Erythropoietin treatment and the risk of hip fractures in hemodialysis patients.

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).

Prophylactic or Early Use of Eculizumab and Graft Survival in Kidney Transplant Recipients With Atypical Hemolytic Uremic Syndrome in the United States: Research Letter.

INTRODUCTION: Among kidney transplant recipients (KTRs) with end-stage kidney disease (ESKD) due to atypical hemolytic uremic syndrome (aHUS), recurrence is associated with poor allograft outcomes. We compared graft and patient survival of aHUS KTRs with and without prophylactic/early use of eculizumab, a monoclonal antibody that binds complement protein C5, at the time of transplantation. METHODS: We conducted a retrospective cohort study using the United States Renal Data System. Out of 123 624 ESKD patients transplanted between January 1, 2008, and June 1, 2016, we identified 348 (0.28%) patients who had "hemolytic uremic syndrome" as the primary cause of ESKD. We then linked these patients to datasets containing the Healthcare Common Procedure Coding System (HCPCS) code for eculizumab infusion. Patients who received eculizumab prior to or within 30 days of transplant represented the exposure group. We calculated crude incidence rates and conducted exact logistic regression, adjusted for recipient age and sex, for the study outcomes of graft loss, death-censored graft loss, and mortality. We also estimated the average treatment effect (ATE) by propensity-score matching, to reduce the bias in the estimated treatment effect on graft loss. RESULTS: Our final study cohort included 335 aHUS KTRs (23 received eculizumab, 312 did not), with a mean duration of follow-up of 5.8 ± 2.7 years. There were no significant differences in baseline demographic and clinical characteristics between the eculizumab versus non-eculizumab group. Patients who received prophylactic/early eculizumab were less likely to experience graft loss compared with those who did not receive eculizumab (0% vs 20%, P = .02), with an adjusted odds ratio of 0.13 (P = .02). In the propensity-score-matched sample, the ATE (eculizumab vs non-eculizumab) was -0.20 (95% confidence interval [CI] = -0.25 to -0.15, P < .001); thus, treatment was associated with an average of 20% reduction in graft loss. There was no significant difference in the risk of death between the 2 groups. CONCLUSIONS: Although there was no significant difference in the risk of death, prophylactic/early use of eculizumab was significantly associated with improved graft survival among aHUS KTRs. Given the high cost of eculizumab, randomized controlled trials are much needed to guide prophylactic strategies to prevent graft loss.

INTRODUCTION: Chez les receveurs d'une greffe rénale (RGR) dont l'insuffisance rénale terminale (IRT) est due au syndrome hémolytique et urémique atypique (SHUa), la récidive est associée à de mauvais résultats d'allogreffe. Nous avons comparé la survie du greffon et des patients RGR-SHUa avec et sans administration prophylactique/précoce d'éculizumab, un anticorps monoclonal qui lie la protéine C5 du complément, au moment de la transplantation. MÉTHODOLOGIE: Nous avons mené une étude de cohorte rétrospective en utilisant le United States Renal Data System. Parmi les 123 624 patients atteints d'IRT transplantés entre le 1er janvier 2008 et le 1er juin 2016, nous avons répertorié 348 (0,28 %) patients présentant un « syndrome hémolytique urémique ¼ comme cause principale de l'IRT. Nous avons ensuite lié ces patients à des ensembles de données contenant le code du Healthcare Common Procedure Coding System (HCPCS) pour la perfusion d'éculizumab. Les patients ayant reçu de l'éculizumab avant l'intervention ou dans les 30 jours suivant la transplantation représentaient le groupe d'exposition. Nous avons calculé les taux bruts d'incidence et procédé à une régression logistique exacte, corrigée selon l'âge et le sexe du receveur, pour les résultats de l'étude concernant la perte du greffon, la perte du greffon censurée par le décès et la mortalité. Nous avons également estimé l'effet de traitement moyen (ETM) par appariement des scores de propension, afin de réduire le biais de l'effet estimé du traitement sur la perte du greffon. RÉSULTATS: Notre cohorte d'étude finale comprenait 335 patients RGR-SHUa (23 ayant reçu de l'éculizumab et 312 n'en ayant pas reçu) dont le suivi s'établissait à 5,8 ± 2,7 ans. Aucune différence significative n'a été observée entre les caractéristiques cliniques et démographiques initiales des deux groupes de sujets. Les patients ayant reçu de l'éculizumab prophylactique/précoce étaient moins susceptibles de subir une perte du greffon que ceux qui n'en avaient pas reçu (0 % vs 20 %; P = 0,02), avec un rapport de cotes corrigé de 0,13 (P = 0,02). Dans l'échantillon aux scores de propension appariés, l'ETM (éculizumab vs sans éculizumab) était de −0,20 (IC 95 %: −0,25 à −0,15; P < 0,001), le traitement a donc été associé à une réduction moyenne de 20 % de la perte du greffon. Aucune différence significative n'a été observée entre les deux groupes quant au risque de décès. CONCLUSION: Bien qu'aucune différence significative n'ait été observée pour le risque de mortalité, l'administration prophylactique/précoce d'éculizumab a été associée de façon significative à une amélioration de la survie du greffon chez les patients RGR-SHUa. Étant donné le coût élevé de l'éculizumab, des essais contrôlés randomisés sont nécessaires pour orienter les stratégies prophylactiques visant à prévenir la perte du greffon.

Concomitant Use of Gabapentinoids with Opioids Is Associated with Increased Mortality and Morbidity among Dialysis Patients.

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.

Racial/Ethnic Disparities in Atrial Fibrillation Treatment and Outcomes among Dialysis Patients in the United States.

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.

An analysis of hot spots of ESRD in the United States: Potential presence of CKD of unknown origin in the USA?

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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Psychiatric Illness and Mortality in Hospitalized ESKD Dialysis Patients.

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.

Epilepsy and antiseizure medications increase all-cause mortality in dialysis patients in the United States.

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.

Association of Race and Poverty With Mortality Among Nursing Home Residents on Maintenance Dialysis.

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.

Pediatric Urinary Stone Disease in the United States: The Urologic Diseases in America Project.

OBJECTIVE: To examine the recent epidemiology of pediatric urinary stone disease (USD) in the United States. METHODS: We utilized the 2004-2016 Optum© Clinformatics® Data Mart database, a de-identified adjudicated administrative health claims database that includes 15-18 million individuals covered annually by commercial insurance in all 50 US states. The analysis included 12,739,125 children aged 0-18 years. We calculated annual rates of USD, ambulatory visits, and procedures, and the prevalence of prescription fills. RESULTS: The 2005-2016 USD rate was 59.5 cases per 100,000 person-years. The annual rate rose gradually from 2005 to a peak of 65.2 cases per 100,000 person-years in 2011. The USD rate increased with increasing age, and was highest among females compared to males, non-Hispanic Whites compared to other race/ethnic groups, and those residing in the South compared to other geographic regions. The overall 2005-2016 rate in the 120 days following a USD episode was 1.9 for ambulatory visits, 0.24 for surgical procedures, and 1.1 for imaging procedures. Ureteroscopy was the most common surgical procedure and CT scan was the most common imaging procedures, although ultrasound utilization increased over time. Medications were filled in 46.9% of cases, and use was lowest among males (43.1%), Asians (34.8%), and in the Northeast (34.3%). Opiate agonists were the most prevalent prescription (39.9%). CONCLUSION: Our study provides one of the most comprehensive examinations of pediatric USD to date, demonstrating shifting rates and treatment patterns over time, as well as differences by age, gender, race/ethnicity, and geographic region.

The TiME Trial: A Fully Embedded, Cluster-Randomized, Pragmatic Trial of Hemodialysis Session Duration.

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.

Risk of Cardiovascular Disease and Mortality in Young Adults With End-stage Renal Disease: An Analysis of the US Renal Data System.

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.

Development and Validation of Prediction Scores for Early Mortality at Transition to Dialysis.

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 m2 or 15 mL/min per 1.73 m2 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 m2 and 15 mL/min per 1.73 m2 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 m2 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 m2 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.

Hypoglycemia-Related Hospitalizations and Mortality Among Patients With Diabetes Transitioning to Dialysis.

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.

Abrupt Decline in Kidney Function Precipitating Initiation of Chronic Renal Replacement Therapy.

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.