Abstract
BackgroundAlthough angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-II receptor blockers (ARB) have been shown to preserve residual kidney function in a select group of Asian patients undergoing continuous ambulatory peritoneal dialysis (PD) in two small randomized clinical trials, the effectiveness of these drugs has yet to be demonstrated in a more diverse population of patients with multiple comorbid conditions. We investigated the association between ACEI/ARB use and development of recorded anuria in a cohort of patients initiating PD in the U.S.MethodsWe conducted a retrospective observational cohort study using the US Renal Data System and electronic health records data from a large national dialysis provider. We identified adult patients who initiated PD from 2007 to 2011. Only patients who participated in the federal prescription drug benefit program, Medicare Part D, for the first 90 days of dialysis were included. Patients who filled a prescription for an ACEI or ARB during those 90 days were considered users. We applied Cox proportional hazards models to an inverse probability of treatment-weighted (IPTW) cohort to estimate the hazard ratio (HR) for anuria (24-h urine volume < 200 ml) in ACEI/ARB users vs. non-users.ResultsAmong 886 patients, 389 (44%) used an ACEI/ARB. Almost a third of these patients were black or Hispanic, and more than a quarter had comorbidities that would have excluded them from the randomized clinical trials of ACEI/ARB. Two hundred eighty patients reached anuria over 840 person-years of follow-up, for a composite event rate of 33 events per 100 person-years. We found no clear association between ACEI/ARB use and progression to anuria [HR: 0.86, 95% CI: 0.73–1.02].ConclusionsACEI/ARB use is common in patients initiating PD in the U.S. but was not associated with a lower risk of anuria. Residual confounding by unmeasured variables is an important limitation of this observational study. Still, these findings suggest that pragmatic clinical trials are warranted to test the effectiveness of ACEI/ARB in slowing the decline of residual kidney function in a diverse population of peritoneal dialysis patients with multiple comorbid conditions.
Highlights
Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-II receptor blockers (ARB) have been shown to preserve residual kidney function in a select group of Asian patients undergoing continuous ambulatory peritoneal dialysis (PD) in two small randomized clinical trials, the effectiveness of these drugs has yet to be demonstrated in a more diverse population of patients with multiple comorbid conditions
They excluded patients with comorbidities common in PD patients, including heart failure, recent myocardial infarction, stroke, valvular disease, and chronic liver disease. Their findings may have limited generalizability to the general PD population in the U.S Further complicating the picture is a large cohort study of incident Dutch PD patients that, in contrast to the randomized trials, showed no benefit associated with angiotensin-converting enzyme inhibitors (ACEI) or ARB use [13]. In this retrospective observational cohort study, we examined whether ACEI or ARB use was associated with preservation of residual kidney function in a large, ethnically and racially diverse cohort of U.S patients initiating PD from 2007 to 2011
We found that ACEI/ARB users had a higher proportion of “late collectors” than non-users (6% vs. 3% p = 0.02), suggesting that anuria was more likely to be under-ascertained in ACEI/ARB users rather than non-users
Summary
Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-II receptor blockers (ARB) have been shown to preserve residual kidney function in a select group of Asian patients undergoing continuous ambulatory peritoneal dialysis (PD) in two small randomized clinical trials, the effectiveness of these drugs has yet to be demonstrated in a more diverse population of patients with multiple comorbid conditions. Two small randomized trials demonstrated a slower rate of decline in residual kidney function in those treated with the ACEI, ramipril, or the ARB, valsartan, vs placebo [10, 11] These trials had several limitations: both were very small and included only Asian patients on continuous ambulatory PD, excluding those on cyclers, the PD modality used by over 50% of U.S PD patients [12]. Their findings may have limited generalizability to the general PD population in the U.S Further complicating the picture is a large cohort study of incident Dutch PD patients that, in contrast to the randomized trials, showed no benefit associated with ACEI or ARB use [13]
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