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IntroductionAnticoagulation is commonly used for stroke prevention among patients with atrial fibrillation (AF); however, end-stage renal disease (ESRD) patients on hemodialysis are at higher risk of bleeding and stroke, even without anticoagulation. It is unclear if patients should be continued on anticoagulation at the time of transition to ESRD. In this study, we validated risk scores for stroke and bleeding in this population and assessed risk of stroke and bleeding among warfarin users compared to nonusers.MethodsWe utilized a cohort of 28,620 pre-dialysis US veterans transitioning to hemodialysis between October 2007 and March 2015. Incident rates for the risks of stroke and bleeding were ascertained based upon CHA2DS2-VASc or HAS-BLED scores, respectively. A propensity score-based competing risk analysis was used to assess risk of stroke and bleeding.FindingsThe mean age of our cohort was 77 ± 9 years, and the median CHA2DS2-VASc and HAS-BLED scores were 7 (5, 8) and 3 (3, 4), respectively. Increasing CHA2DS2-VASc and HAS-BLED scores were predictive of increasing stroke and bleeding rates, respectively. However, warfarin use did not appear to affect the risk of stroke and bleeding (p-interaction = 0.84 for stroke and 0.24 for bleeding). Warfarin use was associated with a higher risk of stroke (adjusted SHR 1.44, 95% CI: 1.23-1.69) and a higher risk of bleeding (adjusted SHR 1.38, 95% CI: 1.25-1.52) when accounting for the competing risk of death.DiscussionThere was no difference in incidence rates of stroke or bleeding among warfarin users versus nonusers. Warfarin was associated with a higher risk of stroke and bleeding after considering mortality risk.

IntroductionErythropoietin stimulating agents (ESA) hyporesposiveness has been associated with increased mortality in hemodialysis (HD) patients. However, the impact of decline of residual kidney function (RKF) on ESA hyporesposiveness has not been adequately elucidated among patients receiving HD.MethodsThe associations of RKF decline with erythropoietin resistance index (ERI; average weekly ESA dose [units])/post-dialysis body weight [kg]/hemoglobin [g/dL]) were retrospectively examined across four strata of annual change in RKF (residual renal urea clearance [KRU]

BackgroundBoth polypharmacy and frailty are highly prevalent among the patients on hemodialysis and associated with adverse outcomes; however, little is known about the association between them.MethodsWe examined 337 patients enrolled in the ACTIVE/ADIPOSE dialysis cohort study between 2009 and 2011. The number of prescribed medications and frailty were assessed at baseline, 12, and 24 months. Frailty was defined based upon the Fried's frailty phenotype. We used logistic regression with generalized estimating equations to model the association of the number of medications and frailty at baseline and over time. A competing-risk regression analysis was also used to assess the association between the number of medications and incidence of frailty.ResultsThe mean number of medications was 10 ± 5, and 94 patients (28%) were frail at baseline. Patients taking >11 medications showed higher odds for frailty than the patients taking fewer than 8 medications (OR 1.54, 95% CI 1.05-2.26). During the 2-year of follow-up, 87 patients developed frailty among those who were nonfrail at baseline. Compared with the patients taking fewer than 8 medications, the incidence of frailty was approximately 2-fold in those taking >11 medications (sub-distribution hazard ratio 2.15, 95% CI 1.32-3.48).ConclusionsUsing a higher number of medications was associated with frailty and the incidence of frailty among hemodialysis patients. Minimizing polypharmacy may reduce the incidence and prevalence of frailty among dialysis patients.

BackgroundWhile direct oral anticoagulants (DOACs) are considered safe among patients without chronic kidney disease (CKD), the evidence is conflicting as to whether they are also safe in the CKD and end-stage kidney disease (ESKD) population. In this observational cohort study, we examined whether DOACs are a safe alternative to warfarin across CKD stages for a variety of anticoagulation indications.MethodsIndividuals on DOACs or warfarin were identified from OptumLabs® Data Warehouse (OLDW), a longitudinal dataset with de-identified administrative claims, from 2010 to 2017. Cox models with sensitivity analyses were used to assess the risk of cardiovascular disease and bleeding outcomes stratified by CKD stage.ResultsAmong 351,407 patients on anticoagulation, 45% were on DOACs. CKD stages 3-5 and ESKD patients comprised approximately 12% of the cohort. The most common indications for anticoagulation were atrial fibrillation (AF, 44%) and venous thromboembolism (VTE, 23%). DOACs were associated with a 22% decrease in the risk of cardiovascular outcomes (HR 0.78, 95% CI: 0.77-0.80, p < 0.001) and a 10% decrease in the risk of bleeding outcomes (HR 0.90, 95% CI: 0.88-0.92, p < 0.001) compared to warfarin after adjustment. On stratified analyses, DOACs maintained a superior safety profile across CKD stages. Patients with AF on DOACs had a consistently lower risk of cardiovascular and bleeding events than warfarin-treated patients, while among other indications (VTE, peripheral vascular disease, and arterial embolism), the risk of cardiovascular and bleeding events was the same among DOAC and warfarin users.ConclusionDOACs may be a safer alternative to warfarin even among CKD and ESKD patients.

Rationale & objectivePatients receiving twice-weekly or less-frequent hemodialysis (HD) may need to undergo higher ultrafiltration rates (UFRs) to maintain acceptable fluid balance. We hypothesized that higher UFRs are associated with faster decline in residual kidney function (RKF) and a higher rate of mortality.Study designRetrospective cohort study.Setting & participants1,524 patients with kidney failure who initiated maintenance HD at a frequency of twice or less per week for at least 6 consecutive weeks at some time between 2007 and 2011 and for whom baseline data for UFR and renal urea clearance were available.PredictorAverage UFR during the first patient-quarter during less-frequent HD (

IntroductionDialysis patients incur disproportionately high costs compared with other Medicare beneficiaries. Care for frail individuals may be even more costly. We examined the extent to which frailty contributes to higher costs among dialysis patients.MethodsWe used ACTIVE/ADIPOSE (A Cohort to Investigate the Value of Exercise/Analyses Designed to Investigate the Paradox of Obesity and Survival in ESRD) enrollees (adult hemodialysis patients evaluated from June 2009 to August 2011) in a retrospective cohort analysis. Individuals using Medicare as the primary payer were included. Fried's frailty phenotype was evaluated at baseline, 12, and 24 months. Costs were derived from linkage with the US Renal Data System (USRDS) and Medicare claims data. We used generalized estimating equations (GEEs) incorporating time-updated frailty and costs to evaluate adjusted point estimates and the marginal cost associated with being frail. We also investigated if frail patients who died during the study incurred higher costs than those who survived.ResultsAmong 771 enrollees in ACTIVE/ADIPOSE, 425 met inclusion criteria. Mean age was 56 ± 13 years, body mass index (BMI) 29.2 ± 7.1 kg/m2, 42.4% were women, and 29.0% were frail at baseline. Over a mean follow-up of 2.3 years, frail individuals incurred 22% (95% confidence interval [CI] 9.6%-35.8%) higher costs compared with nonfrail individuals ($87,600 per patient per year [pppy], 95% CI 76,800-100,000, vs. $71,800 pppy, 95% CI 64,800-79,600), the difference was driven primarily by higher inpatient expenditures. The difference between frail and nonfrail patients' inpatient expenditures was even more pronounced among those who died during the study compared with those who survived.ConclusionsFrail dialysis patients incur a significantly higher cost relative to their nonfrail counterparts, primarily driven by higher inpatient costs. Frail patients near end of life incur even higher costs.

Abnormalities of mineral bone disorder (MBD) parameters have been suggested to be associated with poor renal outcome in predialysis patients. However, the impact of those parameters on decline in residual kidney function (RKF) is uncertain among incident hemodialysis (HD) patients. We performed a retrospective cohort study in 13,772 patients who initiated conventional HD during 2007 to 2011 and survived 6 months of dialysis. We examined the association of baseline serum phosphorus, calcium, intact parathyroid hormone (PTH), and alkaline phosphatase (ALP) with a decline in RKF. Decline in RKF was assessed by estimated slope of renal urea clearance (KRU) over 6 months from HD initiation. Our cohort had a mean ± SD age of 62 ± 15 years; 64% were men, 57% were white, 65% had diabetes, and 51% had hypertension. The median (interquartile range [IQR]) baseline KRU level was 3.4 (2.0, 5.2) mL/min/1.73 m2 . The median (IQR) estimated 6-month KRU slope was -1.47 (-2.24, -0.63) mL/min/1.73 m2 per 6 months. In linear regression models, higher phosphorus categories were associated with a steeper 6-month KRU slope compared with the reference category (phosphorus 4.0 to

IntroductionFrailty and depression are highly prevalent in the dialysis population, but the association between them, the risk factors for their development, and their independent associations with mortality have not been studied.MethodsWe examined 771 patients enrolled in the ACTIVE/ADIPOSE prevalent dialysis cohort study. Fried's frailty phenotype and the Center for Epidemiologic Studies Depression score were used to determine frailty and presence of depressive symptoms, respectively. We assessed the baseline association between frailty and depressive symptoms, whether one entity is a risk factor for development of the other, and associations between frailty and depressive symptoms with mortality.FindingsAt baseline, 13.1% of our population screened positive for depressive symptoms, 21.8% met criteria for frailty, and 10.0% met criteria for both. During follow-up, 26.6% of our population developed frailty and 12.7% developed depressive symptoms. Using multivariable logistic regression, baseline depressive symptoms were associated with 2.14-fold higher odds of being frail at baseline (95% confidence interval [CI] 1.45-3.17) and with a 2.16-fold higher odds of incident frailty during follow-up (95% CI 1.22-3.82). However, baseline frailty was not associated with incident depressive symptoms. Frailty and depressive symptoms were independent predictors of mortality in time-varying survival analysis (meeting frailty criteria: hazard ratio [HR] 1.53, 95% CI 1.05-2.23; depressive symptoms: HR 2.21, 95% CI 1.50-3.25).DiscussionFrailty and depressive symptoms remained highly prevalent over time and were strongly associated with one another and independently associated with mortality among dialysis patients. Future studies should investigate whether interventions for depression could potentially mitigate the appearance of frailty and its associated poor outcomes.

BACKGROUND:High ultrafiltration rate (UFR) has been associated with increased mortality in hemodialysis (HD) patients. However, the impact of UFR on decline of residual kidney function (RKF) has not been elucidated among patients receiving conventional HD. METHODS:We performed a retrospective cohort study of 7,753 patients who initiated conventional HD from 2007 to 2011 and survived the first year of dialysis with baseline UFR and renal urea clearance (KRU) data at baseline and 1 year (5th patient-quarter). The primary exposure was average UFR at the 1st patient-quarter from dialysis initiation (

Purpose of reviewFrailty is highly prevalent in the dialysis population and is associated with mortality. Recent studies have suggested that other dialysis outcomes are compromised in frail individuals. While we do not yet have a consensus as to the best measure of frailty, identification of these poor outcomes and their magnitude of association with frailty will help improve prognostication, allow for earlier interventions, and improve provider-to-patient communication.Recent findingsThe most widely used assessment of frailty is Fried's physical performance criteria. However, regardless of assessment method, frailty remains highly associated with mortality. More recently, frailty has been associated with falls, fractures, cognitive impairment, vascular access failure, and poor quality of life. Recent large cohort studies provide strong evidence that frailty assessment can provide important prognostic information for providers and patients both before and after initiation of dialysis. Trials aimed at improving frailty are limited and show the promise of augmenting quality of life, although more studies are needed to firmly establish mortality benefits.SummaryWe underscore the importance of frailty as a prognostic indicator and identify other recently established consequences of frailty. Widespread adoption of frailty assessment remains limited and researchers continue to find ways of simplifying the data collection process. Timely and regular assessment of frailty may allow for interventions that can mitigate the onset of poor outcomes and identify actionable targets for dialysis providers.