Background Dabigatran and rivaroxaban are new oral anticoagulants that are eliminated through the kidneys. Their use in dialysis patients is discouraged because these drugs can bio-accumulate to precipitate inadvertent bleeding. We wanted to determine if prescription of dabigatran or rivaroxaban was occurring in the dialysis population and if these practices were safe. Methods and Results Prevalence plots were used to describe the point prevalence (monthly) of dabigatran and rivaroxaban use among 29,977 hemodialysis patients with atrial fibrillation (AF). Poisson regression compared the rate of bleeding, stroke, and arterial embolism in patients who started dabigatran, rivaroxaban, or warfarin. The first record of dabigatran prescription among hemodialysis patients occurred 45 days after the drug became available in the US. Since then, dabigatran and rivaroxaban use in the AF-ESRD population has steadily risen where 5.9% of anti-coagulated dialysis patients are started on dabigatrian or rivaroxaban. In covariate adjusted Poisson regression, dabigatran (RR=1.48; 95% CI 1.21-1.81, p=0.0001) and rivaroxaban (RR=1.38; 95% CI 1.03-1.83, p=0.04) associated with a higher risk of hospitalization or death from bleeding when compared to warfarin. The risk of hemorrhagic death was even larger with dabigatran (RR=1.78; 95% CI 1.18-2.68, p=0.006) and rivaroxaban (RR=1.71; 95% CI 0.94-3.12, p=0.07) relative to warfarin. There were too few events in the study to detect meaningful differences in stroke and arterial embolism between the drug groups. Conclusions More dialysis patients are being started on dabigatran and rivaroxaban, even when their use is contraindicated and there are no studies to support the benefits outweigh the risks of these drugs in ESRD.

Accurate identification of risk factors for calcific uremic arteriolopathy (CUA) is necessary to develop preventive strategies for this morbid disease. We investigated whether baseline factors recorded at hemodialysis initiation would identify patients at risk for future CUA in a matched case-control study using data from a large dialysis organization. Hemodialysis patients with newly diagnosed CUA (n=1030) between January 1, 2010, and December 31, 2014, were matched by age, sex, and race in a 1:2 ratio to hemodialysis patients without CUA (n=2060). Mean ages for patients and controls were 54 and 55 years, respectively; 67% of participants were women and 49% were white. Median duration between hemodialysis initiation and subsequent CUA development was 925 days (interquartile range, 273-2185 days). In multivariable conditional logistic regression analyses, diabetes mellitus; higher body mass index; higher levels of serum calcium, phosphorous, and parathyroid hormone; and nutritional vitamin D, cinacalcet, and warfarin treatments were associated with increased odds of subsequent CUA development. Compared with patients with diabetes receiving no insulin injections, those receiving insulin injections had a dose-response increase in the odds of CUA involving lower abdomen and/or upper thigh areas (odds ratio, 1.49; 95% confidence interval, 1.03 to 2.51 for one or two injections per day; odds ratio, 1.88; 95% confidence interval, 1.30 to 3.43 for 3 injections per day; odds ratio, 3.74; 95% confidence interval, 2.28 to 6.25 for more than three injections per day), suggesting a dose-effect relationship between recurrent skin trauma and CUA risk. The presence of risk factors months to years before CUA development observed in this study will direct the design of preventive strategies and inform CUA pathobiology.

Intradialytic hypotension (IH) is a frequent complication of hemodialysis (HD) and is associated with increased patient mortality and cardiovascular events. We studied IH to determine its variability, correlates, and clinical impact in 13 outpatient HD facilities. Blood pressure was captured by machine download. IH was defined as >30 mmHg decrease in systolic blood pressure to <90 mmHg. Risk factors were assessed by logistic regression and hospitalization by Poisson regression. Time to death and first hospitalization were assessed using Kaplan-Meier analysis in patients completing >20 HD treatments. We studied IH in 44,801 treatments (Tx) in 1137 patients. IH was frequent (17.2% of treatments) and highly variable by patient (0-100% Tx) and dialysis facility (11.1-25.8% Tx). 25.1% of patients had no IH (0% Tx) and 16.2% had IH on >35% Tx. Increased IH frequency was associated with age, female gender, diabetes, Hispanic origin, longer end stage renal disease vintage, higher body mass index, higher ultrafiltration volume, the second and third weekly Tx, lower pre-HD systolic blood pressure, higher difference between prescribed and achieved post-HD weight, and higher dialysate temperature. Dialysis facility was an independent predictor of IH frequency. Patients with >35% IH treatments had poorer survival (P = 0.036), and more frequent and longer hospitalization (P = 0.04, P = 0.002, respectively) than patients without IH. In conclusion, IH frequency was highly variable, associated with individual facilities, patient and treatment characteristics, and correlated with mortality and hospitalization. Identifying practice patterns associated with IH coupled with routine reporting of IH will facilitate medical management and may result in the prevention of IH, decreased mortality, and decreased hospitalization.

Nonvitamin K-dependent oral anticoagulant agents (NOACs) are currently recommended for patients with atrial fibrillation at risk for stroke. As a group, NOACs significantly reduce stroke, intracranial hemorrhage, and mortality, with lower to similar major bleeding rates compared with warfarin. All NOACs are dependent on the kidney for elimination, such that patients with creatinine clearance <25 ml/min were excluded from all the pivotal phase 3 NOAC trials. It therefore remains unclear how or if NOACs should be prescribed to patients with advanced chronic kidney disease and those on dialysis. The authors review the current pharmacokinetic, observational, and prospective data on NOACs in patients with advanced chronic kidney disease (creatinine clearance <30 ml/min) and those on dialysis. The authors frame the evidence in terms of risk versus benefit to bring greater clarity to NOAC-related major bleeding and efficacy at preventing stroke specifically in patients with creatinine clearance <30 ml/min.

Background Sudden death is a leading cause of death in patients on maintenance hemodialysis (HD). During HD sessions, the gradient between serum and dialysate levels results in rapid electrolytes shifts, which may contribute to arrhythmias and sudden death. Controversies exist on the optimal electrolyte concentration in the dialysate; specifically, it is unclear whether patient outcomes differ among those treated with dialysate potassium (DK) concentration of 3 mEq/L compared to 2 mEq/L. Study Design Prospective cohort study Setting & Participants 55,183 patients from 20 countries in the Dialysis Outcomes and Practice Patterns Study phases 1–5 (1996–2015). Predictor DK at study entry. Outcomes Cox regression was used to estimate the association between DK and both all-cause mortality and an arrhythmia composite outcome (arrhythmia-related hospitalization or sudden death), adjusting for potential confounders. Results During a median follow-up of 16.5 months, 24% of patients died and 7% had an arrhythmia composite outcome. No meaningful difference in clinical outcomes were observed for patients treated with DK 3 vs. 2 mEq/L; the adjusted hazard ratio (95% CI) was 0.96 (0.91, 1.01) for mortality and 0.98 (0.88, 1.08) for the arrhythmia composite. Results were similar across pre-dialysis serum potassium (SK) levels. As in prior studies, higher SK was associated with adverse outcomes. However, DK only had minimal impact on SK measured pre-dialysis (+0.09 mEq/L SK per 1 mEq/L DK; 95% CI: 0.05, 0.14). Limitations Data were not available on delivered (vs. prescribed) DK and post-dialysis SK; possible unmeasured confounding. Conclusions In combination, these results suggest that approaches other than altering DK concentration (e.g., education on dietary K sources, prescription of K-binding medications) may merit further attention to reduce risks associated with high SK.