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Erythropoietin (EPO) is the primary regulator of bone marrow erythropoiesis. Mouse models have provided evidence that EPO also promotes bone remodeling and that EPO-stimulated erythropoiesis is accompanied by bone loss independent of increased red blood cell production. EPO has been used clinically for three decades to treat anemia in end-stage renal disease, and notably, although the incidence of hip fractures decreased in the United States generally after 1990, it rose among hemodialysis patients coincident with the introduction and subsequent dose escalation of EPO treatment. Given this clinical paradox and findings from studies in mice that elevated EPO affects bone health, we examined EPO treatment as a risk factor for fractures in hemodialysis patients. Relationships between EPO treatment and hip fractures were analyzed using United States Renal Data System (USRDS) datasets from 1997 to 2013 and Consolidated Renal Operations in a Web-enabled Network (CROWNWeb) datasets for 2013. Fracture risks for patients treated with <50 units of EPO/kg/week were compared to those receiving higher doses by multivariable Cox regression. Hip fracture rates for 747,832 patients in USRDS datasets (1997-2013) increased from 12.0 per 1000 patient years in 1997 to 18.9 in 2004, then decreased to 13.1 by 2013. Concomitantly, average EPO doses increased from 11,900 units/week in 1997 to 18,300 in 2004, then decreased to 8,800 by 2013. During this time, adjusted hazard ratios for hip fractures with EPO doses of 50-149, 150-299, and ≥ 300 units/kg/week compared to <50 units/kg/week were 1.08 (95% confidence interval [CI], 1.01-1.15), 1.22 (95% CI, 1.14-1.31), and 1.41 (95% CI, 1.31-1.52), respectively. Multivariable analyses of 128,941 patients in CROWNWeb datasets (2013) replicated these findings. This study implicates EPO treatment as an independent risk factor for hip fractures in hemodialysis patients and supports the conclusion that EPO treatment may have contributed to changing trends in fracture incidence for these patients during recent decades. Published 2021. This article is a U.S. Government work and is in the public domain in the USA. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (Published 2021. This article is a U.S. Government work and is in the public domain in the USA. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Background: Because stroke prevention is a major goal in the management of ESKD hemodialysis patients with atrial fibrillation, investigating racial/ethnic disparities in stroke among such patients is important to those who could benefit from strategies to maximize preventive measures., Methods: We used the United States Renal Data System to identify ESKD patients who initiated hemodialysis from 2006 to 2013 and then identified those with a subsequent atrial fibrillation diagnosis and Medicare Part A/B/D. Patients were followed for 1 year for all-cause stroke, mortality, prescription medications, and cardiovascular disease procedures. The survival mediational g-formula quantified the percentage of excess strokes attributable to lower use of atrial fibrillation treatments by race/ethnicity., Results: The study included 56,587 ESKD hemodialysis patients with atrial fibrillation. Black, white, Hispanic, and Asian patients accounted for 19%, 69%, 8%, and 3% of the population, respectively. Compared with white patients, black, Hispanic, or Asian patients were more likely to experience stroke (13%, 15%, and 16%, respectively) but less likely to fill a warfarin prescription (10%, 17%, and 28%, respectively). Warfarin prescription was associated with decreased stroke rates. Analyses suggested that equalizing the warfarin distribution to that in the white population would prevent 7%, 10%, and 12% of excess strokes among black, Hispanic, and Asian patients, respectively. We found no racial/ethnic disparities in all-cause mortality or use of cardiovascular disease procedures., Conclusions: Racial/ethnic disparities in all-cause stroke among hemodialysis patients with atrial fibrillation are partially mediated by lower use of anticoagulants among black, Hispanic, and Asian patients. The reasons for these disparities are unknown, but strategies to maximize stroke prevention in minority hemodialysis populations should be further investigated., (Copyright © 2020 by the American Society of Nephrology.)

Background: The opioid epidemic is a public health emergency and appropriate medication prescription for pain remains challenging. Physicians have increasingly prescribed gabapentinoids for pain despite limited evidence supporting their use. We determined the prevalence of concomitant gabapentinoid and opioid prescriptions and evaluated their associations with outcomes among dialysis patients., Methods: We used the United States Renal Data System to identify patients treated with dialysis with Part A, B, and D coverage for all of 2010. Patients were grouped into 4 categories of drugs exposure status in 2010: (1) no prescriptions of either an opioid or gabapentinoid, (2) ≥1 prescription of an opioid and no prescriptions of gabapentinoids, (3) no prescriptions of an opioid and ≥1 prescription of gabapenbtinoids, (4) ≥1 prescription of both an opioid and gabapentinoid. Outcomes included 2-year all-cause death, dialysis discontinuation, and hospitalizations assessed in 2011 and 2012., Results: The study population included 153,758 dialysis patients. Concomitant prescription of an opioid and gabapentin (15%) was more common than concomitant prescription of an opioid and pregabalin (4%). In adjusted analyses, concomitant prescription of an opioid and gabapentin compared to no prescription of either was associated with increased risk of death (hazard ratio [HR] 1.16, 95% CI 1.12-1.19), dialysis discontinuation (HR 1.14, 95% CI 1.03-1.27), and hospitalization (HR 1.33, 95% CI 1.31-1.36). Concomitant prescription of an opioid and pregabalin compared to no prescription of either was associated with increased mortality (HR 1.22, 95% CI 1.16-1.28) and hospitalization (HR 1.37, 95% CI 1.33-1.41), but not dialysis discontinuation (HR 1.13, 95% CI 0.95-1.35). Prescription of opioids and gabepentinoids compared to only being prescribed opioids was associated with higher risk of hospitalizations, but not mortality, or dialysis discontinuation., Conclusions: Concomitant prescription of opioids and gabapentinoids among US dialysis patients is common, and both drugs have independent effects on outcomes. Future research should prospectively investigate the potential harms of such drugs and identify safer alternatives for treatment of pain in end-stage renal disease patients., (© 2020 Published by S. Karger AG, Basel.)

We hypothesized that high incidence rates of end-stage renal disease (ESRD) in certain counties of the U.S. are partly due to patients with a type of ESRD resembling chronic kidney disease of uncertain etiology (CKDu), which has been observed in Central America and other countries. Using data on 338,126 incident ESRD patients from the United States Renal Data System (USRDS) (2011 - 2013) and the Behavior Risk Factor Surveillance System (BRFSS) Supplement on county-level variables (2006), we describe both patient-level and county-level characteristics in counties with the highest quartile of ESRD incidence rate standardized for age, sex, and race (> 420 cases/million population/year) compared to the rest of the U.S. and two specific "hotspots" of ESRD: the San Joaquin Valley and the Rio Grande Valley. Logistic regression was used to examine characteristics associated with patients who had either missing cause of ESRD or "unknown" listed as the primary cause of ESRD. High incidence rates of ESRD were observed in southern Texas, the Southeast and parts of California (including the San Joaquin valley area), while low rates were seen in the Northwest and the Mountain Regions. The median crude incidence rate of ESRD was 335 (range 0 - 2,341) new cases per million population per year among counties. Significant predictors of missing/unknown primary cause of ESRD included: older age, white or unknown race, non-Hispanic ethnicity, lack of comorbidities at ESRD onset, lower estimated glomerular filtration rate (eGFR) at initiation, and lack of pre-dialysis care. Large areas of the U.S. have very high rates of ESRD incidence. We cannot confirm that CKDu is present in the U.S. based on this preliminary work. This topic therefore requires further investigation, as many of these patients may well be undocumented aliens working as farm laborers and therefore not registered in the USRDS.
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Seizures have been associated with uremia, but there are few data regarding the prevalence, treatment, and outcomes of patients with end-stage renal disease (ESRD) with epilepsy compared to those with ESRD without epilepsy. Here we conducted a retrospective cohort study using the United States Renal Data System to assess mortality and antiseizure medication prescriptions among patients with ESRD with and without a diagnosis of epilepsy. A modified Poisson regression with a robust variance was used to estimate the association between epilepsy status and mortality, and evaluate effect modification by neurology consultation. Additionally antiseizure medications were assessed in relation to mortality among those with epilepsy. Of 148,294 patients with ESRD in the cohort, 13,094 (8.8%) met a claims-based definition for epilepsy. Among those with epilepsy, 80.9% filled an anticonvulsant or hydantoin prescription in 2013-2014, compared to 33.3% without epilepsy. After adjustment for confounders, the mortality risk among those with epilepsy was 1.11 (95% confidence interval: 1.07, 1.14) times higher than those without. An epilepsy diagnosis was associated with a 15% increase in mortality risk among patients who did not have a neurology consultation (relative risk: 1.15 [95% confidence interval: 1.10, 1.20]), but this risk was attenuated among patients with a neurology consultation (1.07 [1.03, 1.11]). Prescription of gabapentin to patients with an epilepsy diagnosis compared to other antiseizure medications was associated with increased mortality (1.08 [1.01, 1.15]). Thus, patients with ESRD treated with dialysis have a high prevalence of epilepsy, which was associated with increased mortality risk compared to those without epilepsy. Hence, appropriate multidisciplinary care, treatment, and medication selection may reduce mortality among dialysis patients with epilepsy., (Published by Elsevier Inc.)

Background and Objectives: Limited existing data on psychiatric illness in ESKD patients suggest these diseases are common and burdensome, but under-recognized in clinical practice., Design, Setting, Participants, & Measurements: We examined hospitalizations with psychiatric diagnoses using inpatient claims from the first year of ESKD in adult and pediatric Medicare recipients who initiated treatment from 1996 to 2013. We assessed associations between hospitalizations with psychiatric diagnoses and all-cause death after discharge in adult dialysis patients using multivariable-adjusted Cox proportional hazards regression models., Results: In the first ESKD year, 72% of elderly adults, 66% of adults and 64% of children had at least one hospitalization. Approximately 2% of adults and 1% of children were hospitalized with a primary psychiatric diagnosis. The most common primary psychiatric diagnoses were depression/affective disorder in adults and children, and organic disorders/dementias in elderly adults. Prevalence of hospitalizations with psychiatric diagnoses increased over time across groups, primarily from secondary diagnoses. 19% of elderly adults, 25% of adults and 15% of children were hospitalized with a secondary psychiatric diagnosis. Hazards ratios of all-cause death were higher in all dialysis adults hospitalized with either primary (1.29; 1.26 to 1.32) or secondary (1.11; 1.10 to 1.12) psychiatric diagnoses than in those hospitalized without psychiatric diagnoses., Conclusions: Hospitalizations with psychiatric diagnoses are common in pediatric and adult ESKD patients, and are associated with subsequent higher mortality, compared with hospitalizations without psychiatric diagnoses. The prevalence of hospitalizations with psychiatric diagnoses likely underestimates the burden of mental illness in the population., (Copyright © 2019 by the American Society of Nephrology.)

Objectives: The association of race, ethnicity, and socioeconomic factors with survival rates of nursing home (NH) residents with treated end-stage renal disease (ESRD) is unclear. We examined whether race/ethnicity, ZIP code-level, and individual-level indicators of poverty relate to mortality of NH residents on dialysis., Design: Retrospective cohort study., Participants/setting: Using the United States Renal Data System database, we identified 56,194 nursing home residents initiated on maintenance dialysis from January 1, 2007 through December 31, 2013, followed until May 31, 2014., Measurements: We evaluated baseline characteristics of the NH cohort on dialysis, including race and ethnicity. We assessed the Medicare-Medicaid dual eligibility status as an indicator of individual-level poverty and ZIP code-level median household income (MHI) data. We conducted Cox regression analyses with all-cause mortality as the outcome variable, adjusted for clinical and sociodemographic factors including end-of-life preferences., Results: Adjusted Cox analysis showed a significantly lower risk of death among black vs nonblack NH residents [adjusted hazard ratio (AHR) 0.91, 95% confidence interval (CI) 0.89, 0.94]. Dual-eligibility status was significantly associated with lower risk of death compared to those with Medicare alone (AHR 0.80, 95% CI 0.78, 0.82). Compared to those in higher MHI quintile levels, NH ESRD patients in the lowest quintile were significantly associated with higher risk of death (AHR 1.09, 95% CI 1.06, 1.13)., Conclusions/implications: Black and Hispanic NH residents on dialysis had an apparent survival advantage. This "survival paradox" occurs despite well-documented racial/ethnic disparities in ESRD and NH care and warrants further exploration that could generate new insights into means of improving survival of all NH residents on dialysis. Area-level indicator of poverty was independently associated with mortality, whereas dual-eligibility status for Medicare and Medicaid was associated with lower risk of death, which could be partly explained by improved access to care., (Published by Elsevier Inc.)

Background: Data from clinical trials to inform practice in maintenance hemodialysis are limited. Incorporating randomized trials into dialysis clinical care delivery should help generate practice-guiding evidence, but the feasibility of this approach has not been established., Methods: To develop approaches for embedding trials into routine delivery of maintenance hemodialysis, we performed a cluster-randomized, pragmatic trial demonstration project, the Time to Reduce Mortality in ESRD (TiME) trial, evaluating effects of session duration on mortality (primary outcome) and hospitalization rate. Dialysis facilities randomized to the intervention adopted a default session duration ≥4.25 hours (255 minutes) for incident patients; those randomized to usual care had no trial-driven approach to session duration. Implementation was highly centralized, with no on-site research personnel and complete reliance on clinically acquired data. We used multiple strategies to engage facility personnel and participating patients., Results: The trial enrolled 7035 incident patients from 266 dialysis units. We discontinued the trial at a median follow-up of 1.1 years because of an inadequate between-group difference in session duration. For the primary analysis population (participants with estimated body water ≤42.5 L), mean session duration was 216 minutes for the intervention group and 207 minutes for the usual care group. We found no reduction in mortality or hospitalization rate for the intervention versus usual care., Conclusions: Although a highly pragmatic design allowed efficient enrollment, data acquisition, and monitoring, intervention uptake was insufficient to determine whether longer hemodialysis sessions improve outcomes. More effective strategies for engaging clinical personnel and patients are likely required to evaluate clinical trial interventions that are fully embedded in care delivery., (Copyright © 2019 by the American Society of Nephrology.)

Importance: Cardiovascular disease (CVD) is a leading cause of death among patients with end-stage renal disease (ESRD). Young adult (ages 22-29 years) have risks for ESRD-associated CVD that may vary from other ages., Objective: To test the hypothesis that young adult-onset ESRD is associated with higher cardiovascular (CV) hospitalizations and mortality with different characteristics than childhood-onset disease., Design, Setting, and Participants: This population-based cohort study used the US Renal Data System to categorize patients who initiated ESRD care between 2003 and 2013 by age at ESRD onset (1-11, 12-21, and 22-29 years). Cardiovascular hospitalizations were identified via International Classification of Diseases, Ninth Revision discharge codes and CV mortality from the Centers for Medicare & Medicaid ESRD Death Notification Form. Patients were censored at death from non-CVD events, loss to follow-up, recovery, or survival to December 31, 2014. Adjusted proportional hazard models (95% CI) were fit to determine risk of CV hospitalization and mortality by age group. Data analysis occurred from May 2016 and December 2017., Exposures: Onset of ESRD., Main Outcomes and Measures: Cardiovascular mortality and hospitalization., Results: A total of 33 156 patients aged 1 to 29 years were included in the study population. Young adults (aged 22-29 years) had a 1-year CV hospitalization rate of 138 (95% CI, 121-159) per 1000 patient-years. Young adults had a higher risk for CV hospitalization than children (aged 1-11 years; hazard ratio [HR], 0.41 [95% CI, 0.26-0.64]) and adolescents (aged 12-21 years; HR, 0.86 [95% CI, 0.77-0.97]). Of 4038 deaths in young adults, 1577 (39.1%) were owing to CVD. Five-year cumulative incidence of mortality in this group (7.3%) was higher than in younger patients (adolescents, 4.0%; children, 1.7%). Adjusted HRs for CV mortality were higher for young adults with all causes of ESRD than children (cystic, hereditary, and congenital conditions: HR, 0.22 [95% CI, 0.11-0.46]; P < .001; glomerulonephritis: HR, 0.21 [95% CI, 0.10-0.44]; P < .001; other conditions: HR, 0.33 [95% CI, 0.23-0.49]; P < .001). Adolescents had a lower risk for CV mortality than young adults for all causes of ESRD except glomerulonephritis (cystic, hereditary, and congenital conditions: HR, 0.45 [95% CI, 0.27-0.74]; glomerulonephritis: HR, 0.99 [95% CI, 0.76-1.11]; other: HR, 0.47 [95% CI, 0.40-0.57]). Higher risks for CV hospitalization and mortality were associated with lack of preemptive transplant compared with hemodialysis (hospital: HR, 14.24 [95% CI, 5.92-34.28]; mortality: HR, 13.64 [95% CI, 8.79-21.14]) and peritoneal dialysis [hospital: HR, 8.47 [95% CI, 3.50-20.53]; mortality: HR, 7.86 [95% CI, 4.96-12.45]). Nephrology care before ESRD was associated with lower risk for CV mortality (HR, 0.77 [95% CI, 0.70-0.85])., Conclusions and Relevance: Cardiovascular disease accounted for nearly 40% of deaths in young adults with incident ESRD in this cohort. Identified risk factors may inform development of age-appropriate ESRD strategies to improve the CV health of this population.

Rationale & Objective: Diabetic 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 Design: Observational cohort study., Setting & Participants: US veterans from the national Veterans Affairs database with diabetes and chronic kidney disease transitioning to dialysis therapy from October 2007 to September 2011., Exposure: Hypoglycemia-related hospitalizations during the pre-ESRD period and antidiabetic medication regimens., Outcome: The 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 Approach: We 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., Results: Among 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., Limitations: Residual confounding cannot be excluded., Conclusions: Among 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., (Copyright © 2018 National Kidney Foundation, Inc. All rights reserved.)

Objective: To develop and validate a risk prediction model that would help individualize treatment and improve the shared decision-making process between clinicians and patients., Patients and Methods: We developed a risk prediction tool for mortality during the first year of dialysis based on pre-end-stage renal disease characteristics in a cohort of 35,878 US veterans with incident end-stage renal disease who transitioned to dialysis treatment between October 1, 2007, and March 31, 2014 and then externally validated this tool among 4284 patients in the Kaiser Permanente Southern California (KPSC) health care system who transitioned to dialysis treatment between January 1, 2007, and September 30, 2015., Results: To ensure model goodness of fit, 2 separate models were selected for patients whose last estimated glomerular filtration rate (eGFR) before dialysis initiation was less than 15 mL/min per 1.73 m 2 or 15 mL/min per 1.73 m 2 or higher. Model discrimination in the internal validation cohort of veterans resulted in C statistics of 0.71 (95% CI, 0.70-0.72) and 0.66 (95% CI, 0.65-0.67) among patients with eGFR lower than 15 mL/min per 1.73 m 2 and 15 mL/min per 1.73 m 2 or higher, respectively. In the KPSC external validation cohort, the developed risk score exhibited C statistics of 0.77 (95% CI, 0.74-0.79) in men and 0.74 (95% CI, 0.71-0.76) in women with eGFR lower than 15 mL/min per 1.73 m 2 and 0.71 (95% CI, 0.67-0.74) in men and 0.67 (95% CI, 0.62-0.72) in women with eGFR of 15 mL/min per 1.73 m 2 or higher., Conclusion: A new risk prediction tool for mortality during the first year after transition to dialysis (available at www.DialysisScore.com) was developed in the large national Veterans Affairs cohort and validated with good performance in the racially, ethnically, and gender diverse KPSC cohort. This risk prediction tool will help identify high-risk populations and guide management strategies at the transition to dialysis., (Copyright © 2018 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Aggressive pain treatment was advocated for ESRD patients, but new Centers for Disease Control and Prevention guidelines recommend cautious opioid prescription. Little is known regarding outcomes associated with ESRD opioid prescription. We assessed opioid prescriptions and associations between opioid prescription and dose and patient outcomes using 2006-2010 US Renal Data System information in patients on maintenance dialysis with Medicare Part A, B, and D coverage in each study year ( n =671,281, of whom 271,285 were unique patients). Opioid prescription was confirmed from Part D prescription claims. In the 2010 prevalent cohort ( n =153,758), we examined associations of opioid prescription with subsequent all-cause death, dialysis discontinuation, and hospitalization controlled for demographics, comorbidity, modality, and residence. Overall, >60% of dialysis patients had at least one opioid prescription every year. Approximately 20% of patients had a chronic (≥90-day supply) opioid prescription each year, in 2010 usually for hydrocodone, oxycodone, or tramadol. In the 2010 cohort, compared with patients without an opioid prescription, patients with short-term (1-89 days) and chronic opioid prescriptions had increased mortality, dialysis discontinuation, and hospitalization. All opioid drugs associated with mortality; most associated with worsened morbidity. Higher opioid doses correlated with death in a monotonically increasing fashion. We conclude that opioid drug prescription is associated with increased risk of death, dialysis discontinuation, and hospitalization in dialysis patients. Causal relationships cannot be inferred, and opioid prescription may be an illness marker. Efforts to treat pain effectively in patients on dialysis yet decrease opioid prescriptions and dose deserve consideration., (Copyright © 2017 by the American Society of Nephrology.)

Background: Previous reports showed an increased early mortality after chronic dialysis initiation among the end-stage renal disease (ESRD) population. We hypothesized that ESRD patients in the Military Health System (MHS) would have greater access to pre-ESRD care and hence better survival rates during this early high-risk period., Methods: In this retrospective cohort study, using the US Renal Data System database, we identified 1,256,640 patients initiated on chronic dialysis from January 2, 2004 through December 31, 2014, from which a bootstrap sample of 3,984 non-MHS incident dialysis patients were compared with 996 MHS patients. We assessed care by a nephrologist and dietitian, erythropoietin administration, and vascular access use at dialysis initiation as well as all-cause mortality as outcome variables., Results: MHS patients were significantly more likely to have had pre-ESRD nephrology care (adjusted OR [aOR] 2.9; 95% CI 2.3-3.7) and arteriovenous fistula used at dialysis initiation (aOR 2.2; 95% CI 1.7-2.7). Crude mortality rates peaked between the 4th and the 8th week for both cohorts but were reduced among MHS patients. The baseline adjusted Cox model showed significantly lower death rates among MHS vs. non-MHS patients at 6, 9, and 12 months. This survival advantage among MHS patients was attenuated after further adjustment for pre-ESRD nephrology care and dialysis vascular access., Conclusions: MHS patients had improved survival within the first 12 months compared to the general ESRD population, which may be explained in part by differences in pre-ESRD nephrology care and vascular access types., (© 2017 S. Karger AG, Basel.)

Background: A recent study showed an increased risk of death in African Americans compared with whites with end-stage renal disease (ESRD) due to lupus nephritis (LN). We assessed the impact of age stratification, socioeconomic factors, and kidney transplantation on the disparity in patient survival among African American versus non-African American patients with LN-caused ESRD, compared with other causes., Study Design: Retrospective cohort study., Setting & Participants: Using the US Renal Data System database, we identified 12,352 patients with LN-caused ESRD among 1,132,202 patients who initiated maintenance dialysis therapy from January 1, 1995, through December 31, 2006, and were followed up until December 31, 2010., Predictors: Baseline demographics and comorbid conditions, Hispanic ethnicity, socioeconomic factors (employment status, Medicare/Medicaid insurance, and area-level median household income based on zip code as obtained from the 2000 US census), and kidney transplantation as a time-dependent variable., Outcome: All-cause mortality., Measurements: Multivariable Cox and competing-risk regressions., Results: Mean duration of follow-up in the LN-caused ESRD and other-cause ESRD cohorts were 6.24±4.20 (SD) and 4.06±3.61 years, respectively. 6,106 patients with LN-caused ESRD (49.43%) and 853,762 patients with other-cause ESRD (76.24%) died during the study period (P<0.001). Patients with LN-caused ESRD were significantly younger (mean age, 39.92 years) and more likely women (81.65%) and African American (48.13%) than those with other-cause ESRD. In the fully adjusted multivariable Cox regression model, African American (vs non-African American) patients with LN-caused ESRD had significantly increased risk of death at age 18 to 30 years (adjusted HR, 1.43; 95% CI, 1.24-1.65) and at age 31 to 40 years (adjusted HR, 1.17; 95% CI, 1.02-1.34). Among patients with other-cause ESRD, African Americans were at significantly increased risk at age 18 to 30 years (adjusted HR, 1.17; 95% CI, 1.11-1.22)., Limitations: We used zip code-based median household income as a surrogate for patient income. Residual socioeconomic confounders may exist., Conclusions: African Americans are at significantly increased risk of death compared with non-African Americans with LN-caused ESRD at age 18 to 40 years, a racial disparity risk that is 10 years longer than that in the general ESRD population. Accounting for area-level median household income and transplantation significantly attenuated the disparity in mortality of African American versus non-African American patients with LN-caused ESRD., (Published by Elsevier Inc.)

Background: The impact of socioeconomic factors on arteriovenous fistula (AVF) creation in hemodialysis (HD) patients is not well understood. We assessed the association of area and individual-level indicators of poverty and health care insurance on AVF use among incident end-stage renal disease (ESRD) patients initiated on HD., Methods: In this retrospective cohort study using the United States Renal Data System database, we identified 669,206 patients initiated on maintenance HD from January 1, 2007 through December 31, 2012. We assessed the Medicare-Medicaid dual-eligibility status as an indicator of individual-level poverty and ZIP code-level median household income (MHI) data obtained from the 2010 United States Census. We conducted logistic regression of AVF use at start of dialysis as the outcome variable., Results: The proportions of dual-eligible and non-dual-eligible patients who initiated HD with an AVF were 12.53 and 16.17%, respectively (p<0.001). Dual eligibility was associated with significantly lower likelihood of AVF use upon initiation of HD (adjusted odds ratio (aOR) 0.91; 95% CI 0.90-0.93). Patients in the lowest area-level MHI quintile had an aOR of 0.97 (95% CI 0.95-0.99) compared to those in higher quintile levels. However, dual eligibility and area-level MHI were not significant in patients with Veterans Affairs (VA) coverage., Conclusions: Individual- and area-level measures of poverty were independently associated with a lower likelihood of AVF use at the start of HD, the only exception being patients with VA health care benefits. Efforts to improve incident AVF use may require focusing on pre-ESRD care to be successful., (© 2015 S. Karger AG, Basel.)

Background: An analysis of intracranial hemorrhage (ICH) in a national sample of autosomal dominant polycystic kidney disease (ADPKD) patients receiving long-term dialysis has not been reported. It is often assumed that patients with ADPKD are not at increased risk of ICH after starting dialysis. We hypothesized that patients with ADPKD would have a higher subsequent risk of ICH even after the start of chronic dialysis., Methods: Retrospective cohort study of Medicare primary patients with and without ADPKD in the United States Renal Data System (USRDS), initiated on chronic dialysis or transplanted between 1 January 1999 and 3 July 2009, and followed until 31 December 2009. Covariates included age, gender, race, prior stroke, diabetes mellitus, dialysis modality, body mass index, serum albumin and other co-morbid conditions from the Medical Evidence Form. Primary outcome was ICH, based on inpatient and outpatient Medicare claims, and all-cause mortality. Kaplan-Meier analysis was used for unadjusted assessment of time to events. Cox regression was used for assessment of factors associated with ICH and mortality. We performed competing risk regression using kidney transplant and death as competing risks. Kidney transplant was also modeled as a time-dependent covariate in Cox regression., Results: Competing risk regression demonstrated that ADPKD had a subhazard ratio 2.97 for ICH (95% CI 2.27-3.89). Adjusted Cox analysis showed that ADPKD patients had an AHR for death of 0.59 vs. non-ADPKD patients (95% CI 0.57-0.61)., Conclusions: ADPKD is a significant risk factor for ICH among patients on maintenance dialysis. Our Medicare primary cohort was older than in previous studies of intracranial aneurysm rupture among ADPKD patients. There are also limitations inherent to using the USRDS database.

Background: We examined the United States Renal Data System registry to analyze trends in renal transplantation in patients with human immunodeficiency virus (HIV) infection., Methods: A retrospective cohort study was performed using the United States Renal Data System, analyzing patients receiving renal transplants from January 1, 1995, to September 29, 2006. Factors independently associated with transplantation in HIV-infected patients with end-stage renal disease were identified., Results: There was a significant increase in renal transplant recipients who were HIV seropositive who received renal transplants from 2001 to 2006 (n=208, 0.26%) versus 1995 to 2000 era (n=43, 0.06%, P<0.001). Before 2001, only 18 states performed renal transplants in HIV-infected patients, whereas most states transplanted HIV-infected patients in the second era. There were more African American recipients with HIV infection from 2001 to 2006 compared with the earlier cohort (n=118 vs. 8, P<0.001). Patients with HIV infection were more likely to have received induction therapy (n=121 vs. 37, P<0.001) and tacrolimus maintenance suppression (n=105 vs. 13, P<0.001) in the latter era. There were also more deceased donor transplants from 2001 to 2006 (n=143 vs. 25, P<0.001). In logistic regression analysis, when adjusted for multiple factors including recipient and donor age, race, gender, and donor type, patients with HIV infection were more likely to have been transplanted after 2001 (adjusted odds ratio, 2.21; 95% confidence interval=1.49-3.28). In analysis adjusted for multiple factors including hepatitis C virus coinfection, HIV infection was not significantly associated with all-cause graft loss., Conclusions: There has been a dramatic increase in the number of transplants among HIV-infected patients. These findings suggest improved access to transplant wait listing and better management of immunosuppression, especially among African American patients., (© 2011 by Lippincott Williams & Wilkins)

Cardiovascular disease is the most common cause of death after kidney transplantation. However, uncertainties regarding the optimal assessment of cardiovascular risk in potential transplant candidates have produced controversy and inconsistency in pretransplantation cardiac evaluation practices. In this review, we consider the evidence supporting cardiac evaluation in kidney transplant candidates, generally focused on coronary artery disease, according to the World Health Organization principles for screening. The importance of pretransplant cardiac evaluation is supported by the high prevalence of coronary artery disease and the incidence and adverse consequences of acute coronary syndromes in this population. Testing for coronary artery disease may be performed noninvasively by using modalities that include nuclear myocardial perfusion studies and dobutamine stress echocardiography. These tests have prognostic value for mortality, but imperfect sensitivity and specificity for detecting angiographically defined coronary artery disease in patients with end-stage renal disease. Associations of angiographically-defined coronary artery disease with subsequent survival also are inconsistent, likely because plaque instability is more critical for infarction risk than angiographic stenosis. The efficacy and best methods of myocardial revascularization have not been examined in large contemporary clinical trials in patients with end-stage renal disease. Biomarkers, such as cardiac troponin, have prognostic value in end-stage renal disease, but require further study to determine clinical applications in directing more expensive and invasive cardiac evaluation., (Copyright 2009 National Kidney Foundation, Inc. All rights reserved.)

Background: The incidence of new-onset diabetes after initiation of hemodialysis (NODAD) and its impact on survival is not known., Methods: We used data from the United States Renal Data System (USRDS) from January 2000 to December 2001, with at least 3 years of follow-up for this study. Patients aged 18-80 years were included. NODAD was defined as two Medicare institutional claims for diabetes in patients with no history of diabetes prior to starting hemodialysis (HD). Incidence (per 1,000 patient-years), prevalence (%) and hazard ratios for mortality in patients with NODAD were calculated., Results: There were 59,340 incident patients with no history of diabetes prior to starting HD, of which 3,853 met criteria for NODAD. The overall incidence and prevalence of NODAD were 20 per 1,000 patient-years and 7.6%, respectively. In a cohort of 444 patients without diabetes and documented glycosylated hemoglobin A1c, <6% prior to starting HD (from January 2005 and March 2006), at a mean follow-up of 4.7 +/- 2.6 months, 6.8% developed NODAD defined by two Medicare claims for diabetes after initiation of HD. NODAD was associated with a significantly increased risk of death as compared to non-diabetes patients (hazard ratio 1.20, 95% confidence interval 1.14-1.25)., Conclusion: The USRDS showed a high incidence of NODAD, associated with significantly higher mortality compared to those who did not develop NODAD. The mechanism of NODAD needs to be explored further in experimental and clinical studies., (2010 S. Karger AG, Basel.)

Background and Objectives: Billing claims are increasingly examined beyond administrative functions as outcomes measures in observational research. Few studies have described the performance of billing claims as surrogate measures of clinical events among kidney transplant recipients., Design, Setting, Participants, & Measurements: We investigated the sensitivity of Medicare billing claims for clinically verified cardiovascular diagnoses (five categories) and procedures (four categories) in a novel database linking Medicare claims to electronic medical records of one transplant program. Cardiovascular events identified in medical records for 571 Medicare-insured transplant recipients in 1991 through 2002 served as reference measures., Results: Within a claims-ascertainment period spanning +/-30 d of clinically recorded dates, aggregate sensitivity of single claims was higher for case definitions incorporating Medicare Parts A and B for diagnoses and procedures (90.9%) compared with either Part A (82.3%) or Part B (84.6%) alone. Perfect capture of the four procedures was possible within +/-30 d or with short claims window expansion, but sensitivity for the diagnoses trended lower with all study algorithms (91.2% with window up to +/-90 d). Requirement for additional confirmatory diagnosis claims did not appreciably reduce sensitivity. Sensitivity patterns were similar in the early compared with late periods of the study., Conclusions: Combined use of Medicare Parts A and B billing claims composes a sensitive measure of cardiovascular events after kidney transplant. Further research is needed to define algorithms that maximize specificity as well as sensitivity of claims from Medicare and other insurers as research measures in this population.

Background: Limited data exist on the safety and efficacy of bariatric surgery (BS) in patients with kidney failure., Methods: We examined Medicare billing claims within USRDS registry data (1991-2004) to identify BS cases among renal allograft candidates and recipients., Results: Of 188 BS cases, 72 were performed pre-listing, 29 on the waitlist, and 87 post-transplant. Roux-en-Y gastric bypass was the most common procedure. Thirty-day mortality after BS performed on the waitlist and post-transplant was 3.5%, and one transplant recipient lost their graft within 30 days after BS. BMI data were available for a subset and suggested median excess body weight loss of 31%-61%. Comparison to published clinical trials of BS in populations without kidney disease indicates comparable weight loss but higher post-BS mortality in the USRDS sample., Conclusions: Given the substantial contributions of obesity to excess morbidity and mortality, BS warrants prospective study as a strategy for improving outcomes before and after kidney transplantation.

Previous studies have shown that gout is associated with an increased risk for cardiovascular mortality in the general population, but this has not been well studied in patients with ESRD. In this study, the incidence of gout and its association with mortality was evaluated in 259,209 patients in the United States Renal Data System. Overall, the incidence of gout in the first year of dialysis was 5% and in the first 5 yr was 15.4%. Independent risk factors for gout in adjusted analyses included black race, older age, female gender, hypertension, ischemic heart disease, congestive heart failure, and alcohol use. Factors associated with a lower risk for gout included a history of diabetes, smoking, and peripheral vascular disease. Time-dependent Cox regression analysis suggested that an episode of gout was independently associated with a 1.5-fold increase in mortality risk (adjusted hazard ratio 1.49; 95% confidence interval 1.43 to 1.55). The mechanisms underlying this association require further study.

Background and Objectives: Evaluation for ischemic heart disease (IHD) is a nonstandardized practice before kidney transplantation. We retrospectively studied pretransplant cardiac evaluation (CE) practices in a national sample of renal allograft recipients., Design, Setting, Participants, & Measurements: The USRDS data for Medicare beneficiaries transplanted in 1991 to 2004 with Part A&B benefits from dialysis initiation through transplantation were examined. Clinical traits defining "high" expected IHD risk were defined as diabetes, prior IHD, or > or = 2 other coronary risk factors. Pretransplant CE were identified by billing claims for noninvasive stress tests and angiography. Patients were quantified with claims for coronary revascularization procedures between CE and transplant. Post-transplant acute myocardial infarction (AMI) events were abstracted from claims and death records., Results: Among 27,786 eligible patients, 46.3% underwent CE before transplantation. Overall, 9.5% who received CE also received pretransplant revascularization, but only 0.3% of lower-risk patients undergoing CE had revascularization. The adjusted odds of transplant without CE increased sharply with younger age and shorter dialysis duration. Increased likelihood of transplant without CE also correlated with black race, female sex, and certain geographic regions. Among patients transplanted without CE, 3-yr incidence of post-transplant AMI was 3% in lower-risk and 10% in high-risk groups, and varied by individual traits within these groups. Among lower-risk patients transplanted without CE, blacks were higher risk for AMI than whites (adjusted hazards ratio 1.47, 95% CI 1.11-1.93)., Conclusions: Observed practices demonstrate infrequent use of pretransplant revascularization after CE but also raise concern for socio-demographic barriers to evaluation access.

Background: Clinical practice guidelines for management of chronic kidney disease (CKD) have been developed within the Kidney Disease Outcomes Quality Initiative (K/DOQI). Adherence patterns may identify focus areas for quality improvement., Methods: We retrospectively studied contemporary CKD care patterns within a private health system in the United States, and systematically reviewed literature of reported practices internationally. Five hundred and nineteen patients with moderate CKD (estimated GFR 30-59 ml/min) using healthcare benefits in 2002-2005 were identified from administrative insurance records. Thirty-three relevant publications in 2000-2006 describing care in 77,588 CKD patients were reviewed. Baseline demographic traits and provider specialty were considered as correlates of delivered care. Testing consistent with K/DOQI guidelines and prevalence of angiotensin converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARB) medication prescriptions were ascertained from billing claims. Care descriptions in the literature sample were based on medical charts, electronic records and/or claims., Results: KDOQI-consistent measurements of parathyroid hormone (7.1 vs. 0.6%, P = 0.0002), phosphorus (38.2 vs. 1.9%, P < 0.0001) and quantified urinary protein (23.8 vs. 9.4%, P = 0.008) were more common among CKD patients with versus without nephrology referral in the administrative data. Nephrology referral correlated with increased likelihood of testing for parathyroid hormone and phosphorus after adjustment for baseline patient factors. Use of ACEi/ARB medications was more common among patients with nephrology contact (50.0 vs. 30.0%; P = 0.008) but appeared largely driven by higher comorbidity burden. The literature review demonstrated similar practice patterns., Conclusions: Delivery of CKD care may be monitored by administrative data. There is opportunity for improvement in CKD guideline adherence in practice.

Background: Previously, patients with end-stage renal disease (ESRD) with uncontrolled hyperparathyroidism had few options other than parathyroidectomy, which was reserved for patients refractory to medical therapy. Newer calcimimetic agents, such as cinacalcet, may be an alternative, but raise the possibility of indefinite medical treatment that also would increase costs., Study Design: Cost utility analysis., Setting & Population: Base case consisted of prevalent adult US patients with ESRD refractory to management with standard medical therapy. Characteristics were obtained from patients who underwent parathyroidectomy in 2001, and, for purposes of comparison, patients in whom cinacalcet was used were assigned similar characteristics. All data came from preexisting literature and trials or from US Renal Data System analysis files., Intervention: Use of cinacalcet hydrochloride versus parathyroidectomy., Perspective & Time Frame: Medicare and societal costs and quality-adjusted life-years from the date of parathyroidectomy or use of cinacalcet followed up for 2 years, respectively., Model & Outcomes: Primary outcomes were cost (measured in US dollars) and cost utility measured using cost per quality-adjusted life-years., Results: At base-case surgical and drug costs, surgical and drug success rates, complication rates/costs, and benefit from correction of hyperparathyroidism, parathyroidectomy was found to be both less expensive and more cost-effective at 7.25 +/- 0.25 months. Parathyroidectomy became more cost-effective at 15.28 to 16.32 months at the upper limit of sensitivity analysis, when drug/surgical costs and success/complication rates/costs were maximally weighted to favor cinacalcet-based medical therapy., Limitations: We assumed current costs of both cinacalcet and parathyroidectomy and assumed cinacalcet use would be indefinite., Conclusions: For patients with ESRD with uncontrolled hyperparathyroidism who are good candidates for either drug therapy or surgery, cinacalcet hydrochloride is the most cost-effective modality if the patient is to remain on dialysis therapy for 7.25 +/- 0.25 months. Cinacalcet may be more optimal if used in patients who have high risk of mortality or who would expect to receive a kidney transplant quickly. For other subgroups, parathyroidectomy dominated.

Urinary tract infection (UTI) is the most common infection after kidney transplantation. A previous analysis showed that late (>6 mo after transplantation) UTI is associated with earlier graft loss in adults. It was hypothesized that children who are younger than 18 yr would be at higher risk to develop UTI and develop graft loss after both early and late UTI. The US Renal Data System database was analyzed from 1996 to 2000 for Medicare claims (composite of inpatient and outpatient) for UTI up to 36 mo after transplantation. SPSS software and Cox regression models were used to determine association of UTI and age after adjustment for covariates. Early UTI was defined as occurring <6 mo after transplantation, and late UTI was defined as occurring > or =6 mo after transplantation. The risk for graft loss after early UTI was elevated in all children (adjusted hazard ratio [AHR] 5.47; 95% confidence interval [CI] 1.93 to 15.4; P < 0.001) but not after late UTI (AHR 2.09; 95% CI 0.56 to 7.80; P = 0.27). Risk for posttransplantation death was not increased significantly after either early UTI (AHR 1.23; 95% CI 0.37 to 4.08) or late UTI (relative risk 2.22; 95% CI 0.90 to 5.44). Boys aged 2 to 5 (versus age 13 to <18 years) were at significantly higher risk for UTI. In girls, only those in the youngest age category (0 to 1) had higher risk for UTI. Children are at greater risk for graft loss after early but not necessarily late UTI. UTI was not an independent predictor of death in this population.

Background: End-stage renal disease is known to disrupt the cell-mediated immune response that is responsible for the killing of intracellular organisms such as Mycobacterium tuberculosis. Risk factors that contribute to the development of tuberculosis (TB) disease in the US dialysis population have not been studied on a large scale., Methods: A retrospective cohort study of TB disease in 272,024 patients in the US Renal Data System initiated on dialysis therapy between 1 April 1995 and 31 December 1999 with Medicare or Medicaid as primary payer were analysed. A total of 21 risk factors were analysed., Results: Among the US population studied, there is a 1.2 and 1.6% cumulative incidence of TB in patients undergoing either peritoneal or haemodialysis, respectively. Ten risk factors for TB that proved to be statistically significant included advanced age (P<0.001), unemployment (P<0.001), Medicaid insurance (P<0.001), reduced body mass index (P<0.001), decreased serum albumin (P<0.001), haemodialysis (P=0.019), both Asian (P=0.010) and Native American (P=0.020) race, ischaemic heart disease (P=0.032), smoking (P=0.010), illicit drug use (P=0.018) and anaemia (P=0.028). TB was independently associated with increased mortality, adjusted hazard ratio (AHR) 1.42 (95% CI 1.18-1.70, P<0.001)., Conclusions: The prevalence of TB disease in the US dialysis population is low compared with worldwide rates; however, the disease is associated with increased mortality. Of the 10 significant risk factors identified, five are potentially modifiable.

The life expectancy of patients who have dementia and are initiated on dialysis in the United States has not been described in the medical literature. A retrospective cohort study was conducted of 272,024 Medicare/Medicaid primary patients in the US Renal Data System who were started on ESRD therapy between April 1, 1995, and December 31, 1999, and followed through December 31, 2001. Cox regression was used to calculate adjusted hazard ratios for risk for death after initiation of dialysis for patients whose dementia was diagnosed before the initiation of dialysis as shown by Medicare claims. The average time to death for patients with dementia was 1.09 versus 2.7 yr (P < 0.001) with an adjusted hazard ratio of 1.87 (95% confidence interval 1.77 to 1.98). The 2-yr survival for patients with dementia was 24 versus 66% for patients without dementia (P < 0.001 via log rank test). Dementia that is diagnosed before initiation on dialysis is an independent risk factor for subsequent death. Such patients should be considered for time-limited trials of dialysis and careful discussion in choosing whether to pursue initiation of dialysis or palliative care.

Background: The incidence, risk factors, recurrence rates and prognosis of thrombotic microangiopathy (TMA) among long-term dialysis patients in the United States have not been previously described in a national population., Methods: 272 024 Medicare primary patients in the United States Renal Data System (USRDS) initiated on end-stage renal disease (ESRD) therapy between 1 April 1995 and 31 December 1999 with Medicare as primary payer were analysed in a retrospective cohort study of USRDS of TMA. Cox regression was used to calculate adjusted hazard ratios (AHR) for risk of TMA and risk of death after TMA., Results: The incidence of TMA in the first year of dialysis was 0.5% overall. Among patients with renal failure due to haemolytic uraemic syndrome (HUS), the incidence of TMA was highest in the first year of dialysis (HUS, 11.3% first year, 4.5% per year thereafter), while among patients without HUS the incidence of TMA was much lower and more constant over time (0.3% per year). In Cox regression analysis, independent risk factors for TMA were renal failure due to HUS (adjusted hazard ratio (AHR) 179, 95% CI 95-338), paediatric age (

In the general population, a high body mass index (BMI; in kg/m(2)) is associated with increased cardiovascular disease and all-cause mortality. However, the effect of overweight (BMI: 25-30) or obesity (BMI: >30) in patients with chronic kidney disease (CKD) undergoing maintenance hemodialysis (MHD) is paradoxically in the opposite direction; ie, a high BMI is associated with improved survival. Although this "reverse epidemiology" of obesity or dialysis-risk-paradox is relatively consistent in MHD patients, studies in CKD patients undergoing peritoneal dialysis have yielded mixed results. Growing confusion has developed among physicians, some of whom are no longer confident about whether to treat obesity in CKD patients. A similar reverse epidemiology of obesity has been described in geriatric populations and in patients with chronic heart failure (CHF). Possible causes of the reverse epidemiology of obesity include a more stable hemodynamic status, alterations in circulating cytokines, unique neurohormonal constellations, endotoxin-lipoprotein interaction, reverse causation, survival bias, time discrepancies among competitive risk factors, and malnutrition-inflammation complex syndrome. Reverse epidemiology may have significant clinical implications in the management of dialysis, CHF, and geriatric patients, ie, populations with extraordinarily high mortality. Exploring the causes and consequences of the reverse epidemiology of obesity in dialysis patients can enhance our insights into similar paradoxes observed for other conventional risk factors, such as blood pressure and serum cholesterol and homocysteine concentrations, and in other populations such as those with CHF, advanced age, cancer, or AIDS. Weight-gaining interventional studies in dialysis patients are urgently needed to ascertain whether they can improve survival and quality of life.

Complications associated with use of donor hepatitis C-positive kidneys (DHCV+) have been attributed primarily to posttransplantation liver disease (as a result of hepatitis C disease). The role of posttransplantation diabetes has not been explored in this setting. With the use of the United States Renal Data System database, 28,942 Medicare KT recipients were studied from January 1, 1996, through July 31, 2000. Cox proportional hazards regression models were used to calculate adjusted hazard ratios (AHR) for the association of sero-pairs for HCV (D+/R-, D+/R+, D-/R+ and D-/R-) with Medicare claims for de novo posttransplantation HCV and posttransplantation diabetes. The peak risk for posttransplantation HCV was in the first 6 mo after transplantation. The incidence of posttransplantation HCV after transplantation was 9.1% in D+/R-, 6.3% in D+/R+, 2.4% in D-/R+, and 0.2% in D-/R-. The incidence of posttransplantation diabetes after transplantation also peaked early and was 43.8% in D+/R-, 46.6% in D+/R+, 32.3% in D-/R+, and 25.4% in D-/R-. Associations for both complications were significant in adjusted analysis (Cox regression). Both posttransplantation HCV (AHR, 3.36; 95% confidence interval, 2.44 to 4.61) and posttransplantation diabetes (AHR, 1.81; 95% confidence interval, 1.54 to 2.11) were independently associated with an increased risk of death, but posttransplantation diabetes accounted for more years of life lost, particularly among recipients of DHCV+ kidneys. Posttransplantation diabetes may contribute substantially to the increased risk of death associated with use of DHCV+ kidneys and accounts for more years of life lost than posttransplantation HCV. Because HCV infection acquired after transplantation is so difficult to treat, methods that have been shown to reduce viral transmission warrant renewed attention.

Whether transplantation of deceased donor kidney allografts from donors with antibodies against hepatitis C virus (HCV) confers a survival advantage compared with remaining on the kidney transplant waiting list is not yet known. We studied 38,270 USRDS Medicare beneficiaries awaiting kidney transplantation who presented with end-stage renal disease from April 1, 1995 to July 31, 2000. Cox regression was used to compare the adjusted hazard ratios for death among recipients of kidneys from deceased donors, and donors with antibodies against hepatitis C (DHCV+), controlling for demographics and comorbidities. In comparison to staying on the waiting list, transplantation from DHCV+ was associated with improved survival among all patients (adjusted hazard ratio for death 0.76, 95% CI 0.60, 0.96). Of patients receiving DHCV+ kidneys, 52% were themselves hepatitis C antibody positive (HCV+), so outcomes associated with use of these grafts may have particular implications for HCV+ transplant candidates. Recommendations for use of DHCV+ kidneys may require analysis of data not currently collected from either dialysis or transplant patients. However, transplantation of DHCV+ kidneys is associated with improved patient survival compared to remaining wait-listed and dialysis dependent.

Single-center studies have reported that HIV-associated nephropathy (HIVAN) can occur in children and may have a clinical course and prognosis similar to that of adults. However, the prevalence and survival has not been reported for a national sample of children with HIVAN and end-stage renal disease (ESRD) on dialysis in the United States. We utilized the United States Renal Data System (USRDS) database to determine the prevalence, demographic information, and survival of children with HIVAN and ESRD in the United States. The Kaplan-Meier method was used to estimate survival of children with HIVAN and the log-rank test was used to compare their survival with children with focal segmental glomerulosclerosis (FSGS) and adults with HIVAN. Cox regression analysis was used to model adjusted hazard ratios (AHR) with HIVAN as a cause of ESRD and its impact on mortality during the study period, adjusted for potential confounders. Of the 7,732 patients identified with HIVAN, only 60 were younger than 21 years and were classified as children; 50% were males and the majority (88.3%) was black. The cumulative percentage survival of children with HIVAN at 12, 24, and 36 months was better than adults with HIVAN (76%, 62%, and 54% vs. 60%, 43%, and 34%). Survival of children with HIVAN who started dialysis after 1996 was significantly better than those who started dialysis in or before 1996 (log rank P value <0.043). However, the major factor associated with better survival on Cox proportional hazard analysis was female gender (male vs. female AHR 2.85, 95% confidence interval 1.04-6.73). We conclude that only a small number of children with HIVAN and ESRD have received dialysis in the United States. The prognosis of these children is better than that of adults with HIVAN and among children with HIVAN females have better survival than males.

Severity of heart disease of almost all types, as well as mortality risk associated with heart disease, increases in step with severity of kidney disease, although not necessarily in a linear fashion. Heart failure is more common and just as lethal as ischemic heart disease in patients with severe chronic kidney disease (CKD). The incidence of nonfatal heart disease in dialysis and transplant populations has now been described in detail. Although standard risk factors for heart disease that are more common among patients with CKD than in the general population do not adequately explain the greatly increased risk of heart disease in patients with severe CKD, neither do as yet identified "nontraditional" risk factors. However, in addition to the factors not common in the general population, such as anemia, hyperphosphatemia, and markers of systemic inflammation, patients with CKD in the modern era may also exhibit excessive thrombotic tendencies. Screening for heart disease in this population relies mainly on dobutamine stress echocardiography or nuclear scintigraphy. The role of electron beam CT (EBCT) scanning is currently controversial. The indications for coronary angiography are the same for patients with CKD as for the general population, but patients with CKD are at greatly increased risk for contrast-associated nephropathy, the least controversial preventive therapy, which consists of isotonic saline and N-acetylcysteine. Finally, patients with CKD do not currently receive adequate medical therapy for prevention and treatment of heart disease.

Background: The impact of obesity on survival in end-stage renal disease (ESRD) patients as related to dialysis modality (i.e., a direct comparison of hemodialysis with peritoneal dialysis) has not been assessed adjusting for differences in medication use, follow-up > or =2 years, or accounting for changes in dialysis modality., Methods: We performed a retrospective cohort study of the United States Renal Data System (USRDS) Dialysis Morbidity and Mortality Wave II Study (DMMS) patients who started dialysis in 1996, and were followed until October 31 2001. Cox regression analysis was used to model adjusted hazard ratios (AHR) for mortality for categories of body mass index (BMI), both as quartiles and as > or =30 kg/m2 vs. lower. Because such a large proportion of peritoneal dialysis patients changed to hemodialysis during the study period (45.5%), a sensitivity analysis was performed calculating survival time both censoring and not censoring on the date of change from peritoneal dialysis to hemodialysis., Results: There were 1675 hemodialysis and 1662 peritoneal dialysis patients. Among hemodialysis patients, 5-year survival for patients with BMI > or =30 kg/m2 was 39.8% vs. 32.3% for lower BMI (P < 0.01 by log-rank test). Among peritoneal dialysis patients, 5-year survival for patients with BMI >/=30 kg/m2 was 38.7% vs. 40.4% for lower BMI (P > 0.05 by log-rank test). In adjusted analysis, BMI > or = 30 kg/m2 was associated with improved survival in hemodialysis patients (AHR 0.89; 95% CI 0.81, 0.99; P= 0.042) but not peritoneal dialysis patients (AHR = 0.99; 95% CI, 0.86, 1.15; P= 0.89). Results were not different on censoring of change from peritoneal dialysis to hemodialysis., Conclusion: We conclude that any survival advantage associated with obesity among chronic dialysis patients is significantly less likely for peritoneal dialysis patients, compared to hemodialysis patients.

Background: Pulmonary embolism (PE) is the most common preventable cause of death in hospitalized patients. Patients with severe chronic kidney disease (CKD) may be at increased risk for PE in comparison to the general population. Whether severe CKD is associated with increased risk for late venous thromboembolism (VTE) in a population of renal transplant recipients has not been determined., Methods: Using the US Renal Data System database, we studied 28,924 patients receiving a kidney transplant from January 1, 1996, to July 31, 2000, with Medicare as primary payer, followed up until December 31, 2000. Cox proportional hazards regression models were used to calculate the association of transplant recipient estimated glomerular filtration rate (eGFR; by the Modification of Diet in Renal Disease formula) less than 30 mL/min/1.73 m2 (versus >30 mL/min/1.73 m2) 1 year after renal transplantation with Medicare claims for VTE (either deep-venous thrombosis or PE/infarction) 1.5 to 3 years after renal transplantation., Results: The rate of VTE occurring 1.5 to 3 years after transplantation was 2.9 episodes/1,000 person-years. eGFR less than 30 mL/min/1.73 m2 versus higher at the end of the first year after renal transplantation was associated with significantly increased risk for later VTE (adjusted hazard ratio, 2.05; 95% confidence interval, 1.08 to 3.89)., Conclusion: Patients with severe CKD after renal transplantation should be regarded as high risk for late VTE, which is a potentially preventable cause of death in this population.

Kidneys from donors who are positive for hepatitis C virus (DHCV+) have recently been identified as an independent risk factor for mortality after renal transplantation. However, it has not been determined whether risk persists after adjustment for baseline cardiac comorbidity or applies in the era of modern immunosuppression. Therefore, a historical cohort study was conducted of US adult cadaveric renal transplant recipients from January 1, 1996, to May 31, 2001; followed until October 31, 2001. A total of 36,956 patients had valid donor and recipient HCV serology. Cox regression analysis was used to model adjusted hazard ratios for mortality and graft loss, respectively, adjusted for other factors, including comorbid conditions from Center for Medicare and Medicaid Studies Form 2728 and previous dialysis access-related complications. It was found that DHCV+ was independently associated with an increased risk of mortality (adjusted hazard ratio, 2.12, 95% confidence interval, 1.72 to 2.87; P < 0.001), primarily as a result of infection. Mycophenolate mofetil was associated with improved survival in DHCV+ patients, primarily related to fewer infectious deaths. Adjusted analyses limited to recipients who were HCV+, HCV negative, or age 65 and over, or by use of mycophenolate mofetil confirmed that DHCV+ was independently associated with mortality in each subgroup. It is concluded that DHCV+ is independently associated with an increased risk of mortality after renal transplantation adjusted for baseline comorbid conditions in all subgroups. Recipients of DHCV+ organs should be considered at high risk for excessive immunosuppression.

Background: Analysis of the incidence, time to event, and risk factors for thrombotic microangiopathy (TMA) after renal transplantation (RT), has not been reported in a national population., Methods: This is a historical cohort study of 15,870 RT recipients in the United States Renal Data System (USRDS) with Medicare as their primary payer between January 1, 1998, and July 31, 2000, followed until December 31, 2000. Patients with Medicare claims with a diagnosis of TMA (International Classification of Diseases, 9th Revision, codes 283.11x or 446.6x) after RT were assessed by Cox regression., Results: Among patients with end-stage renal disease owing to hemolytic uremic syndrome (HUS), 29.2% later had TMA versus 0.8% of patients with ESRD owing to other causes. The incidence of TMA in RT recipients was 5.6 episodes per 1,000 person-years (PY; 189/1,000 PY; for recurrent TMA versus 4.9/1,000 PY for de novo TMA). The risk of TMA was highest for the first 3 months after transplant. Risk factors for de novo TMA included younger recipient age, older donor age, female recipient, and initial use of sirolimus. Patient survival rate after TMA was approximately 50% at 3 years., Conclusion: De novo TMA is uncommon and may occur later after RT than previously reported. Risk factors for de novo TMA were also identified.

Background: The patient characteristics and mortality associated with renal cell carcinoma (RCC) as a cause of end-stage renal disease (ESRD) have not been characterized for a national population., Methods: An historical cohort study of renal cell carcinoma (RCC) was conducted from April 1, 1995, to December 31, 1999. Included were 360,651 patients in the United States Renal Data System (USRDS) who were initiated on ESRD therapy with valid causes of ESRD., Results: Of the study population, 1646 patients (0.5%) had RCC. The mean age of patients with RCC was 66.8 +/- 14.6 years versus 61.3 +/- 16.4 years for patients with other causes of ESRD (P < 0.01 by Student t test). The unadjusted 3-year survival (censored at the date of renal transplantation) of patients with RCC during the study period was 23% versus 36% in all other patients [adjusted hazard ratio (AHR), 1.10, 95% confidence interval (CI) 1.02-1.19, P = 0.019 by Cox regression]. However, patients with RCC who underwent nephrectomy (bilateral or unilateral) had significantly better survival compared to RCC patients who did not (AHR, 0.73, 95% CI, 0.63-0.85, P < 0.01), and their survival was not significantly different in comparison with nondiabetic ESRD patients. Bilateral nephrectomy (vs. unilateral) was not associated with any difference in adjusted mortality., Conclusion: Among patients with ESRD, the demographics of those with RCC were similar to those of patients with RCC in the general population. Overall, patients with RCC had decreased survival compared to patients with other causes of ESRD; those who underwent nephrectomy had significantly better survival than those who did not, with survival comparable to patients with nondiabetic ESRD.

Background: Risk factors for heart failure (HF) have not been reported previously in a nationally representative sample of dialysis patients., Methods: We conducted a historic cohort study of 1,995 patients enrolled in the US Renal Data System Dialysis Morbidity and Mortality Study Wave 2 who were Medicare eligible at the study start and were followed up until December 31, 1999, or receipt of a renal transplant. Cox regression analysis was used to model associations with time to first hospitalization for both recurrent and de novo HF (International Classification of Diseases, Ninth Revision code 428.x), defined as patients with and without a history of HF, respectively., Results: The incidence density of HF was 71/1,000 person-years. Angiotensin-converting enzyme inhibitors and beta-blockers were each used in less than 25% of patients with a known history of HF. A history of coronary heart disease was associated with an increased total risk for HF, as were hemodialysis (versus peritoneal dialysis), aspirin use, and a history of diabetes. However, hemodialysis and aspirin use were the only factors associated with both de novo and recurrent HF. Widened pulse pressure was associated with de novo HF. The mortality rate after HF was 83% at 3 years (adjusted hazard ratio for mortality, 2.10; 95% confidence interval, 1.80 to 2.45; P < 0.0001)., Conclusion: In chronic dialysis patients, hemodialysis and aspirin use were associated with increased risk for both total and de novo HF. Hospitalized HF was associated with a significantly increased risk for death.

Background: Whether morning shift hemodialysis is associated with improved survival in comparison to patients receiving afternoon shift hemodialysis has not been shown for a representative sample of US chronic hemodialysis patients., Methods: We conducted a historical cohort study of a national database (US Renal Data System Dialysis Morbidity and Mortality Waves III/IV) of 6,939 patients who started hemodialysis therapy from January 1, 1990, through December 31, 1993. Patients were followed up through April 9, 2000, and censored at the time of change to a different modality, including transplantation. We estimated the adjusted hazard ratio for all-cause mortality based on the time of day of hemodialysis (0500 to 1200 for morning shift, 1200 to 1800 for afternoon shift, 1800 to midnight for evening shift). Cox regression analysis was used to adjust for other factors associated with survival., Results: For patients aged 60 years and older, the unadjusted 4-year survival rate for patients on morning shift hemodialysis was 28.8% versus 24.1% for patients on afternoon shift hemodialysis and 38.7% for patients on evening shift hemodialysis (P < 0.01 by log-rank test for both versus afternoon shift hemodialysis). Both morning shift (adjusted hazard ratio, 0.90; 95% confidence interval [CI], 0.83 to 0.98; P = 0.02) and evening shift hemodialysis (adjusted hazard ratio, 0.62; 95% CI, 0.48 to 0.80; P < or = 0.001) were independently associated with a lower risk for mortality compared with afternoon shift hemodialysis. No such differences were seen for patients younger than 60 years. Both morning shift and evening shift hemodialysis were independently associated with improved survival compared with afternoon shift hemodialysis in elderly chronic hemodialysis patients. No such association was found for younger patients.