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IntroductionPatients with advanced non-dialysis-dependent CKD (NDD-CKD) have a reduced ability for maintaining plasma potassium (K) in normal range. Deviation from normal plasma K ranges is associated with increased mortality; however, the average trajectory of plasma K over time in patients with advanced NDD-CKD and the outcomes associated with plasma K trajectory are unknown.MethodsWe identified 34,167 US veterans with advanced NDD-CKD transitioning to dialysis between October 2007 and March 2015 with at least 1 K measurement each year over a 3-year period prior to dialysis transition (3-year prelude). The K trajectory defined as the change in K (slope) per year over the entire 3-year prelude was estimated using linear mixed-effects models. The association between unadjusted (crude) K slope (categorized as stable [-0.09 to 0.09 mEq/L/year], decreasing [≤-0.10 mEq/L/year], and increasing [≥0.10 mEq/L/year]) and time to all-cause and cardiovascular mortality during the 6 months following dialysis initiation was assessed using multivariable-adjusted survival models.ResultsThe crude and multivariable-adjusted K slopes (mean, 95% CI) over the 3-year prelude were 0.008 (0.0059, 0.0110) and -0.15 mEq/L/year (-0.19, -0.11), respectively. Decreasing K slope was associated with higher multivariable-adjusted risk of all-cause mortality (adjusted hazard ratio [95% CI] vs. stable K slope: 1.08 [1.00-1.17]). No association was observed between K slope and cardiovascular mortality.Discussion/conclusionThe average intraindividual plasma K trajectory is remarkably stable in patients with advanced NDD-CKD. A decreasing K slope is associated with higher all-cause mortality risk.

BackgroundAngiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ACEi/ARB) improve predialysis outcomes; however, ACEi/ARB are underused in patients transitioning to dialysis. We examined the association of different patterns of predialysis ACEi/ARB use with postdialysis survival and whether potentially modifiable adverse events are associated with lower predialysis ACEi/ARB use.MethodsThis was a historic cohort study of 34,676 US veterans with, and 10,690 without, ACEi/ARB exposure in the 3-year predialysis period who subsequently transitioned to dialysis between 2007 and 2014. Associations of different patterns of predialysis ACEi/ARB use with postdialysis all-cause mortality and with predialysis acute kidney injury and hyperkalemia events were examined using multivariable adjusted regression analyses.ResultsThe mean age of the cohort was 70 years, 98% were males and 27% were African Americans. Compared to ACEi/ARB nonuse, continuous ACEi/ARB use was associated with lower postdialysis all-cause mortality (adjusted hazard ratio [aHR]; 95% confidence interval [95% CI] 0.87; 0.83-0.92). In analyses modeling the duration of predialysis ACEi/ARB use, ACEi/ARB use of 50%-74% and ≥75% were associated with lower mortality compared to nonuse (adjusted hazard ratio, 95% confidence interval 0.96, 0.92-0.99 and 0.91; 0.88-0.94, respectively), whereas no increase in postdialysis survival was observed with shorter predialysis ACEi/ARB use. Predialysis acute kidney injury was associated with shorter duration (

BackgroundRed blood cell distribution width (RDW) is found to be associated with different types of anemia and has recently been studied as a prognostic marker of mortality in hemodialysis patients. However, the relationship of RDW with mortality and hospitalization rate in peritoneal dialysis (PD) patients is less known.MethodsAmong 14 323 incident PD patients between 2007 and 2011 in the USA, we examined the relationship of baseline and time-varying RDW with the risk of mortality and time to first hospitalization using adjusted Cox models. In addition, we examined the relationship of baseline RDW and hospitalization rate using an adjusted negative-binomial regression model. Sensitivity analyses included competing risk models and subgroup analyses.ResultsThe study population comprised patients 56 ± 16 years of age, including 43% females, 23% African Americans and 62% diabetics, with a mean RDW of 15.3 ± 1.6%. In models adjusted for clinical characteristics and laboratory parameters, RDW exhibited an incremental relationship with the mortality risk, where RDW ≥16.5% had a 40% and 69% higher risk of death in baseline and time-varying analyses, respectively, compared with an RDW of 14.5-15.5%. Moreover, higher baseline RDW ≥16.5% was also associated with a higher risk of time to first hospitalization {hazard ratio 1.22 [95% confidence interval (CI) 1.14-1.29]} and a higher rate of hospitalizations [incidence rate ratio 1.16 (95% CI 1.09-1.23)]. These results were consistent across numerous sensitivity analyses.ConclusionsHigher RDW is associated with a higher risk of mortality and hospitalizations among incident PD patients. Further studies are needed to examine the mechanism behind RDW and adverse outcomes.

IntroductionGiven the high mortality rate within the first year of dialysis initiation, an accurate estimation of postdialysis mortality could help patients and clinicians in decision making about initiation of dialysis. We aimed to use machine learning (ML) by incorporating complex information from electronic health records to predict patients at risk for postdialysis short-term mortality.MethodsThis study was carried out on a contemporary cohort of 27,615 US veterans with incident end-stage renal disease (ESRD). We implemented a random forest method on 49 variables obtained before dialysis transition to predict outcomes of 30-, 90-, 180-, and 365-day all-cause mortality after dialysis initiation.ResultsThe mean (±SD) age of our cohort was 68.7 ± 11.2 years, 98.1% of patients were men, 29.4% were African American, and 71.4% were diabetic. The final random forest model provided C-statistics (95% confidence intervals) of 0.7185 (0.6994-0.7377), 0.7446 (0.7346-0.7546), 0.7504 (0.7425-0.7583), and 0.7488 (0.7421-0.7554) for predicting risk of death within the 4 different time windows. The models showed good internal validity and replicated well in patients with various demographic and clinical characteristics and provided similar or better performance compared with other ML algorithms. Results may not be generalizable to non-veterans. Use of predictors available in electronic medical records has limited the assessment of number of predictors.ConclusionWe implemented and ML-based method to accurately predict short-term postdialysis mortality in patients with incident ESRD. Our models could aid patients and clinicians in better decision making about the best course of action in patients approaching ESRD.

Background Although studies have shown that statin therapy in patients with non-dialysis-dependent chronic kidney disease was associated with a lower risk of death, this was not observed in dialysis patients newly initiated on statins. It is unclear if statin therapy benefits administered during the predialysis period persist after transitioning to end-stage renal disease. Methods and Results In 47 720 veterans who transitioned to end-stage renal disease during 2007 to 2014, we examined the association of statin therapy use 1 year before transition with posttransition all-cause and cardiovascular mortality and hospitalization incidence rates over the first 12 months of follow-up. Associations were examined using multivariable adjusted Cox proportional hazard models and negative binomial regressions. Sensitivity analyses included propensity score and subgroup analyses. The cohort's mean± SD age was 71±11 years, and the cohort included 4% women, 23% blacks, and 66% diabetics. Over 12 months of follow-up, there were 13 411 deaths, with an incidence rate of 35.3 (95% CI , 34.7-35.8) deaths per 100 person-years. In adjusted models, statin therapy compared with no statin therapy was associated with lower risks of 12-month all-cause (hazard ratio [95% CI], 0.79 [0.76-0.82]) and cardiovascular (hazard ratio [95% CI ], 0.83 [0.78-0.88]) mortality, as well as with a lower rate of hospitalizations (incidence rate ratio [95% CI ], 0.89 [0.87-0.92]) after initiating dialysis. These lower outcome risks persisted across strata of clinical characteristics, and in propensity score analyses. Conclusions Among veterans with non-dialysis-dependent chronic kidney disease, treatment with statin therapy within the 1 year before transitioning to end-stage renal disease is associated with favorable early end-stage renal disease outcomes.

Background and aimsConstipation is one of the most frequent symptoms encountered in daily clinical practice and is implicated in the development of atherosclerosis, potentially through altered gut microbiota. However, little is known about its association with incident cardiovascular events.MethodsIn a nationally representative cohort of 3,359,653 US veterans with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 between October 1, 2004 and September 30, 2006 (baseline period), with follow-up through 2013, we examined the association of constipation status (absence or presence; defined using diagnostic codes and laxative use) and laxative use (none, one, or ≥2 types of laxatives) with all-cause mortality, incident coronary heart disease (CHD), and incident ischemic stroke.ResultsAmong 3,359,653 patients, 237,855 (7.1%) were identified as having constipation. After multivariable adjustments for demographics, prevalent comorbidities, medications, and socioeconomic status, patients with (versus without) constipation had 12% higher all-cause mortality (hazard ratio [HR], 1.12; 95% CI, 1.11-1.13), 11% higher incidence of CHD (HR, 1.11; 95% CI, 1.08-1.14), and 19% higher incidence of ischemic stroke (HR, 1.19; 95% CI, 1.15-1.22). Patients with one and ≥2 (versus none) types of laxatives experienced a similarly higher risk of all-cause mortality (HRs [95% CI], 1.15 [1.13-1.16] and 1.14 [1.12-1.15], respectively), incident CHD (HRs [95% CI], 1.11 [1.07-1.15] and 1.10 [1.05-1.15], respectively) and incident ischemic stroke (HRs [95% CI], 1.19 [1.14-1.23] and 1.21 [1.16-1.26], respectively).ConclusionsConstipation status and laxative use are independently associated with higher risk of all-cause mortality and incident CHD and ischemic stroke.

Background/aimsAnemia is common in patients with advanced chronic kidney disease (CKD). A proportion of patients present with macrocytic anemia, manifested by elevated mean corpuscular volume (MCV), which has been associated with worse outcomes in CKD patients. However, it is unknown whether elevated MCV is associated with higher mortality risk in incident hemodialysis (HD) patients.MethodsThis retrospective observational cohort study examined all-cause, cardiovascular, and infectious mortality associations with both baseline and time-varying MCV in 109,501 incident HD patients using Cox proportional hazards models with 3 levels of hierarchical multivariable adjustment. Odds ratios of high versus low baseline MCV were evaluated using logistic regression.ResultsThe mean age of patients was 65 ± 15 (standard deviation) years and the cohort was 44% female, 58% diabetic, and 31% African American. Higher MCV was associated with older age, female sex, non-Hispanic White race-ethnicity, alcohol consumption, and having a decreased albumin or protein intake. Patients with higher MCV levels (> 98 fL) had a higher all-cause, cardiovascular, and infectious mortality risk in both baseline and time varying models, and across all levels of adjustment. In the fully adjusted models, compared to a reference of MCV 92-< 94 fL, patients with a baseline MCV > 100+ fL had a 28% higher risk of all-cause mortality (hazard ratio [HR] 1.28, 95% CI 1.22-1.34), 27% higher risk of cardiovascular mortality (HR 1.27, 95% CI 1.18-1.36), and 18% higher risk of infectious mortality (HR 1.18, 95% CI 1.02-1.38). Associations of higher MCV with these adverse outcomes persisted across all examined subgroups of clinical characteristics.ConclusionsHigher MCV was associated with higher all-cause, cardiovascular, and infectious mortality in HD patients. Further investigation is necessary to understand the underlying nature of the observed association.

Rationale & objectiveDiabetic patients with declining kidney function are at heightened risk for hypoglycemia. We sought to determine whether hypoglycemia-related hospitalizations in the interval before dialysis therapy initiation are associated with post-end-stage renal disease (ESRD) mortality among incident patients with ESRD with diabetes.Study designObservational cohort study.Setting & participantsUS veterans from the national Veterans Affairs database with diabetes and chronic kidney disease transitioning to dialysis therapy from October 2007 to September 2011.ExposureHypoglycemia-related hospitalizations during the pre-ESRD period and antidiabetic medication regimens.OutcomeThe outcome of post-ESRD all-cause mortality was evaluated relative to pre-ESRD hypoglycemia. The outcome of pre-ESRD hypoglycemia-related hospitalization was evaluated relative to antidiabetic medication regimens.Analytic approachWe examined whether the occurrence and frequency of pre-ESRD hypoglycemia-related hospitalizations are associated with post-ESRD mortality using Cox regression models adjusted for case-mix covariates. In a subcohort of patients prescribed 0 to 2 oral antidiabetic drugs and/or insulin, we examined the 12 most commonly prescribed antidiabetic medication regimens and risk for pre-ESRD hypoglycemia-related hospitalization using logistic regression models adjusted for case-mix covariates.ResultsAmong 30,156 patients who met eligibility criteria, the occurrence of pre-ESRD hypoglycemia-related hospitalization(s) was associated with higher post-ESRD mortality risk: adjusted HR (aHR), 1.25; 95% CI, 1.17-1.34 (reference group: no hypoglycemia hospitalization). Increasing frequency of hypoglycemia-related hospitalizations was independently associated with incrementally higher mortality risk: aHRs of 1.21 (95% CI, 1.12-1.30), 1.47 (95% CI, 1.19-1.82), and 2.07 (95% CI, 1.46-2.95) for 1, 2, and 3 or more hypoglycemia-related hospitalizations, respectively (reference group: no hypoglycemia hospitalization). Compared with patients who were prescribed neither oral antidiabetic drugs nor insulin, medication regimens that included sulfonylureas and/or insulin were associated with higher risk for hypoglycemia.LimitationsResidual confounding cannot be excluded.ConclusionsAmong incident patients with ESRD with diabetes, a dose-dependent relationship between frequency of pre-ESRD hypoglycemia-related hospitalizations and post-ESRD mortality was observed. Further study of diabetic management strategies that prevent hypoglycemia as patients with chronic kidney disease transition to ESRD are warranted.

History of psychosis or mania, if uncontrolled, both represent relative contraindications for kidney transplantation. We examined 3680 US veterans who underwent kidney transplantation. The diagnosis of history of psychosis/mania was based on a validated algorithm. Measured confounders were used to create a propensity score-matched cohort (n = 442). Associations between pretransplantation psychosis/mania and death with functioning graft, all-cause death, graft loss, and rejection were examined in survival models and logistic regression models. Post-transplant medication nonadherence was assessed using proportion of days covered (PDC) for tacrolimus and mycophenolic acid in both groups. The mean ± SD age of the cohort at baseline was 61 ± 11 years, 92% were male, and 66% and 27% of patients were white and African-American, respectively. Compared to patients without history of psychosis/mania, patients with a history of psychosis/mania had similar risk of death with functioning graft [subhazard ratio (SHR) (95% confidence interval (CI)): 0.94(0.42-2.09)], all-cause death [hazard ratio (95% CI): 1.04 (0.51-2.14)], graft loss [SHR (95% CI): 1.07 (0.45-2.57)], and rejection [odds ratio(95% CI): 1.23(0.60-2.53)]. Moreover, there was no difference in immunosuppressive drug PDC in patients with and without history of psychosis/mania (PDC: 76 ± 21% vs. 78 ± 19%, P = 0.529 for tacrolimus; PDC: 78 ± 17% vs. 79 ± 18%, P = 0.666 for mycophenolic acid). After careful selection, pretransplantation psychosis/mania is not associated with adverse outcomes in kidney transplant recipients.

Introduction:Abrupt declines in kidney function often occur in patients with advanced chronic kidney disease and may exacerbate the need to initiate dialysis treatment. It is unclear how frequently such events occur in patients transitioning to chronic dialysis therapy, and what outcomes they are associated with. Methods:We examined a national cohort of 23,349 US veterans with incident end-stage renal disease (ESRD) and with available pre-ESRD estimated glomerular filtration rate (eGFR) to identify abrupt declines in kidney function, defined as an unexpected >50% decrease in eGFR at the time of chronic dialysis transition. Associations with all-cause mortality and with renal recovery were examined in Cox proportional hazard and competing risk regression models. Results:A total of 4804 (21%) patients experienced an abrupt decline in kidney function at dialysis transition. Renal recovery occurred in 586 (12.2%) and 297 (1.6%) patients with and without an abrupt decline, respectively (adjusted subhazard ratio: 4.42; 95% confidence interval [CI]: 3.72-5.27; P < 0.001). In the first 6 months after dialysis transition 1178 patients (24.5%) with abrupt decline died (annualized mortality rate 574/1000 patient-years), compared with 2354 deaths (12.7%) in patients without abrupt decline (274 deaths/1000 patient-years). An abrupt decline was associated with 45% higher mortality after multivariable adjustments (hazard ratio: 1.45; 95% CI: 1.33-1.57). Conclusion:Abrupt declines in kidney function are common in patients transitioning to chronic dialysis, and are associated with higher mortality. Patients with abrupt declines also experience a higher rate of renal recovery; hence, careful attention to residual kidney function is warranted in these patients.

BackgroundPrevious studies have demonstrated that early pre-end-stage renal disease (ESRD) nephrology care could improve postdialysis prognosis. However, less is known about the specific types of interventions responsible for the improved outcomes. We hypothesized that more frequent predialysis laboratory testing is associated with better postdialysis outcomes in incident ESRD patients.MethodsIn all, 23 089 patients with available outpatient laboratory tests performed during the 2-year predialysis (i.e. prelude) period were identified from a total of 52 172 American veterans with chronic kidney disease (CKD) transitioning to dialysis between October 2007 and September 2011. The associations between the frequency of combined laboratory tests, including serum creatinine, serum potassium and hemoglobin (test trio), with postdialysis mortality and hospitalization were examined in multivariable adjusted Cox and logistic regression models.ResultsWhen entering the 2-year prelude period, the mean age (Standard Deviation) of the patients was 66.2 (SD 11.3) years and the mean estimated glomerular filtration rate was 46.8 (SD 23.9) mL/min/1.73 m2. In all, 14% of patients had the test trio performed less than twice in 24 months and 8.9% had the trio measured more often than every other month. Over a 2.5-year median postdialysis follow-up period, 15 303 (66.3%) patients died (mortality rate 260/1000 patient-years). The adjusted hazard ratio of all-cause mortality and adjusted odds ratio of the composite of hospitalization or death associated with lab testing done >12/24 months compared with 2-≤4/24 months were 0.68 [95% confidence interval (CI) 0.65-0.73] and 0.70 (95% CI 0.62-0.79), respectively.ConclusionsMore frequent laboratory testing in patients with advanced CKD is associated with better clinical outcomes after dialysis. Further examination in clinical trials is needed before the implementation of more frequent laboratory testing in clinical practice.

BackgroundHigher serum alkaline phosphatase (ALP) levels have been associated with excess mortality in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) and end-stage renal disease (ESRD). However, little is known about the impact of late-stage NDD-CKD ALP levels on outcomes after dialysis initiation.MethodsAmong 17 732 US veterans who transitioned to dialysis between October 2007 and September 2011, we examined the association of serum ALP levels averaged over the last 6 months of the pre-ESRD transition period ('prelude period') with all-cause, cardiovascular and infection-related mortality following dialysis initiation, using Cox (for all-cause mortality) and competing risk (for cause-specific mortality) regressions adjusted for demographics, comorbidities, medications, estimated glomerular filtration rate and serum albumin levels over the 6-month prelude period, and vascular access type at dialysis initiation.ResultsDuring a median follow-up of 2.0 (interquartile range, 1.1-3.2) years following dialysis initiation, a total of 9196 all-cause deaths occurred. Higher ALP levels were incrementally associated with higher all-cause, cardiovascular and infection-related mortality. Compared with patients in the lowest ALP quartile (

ObjectivesHigher SBP visit-to-visit variability (SBPV) has been associated with increased risk of adverse events in patients with chronic kidney disease, but the association of SBPV in advanced nondialysis-dependent chronic kidney disease with mortality after the transition to end-stage renal disease (ESRD) remains unknown.MethodsAmong 17 729 US veterans transitioning to dialysis between October 2007 and September 2011, we assessed SBPV calculated from the SD of at least three intraindividual outpatient SBP values during the last year prior to dialysis transition (prelude period). Outcomes included factors associated with higher prelude SBPV and post-transition all-cause, cardiovascular, and infection-related mortality, assessed using multivariable linear regression and Cox and competing risk regressions, respectively, adjusted for demographics, comorbidities, medications, cardiovascular medication adherence, SBP, BMI, estimated glomerular filtration rate, and type of vascular access.ResultsModifiable clinical factors associated with higher prelude SBPV included higher SBP, use of antihypertensive medications and erythropoiesis-stimulating agents, inadequate cardiovascular medication adherence, and catheter use. After multivariable adjustment, higher prelude SBPV was significantly associated with higher post-ESRD all-cause and infection-related mortality, but not cardiovascular mortality [hazard/subhazard ratios (95% confidence interval) for the highest (vs. lowest) quartile of SBPV, 1.08 (1.01-1.16), 1.02 (0.89-1.15), and 1.41 (1.10-1.80) for all-cause, cardiovascular, and infection-related mortality, respectively].ConclusionHigh pre-ESRD SBPV is potentially modifiable and associated with higher all-cause and infection-related mortality following dialysis initiation. Further studies are needed to test whether modification of pre-ESRD SBPV can improve clinical outcomes in incident ESRD patients. VIDEO ABSTRACT:.

Background and objectivesDepression in patients with nondialysis-dependent CKD is often undiagnosed, empirically overlooked, and associated with higher risk of death, progression to ESRD, and hospitalization. However, there is a paucity of evidence on the association between the presence of depression in patients with advanced nondialysis-dependent CKD and post-ESRD mortality, particularly among those in the transition period from late-stage nondialysis-dependent CKD to maintenance dialysis.Design, setting, participants, & measurementsFrom a nation-wide cohort of 45,076 United States veterans who transitioned to ESRD over 4 contemporary years (November of 2007 to September of 2011), we identified 10,454 (23%) patients with a depression diagnosis during the predialysis period. We examined the association of pre-ESRD depression with all-cause mortality after transition to dialysis using Cox proportional hazards models adjusted for sociodemographics, comorbidities, and medications.ResultsPatients were 72±11 years old (mean±SD) and included 95% men, 66% patients with diabetes, and 23% blacks. The crude mortality rate was similar in patients with depression (289/1000 patient-years; 95% confidence interval, 282 to 297) versus patients without depression (286/1000 patient-years; 95% confidence interval, 282 to 290). Compared with patients without depression, patients with depression had a 6% higher all-cause mortality risk in the adjusted model (hazard ratio, 1.06; 95% confidence interval, 1.03 to 1.09). Similar results were found across all selected subgroups as well as in sensitivity analyses using alternate definitions of depression.ConclusionPre-ESRD depression has a weak association with post-ESRD mortality in veterans transitioning to dialysis.

BackgroundRecent studies suggest that potassium levels may differ by race. The basis for these differences and whether associations between potassium levels and adverse outcomes differ by race are unknown.Study designObservational study.Setting & participantsAssociations between race and potassium level and the interaction of race and potassium level with outcomes were investigated in the Racial and Cardiovascular Risk Anomalies in Chronic Kidney Disease (RCAV) Study, a cohort of US veterans (N=2,662,462). Associations between African ancestry and potassium level were investigated in African Americans in the Atherosclerosis Risk in Communities (ARIC) Study (N=3,450).PredictorsRace (African American vs non-African American and percent African ancestry) for cross-sectional analysis; serum potassium level for longitudinal analysis.OutcomesPotassium level for cross-sectional analysis; mortality and end-stage renal disease for longitudinal analysis.ResultsThe RCAV cohort was 18% African American (N=470,985). Potassium levels on average were 0.162mmol/L lower in African Americans compared with non-African Americans, with differences persisting after adjustment for demographics, comorbid conditions, and potassium-altering medication use. In the ARIC Study, higher African ancestry was related to lower potassium levels (-0.027mmol/L per each 10% African ancestry). In both race groups, higher and lower potassium levels were associated with mortality. Compared to potassium level of 4.2mmol/L, mortality risk associated with lower potassium levels was lower in African Americans versus non-African Americans, whereas mortality risk associated with higher levels was slightly greater. Risk relationships between potassium and end-stage renal disease were weaker, with no difference by race.LimitationsNo data for potassium intake.ConclusionsAfrican Americans had slightly lower serum potassium levels than non-African Americans. Consistent associations between potassium levels and percent African ancestry may suggest a genetic component to these differences. Higher and lower serum potassium levels were associated with mortality in both racial groups.

BackgroundMortality is extremely high immediately after the transition to dialysis therapy, but the association of blood pressure (BP) before dialysis therapy initiation with mortality after dialysis therapy initiation remains unknown.Study designObservational study.Setting & participants17,729 US veterans transitioning to dialysis therapy in October 2007 to September 2011, with a median follow-up of 2.0 years.PredictorSystolic (SBP) and diastolic BP (DBP) averaged over the last 1-year predialysis transition period as 6 (

BackgroundHeart failure (HF) is associated with poor cardiac outcomes and mortality. It is not known whether HF leads to poor renal outcomes in patients with normal kidney function. We hypothesized that HF is associated with worse long-term renal outcomes.Methods and resultsAmong 3 570 865 US veterans with estimated glomerular filtration rate (eGFR) ≥60 mL min-1 1.73 m-2 during October 1, 2004 to September 30, 2006, we identified 156 743 with an International Classification of Diseases, Ninth Revision, diagnosis of HF. We examined the association of HF with incident chronic kidney disease (CKD), the composite of incident CKD or mortality, and rapid rate of eGFR decline (slopes steeper than -5 mL min-1 1.73 m-2 y-1) using Cox proportional hazard analyses and logistic regression. Adjustments were made for various confounders. The mean±standard deviation baseline age and eGFR of HF patients were 68±11 years and 78±14 mL min-1 1.73 m-2 and in patients without HF were 59±14 years and 84±16 mL min-1 1.73 m-2, respectively. HF patients had higher prevalence of hypertension, diabetes mellitus, cardiac, peripheral vascular and chronic lung diseases, stroke, and dementia. Incidence of CKD was 69.0/1000 patient-years in HF patients versus 14.5/1000 patient-years in patients without HF, and 22% of patients with HF had rapid decline in eGFR compared with 8.5% in patients without HF. HF patients had a 2.12-, 2.06-, and 2.13-fold higher multivariable-adjusted risk of incident CKD, composite of CKD or mortality, and rapid eGFR decline, respectively.ConclusionsHF is associated with significantly higher risk of incident CKD, incident CKD or mortality, and rapid eGFR decline. Early diagnosis and management of HF could help reduce the risk of long-term renal complications.

BackgroundMortality in the immediate post-hemodialysis transition period is extremely high. Many end-stage renal disease (ESRD) patients in the US start dialysis in an inpatient setting, but the characteristics of patients starting dialysis as inpatients, and the association of inpatient hemodialysis transition with mortality remain unclear.MethodsWe examined 48,261 US veterans who transitioned to hemodialysis between October 2007 and September 2011. Associations of inpatient hemodialysis starting with all-cause mortality were examined in Cox proportional hazard models, with adjustments for demographics, comorbidities, vascular access type, pre-dialysis nephrology care and medication use, and last pre-ESRD estimated glomerular filtration rate and hemoglobin.ResultsA total of 22,338 (46.3%) patients received the first hemodialysis treatment in an inpatient setting. Inpatient hemodialysis transition was associated with older age, presence of a tunneled catheter, higher comorbidity burden, and lack of pre-dialysis nephrology care. A total of 8,674 patients died (mortality rate 405/1,000 patient-years, 95% CI 397-413) during the first 6 months after transition to hemodialysis. The starting of inpatient vs. outpatient hemodialysis was associated with significantly higher crude all-cause mortality, but this association was attenuated after multivariable adjustments.ConclusionsTransition to hemodialysis in an inpatient setting is more common in older and sicker individuals, and in patients without pre-dialysis nephrology care and those who used a catheter for vascular access. Future studies are needed to determine if a higher proportion of patients could start hemodialysis treatment in outpatient clinics, through interventions targeting modifiable risk factors such as timely vascular access placement or earlier nephrology referrals.

BackgroundConservative management may be a desirable option for elderly, fragile, or demented patients who reach end-stage renal disease (ESRD), yet some patients with dementia are placed on renal replacement therapy nonetheless.MethodsFrom a nationwide cohort of 45,076 US veterans who transitioned to ESRD over 4 contemporary years (October 1, 2007 to September 30, 2011), we identified 1,336 (3.0%) patients with International Classification of Diseases, Ninth Revision, Clinical Modification code-based dementia diagnosis during the prelude (predialysis) period. We examined the association of prelude dementia with all-cause mortality within the first 6 months following transition to dialysis, using a propensity-matched cohort and Cox proportional hazards models.ResultsIn the entire cohort, the overall mean ± standard deviation age at baseline was 72 ± 11 years, 95% were male, 23% were African-American, and 66% were diabetic. There were 8,080 (18.5%) deaths (mortality rate, 412; 95% confidence interval [CI], 403-421/1,000 patient-years) in the dementia-negative group, and 396 (29.6%) deaths (mortality rate, 708; 95% CI, 642-782/1,000 patient-years) in the dementia-positive group in the entire cohort in the first 6 months after dialysis initiation. Presence of dementia was associated with higher risk of all-cause mortality (adjusted hazard ratio, 1.25; 95% CI, 1.12-1.38) compared to dementia-free patients in the first 6 months after dialysis initiation.ConclusionPre-ESRD dementia is associated with increased risk of early post-ESRD mortality in veterans transitioning to dialysis.

Background/aimsAll hemodialysis (HD) patients are generally recommended to create a fistula first; but to create a mature arteriovenous fistula (AVF) can be challenging in elderly individuals. It is unclear if elderly incident HD patients derive a survival benefit from an AVF over an arteriovenous graft (AVG) or a tunneled central venous catheter (TDC).MethodsWe examined the association of vascular access type (AVF, AVG, and TDC with and without a maturing AVF/AVG at dialysis transition) at HD initiation with all-cause, cardiovascular (CV), and infection-related mortality in 46,786 US veterans using Cox models with adjustment for confounders. Effect modification by age was examined by examining associations in pre-specified age subgroups (

BackgroundHemoglobin variability (Hb-var) has been associated with increased mortality both in non-dialysis dependent chronic kidney disease (NDD-CKD) and end-stage renal disease (ESRD) patients. However, the impact of Hb-var in advanced NDD-CKD on outcomes after dialysis initiation remains unknown.MethodsAmong 11,872 US veterans with advanced NDD-CKD transitioning to dialysis between October 2007 through September 2011, we assessed Hb-var calculated from the residual SD of at least 3 Hb values during the last 6 months before dialysis initiation (prelude period) using within-subject linear regression models, and stratified into quartiles. Outcomes included post-transition all-cause, cardiovascular, and infection-related mortality, assessed in Cox proportional hazards models and adjusted for demographics, comorbidities, length of hospitalization, medications, estimated glomerular filtration rate (eGFR), type of vascular access, Hb parameters (baseline Hb [i.e., intercept] and change in Hb [i.e., slope]), and number of Hb measurements.ResultsHigher prelude Hb-var was associated with use of iron and antiplatelet agents, tunneled dialysis catheter use, higher levels of baseline Hb, change in Hb, eGFR, and serum ferritin. After multivariable adjustment, higher prelude Hb-var was associated with higher post-ESRD all-cause and infection-related mortality, but not cardiovascular mortality (adjusted hazard ratios [95% CI] for the highest [vs. lowest] quartile of Hb-var, 1.10 [1.02-1.19], 1.28 [0.93-1.75], and 0.93 [0.79-1.10], respectively).ConclusionsHigh pre-ESRD Hb-var is associated with higher mortality, particularly from infectious causes rather than cardiovascular causes. Further research is required to clarify the underlying mechanisms and true causal nature of the observed association.

ObjectiveIt is not known if patients with diabetes with depression have an increased risk of chronic kidney disease (CKD). We examined the association between depression and incident CKD, mortality, and incident cardiovascular events in U.S. veterans with diabetes.Research design and methodsAmong a nationally representative prospective cohort of >3 million U.S. veterans with baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2, we identified 933,211 patients with diabetes. Diabetes was ascertained by an ICD-9-CM code for diabetes, an HbA1c >6.4%, or receiving antidiabetes medication during the inclusion period. Depression was defined by an ICD-9-CM code for depression or by antidepressant use during the inclusion period. Incident CKD was defined as two eGFR levels 25% decline in baseline eGFR. The associations between depression and outcomes were assessed using Cox proportional regression.ResultsDepression was present in 340,806 patients at enrollment. Depressed patients were younger (61 ± 11 vs. 65 ± 11 years), had higher eGFR (84 ± 15 vs. 81 ± 14 mL/min/1.73 m2), but had more comorbidities. Incident CKD developed in 180,343 patients. Depression was associated with 20% higher risk of incident CKD (adjusted hazard ratio [aHR] and 95% CI: 1.20 [1.19-1.21]). Similarly, depression was associated with increased all-cause mortality (aHR and 95% CI: 1.25 [1.24-1.26]).ConclusionsThe presence of depression in patients with diabetes is associated with higher risk of developing CKD compared with nondepressed patients. Intervention studies should determine if effective treatment of depression in patients with diabetes would prevent major renal and cardiovascular complications.

BackgroundMedication nonadherence is a known risk factor for adverse outcomes in the general population. However, little is known about the association of predialysis medication adherence among patients with advanced chronic kidney disease and mortality following their transition to dialysis.Study designObservational study.Setting & participants32,348 US veterans who transitioned to dialysis during 2007 to 2011.PredictorsAdherence to treatment with cardiovascular drugs, ascertained from pharmacy database records using proportion of days covered (PDC) and persistence during the predialysis year.OutcomesPost-dialysis therapy initiation all-cause and cardiovascular mortality, using Cox models with adjustment for confounders.ResultsMean age of the cohort was 72±11 (SD) years; 96% were men, 74% were white, 23% were African American, and 69% had diabetes. During a median follow-up of 23 (IQR, 9-36) months, 18,608 patients died. Among patients with PDC>80%, there were 14,006 deaths (mortality rate, 283 [95% CI, 278-288]/1,000 patient-years]); among patients with PDC>60% to 80%, there were 3,882 deaths (mortality rate, 294 [95% CI, 285-304]/1,000 patient-years); among patients with PDC≤60%, there were 720 deaths (mortality rate, 291 [95% CI, 271-313]/1,000 patient-years). Compared with patients with PDC>80%, the adjusted HR for post-dialysis therapy initiation all-cause mortality for patients with PDC>60% to 80% was 1.12 (95% CI, 1.08-1.16), and for patients with PDC≤60% was 1.21 (95% CI, 1.11-1.30). In addition, compared with patients showing medication persistence, adjusted HR risk for post-dialysis therapy initiation all-cause mortality for patients with nonpersistence was 1.11 (95% CI, 1.05-1.16). A similar trend was detected for cardiovascular mortality and in subgroup analyses.LimitationsLarge number of missing values; results may not be generalizable to women or the general US population.ConclusionsPredialysis cardiovascular medication nonadherence is an independent risk factor for postdialysis mortality in patients with advanced chronic kidney disease transitioning to dialysis therapy. Further studies are needed to assess whether interventions targeting adherence improve survival after dialysis therapy initiation.

ObjectivesTo compare the mortality of elderly adults with end-stage renal disease (ESRD) treated with home hemodialysis (HD) with that of those receiving a kidney transplant (KTx).DesignProspective cohort.SettingPertinent data for the two groups were obtained from electronic medical records from a large dialysis provider and the U.S. Renal Data System.ParticipantsUsing data from elderly adults (aged ≥65) who started home HD and underwent KTx in the US between 2007 and 2011, a 1:1 propensity score (PS)-matched cohort of 960 elderly adults was created, and the association between treatment modality and all-cause mortality was examined using Cox proportional hazards and competing risk regression survival models using modality failure as a competing event.MeasurementsModality of renal replacement therapy.ResultsThe baseline mean age ± standard deviation of the PS-matched individuals undergoing home HD was 71 ± 6, and that of KTx recipients was 71 ± 5, 69% of both groups were male, 81% of those undergoing home HD and 79% of KTx recipients were white, and 11% and 12%, respectively, were African American. Median follow-up time was 205 days (interquartile range (IQR) 78-364 days) for those undergoing home HD and 795 days (IQR 366-1,221 days) for KTx recipients. There were 97 deaths (20%, 253/1,000 patient-years, 95% confidence interval (CI) = 207-309/1,000 patient-years) in the home HD group and 48 deaths (10%, 45/1,000 patient-years, 95% CI = 34-60/1,000 patient-years) in the KTx group. Elderly adults undergoing home HD had a risk of mortality that was almost five times as high as that of KTx recipients (hazard ratio = 4.74, 95% CI = 3.25-6.91). Similar results were seen in competing risk regression analyses (subhazard ratio = 4.71, 95% CI = 3.27-6.79). Results were consistent across different types of kidney donors and subgroups divided according to various recipient characteristics.ConclusionElderly adults with ESRD who receive a KTx have greater survival than those who undergo home HD. Further studies are needed to assess whether KTx receipt is associated with other benefits such as better quality of life and lower hospitalization rates.

BackgroundHigher mean platelet volume (MPV) is an indicator of larger, reactive platelets, and has been associated with a higher risk of thrombosis and cardiovascular events in the general population. Hemodialysis patients have a higher risk for cardiovascular death and predisposition to platelet dysfunction (thrombosis and bleeding diathesis), but the relationship between MPV and mortality in this population is unknown.MethodsAmong a 5-year cohort (1/2007-12/2011) of 149,118 incident hemodialysis patients from a large national dialysis organization, we examined the association between MPV and all-cause mortality. In primary analyses, we granularly analyzed MPV across five categories: 7.2-7.5, >7.5-9.5, >9.5-11.5, >11.5-13.5, and >13.5-15.0fL. In secondary analyses, we examined MPV categorized as low, normal, and high based on thresholds in the general population: 7.2-7.5, >7.5-11.5, and >11.5fL, respectively. Associations between baseline and time-dependent MPV with mortality were estimated using traditional and time-dependent Cox models in order to determine long-term and short-term exposure-mortality associations, respectively, using three adjustment levels: unadjusted, case-mix, and case-mix+laboratory models.ResultsIn primary analyses, higher baseline and time-dependent MPV levels were associated with incrementally higher death risk in case-mix+laboratory analyses (reference: >9.5-11.5fL). In secondary analyses, high baseline and time-dependent MPV levels were associated with higher mortality, whereas low MPV was associated with lower death risk across all multivariable models (reference: normal MPV).ConclusionsHemodialysis patients with higher MPV have heightened mortality risk. Further studies are needed to determine the pathophysiologic basis for the higher risk, and if modification of MPV ameliorates mortality in this population.

BackgroundIn the general population, compared wtih their White peers, African Americans suffer premature all-cause and cardiovascular (CV) deaths, attributed in part to reduced access to care and lower socioeconomic status. Prior reports indicated younger (aged 35 to 44 years) African Americans had a signficantly greater age-adjusted risk of death. Recent studies suggest that in a more egalitarian health care structure than typical United States (US) health care structures, African Americans may have similar or even better CV outcomes, but the impact of age is less well-known.MethodsWe examined age stratified all-cause mortality, and incident coronary heart disease (CHD) and ischemic stroke in 3,072,966 patients (547,441 African American and 2,525,525 White) with an estimated glomerular filtration rate (eGFR)>60 mL/min/1.73m(2) receiving care from the US Veterans Health Administration. Outcomes were examined in Cox models adjusted for demographics, comorbidities, kidney function, blood pressure, socioeconomics and indicators of the quality of health care delivery.ResultsAfrican Americans had an overall 30% lower all-cause mortality (P

BackgroundRed cell distribution width (RDW) is an index of red blood cell volume variability that has historically been used as a marker of iron deficiency anemia. More recently, studies have shown that elevated RDW is associated with higher mortality risk in the general population. However, there is lack of data demonstrating the association between RDW and mortality risk in hemodialysis (HD) patients. We hypothesized that higher RDW is associated with higher mortality in HD patients.Study designRetrospective observational study using a large HD patient cohort.Setting & participants109,675 adult maintenance HD patients treated in a large dialysis organization from January 1, 2007, to December 31, 2011.PredictorBaseline and time-varying RDW, grouped into 5 categories:

BackgroundFew trials of acute kidney injury (AKI) prevention after surgery have been conducted, and most observational studies focus on AKI following cardiac surgery. The frequency of, risk factors for, and outcomes after AKI following other types of major surgery have not been well characterized and may present additional opportunities for trials in AKI.Study designObservational cohort study.Setting & participants3.6 million US veterans followed up from 2004 to 2011 for the receipt of major surgery (cardiac; general; ear, nose, and throat; thoracic; vascular; urologic; and orthopedic) and postoperative outcomes.FactorsDemographics, health characteristics, and type of surgery.OutcomesPostoperative AKI defined by the KDIGO creatinine criteria, postoperative length of stay, end-stage renal disease, and mortality.ResultsPostoperative AKI occurred in 11.8% of the 161,185 major surgery hospitalizations (stage 1, 76%; stage 2, 15%, stage 3 [without dialysis], 7%; and AKI requiring dialysis, 2%). Cardiac surgery had the highest postoperative AKI risk (relative risk [RR], 1.22; 95% CI, 1.17-1.27), followed by general (reference), thoracic (RR, 0.92; 95% CI, 0.87-0.98), orthopedic (RR, 0.70; 95% CI, 0.67-0.73), vascular (RR, 0.68; 95% CI, 0.64-0.71), urologic (RR, 0.65; 95% CI, 0.61-0.69), and ear, nose, and throat (RR, 0.32; 95% CI, 0.28-0.37) surgery. Risk factors for postoperative AKI included older age, African American race, hypertension, diabetes mellitus, and, for estimated glomerular filtration rate < 90mL/min/1.73m(2), lower estimated glomerular filtration rate. Participants with postoperative AKI had longer lengths of stay (15.8 vs 8.6 days) and higher rates of 30-day hospital readmission (21% vs 13%), 1-year end-stage renal disease (0.94% vs 0.05%), and mortality (19% vs 8%), with similar associations by type of surgery and more severe stage of AKI relating to poorer outcomes.LimitationsUrine output was not available to classify AKI; cohort included mostly men.ConclusionsAKI was common after major surgery, with similar risk factor and outcome associations across surgery type. These results can inform the design of clinical trials in postoperative AKI to the noncardiac surgery setting.

ObjectivesHemoglobin A1c levels less than 7.0% and systolic blood pressure (SBP) less than 140 mmHg are each associated with lower risk of vascular complications in patients with diabetes mellitus. Associations between combined A1c level and SBP categories and risk of mortality and morbidity in diabetic patients are not well characterized.MethodsWe examined 891 670 US diabetic veterans with baseline estimated glomerular filtration rates more than 60 ml/min per 1.73 m (mean age 67 ± 11 years, 97% men, 17% African-Americans). The associations of mutually exclusive combined categories of A1c (

Resistin is an adipocytokine that is associated with inflammation, coronary artery disease, and other types of cardiovascular disease among patients with normal kidney function. However, little is known about the association of resistin with outcomes in kidney transplant recipients. We collected socio-demographic and clinical parameters, medical and transplant history, and laboratory data from 988 prevalent kidney transplant recipients enrolled in the Malnutrition-Inflammation in Transplant-Hungary Study (MINIT-HU study). Serum resistin levels were measured at baseline. Associations between serum resistin level and death with a functioning graft over a 6-year follow-up period were examined in unadjusted and adjusted models. The mean±SD age of the study population was 51 ± 13 years, among whom 57% were men and 21% were diabetics. Median serum resistin concentrations were significantly higher in patients who died with a functioning graft as compared to those who did not die during the follow-up period (median [IQR]: 22[15-26] vs. 19[14-22] ng/ml, respectively; P < 0.001). Higher serum resistin level was associated with higher mortality risk in both unadjusted and fully adjusted models: HRs (95% CI): 1.33(1.16-1.54) and 1.21(1.01-1.46), respectively. In prevalent kidney transplant recipients, serum resistin was an independent predictor of death with a functioning graft.

The effect on post-operative outcomes after coronary artery bypass graft (CABG) surgery is not clear. Among 17,812 patients who underwent CABG during October 1,2006-September 28,2012 in any Department of US Veterans Affairs (VA) hospital, we identified 5,968 with available preoperative urine albumin-creatinine ratio (UACR) measurements. We examined the association of UACR=300 mg/g with 30/90/180/365-day and overall all-cause mortality, and hospitalization length >10 days, and with acute kidney injury(AKI). Mean ± SD baseline age and eGFR were 66 ± 8 years and 77 ± 19 ml/min/1.73 m(2), respectively. 788 patients (13.2%) died during a median follow-up of 3.2 years, and 26.8% patients developed AKI (23.1%-Stage 1; 2.9%-Stage 2; 0.8%-Stage 3) within 30 days of CABG. The median lengths of stay were 8 days (IQR: 6-13 days), 10 days (IQR: 7-14 days) and 12 days (IQR: 8-19 days) for groups with UACR < 30 mg/g, 30-299 mg/g and ≥300 mg/g, respectively. Higher UACR conferred 72 to 85% higher 90-, 180-, and 365-day mortality compared to UACR

Background and objectivesAlthough a peritoneal equilibration test yields data on three parameters (4-hour dialysate/plasma creatinine, 4- to 0-hour dialysate glucose, and 4-hour ultrafiltration volume), all studies have focused on the prognostic value of dialysate/plasma creatinine for patients undergoing peritoneal dialysis. Because dialysate 4- to 0-hour glucose and ultrafiltration volume may be superior in predicting daily ultrafiltration, the likely mechanism for the association of peritoneal equilibration test results with outcomes, we hypothesized that they are superior to dialysate/plasma creatinine for risk prediction.Design, setting, participants, & measurementsWe examined unadjusted and adjusted associations of three peritoneal equilibration test parameters with all-cause mortality, technique failure, and hospitalization rate in 10,142 patients on peritoneal dialysis treated between January 1, 2007 and December 31, 2011 in 764 dialysis facilities operated by a single large dialysis organization in the United States, with a median follow-up period of 15.8 months; 87% were treated with automated peritoneal dialysis.ResultsDemographic and clinical parameters explained only 8% of the variability in dialysate/plasma creatinine. There was a linear association between dialysate/plasma creatinine and mortality (adjusted hazards ratio per 0.1 unit higher, 1.07; 95% confidence interval, 1.02 to 1.13) and hospitalization rate (adjusted incidence rate ratio per 0.1 unit higher, 1.05; 95% confidence interval, 1.03 to 1.06). Dialysate/plasma creatinine and dialysate glucose were highly correlated (r=-0.84) and yielded similar risk prediction. Ultrafiltration volume was inversely related with hospitalization rate but not with all-cause mortality. None of the parameters were associated with technique failure. Adding 4- to 0-hour dialysate glucose, ultrafiltration volume, or both did not result in any improvement in risk prediction with dialysate/plasma creatinine alone.ConclusionsThis analysis from a large contemporary cohort treated primarily with automated peritoneal dialysis validates dialysate/plasma creatinine as a robust predictor of outcomes in patients treated with peritoneal dialysis.

BackgroundIn the general population, blacks experience higher mortality than their white peers, attributed in part to their lower socioeconomic status, reduced access to care, and possibly intrinsic biological factors. Patients with kidney disease are a notable exception, among whom blacks experience lower mortality. It is unclear if similar differences affecting outcomes exist in patients with no kidney disease but with equal or similar access to health care.Methods and resultsWe compared all-cause mortality, incident coronary heart disease, and incident ischemic stroke using multivariable-adjusted Cox models in a nationwide cohort of 547 441 black and 2 525 525 white patients with baseline estimated glomerular filtration rate ≥ 60 mL·min⁻¹·1.73 m⁻² receiving care from the US Veterans Health Administration. In parallel analyses, we compared outcomes in black versus white individuals in the National Health and Nutrition Examination Survey (NHANES) 1999 to 2004. After multivariable adjustments in veterans, black race was associated with 24% lower all-cause mortality (adjusted hazard ratio, 0.76; 95% confidence interval, 0.75-0.77; P

It was recently reported that residential altitude is inversely associated with all-cause mortality among incident dialysis patients; however, no adjustment was made for key case-mix and laboratory variables. We re-examined this question in a contemporary patient database with comprehensive clinical and laboratory data. In a contemporary 8-year cohort of 144,892 maintenance dialysis patients from a large dialysis organization, we examined the relationship between residential altitude and all-cause mortality. Using data from the US Geological Survey, the average residential altitudes per approximately 43,000 US zip codes were compiled and linked to the residential zip codes of each patient. Mortality risks for these patients were estimated by Cox proportional hazard ratios. The study population's mean ± standard deviation age was 61 ± 15 years. Forty-five percent of patients were women, and 57% of patients had diabetes. In fully adjusted analysis, those residing in the highest altitude strata (≥ 6000 ft) had a lower all-cause mortality risk in fully adjusted analyses: death hazard ratio: 0.92 (95% confidence interval, 0.86-0.99), as compared with patients in the reference group (

BackgroundPrevious studies have indicated U-shaped associations between blood pressure (BP) and mortality in dialysis patients. We hypothesized that a similar association exists between pre-transplant BP and post-transplant outcomes in dialysis patients who undergo successful kidney transplantation.MethodsData from the Scientific Registry of Transplant Recipients were linked to the five-yr cohort of a large dialysis organization in the United States. We identified all dialysis patients who received a kidney transplant during this period. Unadjusted and multivariate adjusted predictors of transplant outcomes were examined.ResultsA total of 13 881 patients included in our study were 47 ± 14 yr old and included 42% women. There was no association between pre-transplant systolic BP and post-transplant mortality, although a decreased risk trend was observed in those with low post-dialysis systolic BP. Compared to patients with pre-dialysis diastolic BP 70 to

ObjectivesThe study objective was to assess the association between angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) use and mortality in patients with chronic kidney disease (CKD).BackgroundThere is insufficient evidence about the association of ACEI or ARBs with mortality in patients with CKD.MethodsA logistic regression analysis was used to calculate the propensity of ACEI/ARB initiation in 141,413 U.S. veterans with nondialysis CKD who were previously unexposed to ACEI/ARB treatment. We examined the association of ACEI/ARB administration with all-cause mortality in patients matched by propensity scores using the Kaplan-Meier method and Cox models in "intention-to-treat" analyses and in generalized linear models with binary outcomes and inverse probability of treatment weights in "as-treated" analyses.ResultsThe age of the patients at baseline was 75 ± 10 years, 8% of patients were black, and 22% were diabetic. ACEI/ARB administration was associated with a significantly lower risk of mortality both in the intention-to-treat analysis (hazard ratio: 0.81, 95% confidence interval: 0.78 to 0.84; p < 0.001) and the as-treated analysis with inverse probability of treatment weights (odds ratio: 0.37, 95% confidence interval: 0.34 to 0.41; p < 0.001). The association of ACEI/ARB treatment with lower risk of mortality was present in all examined subgroups.ConclusionsIn this large contemporary cohort of nondialysis-dependent patients with CKD, ACEI/ARB administration was associated with greater survival.

BackgroundIn hemodialysis patients, higher serum creatinine (Cr) concentration represents larger muscle mass and predicts greater survival. However, this association remains uncertain in peritoneal dialysis (PD) patients.MethodsIn a cohort of 10 896 PD patients enrolled from 1 July 2001 to 30 June 2006, the association of baseline serum Cr level and change during the first 3 months after enrollment with all-cause mortality was examined.ResultsThe cohort mean ± SD age was 55 ± 15 years old and included 52% women, 24% African-Americans and 48% diabetics. Compared with patients with serum Cr levels of 8.0–9.9 mg/dL, patients with serum Cr levels of

ObjectiveHypo- and hyperphosphatemia have each been associated with increased mortality in maintenance hemodialysis (MHD) patients. There has not been previous evaluation of a differential relationship between serum phosphorus level and death risk across varying age groups in MHD patients.Design and SettingsIn a 6-year cohort of 107,817 MHD patients treated in a large dialysis organization, we examined the association between serum phosphorus levels with all-cause and cardiovascular mortality within 5 age categories (15-5.5 mg/dl) was consistently associated with increased all-cause and cardiovascular mortality risks across all age categories including after adjustment for case-mix and MICS-related covariates. In fully adjusted models, a low serum phosphorus level (

ObjectivesThis study sought to compare the association of microalbuminuria with outcomes in patients with different comorbidities.BackgroundThe risk of adverse outcomes associated with lower levels proteinuria has been found to be linearly decreasing with even low-normal levels of microalbuminuria. It is unclear whether comorbid conditions change these associations.MethodsWe examined the association of urine microalbumin-creatinine ratio (UACR) with mortality and the slopes of estimated glomerular filtration rate (eGFR) in a nationally representative cohort of 298,875 U.S. veterans. Associations of UACR with all-cause mortality overall and in subgroups of patients with and without diabetes mellitus, hypertension, cardiovascular disease, congestive heart failure, and advanced chronic kidney disease (CKD) were examined in Cox models, and with the slopes of eGFR in linear and logistic regression models.ResultsVery low levels of UACR were linearly associated with decreased mortality and less progression of CKD overall: adjusted mortality hazard ratio and estimated glomerular filtration rate slope (95% confidence interval [CI]) associated with UACR ≥200 μg/mg, compared to

BackgroundBlack dialysis patients have significantly lower mortality compared to white patients, in contradistinction to the higher mortality seen in blacks in the general population. It is unclear if a similar paradox exists in non–dialysis-dependent CKD, and if it does, what its underlying reasons are.Study DesignHistorical cohort.Setting & Participants518,406 white and 52,402 black male US veterans with non-dialysis dependent CKD stages 3–5.PredictorBlack race.Outcomes & MeasurementsWe examined overall and CKD stage-specific all-cause mortality using parametric survival models. The effect of sociodemographic characteristics, comorbidities and laboratory characteristics on the observed differences was explored in multivariable models.ResultsOver a median follow-up of 4.7 years 172,093 patients died (mortality rate, 71.0 [95% CI, 70.6–71.3] per 1000 patient-years). Black race was associated with significantly lower crude mortality (HR, 0.95; 95% CI, 0.94–0.97; p

BackgroundAfrican Americans are at greater risk to reach end-stage renal disease and this risk may carry over in a kidney transplant recipient after kidney transplantation.MethodsLinking the five-yr patient data of a large dialysis organization to the Scientific Registry of Transplant Recipients, we identified 13 692 hemodialysis patients who underwent first kidney transplantation. Mortality or graft failure and delayed graft function risks were estimated by Cox's regression (hazard ratio [HR] and 95% confidence interval) and logistic regression, respectively.ResultsPatients were 48 ± 14 yr old and included 39% women and 26% patients with diabetes. After adjusting for several relevant clinical and transplant-related variables, African American donor race was associated with higher all-cause mortality, with HR of 1.39 (1.09-1.78) for all-cause mortality, 1.80 (1.17-2.76) for cardiovascular mortality, 1.30 (1.03-1.64) for death-censored graft loss and 1.31 (1.10-1.57) for combined outcome over the six-yr observation period. In the non-African American recipient subcohort, but not in the African American recipient subcohort, African American donor race was associated with higher risk of death-censored graft loss (2.24 [1.44-3.49]) in our fully adjusted model.ConclusionsAfrican American donor race was associated with increased all-cause and cardiovascular mortality and graft loss.

PurposeSeveral observational studies have indicated that vitamin D receptor activators (VDRA), including paricalcitol, are associated with greater survival in maintenance hemodialysis (MHD) patients. However, patients with higher serum parathyroid hormone, a surrogate of higher death risk, are usually given higher VDRA doses, which can lead to confounding by indication and attenuate the expected survival advantage of high VDRA doses.MethodsWe examined mortality-predictability of low (>1 but

BackgroundWhether peritoneal dialysis (PD) treatment leads to greater weight gain than with hemodialysis (HD) and if this limits access of obese end-stage renal disease patients to renal transplantation has not been examined. We undertook this study to determine the interrelationship between body size and initial dialysis modality on transplantation, mortality and weight gain.MethodsTime to transplantation, time to death and weight gain were estimated in a 1:1 propensity score-matched cohort of incident HD and PD patients treated in facilities owned by DaVita Inc. between 1 July 2001 through 30 June 2006 followed through 30 June 2007 (4008 pairs) in four strata of body mass index (BMI) (18.5 kg/m(2), including with BMI ≥ 30 kg/m(2) (aHR 1.45, 95% CI 1.11-1.89). PD patients had significantly lower all-cause mortality for patients with BMI 18.50-29.99 kg/m(2). Both these findings were confirmed on analyses of the entire unmatched incident cohort (PD 4008; HD 58 471). The effect of dialysis modality on weight gain was tested in 687 propensity score-matched pairs; the odds of >2, >5 or >10% weight gain were significantly lower in PD patients.ConclusionTreatment with PD is less likely to be associated with a significant weight gain and does not limit the access of obese patients to renal transplantation.

BackgroundThe role of pre-transplant erythropoiesis-stimulating agent (ESA) responsiveness in affecting post-transplant outcomes is not clear.MethodsLinking the 5-year patient data of a large dialysis organization to the 'Scientific Registry of Transplant Recipients', we identified 8795 hemodialyzed patients who underwent first kidney transplantation. Mortality or graft failure, delayed graft function (DGF) and acute rejection risks were estimated by Cox regression [hazard ratio (HR)] and logistic regression, respectively.ResultsPatients were 48 ± 14 years old and included 38% women and 36% diabetics. Compared to renal allograft recipients who were in the first quartile of pre-transplant ESA responsiveness index (ERI), i.e. ESA dose divided by hemoglobin and weight, recipients in second, third and fourth quartiles had higher adjusted graft-censored death HR (and 95% confidence intervals) of 1.7 (1.0-2.7), 1.8 (1.1-2.9) and 2.3 (1.4-3.9) and higher death-censored graft failure HR of 1.6 (1.0-2.5), 2.0 (1.2-3.1) and 1.6 (0.9-2.6), respectively. No significant association between pre-transplant ERI and post-transplant DGF or acute rejection was detected.ConclusionsHigher pre-transplant ERI during the hemodialysis treatment period was associated with worse post-transplant long-term outcomes including increased all-cause death and higher risk of graft failure.

BackgroundRecent observational studies and a controlled trial suggest more favorable outcomes upon later dialysis initiation in chronic kidney disease. The role of estimated glomerular filtration rate (eGFR) in predicting outcome at reinitiation of dialysis in failed kidney transplant recipients is unclear.MethodsFive-year data in a large dialysis organization was linked to the 'Scientific Registry of Transplant Recipients' to identify 747 failed kidney transplant patients with CKD Stage 5, who had restarted dialysis therapy. A propensity score for early (eGFR>10.5 mL/min/1.73 m2) versus late reinitiation of dialysis was fit by logistic regression. The mortality hazard ratio (HR) was estimated across tertiles of the fitted score.ResultsPatients were 44±14 years old and included 42% women. Male gender {odds ratio (OR), [95% confidence interval (CI)]: 1.82 (1.22-2.73)}, diabetes mellitus [OR: 1.75 (1.14-2.68)] and peripheral vascular disease [OR: 3.55 (1.17-10.77)] were associated with higher odds of early dialysis reinitiation. Each mL/min/1.73 m2 higher eGFR was associated with 6% higher death risk in unadjusted model [HR: 1.06 (1.01-1.11)], and although not significant in fully adjusted models [HR: 1.02 (0.96-1.07)], it was significant in some subgroups including women and younger patients. The death HR of higher eGFR across lowest to highest tertiles of propensity score of early dialysis initiation (corresponding healthiest to sickest patients) were 1.10 (0.98-1.24), 1.00 (0.91-1.10) and 0.99 (0.92-1.07), respectively (P for trend

BackgroundMaintenance hemodialysis (MHD) patients with polycystic kidney disease (PKD) have better survival than non-PKD patients. Mineral and bone disorders (MBD) are associated with accelerated atherosclerosis and cardiovascular death in MHD patients. It is unknown whether the different MBD mortality association between MHD populations with and without PKD can explain the survival differential.MethodsSurvival models were examined to assess the association between different laboratory markers of MBD [such as serum phosphorous, parathyroid hormone (PTH), calcium and alkaline phosphatase] and mortality in a 6-year cohort of 60,089 non-PKD and 1501 PKD MHD patients.ResultsPKD and non-PKD patients were 57±13 and 62±15 years old and included 46 and 45% women and 14 and 32% Blacks, respectively. Whereas PKD individuals with PTH 150 to

BackgroundRacial and ethnic disparities among North American patients with chronic kidney disease have received significant attention. In contrast, little is known about health-related outcomes of patients with end-stage renal disease among the Roma minority, also known as gypsies, compared to Caucasian individuals. We prospectively assessed the association between Roma ethnicity and long-term clinical outcomes in kidney transplant recipients.MethodsIn a prevalent cohort of renal transplant recipients, followed up over a median of 94 months, we prospectively collected socio-demographic, medical (and transplant related) characteristics and laboratory data at baseline from 60 Roma and 1,003 Caucasian patients (mean age 45 (SD = 11) and 49 (SD = 13) years, 33 and 41% women, 18 and 17% with diabetes mellitus, respectively). Survival analyses examined the associations between Roma ethnicity and all-cause mortality and death-censored graft loss or death with functioning renal allograft.ResultsDuring the follow-up period, 341 patients (32%) died. Two-hundred eighty (26%) patients died with a functioning graft and 201 patients (19%) returned to dialysis. After multivariable adjustments, Roma ethnicity was associated with 77% higher risk of all-cause mortality (Hazard Ratio (HR): 1.77; 95% confidence interval (CI): 1.02, 3.07), two times higher risk of mortality with functioning graft (2.04 [1.17-3.55]) and 77% higher risk of graft loss (1.77 [1.01-3.13]), respectively.ConclusionsRoma ethnicity is independently associated with increased mortality risk and worse graft outcome in kidney transplant recipients. Further studies should identify the factors contributing to worse outcomes among Roma patients.

BackgroundRecent studies show a survival advantage with kidney transplant in elderly patients compared with those on dialysis therapy.Study designIn our present study, we examined and compared the association of expanded criteria donor (ECD) kidney and living kidney donation with the outcome of kidney transplant across different ages, including elderly recipients.Setting & participantsUsing the Scientific Registry of Transplant Recipients, we identified 145,470 adult kidney transplant patients. Mortality and death-censored transplant failure risks were estimated by Cox proportional regression analyses during follow-up with a median of 3.9 years.PredictorsECD kidney and living kidney donation and age compared with others.OutcomesMortality and death-censored transplant failure risk.ResultsPatients were aged 45 ± 16 years and included 40% women and 19% patients with diabetes. Compared with transplant recipients 55 to younger than 65 years, the fully adjusted death-censored transplant failure risk was higher in patients 75 years and older (HR, 1.30; 95% CI, 1.09-1.56), 35 to younger than 55 years (HR, 1.13; 95% CI, 1.08-1.17), and 18 to younger than 35 years (HR, 1.64; 95% CI, 1.57-1.71). Compared with non-ECD kidneys, ECD kidneys were significant predictors of mortality in nonelderly patients (18-

BackgroundSeveral studies have shown an association between erythropoietin-stimulating agent (ESA) responsiveness and mortality in chronic kidney disease (CKD) patients. In our present study, we examined the association between prescribed ESA dose and mortality in peritoneal dialysis (PD) and hemodialysis (HD) patients. We hypothesized that PD patients received lower ESA dose for the same achieved hemoglobin compared to HD patients and that ESA dose-mortality associations were different between PD and HD patients.MethodsWe compared the prescribed doses of ESA between 139,103 HD and 10,527 PD patients treated in DaVita dialysis clinics from 7/2001 through 6/2006 using adjusted Poisson regression and examined mortality-predictability of prescribed ESA dose and ESA responsiveness index (ESA/hemoglobin) in PD and HD with follow-up through 6/2007 using Cox regression models.ResultsPoisson adjusted ratio of ESA dose of HD to PD was 3.6 (95% CI 3.5-3.7). In PD patients, adjusted all-cause death hazard ratios (HR) for ESA doses of 3,000-5,999, 6,000-8,999 and ≥9,000 U/week (reference