI 10.1016/j.ahj.2011.05.004

    View details for PubMedID 21835294

  • Burden on caregivers as perceived by hemodialysis patients in the Frequent Hemodialysis Network (FHN) trials NEPHROLOGY DIALYSIS TRANSPLANTATION Suri, R. S., Larive, B., Garg, A. X., Hall, Y. N., Pierratos, A., Chertow, G. M., Gorodetskeya, I., Kliger, A. S. 2011; 26 (7): 2316-2322

    Abstract

    Patients with end-stage renal disease often rely on unpaid caregivers to assist them with their daily living and medical needs. We characterized the degree to which patients enrolled in the Frequent Hemodialysis Network (FHN) trials perceived burden on their unpaid caregivers.Participants completed the Cousineau Perceived Burden Scale, a 10-question scale previously developed in hemodialysis (HD) patients. Associations between baseline burden score and prespecified variables were evaluated using multivariable linear regression.Of 412 participants, 236 (57%) reported having unpaid caregivers. Compared to those without unpaid caregivers, these participants had greater comorbidity (Charlson mean 1.8 ± 1.8 versus 1.2 ± 1.7, P < 0.001), lower Short Form-36 (SF-36) Physical Health Composite (PHC) scores (median 33 versus 41, P < 0.001, higher Beck Depression scores (mean 16 ± 11 versus 12 ± 9, P < 0.001), and worse physical function. Median Cousineau score was 35 (interquartile range 20-53) (theoretical range 0-100). Over 50% felt their caregivers were overextended, yet 60% were confident that their caregivers could handle the demands of caring for them. Higher perceived burden was not associated with ability to be randomized. In adjusted analyses, Cousineau score was inversely associated with SF-36 PHC and Mental Health Composite scores and directly associated with Beck Depression score (each P < 0.001).Most HD patients in the FHN trials perceived substantial burden on their unpaid caregivers, and self-perceived burden was associated with worse depression and quality of life. Evaluation of the effects of frequent HD on perceived burden borne by caregivers in the FHN trials will help to establish the net benefits/determents of these intensive dialytic strategies.

    View details for DOI 10.1093/ndt/gfr007

    View details for Web of Science ID 000292329500040

    View details for PubMedID 21421590

  • Risk of Cardiovascular Events after Infection-Related Hospitalizations in Older Patients on Dialysis CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Dalrymple, L. S., Mohammed, S. M., Mu, Y., Johansen, K. L., Chertow, G. M., Grimes, B., Kaysen, G. A., Nguyen, D. V. 2011; 6 (7): 1708-1713

    Abstract

    Infection and cardiovascular disease are leading causes of hospitalization and death in patients on dialysis. The objective of this study was to determine whether an infection-related hospitalization increased the short-term risk of a cardiovascular event in older patients on dialysis.With use of the United States Renal Data System, patients aged 65 to 100 years who started dialysis between January 1, 2000, and December 31, 2002, were examined. All hospitalizations were examined from study entry until time of transplant, death, or December 31, 2004. All discharge diagnoses were examined to determine if an infection occurred during hospitalization. Only principal discharge diagnoses were examined to ascertain cardiovascular events of interest. We used the self-controlled case-series method to estimate the relative incidence of a cardiovascular event within 90 days after an infection-related hospitalization as compared with other times not within 90 days of such a hospitalization.A total of 16,874 patients had at least one cardiovascular event and were included in the self-controlled case-series analysis. The risk of a cardiovascular event was increased by 25% in the first 30 days after an infection and was overall increased 18% in the 90 days after an infection-related hospitalization relative to control periods.The first 90 days, and in particular the first 30 days, after an infection-related hospitalization is a high-risk period for cardiovascular events and may be an important timeframe for cardiovascular risk reduction, monitoring, and intervention in older patients on dialysis.

    View details for DOI 10.2215/CJN.10151110

    View details for Web of Science ID 000292618300027

    View details for PubMedID 21566109

    View details for PubMedCentralID PMC3133476

  • Incidence, Correlates, and Consequences of Acute Kidney Injury in Patients With Pulmonary Arterial Hypertension Hospitalized With Acute Right-Side Heart Failure JOURNAL OF CARDIAC FAILURE Haddad, F., Fuh, E., Peterson, T., Skhiri, M., Kudelko, K. T., Perez, V. D., Winkelmayer, W. C., Doyle, R. L., Chertow, G. M., Zamanian, R. T. 2011; 17 (7): 533-539

    Abstract

    Though much is known about the prognostic influence of acute kidney injury (AKI) in left-side heart failure, much less is known about AKI in patients with pulmonary arterial hypertension (PAH).We identified consecutive patients with PAH who were hospitalized at Stanford Hospital for acute right-side heart failure. AKI was diagnosed according to the criteria of the Acute Kidney Injury Network. From June 1999 to June 2009, 105 patients with PAH were hospitalized for acute right-side heart failure (184 hospitalizations). AKI occurred in 43 hospitalizations (23%) in 34 patients (32%). The odds of developing AKI were higher among patients with chronic kidney disease (odds ratio [OR] 3.9, 95% confidence interval [CI] 1.8-8.5), high central venous pressure (OR 1.8, 95% CI 1.1-2.4, per 5 mm Hg), and tachycardia on admission (OR 4.3, 95% CI 2.1-8.8). AKI was strongly associated with 30-day mortality after acute right-side heart failure hospitalization (OR 5.3, 95% CI 2.2-13.2).AKI is relatively common in patients with PAH and associated with a short-term risk of death.

    View details for DOI 10.1016/j.cardfail.2011.03.003

    View details for PubMedID 21703524

  • Update in Nephrology: Evidence Published in 2010 ANNALS OF INTERNAL MEDICINE Arora, N., Chertow, G. M. 2011; 154 (12): 824-U79

    View details for PubMedID 21464341

  • Modeled Urea Distribution Volume and Mortality in the HEMO Study CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Daugirdas, J. T., Greene, T., Depner, T. A., Levin, N. W., Chertow, G. M. 2011; 6 (5): 1129-1138

    Abstract

    In the Hemodialysis (HEMO) Study, observed small decreases in achieved equilibrated Kt/V(urea) were noncausally associated with markedly increased mortality. Here we examine the association of mortality with modeled volume (V(m)), the denominator of equilibrated Kt/V(urea).Parameters derived from modeled urea kinetics (including V(m)) and blood pressure (BP) were obtained monthly in 1846 patients. Case mix-adjusted time-dependent Cox regressions were used to relate the relative mortality hazard at each time point to V(m) and to the change in V(m) over the preceding 6 months. Mixed effects models were used to relate V(m) to changes in intradialytic systolic BP and to other factors at each follow-up visit.Mortality was associated with V(m) and change in V(m) over the preceding 6 months. The association between change in V(m) and mortality was independent of vascular access complications. In contrast, mortality was inversely associated with V calculated from anthropometric measurements (V(ant)). In case mix-adjusted analysis using V(m) as a time-dependent covariate, the association of mortality with V(m) strengthened after statistical adjustment for V(ant). After adjustment for V(ant), higher V(m) was associated with slightly smaller reductions in intradialytic systolic BP and with risk factors for mortality including recent hospitalization and reductions in serum albumin concentration and body weight.An increase in V(m) is a marker for illness and mortality risk in hemodialysis patients.

    View details for DOI 10.2215/CJN.06340710

    View details for Web of Science ID 000290372600025

    View details for PubMedID 21511841

    View details for PubMedCentralID PMC3087780

  • Dialysate sodium and sodium gradient in maintenance hemodialysis: a neglected sodium restriction approach? Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association Munoz Mendoza, J., Sun, S., Chertow, G. M., Moran, J., Doss, S., Schiller, B. 2011; 26 (4): 1281-1287

    Abstract

    A higher sodium gradient (dialysate sodium minus pre-dialysis plasma sodium) during hemodialysis (HD) has been associated with sodium loading; however, its role is not well studied. We hypothesized that a sodium dialysate prescription resulting in a higher sodium gradient is associated with increases in interdialytic weight gain (IDWG), blood pressure (BP) and thirst.We conducted a cross-sectional study on 1084 clinically stable patients on HD. A descriptive analysis of the sodium prescription was performed and clinical associations with sodium gradient were analyzed.The dialysate sodium prescription varied widely across dialysis facilities, ranging from 136 to 149 mEq/L, with a median of 140 mEq/L. The mean pre-HD plasma sodium was 136.7 ± 2.9 mEq/L, resulting in the majority of subjects (n = 904, 83%) being dialyzed against a positive sodium gradient, while the mean sodium gradient was 4.6 ± 4.4 mEq/L. After HD, the plasma sodium increased in nearly all patients (91%), reaching a mean post-HD plasma sodium of 141.3 ± 2.5 mEq/L. We found a direct correlation between IDWG and sodium gradient (r = 0.21, P < 0.0001). After adjustment for confounders and clustering by facilities, the sodium gradient was independently associated with IDWG (70 g/mEq/L, P < 0.0001). There were no significant associations among sodium gradient and BP, whether measured as pre-HD systolic (r = -0.02), diastolic (r = -0.06) or mean arterial pressure (r = -0.04). Post-HD thirst was directly correlated with sodium gradient (r = 0.11, P = 0.02).Sodium gradient is associated with statistically significant and clinically meaningful differences in IDWG in stable patients on HD.

    View details for DOI 10.1093/ndt/gfq807

    View details for PubMedID 21303968

    View details for PubMedCentralID PMC3108351

  • Dialysate sodium and sodium gradient in maintenance hemodialysis: a neglected sodium restriction approach? NEPHROLOGY DIALYSIS TRANSPLANTATION Mendoza, J. M., Sun, S., Chertow, G. M., Moran, J., Doss, S., Schiller, B. 2011; 26 (4): 1281-1287

    Abstract

    A higher sodium gradient (dialysate sodium minus pre-dialysis plasma sodium) during hemodialysis (HD) has been associated with sodium loading; however, its role is not well studied. We hypothesized that a sodium dialysate prescription resulting in a higher sodium gradient is associated with increases in interdialytic weight gain (IDWG), blood pressure (BP) and thirst.We conducted a cross-sectional study on 1084 clinically stable patients on HD. A descriptive analysis of the sodium prescription was performed and clinical associations with sodium gradient were analyzed.The dialysate sodium prescription varied widely across dialysis facilities, ranging from 136 to 149 mEq/L, with a median of 140 mEq/L. The mean pre-HD plasma sodium was 136.7 ± 2.9 mEq/L, resulting in the majority of subjects (n = 904, 83%) being dialyzed against a positive sodium gradient, while the mean sodium gradient was 4.6 ± 4.4 mEq/L. After HD, the plasma sodium increased in nearly all patients (91%), reaching a mean post-HD plasma sodium of 141.3 ± 2.5 mEq/L. We found a direct correlation between IDWG and sodium gradient (r = 0.21, P < 0.0001). After adjustment for confounders and clustering by facilities, the sodium gradient was independently associated with IDWG (70 g/mEq/L, P < 0.0001). There were no significant associations among sodium gradient and BP, whether measured as pre-HD systolic (r = -0.02), diastolic (r = -0.06) or mean arterial pressure (r = -0.04). Post-HD thirst was directly correlated with sodium gradient (r = 0.11, P = 0.02).Sodium gradient is associated with statistically significant and clinically meaningful differences in IDWG in stable patients on HD.

    View details for DOI 10.1093/ndt/gfq807

    View details for Web of Science ID 000289309400026

    View details for PubMedCentralID PMC3108351

  • The ADVANCE study: a randomized study to evaluate the effects of cinacalcet plus low-dose vitamin D on vascular calcification in patients on hemodialysis NEPHROLOGY DIALYSIS TRANSPLANTATION Raggi, P., Chertow, G. M., Torres, P. U., Csiky, B., Naso, A., Nossuli, K., Moustafa, M., Goodman, W. G., Lopez, N., Downey, G., Dehmel, B., Floege, J. 2011; 26 (4): 1327-1339

    Abstract

    This prospective, randomized, controlled trial compared the progression of vascular and cardiac valve calcification in 360 prevalent adult hemodialysis patients with secondary hyperparathyroidism treated with either cinacalcet plus low-dose vitamin D sterols or flexible doses of vitamin D sterols alone.Eligible subjects were on hemodialysis for ≥ 3 months with parathyroid hormone (PTH) > 300 pg/mL or PTH 150-300 pg/mL with calcium-phosphorus product > 50 mg(2)/dL(2) while receiving vitamin D. All subjects received calcium-based phosphate binders. Coronary artery calcification (CAC) and aorta and cardiac valve calcium scores were determined both by Agatston and volume scoring using multi-detector computed tomography. Subjects with Agatston CAC scores ≥ 30 were randomized to cinacalcet (30- 180 mg/day) plus low-dose calcitriol or vitamin D analog (≤ 2 μg paricalcitol equivalent/dialysis), or flexible vitamin D therapy. The primary end point was percentage change in Agatston CAC score from baseline to Week 52.Median (P10, P90) Agatston CAC scores increased 24% (-22%, 119%) in the cinacalcet group and 31% (-9%, 179%) in the flexible vitamin D group (P = 0.073). Corresponding changes in volume CAC scores were 22% (-12%, 105%) and 30% (-6%, 133%; P = 0.009). Increases in calcification scores were consistently less in the aorta, aortic valve and mitral valve among subjects treated with cinacalcet plus low-dose vitamin D sterols, and the differences between groups were significant at the aortic valve.In hemodialysis patients with moderate to severe secondary hyperparathyroidism, cinacalcet plus low-dose vitamin D sterols may attenuate vascular and cardiac valve calcification.

    View details for DOI 10.1093/ndt/gfq725

    View details for Web of Science ID 000289309400032

    View details for PubMedID 21148030

  • Racial Ethnic Differences in Rates and Determinants of Deceased Donor Kidney Transplantation JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Hall, Y. N., Choi, A. I., Xu, P., O'Hare, A. M., Chertow, G. M. 2011; 22 (4): 743-751

    Abstract

    Contemporary studies have not comprehensively compared waiting times and determinants of deceased donor kidney transplantation across all major racial ethnic groups in the Unites States. Here, we compared relative rates and determinants of waitlisting and deceased donor kidney transplantation among 503,090 nonelderly adults of different racial ethnic groups who initiated hemodialysis between1995 and 2006 with follow-up through 2008. Annual rates of deceased donor transplantation from the time of dialysis initiation were lowest in American Indians/Alaska Natives (2.4%) and blacks (2.8%), intermediate in Pacific Islanders (3.1%) and Hispanics (3.2%), and highest in whites (5.9%) and Asians (6.4%). Lower rates of deceased donor transplantation among most racial ethnic minority groups appeared primarily to reflect differences in time from waitlisting to transplantation, but this was not the result of higher rates of waitlist inactivity or removal from the waitlist. The fraction of the reduced transplant rates attributable to measured factors (e.g., demographic, clinical, socioeconomic, linguistic, and geographic factors) varied from 14% in blacks to 43% in American Indians/Alaska Natives compared with whites. In conclusion, adjusted rates of deceased donor kidney transplantation remain significantly lower among racial ethnic minorities compared with whites; generally, differences in time to waitlisting were not as pronounced as differences in time between waitlisting and transplantation. Determinants of delays in time to transplantation differed substantially by racial ethnic group. Area-based efforts targeted to address racial- and ethnic-specific delays in transplantation may help to reduce overall disparities in deceased donor kidney transplantation in the United States.

    View details for DOI 10.1681/ASN.2010080819

    View details for Web of Science ID 000289494600021

    View details for PubMedID 21372209

    View details for PubMedCentralID PMC3065229

  • Aspirin and Arteriovenous Graft Thrombosis in Hemodialysis: Just What the Doctor Ordered? JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Bech, F. R., Chertow, G. M. 2011; 22 (4): 595-597

    View details for DOI 10.1681/ASN.2011020181

    View details for Web of Science ID 000289494600006

    View details for PubMedID 21415154

  • The 2011 ESRD Prospective Payment System: An Uncontrolled Experiment AMERICAN JOURNAL OF KIDNEY DISEASES Winkelmayer, W. C., Chertow, G. M. 2011; 57 (4): 542-546

    View details for DOI 10.1053/j.ajkd.2011.01.013

    View details for Web of Science ID 000288657100373

    View details for PubMedID 21333428

  • Frequent versus Standard Hemodialysis REPLY NEW ENGLAND JOURNAL OF MEDICINE Chertow, G. M., Levin, N. W., Kliger, A. S. 2011; 364 (10): 976
  • Effluent Volume in Continuous Renal Replacement Therapy Overestimates the Delivered Dose of Dialysis CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Claure-Del Gramdo, R., Macedo, E., Chertow, G. M., Soroko, S., Himmelfarb, J., Ikizler, T. A., Paganini, E. P., Mehta, R. L. 2011; 6 (3): 467-475

    Abstract

    Studies examining dose of continuous renal replacement therapy (CRRT) and outcomes have yielded conflicting results. Most studies considered the prescribed dose as the effluent rate represented by ml/kg per hour and reported this volume as a surrogate of solute removal. Because filter fouling can reduce the efficacy of solute clearance, the actual delivered dose may be substantially lower than the observed effluent rate.Data were examined from 52 critically ill patients with acute kidney injury (AKI) requiring dialysis. All patients were treated with predilution continuous venovenous hemodiafiltration (CVVHDF) and regional citrate anticoagulation. Filter performance was monitored during the entire course of therapy by measuring blood urea nitrogen (BUN) and dialysis fluid urea nitrogen (FUN) at initiation and every 12 hours. Filter efficacy was assessed by calculating FUN/BUN ratios every 12 hours of filter use. Prescribed urea clearance (K, ml/min) was determined from the effluent rate. Actual delivered urea clearance was determined using dialysis-side measurements.Median daily treatment time was 1413 minutes (1260 to 1440) with a total effluent volume of 46.4 ± 17.4 L and urea mass removal of 13.0 ± 7.6 mg/min. Prescribed clearance overestimated the actual delivered clearance by 23.8%. This gap between prescribed and delivered clearance was related to the decrease in filter function assessed by the FUN/BUN ratio.Effluent volume significantly overestimates delivered dose of small solutes in CRRT. To assess adequacy of CRRT, solute clearance should be measured rather than estimated by the effluent volume.

    View details for DOI 10.2215/CJN.02500310

    View details for Web of Science ID 000288480100003

    View details for PubMedID 21115626

    View details for PubMedCentralID PMC3082402

  • World Kidney Day 2011 JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Hostetter, T. H., Kochis, D. J., Shaffer, R. N., Chertow, G., Harmon, W. E., Klotman, P. E., Powe, N. R., Sedor, J. R., Smedberg, P. C., Watnick, S., Winkelmayer, W. C. 2011; 22 (3): 397-398

    View details for DOI 10.1681/ASN.2011020115

    View details for Web of Science ID 000288778800001

    View details for PubMedID 21355055

  • Sepsis as a cause and consequence of acute kidney injury: Program to Improve Care in Acute Renal Disease INTENSIVE CARE MEDICINE Mehta, R. L., Bouchard, J., Soroko, S. B., Ikizler, T. A., Paganini, E. P., Chertow, G. M., Himmelfarb, J. 2011; 37 (2): 241-248

    Abstract

    Sepsis commonly contributes to acute kidney injury (AKI); however, the frequency with which sepsis develops as a complication of AKI and the clinical consequences of this sepsis are unknown. This study examined the incidence of, and outcomes associated with, sepsis developing after AKI.We analyzed data from 618 critically ill patients enrolled in a multicenter observational study of AKI (PICARD). Patients were stratified according to their sepsis status and timing of incident sepsis relative to AKI diagnosis.We determined the associations among sepsis, clinical characteristics, provision of dialysis, in-hospital mortality, and length of stay (LOS), comparing outcomes among patients according to their sepsis status. Among the 611 patients with data on sepsis status, 174 (28%) had sepsis before AKI, 194 (32%) remained sepsis-free, and 243 (40%) developed sepsis a median of 5 days after AKI. Mortality rates for patients with sepsis developing after AKI were higher than in sepsis-free patients (44 vs. 21%; p < 0.0001) and similar to patients with sepsis preceding AKI (48 vs. 44%; p = 0.41). Compared with sepsis-free patients, those with sepsis developing after AKI were also more likely to be dialyzed (70 vs. 50%; p < 0.001) and had longer LOS (37 vs. 27 days; p < 0.001). Oliguria, higher fluid accumulation and severity of illness scores, non-surgical procedures after AKI, and provision of dialysis were predictors of sepsis after AKI.Sepsis frequently develops after AKI and portends a poor prognosis, with high mortality rates and relatively long LOS. Future studies should evaluate techniques to monitor for and manage this complication to improve overall prognosis.

    View details for DOI 10.1007/s00134-010-2089-9

    View details for Web of Science ID 000286633500009

    View details for PubMedID 21152901

    View details for PubMedCentralID PMC3028102

  • Vascular Risk Factors and Cognitive Impairment in Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort (CRIC) Study CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Tamura, M. K., Xie, D., Yaffe, K., Cohen, D. L., Teal, V., Kasner, S. E., Messe, S. R., Sehgal, A. R., Kusek, J., DeSalvo, K. B., Cornish-Zirker, D., Cohan, J., Seliger, S. L., Chertow, G. M., Go, A. S. 2011; 6 (2): 248-256

    Abstract

    Cognitive impairment is common among persons with chronic kidney disease, but the extent to which nontraditional vascular risk factors mediate this association is unclear.We conducted cross-sectional analyses of baseline data collected from adults with chronic kidney disease participating in the Chronic Renal Insufficiency Cohort study. Cognitive impairment was defined as a Modified Mini-Mental State Exam score>1 SD below the mean score.Among 3591 participants, the mean age was 58.2±11.0 years, and the mean estimated GFR (eGFR) was 43.4±13.5 ml/min per 1.73 m2. Cognitive impairment was present in 13%. After adjustment for demographic characteristics, prevalent vascular disease (stroke, coronary artery disease, and peripheral arterial disease) and traditional vascular risk factors (diabetes, hypertension, smoking, and elevated cholesterol), an eGFR<30 ml/min per 1.73 m2 was associated with a 47% increased odds of cognitive impairment (odds ratio 1.47, 95% confidence interval 1.05, 2.05) relative to those with an eGFR 45 to 59 ml/min per 1.73 m2. This association was attenuated and no longer significant after adjustment for hemoglobin concentration. While other nontraditional vascular risk factors including C-reactive protein, homocysteine, serum albumin, and albuminuria were correlated with cognitive impairment in unadjusted analyses, they were not significantly associated with cognitive impairment after adjustment for eGFR and other confounders.The prevalence of cognitive impairment was higher among those with lower eGFR, independent of traditional vascular risk factors. This association may be explained in part by anemia.

    View details for DOI 10.2215/CJN.02660310

    View details for PubMedID 20930087

  • Systolic blood pressure and mortality in prevalent haemodialysis patients in the HEMO study JOURNAL OF HUMAN HYPERTENSION Chang, T. I., Friedman, G. D., Cheung, A. K., Greene, T., Desai, M., Chertow, G. M. 2011; 25 (2): 98-105

    Abstract

    Previous studies of blood pressure and mortality in haemodialysis have yielded mixed results, perhaps due to confounding by comorbid conditions. We hypothesized that after improved accounting for confounding factors, higher systolic blood pressure (SBP) would be associated with higher all-cause mortality. We conducted a secondary analysis of data from the haemodialysis study, a randomized trial in prevalent haemodialysis patients. We used three proportional hazard models to determine the relative hazard at different levels of SBP: (1) Model-BL used baseline SBP; (2) Model-TV used SBP as a time-varying variable; and (3) Model-TV-Lag added a 3-month lag to Model-TV to de-emphasize changes in SBP associated with acute illness. In all the models, pre-dialysis SBP <120 mm Hg was associated with a higher risk of mortality compared with the referent group (140-159 mm Hg); higher pre-dialysis SBP was not associated with higher risk of mortality. In conclusion, we observed a robust association between lower pre-dialysis SBP and higher risk for all-cause and cardiovascular mortality in a well-characterized cohort of prevalent haemodialysis patients. Randomized clinical trials are needed to define optimal blood pressure targets in the haemodialysis population.

    View details for DOI 10.1038/jhh.2010.42

    View details for PubMedID 20410919

  • Baseline Characteristics of Participants in the Frequent Hemodialysis Network (FHN) Daily and Nocturnal Trials AMERICAN JOURNAL OF KIDNEY DISEASES Rocco, M. V., Larive, B., Eggers, P. W., Beck, G. J., Chertow, G. M., Levin, N. W., Kliger, A. S. 2011; 57 (1): 90-100

    Abstract

    The annual mortality rate for maintenance hemodialysis patients in the United States is unacceptably high at 15%-20%. In 2004, we initiated the Frequent Hemodialysis Network (FHN) clinical trials. This report presents baseline characteristics of FHN Trial participants and compares them with hemodialysis patients tracked in US Renal Data System (USRDS) data.2 separate randomized clinical trials.FHN includes 332 patients with chronic kidney disease requiring long-term dialysis therapy enrolled in 2 separate randomized clinical trials. The FHN Daily Trial (245 randomly assigned participants) was designed to compare outcomes of 6-times-weekly in-center daily hemodialysis (1.5-2.75 h/session) with conventional 3-times-weekly in-center hemodialysis. The FHN Nocturnal Trial (87 randomly assigned participants) was designed to compare outcomes of 6-times-weekly home nocturnal (6-8 h/session) with conventional 3-times-weekly hemodialysis. USRDS data include 338,109 incident and prevalent long-term hemodialysis patients from the calendar year 2007.Participants in both trials were on average younger than the average hemodialysis patient in the United States (Daily Trial, 50.4 years; P < 0.001; Nocturnal Trial, 52.8 years; P < 0.001). Compared with USRDS data, whites were under-represented in the Daily Trial (36% vs 55%; P < 0.001), whereas Hispanics were under-represented in the Nocturnal Trial and over-represented in the Daily Trial (0% vs 28%; P < 0.001). In addition, there were more fistulas and fewer catheters in the Daily Trial (61% and 20%, respectively; P < 0.001 for both) and fewer grafts and more catheters in the Nocturnal Trial (10% and 44%, respectively; P < 0.005 for both).Clinical trial exclusion criteria and patient willingness to participate limit comparisons with the USRDS.FHN participants were younger and the racial composition for each study was different from the racial composition of the aggregate US dialysis population. Catheters for vascular access were more common in FHN Nocturnal Trial participants.

    View details for DOI 10.1053/j.ajkd.2010.08.024

    View details for Web of Science ID 000285621600014

    View details for PubMedID 21122961

    View details for PubMedCentralID PMC3058226

  • The Phosphate Binder Equivalent Dose SEMINARS IN DIALYSIS Daugirdas, J. T., Finn, W. F., Emmett, M., Chertow, G. M. 2011; 24 (1): 41-49

    Abstract

    Phosphate binders include calcium acetate or carbonate, sevelamer hydrochloride or carbonate, magnesium and lanthanum carbonate, and aluminum carbonate or hydroxide. Their relative phosphate-binding capacity has been assessed in human, in vivo studies that have measured phosphate recovery from stool and/or changes in urinary phosphate excretion or that have compared pairs of different binders where dose of binder in each group was titrated to a target level of serum phosphate. The relative phosphate-binding coefficient (RPBC) based on weight of each binder can be estimated relative to calcium carbonate, the latter being set to 1.0. A systematic review of these studies gave the following estimated RPBC: for elemental lanthanum, 2.0, for sevelamer hydrochloride or carbonate 0.75, for calcium acetate 1.0, for anhydrous magnesium carbonate 1.7, and for "heavy" or hydrated, magnesium carbonate 1.3. Estimated RPBC for aluminum-containing binders were 1.5 for aluminum hydroxide and 1.9 for aluminum carbonate. The phosphate-binding equivalent dose was then defined as the dose of each binder in g × its RPBC, which would be the binding ability of an equivalent weight of calcium carbonate. The phosphate-binding equivalent dose may be useful in comparing changes in phosphate binder prescription over time when multiple binders are being prescribed, when estimating an initial binder prescription, and also in phosphate kinetic modeling.

    View details for DOI 10.1111/j.1525-139X.2011.00849.x

    View details for Web of Science ID 000287579100014

    View details for PubMedID 21338393

  • RELATIONSHIP OF BODY SIZE AND MORTALITY AMONG US ASIANS AND PACIFIC ISLANDERS ON DIALYSIS ETHNICITY & DISEASE Hall, Y. N., Xu, P., Chertow, G. M. 2011; 21 (1): 40-46

    Abstract

    The influence of body size on dialysis-related mortality among Asians and Pacific Islanders--heterogeneous ethnic groups with dissimilar body compositions--is poorly understood. Our study objective was to compare the relations of body size and mortality among patients with end-stage renal disease of different ethnicities.We examined data from a cohort of 21,492 adult Asians, Pacific Islanders and non-Hispanic Whites who initiated dialysis during 1995-2003 within California, Hawaii and the US Pacific Islands.Time to death through September 22, 2008.Among both men and women, Pacific Islanders were the heaviest and Whites the tallest of the ethnic groups examined. Annual mortality rates were highest among Whites (29.6%), intermediate among Pacific Islanders (18.8%) and lowest among Asians (17.3%). Larger body size was associated with lower mortality among Pacific Islanders, Whites and most Asians on dialysis after adjustment for patient-level sociodemographic and clinical factors, area-based socioeconomic status and geographic clustering. Filipinos were the exception to this rule and showed a trend towards higher mortality with increasing body size. These findings were consistent irrespective of how body size was measured.Larger body size is associated with lower mortality among Pacific Islanders, Whites and most Asians on dialysis. Use of disaggregated ethnicity data may enhance our understanding of how ethnicity- or community-specific factors influence body size, body composition and dialysis-related outcomes in these diverse populations.

    View details for Web of Science ID 000288821700007

    View details for PubMedID 21462728

  • Baseline Physical Performance, Health, and Functioning of Participants in the Frequent Hemodialysis Network (FHN) Trial AMERICAN JOURNAL OF KIDNEY DISEASES Kaysen, G. A., Larive, B., Painter, P., Craig, A., Lindsay, R. M., Rocco, M. V., Daugirdas, J. T., Schulman, G., Chertow, G. M. 2011; 57 (1): 101-112

    Abstract

    Self-reported physical health and functioning and direct measures of physical performance are decreased in hemodialysis patients and are associated with mortality and hospitalization.We determined baseline cross-sectional associations of physical performance, health, and functioning with demographics, clinical characteristics, nutritional indexes, laboratory benchmarks, and measures of body composition in participants in the Frequent Hemodialysis Network (FHN) trial.375 persons enrolled in the FHN with data for physical performance, health, and functioning.Explanatory variables were categorized into fixed factors of age, race, comorbid conditions (diabetes mellitus, heart failure, and peripheral arterial disease) and potentially modifiable factors of dialysis dose, phosphorus level, hemoglobin level, equilibrated normalized protein catabolic rate (enPCR), body composition, body mass index, phase angle, and ratio of intracellular water volume to body weight (calculated from bioelectrical impedance).Scores on tests of physical performance, health, and functioning.Physical performance measured using the Short Physical Performance Battery, self-reported physical health and functioning using the 36-Item Short Form Health Survey (SF-36). Body composition (body mass index and bioimpedance analysis) and laboratory data were obtained from affiliated dialysis providers.Relative to population norms, scores for all 3 physicality metrics were low. Poorer scores on all 3 metrics were associated with diabetes mellitus and peripheral arterial disease. Poorer scores on the SF-36 Physical Functioning subscale and Short Physical Performance Battery also were associated with age, lower ratio of intracellular water volume to body weight, and lower enPCR. Black race was associated with poorer scores on the Short Physical Performance Battery.This was a cross-sectional study of individuals agreeing to participate in the FHN study and may not be generalizable to the general dialysis population.Hemodialysis patients show markedly impaired physical performance, health, and functioning relative to population norms. Although some factors associated with these impairments are not modifiable, others may change with improvement in nutritional status or body composition.

    View details for DOI 10.1053/j.ajkd.2010.08.021

    View details for Web of Science ID 000285621600015

    View details for PubMedID 21184919

    View details for PubMedCentralID PMC3073398

  • End-stage Renal Disease. American family physician Abbasi, M., Chertow, G., Hall, Y. 2010; 82 (12): 1512-?

    View details for PubMedID 21166372

  • In-Center Hemodialysis Six Times per Week versus Three Times per Week NEW ENGLAND JOURNAL OF MEDICINE Chertow, G. M., Levin, N. W., Beck, G. J., Depner, T. A., Eggers, P. W., Gassman, J. J., Gorodetskaya, I., Greene, T., James, S., Larive, B., Lindsay, R. M., Mehta, R. L., Miller, B., Ornt, D. B., Rajagopalan, S., Rastogi, A., Rocco, M. V., Schiller, B., Sergeyeva, O., Schulman, G., Ting, G. O., Unruh, M. L., Star, R. A., Kliger, A. S. 2010; 363 (24): 2287-2300

    Abstract

    In this randomized clinical trial, we aimed to determine whether increasing the frequency of in-center hemodialysis would result in beneficial changes in left ventricular mass, self-reported physical health, and other intermediate outcomes among patients undergoing maintenance hemodialysis.Patients were randomly assigned to undergo hemodialysis six times per week (frequent hemodialysis, 125 patients) or three times per week (conventional hemodialysis, 120 patients) for 12 months. The two coprimary composite outcomes were death or change (from baseline to 12 months) in left ventricular mass, as assessed by cardiac magnetic resonance imaging, and death or change in the physical-health composite score of the RAND 36-item health survey. Secondary outcomes included cognitive performance; self-reported depression; laboratory markers of nutrition, mineral metabolism, and anemia; blood pressure; and rates of hospitalization and of interventions related to vascular access.Patients in the frequent-hemodialysis group averaged 5.2 sessions per week; the weekly standard Kt/V(urea) (the product of the urea clearance and the duration of the dialysis session normalized to the volume of distribution of urea) was significantly higher in the frequent-hemodialysis group than in the conventional-hemodialysis group (3.54±0.56 vs. 2.49±0.27). Frequent hemodialysis was associated with significant benefits with respect to both coprimary composite outcomes (hazard ratio for death or increase in left ventricular mass, 0.61; 95% confidence interval [CI], 0.46 to 0.82; hazard ratio for death or a decrease in the physical-health composite score, 0.70; 95% CI, 0.53 to 0.92). Patients randomly assigned to frequent hemodialysis were more likely to undergo interventions related to vascular access than were patients assigned to conventional hemodialysis (hazard ratio, 1.71; 95% CI, 1.08 to 2.73). Frequent hemodialysis was associated with improved control of hypertension and hyperphosphatemia. There were no significant effects of frequent hemodialysis on cognitive performance, self-reported depression, serum albumin concentration, or use of erythropoiesis-stimulating agents.Frequent hemodialysis, as compared with conventional hemodialysis, was associated with favorable results with respect to the composite outcomes of death or change in left ventricular mass and death or change in a physical-health composite score but prompted more frequent interventions related to vascular access. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov number, NCT00264758.).

    View details for DOI 10.1056/NEJMoa1001593

    View details for Web of Science ID 000285092100004

    View details for PubMedID 21091062

    View details for PubMedCentralID PMC3042140

  • Low level of self-reported physical activity in ambulatory patients new to dialysis KIDNEY INTERNATIONAL Johansen, K. L., Chertow, G. M., Kutner, N. G., Dalrymple, L. S., Grimes, B. A., Kaysen, G. A. 2010; 78 (11): 1164-1170

    Abstract

    Physical inactivity contributes to the frailty and the decline in function that develops over time among patients with end-stage renal disease. We assessed physical activity among 1547 ambulatory patients new to dialysis in the United States Renal Data System Comprehensive Dialysis Study. We used a self-reporting Human Activity Profile that included Maximal and Adjusted Activity Scores and compared results to established norms by age and gender. Physical activity was found to be extremely low with scores for all age and gender categories below the 5th percentile of healthy individuals and 95% of patients had scores consonant with low fitness. Older age, female gender, diabetes, atherosclerotic disease, and a low level of education were associated with lower activity scores assessed by univariate and multivariable linear regression analysis. Higher serum albumin, creatinine, and lower body mass index, but not hemoglobin levels, were associated with greater physical activity. By multivariable analysis, patients on hemodialysis using a catheter reported lower levels of physical activity compared to those on peritoneal dialysis, hemodialysis using an arteriovenous fistula, or with a graft. Lower Maximal and Adjusted Activity Scores were associated with poor physical function and mental health. Hence, physical activity is distressingly low among patients new to dialysis. Thus, strategies to enhance activity in these patients should be explored.

    View details for DOI 10.1038/ki.2010.312

    View details for Web of Science ID 000284173300015

    View details for PubMedID 20811334

  • Blood Pressure Control in Type 2 Diabetes Mellitus AMERICAN JOURNAL OF KIDNEY DISEASES Chang, T. I., Cheung, A. K., Chertow, G. M. 2010; 56 (6): 1029-1031

    View details for DOI 10.1053/j.ajkd.2010.08.007

    View details for PubMedID 20870328

  • Curbing the Use of Ultrasonography in the Diagnosis of Acute Kidney Injury Penny Wise or Pound Foolish? ARCHIVES OF INTERNAL MEDICINE Liu, K. D., Chertow, G. M. 2010; 170 (21): 1907-1908

    View details for Web of Science ID 000284480000010

    View details for PubMedID 21098349

  • Off-Label Use of Phosphate Binders in Non-Dialysis-Dependent CKD AMERICAN JOURNAL OF KIDNEY DISEASES Winkelmayer, W. C., Chertow, G. M. 2010; 56 (5): 813-816

    View details for DOI 10.1053/j.ajkd.2010.09.004

    View details for Web of Science ID 000283261700006

    View details for PubMedID 20970022

  • Determinants of Cardiac Autonomic Dysfunction in ESRD CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Chan, C. T., Levin, N. W., Chertow, G. M., Lariye, B., Schulman, G., Kotanko, P. 2010; 5 (10): 1821-1827

    Abstract

    Cardiovascular events are common in patients with ESRD. Whether sympathetic overactivity or vagal withdrawal contribute to cardiovascular events is unclear. We determined the general prevalence and clinical correlates of heart rate variability in patients on hemodialysis.We collected baseline information on demographics, clinical conditions, laboratory values, medications, physical performance, left ventricular mass (LVM), and 24-hour Holter monitoring on 239 subjects enrolled in the Frequent Hemodialysis Network Daily Trial.The mean R-R interval was 812 ± 217 ms. The SD of R-R intervals was 79.1 ± 40.3 ms. Spectral power analyses showed low-frequency (sympathetic modulation of heart rate) and high-frequency power (HF; vagal modulation of heart rate) to be 106.0 (interquartile range, 48.0 to 204 ms(2)) and 42.4 ms(2) (interquartile range, 29.4 to 56.3 ms(2)), respectively. LVM was inversely correlated with log HF (-0.02 [-0.0035; -0.0043]) and the R-R interval (-1.00 [-1.96; -0.032]). Physical performance was associated with mean R-R intervals (1.98 [0.09; 3.87]) and SD of R-R intervals (0.58 [0.049; 1.10]). After adjustment for age, race, ESRD vintage, diabetes, and physical performance, the relationship between log HF and LVM (per 10 g) remained significant (-0.025 [-0.042; -0.0085]).Holter findings in patients on hemodialysis are characterized by sympathetic overactivity and vagal withdrawal and are associated with higher LVM and impaired physical performance. Understanding the spectrum of autonomic heart rate modulation and its determinants could help to guide preventive and therapeutic strategies.

    View details for DOI 10.2215/CJN.03080410

    View details for Web of Science ID 000282836400017

    View details for PubMedID 20616163

    View details for PubMedCentralID PMC2974383

  • Updated comorbidity assessments and outcomes in prevalent hemodialysis patients HEMODIALYSIS INTERNATIONAL Chang, T. I., Paik, J., Greene, T., Miskulin, D. C., Chertow, G. M. 2010; 14 (4): 478-485

    Abstract

    When evaluating clinical characteristics and outcomes in patients on hemodialysis, the prevalence and severity of comorbidity may change over time. Knowing whether updated assessments of comorbidity enhance predictive power will assist the design of future studies. We conducted a secondary data analysis of 1846 prevalent hemodialysis patients from 15 US clinical centers enrolled in the HEMO study. Our primary explanatory variable was the Index of Coexistent Diseases score, which aggregates comorbidities, as a time-constant and time-varying covariate. Our outcomes of interest were all-cause mortality, time to first hospitalization, and total hospitalizations. We used Cox proportional hazards regression. Accounting for an updated comorbidity assessment over time yielded a more robust association with mortality than accounting for baseline comorbidity alone. The variation explained by time-varying comorbidity assessments on time to death was greater than age, baseline serum albumin, diabetes, or any other covariates. There was a less pronounced advantage of updated comorbidity assessments on determining time to hospitalization. Updated assessments of comorbidity significantly strengthen the ability to predict death in patients on hemodialysis. Future studies in dialysis should invest the necessary resources to include repeated assessments of comorbidity.

    View details for DOI 10.1111/j.1542-4758.2010.00468.x

    View details for PubMedID 20955281

  • Can Rescaling Dose of Dialysis to Body Surface Area in the HEMO Study Explain the Different Responses to Dose in Women versus Men? CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Daugirdas, J. T., Greene, T., Chertow, G. M., Depner, T. A. 2010; 5 (9): 1628-1636

    Abstract

    In the Hemodialysis (HEMO) Study, the lower death rate in women but not in men assigned to the higher dose (Kt/V) could have resulted from use of "V" as the normalizing factor, since women have a lower anthropometric V per unit of surface area (V/SA) than men.The effect of Kt/V on mortality was re-examined after normalizing for surface area and expressing dose as surface area normalized standard Kt/V (SAn-stdKt/V).Both men and women in the high-dose group received approximately 16% more dialysis (when expressed as SAn-stdKt/V) than the controls. SAn-stdKt/V clustered into three levels: 2.14/wk for conventional dose women, 2.44/wk for conventional dose men or 2.46/wk for high-dose women, and 2.80/wk for high-dose men. V/SA was associated with the effect of dose assignment on the risk of death; above 20 L/m(2), the mortality hazard ratio = 1.23 (0.99 to 1.53); below 20 L/m(2), hazard ratio = 0.78 (0.65 to 0.95), P = 0.002. Within gender, V/SA did not modify the effect of dose on mortality.When normalized to body surface area rather than V, the dose of dialysis in women in the HEMO Study was substantially lower than in men. The lowest surface-area-normalized dose was received by women randomized to the conventional dose arm, possibly explaining the sex-specific response to dialysis dose. Results are consistent with the hypothesis that when dialysis dose is expressed as Kt/V, women, due to their lower V/SA ratio, require a higher amount than men.

    View details for DOI 10.2215/CJN.02350310

    View details for Web of Science ID 000281685600015

    View details for PubMedID 20595687

    View details for PubMedCentralID PMC2974404

  • On the relative safety of intravenous iron formulations: New answers, new questions AMERICAN JOURNAL OF HEMATOLOGY Chertow, G. M., Winkelmayer, W. C. 2010; 85 (9): 643-644

    View details for DOI 10.1002/ajh.21835

    View details for Web of Science ID 000281601900002

    View details for PubMedID 20687100

  • Infection-Related Hospitalizations in Older Patients With ESRD AMERICAN JOURNAL OF KIDNEY DISEASES Dalrymple, L. S., Johansen, K. L., Chertow, G. M., Cheng, S., Grimes, B., Gold, E. B., Kaysen, G. A. 2010; 56 (3): 522-530

    Abstract

    Infection is an important cause of hospitalization and death in patients receiving dialysis. Few studies have examined the full range of infections experienced by dialysis patients. The purpose of this study is to examine types, rates, and risk factors for infection in older persons starting dialysis therapy.Retrospective observational cohort study.The cohort was assembled from the US Renal Data System and included patients aged 65-100 years who initiated dialysis therapy between January 1, 2000, and December 31, 2002. Exclusions included prior kidney transplant, unknown dialysis modality, or death, loss to follow-up, or transplant during the first 90 days of dialysis therapy. Patients were followed up until death, transplant, or study end on December 31, 2004.Baseline demographics, comorbid conditions, and serum albumin and hemoglobin levels.Infection-related hospitalizations were ascertained using discharge International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Hospitalization rates were calculated for each type of infection. The Wei-Lin-Weissfeld model was used to examine risk factors for up to 4 infection-related events.119,858 patients were included, 7,401 of whom were on peritoneal dialysis therapy. During a median follow-up of 1.9 years, infection-related diagnoses were observed in approximately 35% of all hospitalizations. Approximately 50% of patients had at least 1 infection-related hospitalization. Rates (per 100 person-years) of pulmonary, soft-tissue, and genitourinary infections ranged from 8.3-10.3 in patients on peritoneal dialysis therapy and 10.2-15.3 in patients on hemodialysis therapy. Risk factors for infection included older age, female sex, diabetes, heart failure, pulmonary disease, and low serum albumin level.Use of ICD-9-CM codes, reliance on Medicare claims to capture hospitalizations, use of the Medical Evidence Form to ascertain comorbid conditions, and absence of data for dialysis access.Infection-related hospitalization is frequent in older patients on dialysis therapy. A broad range of infections, many unrelated to dialysis access, result in hospitalization in this population.

    View details for DOI 10.1053/j.ajkd.2010.04.016

    View details for Web of Science ID 000281203200015

    View details for PubMedID 20619518

    View details for PubMedCentralID PMC2926212

  • Prevalence and Correlates of Cognitive Impairment in Hemodialysis Patients: The Frequent Hemodialysis Network Trials CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Tamura, M. K., Larive, B., Unruh, M. L., Stokes, J. B., Nissenson, A., Mehta, R. L., Chertow, G. M. 2010; 5 (8): 1429-1438

    Abstract

    Cognitive impairment is common among persons with ESRD, but the underlying mechanisms are unknown. This study evaluated the prevalence of cognitive impairment and association with modifiable ESRD- and dialysis-associated factors in a large group of hemodialysis patients.Cross-sectional analyses were conducted on baseline data collected from 383 subjects participating in the Frequent Hemodialysis Network trials. Global cognitive impairment was defined as a score <80 on the Modified Mini-Mental State Exam, and impaired executive function was defined as a score >or=300 seconds on the Trailmaking B test. Five main categories of explanatory variables were examined: urea clearance, nutritional markers, hemodynamic measures, anemia, and central nervous system (CNS)-active medications.Subjects had a mean age of 51.6 +/- 13.3 years and a median ESRD vintage of 2.6 years. Sixty-one subjects (16%) had global cognitive impairment, and 110 subjects (29%) had impaired executive function. In addition to several nonmodifiable factors, the use of H1-receptor antagonists and opioids were associated with impaired executive function. No strong association was found between several other potentially modifiable factors associated with ESRD and dialysis therapy, such as urea clearance, proxies of dietary protein intake and other nutritional markers, hemodynamic measures, and anemia with global cognition and executive function after adjustment for case-mix factors.Cognitive impairment, especially impaired executive function, is common among hemodialysis patients, but with the exception of CNS-active medications, is not strongly associated with several ESRD- and dialysis-associated factors.

    View details for DOI 10.2215/CJN.01090210

    View details for PubMedID 20576825

  • Vitamin D deficiency and frailty in older Americans JOURNAL OF INTERNAL MEDICINE Wilhelm-Leen, E. R., Hall, Y. N., DEBOER, I. H., Chertow, G. M. 2010; 268 (2): 171-180

    Abstract

    To explore the relation between 25-hydroxyvitamin D deficiency and frailty. Frailty is a multidimensional phenotype that describes declining physical function and a vulnerability to adverse outcomes in the setting of physical stress such as illness or hospitalization. Low serum concentrations of 25-hydroxyvitamin D are known to be associated with multiple chronic diseases such as cardiovascular disease and diabetes, in addition to all cause mortality.Using data from the Third National Health and Nutrition Survey (NHANES III), we evaluated the association between low serum 25-hydroxyvitamin D concentration and frailty, defined according to a set of criteria derived from a definition previously described and validated.Nationally representative survey of noninstitutionalized US residents collected between 1988 and 1994.25-Hydroxyvitamin D deficiency, defined as a serum concentration <15 ng mL(-1), was associated with a 3.7-fold increase in the odds of frailty amongst whites and a fourfold increase in the odds of frailty amongst non-whites. This association persisted after sensitivity analyses adjusting for season of the year and latitude of residence, intended to reduce misclassification of persons as 25-hydroxyvitamin D deficient or insufficient.Low serum 25-hydroxyvitamin D concentrations are associated with frailty amongst older adults.

    View details for DOI 10.1111/j.1365-2796.2010.02248.x

    View details for PubMedID 20528970

  • Hyperparathyroidism with hypercalcaemia in chronic kidney disease: primary or tertiary? NDT plus Lunn, M. R., Muñoz Mendoza, J., Pasche, L. J., Norton, J. A., Ayco, A. L., Chertow, G. M. 2010; 3 (4): 366-371

    Abstract

    Objective . This study aims to highlight the challenges in the diagnosis of hyperparathyroidism (HPT) in patients with advanced chronic kidney disease (CKD). Methods . In this report, we describe a middle-aged Filipino gentleman with underlying CKD who presented with intractable nausea, vomiting, severe and medically refractory hypercalcaemia and parathyroid hormone (PTH) concentrations in excess of 2400 pg/mL. The underlying pathophysiology as well as the aetiologies and current relevant literature are discussed. We also suggest an appropriate diagnostic approach to identify and promptly treat patients with CKD, HPT and hypercalcaemia. Results . Evaluation confirmed the presence of a large parathyroid adenoma; HPT and hypercalcaemia resolved rapidly following resection. Conclusion . This case report is remarkable for its severe hypercalcaemia requiring haemodialysis, large adenoma size, acute-on-chronic kidney injury and markedly elevated PTH concentration in association with primary HPT in CKD.

    View details for DOI 10.1093/ndtplus/sfq077

    View details for PubMedID 25949433

  • Projected Effect of Dietary Salt Reductions on Future Cardiovascular Disease EDITORIAL COMMENT OBSTETRICAL & GYNECOLOGICAL SURVEY Bibbins-Domingo, K., Chertow, G. M., Coxson, P. G., Moran, A., Lightwood, J. M., Pletcher, M. J., Goldman, L. 2010; 65 (7): 441–42
  • Reexploring Differences among For-Profit and Nonprofit Dialysis Providers HEALTH SERVICES RESEARCH Lee, D. K., Chertow, G. M., Zenios, S. A. 2010; 45 (3): 633-646

    Abstract

    To determine whether profit status is associated with differences in hospital days per patient, an outcome that may also be influenced by provider financial goals.United States Renal Data System Standard Analysis Files and Centers for Medicare and Medicaid Services cost reports.We compared the number of hospital days per patient per year across for-profit and nonprofit dialysis facilities during 2003. To address possible referral bias in the assignment of patients to dialysis facilities, we used an instrumental variable regression method and adjusted for selected patient-specific factors, facility characteristics such as size and chain affiliation, as well as metrics of market competition.All patients who received in-center hemodialysis at any time in 2003 and for whom Medicare was the primary payer were included (N=170,130; roughly two-thirds of the U.S. hemodialysis population). Patients dialyzed at hospital-based facilities and patients with no dialysis facilities within 30 miles of their residence were excluded.Overall, adjusted hospital days per patient were 17+/-5 percent lower in nonprofit facilities. The difference between nonprofit and for-profit facilities persisted with the correction for referral bias. There was no association between hospital days per patient per year and chain affiliation, but larger facilities had inferior outcomes (facilities with 73 or more patients had a 14+/-1.7 percent increase in hospital days relative to facilities with 35 or fewer patients). Differences in outcomes among for-profit and nonprofit facilities translated to 1,600 patient-years in hospital that could be averted each year if the hospital utilization rates in for-profit facilities were to decrease to the level of their nonprofit counterparts.Hospital days per patient-year were statistically and clinically significantly lower among nonprofit dialysis providers. These findings suggest that the indirect incentives in Medicare's current payment system may provide insufficient incentive for for-profit providers to achieve optimal patient outcomes.

    View details for DOI 10.1111/j.1475-6773.2010.01103.x

    View details for Web of Science ID 000277291400003

    View details for PubMedID 20403066

    View details for PubMedCentralID PMC2875752

  • Study design and subject baseline characteristics in the ADVANCE study: effects of cinacalcet on vascular calcification in haemodialysis patients NEPHROLOGY DIALYSIS TRANSPLANTATION Floege, J., Raggi, P., Block, G. A., Torres, P. U., Csiky, B., Naso, A., Nossuli, K., Moustafa, M., Goodman, W. G., Lopez, N., Downey, G., Dehmel, B., Chertow, G. M. 2010; 25 (6): 1916-1923

    Abstract

    The ADVANCE (A Randomized Study to Evaluate the Effects of Cinacalcet plus Low-Dose Vitamin D on Vascular Calcification in Subjects with Chronic Kidney Disease Receiving Haemodialysis) Study objective is to assess the effect of cinacalcet plus low-dose active vitamin D versus flexible dosing of active vitamin D on progression of coronary artery calcification (CAC) in haemodialysis patients. We report the ADVANCE Study design and baseline subject characteristics.ADVANCE is a multinational, multicentre, randomized, open-label study. Adult haemodialysis patients with moderate to severe secondary hyperparathyroidism (intact parathyroid hormone [iPTH] >300 pg/mL or bio-intact PTH >160 pg/mL) and baseline CAC score >or=30 were stratified by CAC score (>or=30-399, >or=400-999, >or=1000) and randomized in a 1:1 ratio to cinacalcet (30-180 mg/day) plus low-dose active vitamin D (cinacalcet group) or flexible dosing of active vitamin D alone (control). The study had three phases: screening, 20-week dose titration and 32-week follow-up. CAC scores obtained by cardiac computed tomography were determined at screening and weeks 28 and 52. The primary end point was percentage change in CAC score from baseline to Week 52.Subjects (n = 360) were randomized to cinacalcet or control. Mean age was 61.5 years, 43% were women, and median dialysis vintage was 36.7 months (range, 2.7-351.5 months). The baseline geometric mean CAC score by the Agatston method was 548.7 (95% confidence interval, 480.5-626.6). Baseline CAC score was independently associated with age, sex, dialysis vintage, diabetes and iPTH. Subjects also had extensive aortic and valvular calcification at baseline.Subjects enrolled in ADVANCE have extensive CAC at baseline. The ADVANCE Study should help determine whether cinacalcet attenuates progression of vascular calcification.

    View details for DOI 10.1093/ndt/gfp762

    View details for Web of Science ID 000280027400033

    View details for PubMedID 20110249

  • Kidney Disease, Hospitalized Hypertension, and Cardiovascular Events: Cause or Consequence? CIRCULATION Chertow, G. M., Chang, T. I. 2010; 121 (20): 2160-2161
  • Chronic Kidney Disease in the Urban Poor CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Hall, Y. N., Choi, A. I., Chertow, G. M., Bindman, A. B. 2010; 5 (5): 828-835

    Abstract

    In the United States, relatively little is known about clinical outcomes of chronic kidney disease (CKD) in vulnerable populations utilizing public health systems. The primary study objectives were to describe patient characteristics, incident ESRD, and mortality in adults with nondialysis-dependent CKD receiving care in the health care safety net.Time to ESRD and time to death were examined among a cohort of 15,353 ambulatory adults with nondialysis-dependent CKD from the Community Health Network of San Francisco.The mean age of the CKD cohort was 59.0 +/- 13.8 years; 50% of the cohort was younger than 60 years and 26% was younger than 50 years. Most (72%) were members of nonwhite racial-ethnic groups, 73% were indigent (annual income <$15,000) and 18% were uninsured. In adjusted analyses, blacks [hazard ratio (95% confidence interval), 4.00 (2.99 to 5.35)], Hispanics [2.20 (1.46 to 3.30)], and Asians/Pacific Islanders [3.84 (2.73 to 5.40)] had higher risks of progression to ESRD than non-Hispanic whites. The higher risk of progression to ESRD among nonwhite compared with white persons with CKD was not explained by lower relative mortality.Adults with CKD stages 3 to 5 cared for within an urban public health system were relatively young and predominantly nonwhite-both factors associated with a higher risk of progression to ESRD. These findings call for targeted efforts to assess the burden and progression of CKD within other public and safety-net health systems in this country.

    View details for DOI 10.2215/CJN.09011209

    View details for Web of Science ID 000277483300016

    View details for PubMedID 20200149

    View details for PubMedCentralID PMC2863975

  • Weekend Hospital Admission, Acute Kidney Injury, and Mortality JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY James, M. T., Wald, R., Bell, C. M., Tonelli, M., Hemmelgarn, B. R., Waikar, S. S., Chertow, G. M. 2010; 21 (5): 845-851

    Abstract

    Admission to the hospital on weekends is associated with increased mortality for several acute illnesses. We investigated whether patients admitted on a weekend with acute kidney injury (AKI) were more likely to die than those admitted on a weekday. Using the Nationwide Inpatient Sample, a large database of admissions to acute care, nonfederal hospitals in the United States, we identified 963,730 admissions with a diagnosis of AKI between 2003 and 2006. Of these, 214,962 admissions (22%) designated AKI as the primary reason for admission (45,203 on a weekend and 169,759 on a weekday). We used logistic regression models to examine the adjusted odds of in-hospital mortality associated with weekend versus weekday admission. Compared with admission on a weekday, patients admitted with a primary diagnosis of AKI on a weekend had a higher odds of death [adjusted odds ratio (OR) 1.07, 95% confidence interval (CI) 1.02 to 1.12]. The risk for death with admission on a weekend for AKI was more pronounced in smaller hospitals (adjusted OR 1.17, 95% CI 1.03 to 1.33) compared with larger hospitals (adjusted OR 1.07, 95% CI 1.01 to 1.13). Increased mortality was also associated with weekend admission among patients with AKI as a secondary diagnosis across a spectrum of co-existing medical diagnoses. In conclusion, among patients hospitalized with AKI, weekend admission is associated with a higher risk for death compared with admission on a weekday.

    View details for DOI 10.1681/ASN.2009070682

    View details for Web of Science ID 000277600400019

    View details for PubMedID 20395373

    View details for PubMedCentralID PMC2865737

  • Standard Kt/V-urea: a method of calculation that includes effects of fluid removal and residual kidney clearance KIDNEY INTERNATIONAL Daugirdas, J. T., Depner, T. A., Greene, T., Levin, N. W., Chertow, G. M., Rocco, M. V. 2010; 77 (7): 637-644

    Abstract

    Standard Kt/V(urea) (stdKt/V) is a hypothetical continuous clearance in patients treated with intermittent hemodialysis based on the generation rate of urea nitrogen and the average predialysis urea nitrogen. Previous equations to estimate stdKt/V were derived using a fixed-volume model. To determine the impact of fluid removal as well as residual urea clearance on stdKt/V, we modeled 245 hemodialysis sessions (including conventional 3/week, in-center 6/week, and at-home nocturnal 6/week) in 210 patients enrolled in the Frequent Hemodialysis Network Daily and Nocturnal clinical trials. To examine the role of fluid removal, modeled stdKt/V was compared to stdKt/V estimated from a previously published simplified equation. In a subgroup of 45 sessions with residual urea clearance over 1.5 ml/min, the contribution of residual urea clearance to stdKt/V was measured. For all dialysis schedules, the fixed-volume equation predicted stdKt/V well when both fluid removal and residual urea clearance were set to zero. When fluid removal was included, modeled stdKt/V was slightly underestimated for all three modes of hemodialysis. The shortfall correlated directly with weekly fluid removal and inversely with modeled urea volume. Modeled stdKt/V compressed residual urea clearance to about 70% of its measured value and the fractional downsizing significantly correlated inversely with treatment Kt/V. Our new equation predicted modeled stdKt/V with a high level of accuracy, even when substantial fluid removal and residual urea clearance were present.

    View details for DOI 10.1038/ki.2009.525

    View details for Web of Science ID 000275573500012

    View details for PubMedID 20107428

  • GFR estimating equations, CKD prevalence and the public health JOURNAL OF INTERNAL MEDICINE Chang, T. I., Chertow, G. M. 2010; 267 (4): 354-356
  • Shorter dialysis times are associated with higher mortality among incident hemodialysis patients KIDNEY INTERNATIONAL Brunelli, S. M., Chertow, G. M., Ankers, E. D., Lowrie, E. G., Thadhani, R. 2010; 77 (7): 630-636

    Abstract

    There is an association between hemodialysis session length and mortality independent of the effects of session duration on urea clearance. However, previous studies did not consider changes in session length over time nor did they control for the influence of time-dependent confounding. Using data from a national cohort of 8552 incident patients on thrice-weekly, in-center hemodialysis, we applied marginal structural analysis to determine the association between session length and mortality. Exposure was based on prescribed session length with the outcome being death from any cause. On the 31st day after initiating dialysis, the patients were considered at-risk and remained so until death, censoring, or completion of 1 year on dialysis. On primary marginal structural analysis, session lengths <4 h were associated with a 42% increase in mortality. Sensitivity analyses showed a dose-response relationship between session duration and mortality, and a consistency of findings across prespecified subgroups. Our study suggests that shorter hemodialysis sessions are associated with higher mortality when marginal structural analysis was used to adjust for time-dependent confounding. Further studies are needed to confirm these findings and determine causality.

    View details for DOI 10.1038/ki.2009.523

    View details for Web of Science ID 000275573500011

    View details for PubMedID 20090666

    View details for PubMedCentralID PMC2864594

  • The elderly patients on hemodialysis. Minerva urologica e nefrologica = The Italian journal of urology and nephrology Anand, S., Kurella Tamura, M., Chertow, G. M. 2010; 62 (1): 87-101

    Abstract

    Nephrologists care for an increasing number of elderly patients on hemodialysis. As such, an understanding of the overlap among complications of hemodialysis and geriatric syndromes is crucial. This article reviews hemodialysis management issues including vascular access, hypertension, anemia and bone and mineral disorders with an attention towards the distinct medical needs of the elderly. Key concepts of geriatrics frailty, dementia and palliative care are also discussed, as nephrologists frequently participate in decision-making directed toward balancing longevity, functional status and the burden of therapy.

    View details for PubMedID 20424572

  • The elderly patients on hemodialysis MINERVA UROLOGICA E NEFROLOGICA Anand, S., Tamura, M. K., Chertow, G. M. 2010; 62 (1): 87-101

    Abstract

    Nephrologists care for an increasing number of elderly patients on hemodialysis. As such, an understanding of the overlap among complications of hemodialysis and geriatric syndromes is crucial. This article reviews hemodialysis management issues including vascular access, hypertension, anemia and bone and mineral disorders with an attention towards the distinct medical needs of the elderly. Key concepts of geriatrics frailty, dementia and palliative care are also discussed, as nephrologists frequently participate in decision-making directed toward balancing longevity, functional status and the burden of therapy.

    View details for Web of Science ID 000208661300008

  • Projected Effect of Dietary Salt Reductions on Future Cardiovascular Disease NEW ENGLAND JOURNAL OF MEDICINE Bibbins-Domingo, K., Chertow, G. M., Coxson, P. G., Moran, A., Lightwood, J. M., Pletcher, M. J., Goldman, L. 2010; 362 (7): 590-599

    Abstract

    The U.S. diet is high in salt, with the majority coming from processed foods. Reducing dietary salt is a potentially important target for the improvement of public health.We used the Coronary Heart Disease (CHD) Policy Model to quantify the benefits of potentially achievable, population-wide reductions in dietary salt of up to 3 g per day (1200 mg of sodium per day). We estimated the rates and costs of cardiovascular disease in subgroups defined by age, sex, and race; compared the effects of salt reduction with those of other interventions intended to reduce the risk of cardiovascular disease; and determined the cost-effectiveness of salt reduction as compared with the treatment of hypertension with medications.Reducing dietary salt by 3 g per day is projected to reduce the annual number of new cases of CHD by 60,000 to 120,000, stroke by 32,000 to 66,000, and myocardial infarction by 54,000 to 99,000 and to reduce the annual number of deaths from any cause by 44,000 to 92,000. All segments of the population would benefit, with blacks benefiting proportionately more, women benefiting particularly from stroke reduction, older adults from reductions in CHD events, and younger adults from lower mortality rates. The cardiovascular benefits of reduced salt intake are on par with the benefits of population-wide reductions in tobacco use, obesity, and cholesterol levels. A regulatory intervention designed to achieve a reduction in salt intake of 3 g per day would save 194,000 to 392,000 quality-adjusted life-years and $10 billion to $24 billion in health care costs annually. Such an intervention would be cost-saving even if only a modest reduction of 1 g per day were achieved gradually between 2010 and 2019 and would be more cost-effective than using medications to lower blood pressure in all persons with hypertension.Modest reductions in dietary salt could substantially reduce cardiovascular events and medical costs and should be a public health target.

    View details for DOI 10.1056/NEJMoa0907355

    View details for Web of Science ID 000274571200007

    View details for PubMedID 20089957

    View details for PubMedCentralID PMC3066566

  • Chronic Kidney Disease and Cognitive Function in Older Adults: Findings from the Chronic Renal Insufficiency Cohort Cognitive Study JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Yaffe, K., Ackerson, L., Tamura, M. K., Le Blanc, P., Kusek, J. W., Sehgal, A. R., Cohen, D., Anderson, C., Appel, L., DeSalvo, K., Ojo, A., Seliger, S., Robinson, N., Makos, G., Go, A. S. 2010; 58 (2): 338-345

    Abstract

    To investigate cognitive impairment in older, ethnically diverse individuals with a broad range of kidney function, to evaluate a spectrum of cognitive domains, and to determine whether the relationship between chronic kidney disease (CKD) and cognitive function is independent of demographic and clinical factors.Cross-sectional.Chronic Renal Insufficiency Cohort Study.Eight hundred twenty-five adults aged 55 and older with CKD.Estimated glomerular filtration rate (eGFR, mL/min per 1.73 m(2)) was estimated using the four-variable Modification of Diet in Renal Disease equation. Cognitive scores on six cognitive tests were compared across eGFR strata using linear regression; multivariable logistic regression was used to examine level of CKD and clinically significant cognitive impairment (score < or =1 standard deviations from the mean).Mean age of the participants was 64.9, 50.4% were male, and 44.5% were black. After multivariable adjustment, participants with lower eGFR had lower cognitive scores on most cognitive domains (P<.05). In addition, participants with advanced CKD (eGFR<30) were more likely to have clinically significant cognitive impairment on global cognition (adjusted odds ratio (AOR) 2.0, 95% CI=1.1-3.9), naming (AOR=1.9, 95% CI=1.0-3.3), attention (AOR=2.4, 95% CI=1.3-4.5), executive function (AOR=2.5, 95% CI=1.9-4.4), and delayed memory (AOR=1.5, 95% CI=0.9-2.6) but not on category fluency (AOR=1.1, 95% CI=0.6-2.0) than those with mild to moderate CKD (eGFR 45-59).In older adults with CKD, lower level of kidney function was associated with lower cognitive function on most domains. These results suggest that older patients with advanced CKD should be screened for cognitive impairment.

    View details for DOI 10.1111/j.1532-5415.2009.02670.x

    View details for Web of Science ID 000274183800017

    View details for PubMedID 20374407

    View details for PubMedCentralID PMC2852884

  • Comparison of methods for estimating glomerular filtration rate in critically ill patients with acute kidney injury NEPHROLOGY DIALYSIS TRANSPLANTATION Bouchard, J., Macedo, E., Soroko, S., Chertow, G. M., Himmelfarb, J., Ikizler, T. A., Paganini, E. P., Mehta, R. L. 2010; 25 (1): 102-107

    Abstract

    In critically ill patients with acute kidney injury, estimates of kidney function are used to modify drug dosing, adjust nutritional therapy and provide dialytic support. However, estimating glomerular filtration rate is challenging due to fluctuations in kidney function, creatinine production and fluid balance. We hypothesized that commonly used glomerular filtration rate prediction equations overestimate kidney function in patients with acute kidney injury and that improved estimates could be obtained by methods incorporating changes in creatinine generation and fluid balance.We analysed data from a multicentre observational study of acute kidney injury in critically ill patients. We identified 12 non-dialysed, non-oliguric patients with consecutive increases in creatinine for at least 3 and up to 7 days who had measurements of urinary creatinine clearance. Glomerular filtration rate was estimated by Cockcroft-Gault, Modification of Diet in Renal Disease, Jelliffe equation and Jelliffe equation with creatinine adjusted for fluid balance (Modified Jelliffe) and compared to measured urinary creatinine clearance.Glomerular filtration rate estimated by Jelliffe and Modification of Diet in Renal Disease equation correlated best with urinary creatinine clearances. Estimated glomerular filtration rate by Cockcroft-Gault, Modification of Diet in Renal Disease and Jelliffe overestimated urinary creatinine clearance was 80%, 33%, 10%, respectively, and Modified Jelliffe underestimated GFR by 2%.In patients with acute kidney injury, glomerular filtration rate estimating equations can be improved by incorporating data on creatinine generation and fluid balance. A better assessment of glomerular filtration rate in acute kidney injury could improve evaluation and management and guide interventions.

    View details for DOI 10.1093/ndt/gfp392

    View details for Web of Science ID 000273113100019

    View details for PubMedID 19679558

    View details for PubMedCentralID PMC2910324

  • End-stage renal disease. Clinical evidence Abbasi, M. A., Chertow, G. M., Hall, Y. N. 2010; 2010

    Abstract

    End-stage renal disease (ESRD) affects more than 1500 people per million population in countries with a high prevalence, such as Japan, Taiwan, and the US. Approximately two-thirds of people with ESRD receive haemodialysis, one quarter have kidney transplants, and one tenth receive peritoneal dialysis. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of different doses for peritoneal dialysis? What are the effects of different doses and membrane fluxes for haemodialysis? What are the effects of interventions aimed at preventing secondary complications? We searched: Medline, Embase, The Cochrane Library, and other important databases up to October 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).We found 26 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.In this systematic review we present information relating to the effectiveness and safety of the following interventions: cinacalcet, darbepoetin, erythropoietin, haemodialysis (standard-dose, increased-dose), high membrane-flux haemodialysis, increased-dose peritoneal dialysis, low membrane-flux haemodialysis, mupirocin, sevelamer, standard-dose dialysis, and statins.

    View details for PubMedID 21418665

  • Use of Standard Kt/V for Comparison of Efficiency Between Continuous Renal Replacement Therapies and Intermittent Hemodialysis in Acute Kidney Injury Claure-Del Granado, R., Macedo, E., Soroko, S., Chertow, G. M., Himmelfarb, J., Ikizler, A., Paganini, E. P., Mehta, R. L. KARGER. 2010: 229–30
  • Fluid accumulation, recognition and staging of acute kidney injury in critically-ill patients CRITICAL CARE Macedo, E., Bouchard, J., Soroko, S. H., Chertow, G. M., Himmelfarb, J., Ikizler, T. A., Paganini, E. P., Mehta, R. L. 2010; 14 (3)

    Abstract

    Serum creatinine concentration (sCr) is the marker used for diagnosing and staging acute kidney injury (AKI) in the RIFLE and AKIN classification systems, but is influenced by several factors including its volume of distribution. We evaluated the effect of fluid accumulation on sCr to estimate severity of AKI.In 253 patients recruited from a prospective observational study of critically-ill patients with AKI, we calculated cumulative fluid balance and computed a fluid-adjusted sCr concentration reflecting the effect of volume of distribution during the development phase of AKI. The time to reach a relative 50% increase from the reference sCr using the crude and adjusted sCr was compared. We defined late recognition to estimate severity of AKI when this time interval to reach 50% relative increase between the crude and adjusted sCr exceeded 24 hours.The median cumulative fluid balance increased from 2.7 liters on day 2 to 6.5 liters on day 7. The difference between adjusted and crude sCr was significantly higher at each time point and progressively increased from a median difference of 0.09 mg/dL to 0.65 mg/dL after six days. Sixty-four (25%) patients met criteria for a late recognition to estimate severity progression of AKI. This group of patients had a lower urine output and a higher daily and cumulative fluid balance during the development phase of AKI. They were more likely to need dialysis but showed no difference in mortality compared to patients who did not meet the criteria for late recognition of severity progression.In critically-ill patients, the dilution of sCr by fluid accumulation may lead to underestimation of the severity of AKI and increases the time required to identify a 50% relative increase in sCr. A simple formula to correct sCr for fluid balance can improve staging of AKI and provide a better parameter for earlier recognition of severity progression.

    View details for DOI 10.1186/cc9004

    View details for Web of Science ID 000283781800028

    View details for PubMedID 20459609

    View details for PubMedCentralID PMC2911707

  • Effects of Reduced Intradialytic Urea Generation Rate and Residual Renal Clearance on Modeled Urea Distribution Volume and Kt/V in Conventional, Daily, and Nocturnal Dialysis SEMINARS IN DIALYSIS Daugirdas, J. T., Depner, T. A., Greene, T., Levin, N. W., Chertow, G. M., Rocco, M. V., Stokes, J. B. 2010; 23 (1): 19-24

    Abstract

    Classic urea modeling assumes that both urea generation rate (G) and residual renal urea clearance (Kru) are constant throughout the week, but this may not be true. Reductions in intradialysis G could be caused by lower plasma amino acid levels due to predialysis/intradialysis fasting and also to losses of amino acids into the dialysate. Intradialytic reductions in Kru could be due to lower intravascular volume, blood pressure, or osmotic load. To determine the possible effects of reduced G or Kru during dialysis on the calculation of the volume of distribution (V) and Kt/Vurea, we modeled 3 and 6/week nocturnal, 6/week short daily, and 3/week conventional hemodialysis. A modified 2-pool mathematical model of urea mass balance with a constant time-averaged G was used, but the model was altered to allow adjustment of the ratio of dialytic/interdialytic G (Gd/Gid) and dialytic/total Kru (Krud/Kru) to vary from 1.0 down to near zero. In patients dialyzed six times per week for 400 minutes per session, when Gd/Gid was decreased from 1.0 to 0.05, the predicted urea reduction ratio (URR) increased from 68.9% to 80.2%. To achieve an increased URR of this magnitude under conditions of constant G (Gd/Gid=1.0) required a decrease in modeled urea volume (V) of 36%. At Gd/Gid ratios of 0.8 or 0.6 (corresponding to 20% or 40% reductions in intradialysis G), the modeled URR was increased to 71.0% or 73.3%, causing a 7% or 15% factitious decrease in V. The error was intermediate for the 3/week nocturnal schedule, and was much less pronounced for the 6/week daily and 3/week conventional treatments. Reductions in intradialytic Kru had the opposite effect, lowering the predicted URR and increasing the apparent V, but here the errors were of much lesser amplitude. The results suggest that, particularly for nocturnal dialysis, the standard "constant G" urea kinetic model may need to be modified.

    View details for DOI 10.1111/j.1525-139X.2009.00688.x

    View details for Web of Science ID 000274806000007

    View details for PubMedID 20331814

  • Preexisting Chronic Kidney Disease: A Potential for Improved Outcomes from Acute Kidney Injury CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Khosla, N., Soroko, S. B., Chertow, G. M., Himmelfarb, J., Ikizler, T. A., Paganini, E., Mehta, R. L. 2009; 4 (12): 1914-1919

    Abstract

    Acute kidney injury (AKI) is associated with adverse outcomes in critically ill patients. The influence of preexisting chronic kidney disease (CKD) on AKI outcomes is unclear.We analyzed data from a prospective observational cohort study of AKI in critically ill patients who received nephrology consultation: the Program to Improve Care in Acute Renal Disease. In-hospital mortality rate, length of stay, and dialysis dependence were compared in patients with and without a prior history of CKD, defined by an elevated serum creatinine, proteinuria, and/or abnormal renal ultrasound within a year before hospitalization. We hypothesized that patients with AKI and prior history of CKD would have lower mortality rates, shorter lengths of stay, and higher rates of dialysis dependence than patients without prior history of CKD.Patients with AKI and a prior history of CKD were older and underwent nephrology consultation earlier in the course of AKI. In-hospital mortality rate was lower (31 versus 40%, P = 0.04), and median intensive care unit length of stay was 4.6 d shorter (14.7 versus 19.3 d, P = 0.001) in patients with a prior history of CKD. Among dialyzed survivors, patients with prior CKD were also more likely to be dialysis dependent at hospital discharge. Differences in outcome were most evident in patients with lower severity of illness.Among critically ill patients with AKI, those with prior CKD experience a lower mortality rate but are more likely to be dialysis dependent at hospital discharge. Future studies should determine optimal strategies for managing AKI with and without a prior history of CKD.

    View details for DOI 10.2215/CJN.01690309

    View details for Web of Science ID 000272587100005

    View details for PubMedID 19965524

    View details for PubMedCentralID PMC2798877

  • Medication errors in chronic kidney disease: one piece in the patient safety puzzle KIDNEY INTERNATIONAL Fink, J. C., Chertow, G. M. 2009; 76 (11): 1123-1125

    Abstract

    Patients with chronic kidney disease (CKD) are at increased risk of harm as a consequence of errors in medical care. Hug and colleagues highlight the significance of adverse drug events in hospitalized patients with CKD. Their findings demonstrate the role adverse drug events play in the safety of patients with CKD and underscore the importance of novel strategies intended to reduce such medical errors.

    View details for DOI 10.1038/ki.2009.315

    View details for Web of Science ID 000271815900001

    View details for PubMedID 19910946

  • Increased fluid intake does not augment capacity to lay down new collagen in nursing home residents at risk for pressure ulcers: A randomized, controlled clinical trial WOUND REPAIR AND REGENERATION Stotts, N. A., Hopf, H. W., Kayser-Jones, J., Chertow, G. M., Cooper, B. A., Wu, H. 2009; 17 (6): 780-788

    Abstract

    Prevention of pressure ulcers is fundamental to safe care of nursing home residents yet the role of hydration in pressure ulcer prevention has not been systematically examined. This randomized clinical trial was undertaken to determine whether administration of supplemental fluid to nursing home residents at risk for pressure ulcers would enhance collagen deposition, increase estimated total body water, augment subcutaneous tissue oxygenation, and was safe. After a baseline period, 64 subjects were randomized to receive the fluid volume prescribed or additional fluid (prescribed plus 10 mL/kg) for 5 days. Participants' potential to heal as measured with hydroxyproline was low at baseline and did not increase significantly during treatment when additional fluid was systematically provided. Fluid intake increased significantly during treatment. Estimates of total body water and subcutaneous oxygen did not increase, indicating hydration was not improved. Supplemental fluid did not result in overhydration as measured by clinical parameters. Further work is needed to examine the relationship between fluid intake and hydration in nursing home residents as well as the role of hydration in pressure ulcer prevention.

    View details for DOI 10.1111/j.1524-475X.2009.00539.x

    View details for Web of Science ID 000271314900003

    View details for PubMedID 19821962

  • Fetuin-A and Change in Body Composition in Older Persons JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Ix, J. H., Wassel, C. L., Chertow, G. M., Koster, A., Johnson, K. C., Tylavsky, F. A., Cauley, J. A., Cummings, S. R., Harris, T. B., Shlipak, M. G. 2009; 94 (11): 4492-4498

    Abstract

    Fetuin-A inhibits the insulin receptor in vitro. Higher serum fetuin-A concentrations are associated with type 2 diabetes longitudinally and greater adiposity in cross-sectional analyses. Whether higher fetuin-A concentrations are associated with accumulation of adiposity over time is unknown.To determine the association of fetuin-A levels with changes in body composition over 5 yr.Observational cohort study nested in the Health Aging and Body Composition Study.Serum fetuin-A levels.Visceral adipose tissue (VAT), abdominal sc adipose tissue, and thigh muscle area by computed tomography, and waist circumference and body mass index were measured at baseline and again after 5 yr. Percent change and extreme change (>1.5 sds) in each measure were calculated.Over 5 yr, subjects lost body mass in each measure, including 6% decline in VAT. Yet each sd (0.42 g/liter) higher fetuin-A concentration was associated with a 5.5% increase in VAT over 5 yr (95% confidence interval 1.9-9.2%; P = 0.003) in models adjusted for age, sex, race, clinical site, diabetes, physical activity, triglycerides, kidney function, and the baseline VAT score. Similarly, higher fetuin-A concentrations were associated with extreme VAT gain (relative risk 1.70, 95% confidence interval 1.12-2.60, P = 0.01). Fetuin-A concentrations were not statistically significant associated with change in any other measures of body composition (P > 0.20).Higher fetuin-A concentrations are associated with the accumulation of VAT in well-functioning, community-living older persons. The mechanisms linking fetuin-A, VAT, and insulin resistance remain to be determined.

    View details for DOI 10.1210/jc.2009-0916

    View details for Web of Science ID 000271470800048

    View details for PubMedID 19820014

    View details for PubMedCentralID PMC2775641

  • Functional Status of Elderly Adults before and after Initiation of Dialysis NEW ENGLAND JOURNAL OF MEDICINE Tamura, M. K., Covinsky, K. E., Chertow, G. M., Yaffe, K., Landefeld, C. S., McCulloch, C. E. 2009; 361 (16): 1539-1547

    Abstract

    It is unclear whether functional status before dialysis is maintained after the initiation of this therapy in elderly patients with end-stage renal disease (ESRD).Using a national registry of patients undergoing dialysis, which was linked to a national registry of nursing home residents, we identified all 3702 nursing home residents in the United States who were starting treatment with dialysis between June 1998 and October 2000 and for whom at least one measurement of functional status was available before the initiation of dialysis. Functional status was measured by assessing the degree of dependence in seven activities of daily living (on the Minimum Data Set-Activities of Daily Living [MDS-ADL] scale of 0 to 28 points, with higher scores indicating greater functional difficulty).The median MDS-ADL score increased from 12 during the 3 months before the initiation of dialysis to 16 during the 3 months after the initiation of dialysis. Three months after the initiation of dialysis, functional status had been maintained in 39% of nursing home residents, but by 12 months after the initiation of dialysis, 58% had died and predialysis functional status had been maintained in only 13%. In a random-effects model, the initiation of dialysis was associated with a sharp decline in functional status, indicated by an increase of 2.8 points in the MDS-ADL score (95% confidence interval [CI], 2.5 to 3.0); this decline was independent of age, sex, race, and functional-status trajectory before the initiation of dialysis. The decline in functional status associated with the initiation of dialysis remained substantial (1.7 points; 95% CI, 1.4 to 2.1), even after adjustment for the presence or absence of an accelerated functional decline during the 3-month period before the initiation of dialysis.Among nursing home residents with ESRD, the initiation of dialysis is associated with a substantial and sustained decline in functional status.

    View details for PubMedID 19828531

  • Dialysis-requiring acute renal failure increases the risk of progressive chronic kidney disease KIDNEY INTERNATIONAL Lo, L. J., Go, A. S., Chertow, G. M., McCulloch, C. E., Fan, D., Ordonez, J. D., Hsu, C. 2009; 76 (8): 893-899

    Abstract

    To determine whether acute renal failure (ARF) increases the long-term risk of progressive chronic kidney disease (CKD), we studied the outcome of patients whose initial kidney function was normal or near normal but who had an episode of dialysis-requiring ARF and did not develop end-stage renal disease within 30 days following hospital discharge. The study encompassed 556,090 adult members of Kaiser Permanente of Northern California hospitalized over an 8 year period, who had pre-admission estimated glomerular filtration rates (eGFR) equivalent to or greater than 45 ml/min/1.73 m(2) and who survived hospitalization. After controlling for potential confounders such as baseline level of eGFR and diabetes status, dialysis-requiring ARF was independently associated with a 28-fold increase in the risk of developing stage 4 or 5 CKD and more than a twofold increased risk of death. Our study shows that in a large, community-based cohort of patients with pre-existing normal or near normal kidney function, an episode of dialysis-requiring ARF was a strong independent risk factor for a long-term risk of progressive CKD and mortality.

    View details for DOI 10.1038/ki.2009.289

    View details for Web of Science ID 000270354700018

    View details for PubMedID 19641480

    View details for PubMedCentralID PMC2771754

  • Fluid accumulation, survival and recovery of kidney function in critically ill patients with acute kidney injury 41st Annual Meeting of the American-Society-of-Nephrology/Annual Renal Week Bouchard, J., Soroko, S. B., Chertow, G. M., Himmelfarb, J., Ikizler, T. A., Paganini, E. P., Mehta, R. L. NATURE PUBLISHING GROUP. 2009: 422–27

    Abstract

    Fluid accumulation is associated with adverse outcomes in critically ill patients. Here, we sought to determine if fluid accumulation is associated with mortality and non-recovery of kidney function in critically ill adults with acute kidney injury. Fluid overload was defined as more than a 10% increase in body weight relative to baseline, measured in 618 patients enrolled in a prospective multicenter observational study. Patients with fluid overload experienced significantly higher mortality within 60 days of enrollment. Among dialyzed patients, survivors had significantly lower fluid accumulation when dialysis was initiated compared to non-survivors after adjustments for dialysis modality and severity score. The adjusted odds ratio for death associated with fluid overload at dialysis initiation was 2.07. In non-dialyzed patients, survivors had significantly less fluid accumulation at the peak of their serum creatinine. Fluid overload at the time of diagnosis of acute kidney injury was not associated with recovery of kidney function. However, patients with fluid overload when their serum creatinine reached its peak were significantly less likely to recover kidney function. Our study shows that in patients with acute kidney injury, fluid overload was independently associated with mortality. Whether the fluid overload was the result of a more severe renal failure or it contributed to its cause will require clinical trials in which the role of fluid administration to such patients is directly tested.

    View details for DOI 10.1038/ki.2009.159

    View details for Web of Science ID 000268536800011

    View details for PubMedID 19436332

  • Characteristics of Uninsured Americans with Chronic Kidney Disease JOURNAL OF GENERAL INTERNAL MEDICINE Hall, Y. N., Rodriguez, R. A., Boyko, E. J., Chertow, G. M., O'Hare, A. M. 2009; 24 (8): 917-922

    Abstract

    In the United States, public health insurance is available for nearly all persons with end-stage renal disease (ESRD). Little is known about the extent of health insurance coverage for persons with non-dialysis dependent chronic kidney disease (CKD).To describe patterns of health insurance coverage for adults with non-dialysis dependent CKD and to examine risk factors for progression of CKD to ESRD and management of hypertension among those lacking insurance.Cross-sectional analysis of data from a nationally representative sample of 16,148 US adults aged 20 years or older who participated in the National Health and Nutrition Examination Survey 1999-2006.National prevalence estimates of health insurance coverage, ESRD risk factors, and treatment of hypertension.An estimated 10.0% (95% CI, 8.3%-12.0%) of US adults with non-dialysis dependent CKD were uninsured, 60.9% (95% CI, 58.2%-63.7%) had private insurance and 28.7% (95% CI, 26.4%-31.1%) had public insurance alone. Uninsured persons with non-dialysis dependent CKD were more likely to be under the age of 50 (62.8% vs. 23.0%, P < 0.001) and nonwhite (58.7%, vs. 21.8%, P < 0.001) compared with their insured counterparts. Approximately two-thirds of uninsured adults with non-dialysis dependent CKD had at least one modifiable risk factor for CKD progression, including 57% with hypertension, 40% who were obese, 22% with diabetes, and 13% with overt albuminuria. In adjusted analyses, uninsured persons with non-dialysis dependent CKD were less likely to be treated for their hypertension (OR, 0.59; 95% CI, 0.40-0.85) and less likely to be receiving recommended therapy with angiotensin inhibitors (OR, 0.45; 95% CI, 0.26-0.77) compared with those with insurance coverage.Uninsured persons with non-dialysis dependent CKD are at higher risk for progression to ESRD than their insured counterparts but are less likely to receive recommended interventions to slow disease progression. Lack of public health insurance for patients with non-dialysis dependent CKD may result in missed opportunities to slow disease progression and thereby reduce the public burden of ESRD.

    View details for DOI 10.1007/s11606-009-1028-3

    View details for Web of Science ID 000268069500005

    View details for PubMedID 19506974

    View details for PubMedCentralID PMC2710472

  • Frailty and Chronic Kidney Disease: The Third National Health and Nutrition Evaluation Survey AMERICAN JOURNAL OF MEDICINE Wilhelm-Leen, E. R., Hall, Y. N., Tamura, M. K., Chertow, G. M. 2009; 122 (7): 664-U86

    Abstract

    Frailty is common in the elderly and in persons with chronic diseases. Few studies have examined the association of frailty with chronic kidney disease.We used data from the Third National Health and Nutrition Examination Survey to estimate the prevalence of frailty among persons with chronic kidney disease. We created a definition of frailty based on established validated criteria, modified to accommodate available data. We used logistic regression to determine whether and to what degree stages of chronic kidney disease were associated with frailty. We also examined factors that might mediate the association between frailty and chronic kidney disease.The overall prevalence of frailty was 2.8%. However, among persons with moderate to severe chronic kidney disease (estimated glomerular filtration rate < 45 mL/min/1.73 m2), 20.9% were frail. The odds of frailty were significantly increased among all stages of chronic kidney disease, even after adjustment for the residual effects of age, sex, race, and prevalent chronic diseases. The odds of frailty associated with chronic kidney disease were only marginally attenuated with additional adjustment for sarcopenia, anemia, acidosis, inflammation, vitamin D deficiency, hypertension, and cardiovascular disease. Frailty and chronic kidney disease were independently associated with mortality.Frailty is significantly associat