Long-term effects of spironolactone in peritoneal dialysis patients

Abstract

ESRD treated with dialysis is associated with increased left ventricular hypertrophy, which, in turn, is related to high mortality. Mineralocorticoid receptor antagonists improve survival in patients with chronic heart failure; however, the effects in patients undergoing dialysis remain uncertain. We conducted a multicenter, open-label, prospective, randomized trial with 158 patients receiving angiotensin-converting enzyme inhibitor or angiotensin type 1 receptor antagonist and undergoing peritoneal dialysis with and without (control group) spironolactone for 2 years. As a primary endpoint, rate of change in left ventricular mass index assessed by echocardiography improved significantly at 6 (P=0.03), 18 (P=0.004), and 24 (P=0.01) months in patients taking spironolactone compared with the control group. Rate of change in left ventricular ejection fraction improved significantly at 24 weeks with spironolactone compared with nontreatment (P=0.02). The benefits of spironolactone were clear in patients with reduced residual renal function. As secondary endpoints, renal Kt/V and dialysate-to-plasma creatinine ratio did not differ significantly between groups during the observation period. No serious adverse effects, such as hyperkalemia, occurred. In this trial, spironolactone prevented cardiac hypertrophy and decreases in left ventricular ejection fraction in patients undergoing peritoneal dialysis, without significant adverse effects. Further studies, including those to determine relative effectiveness in women and men and to evaluate additional secondary endpoints, should confirm these data in a larger cohort.

Figure 1.

Number of patients enrolled, randomly assigned, and analyzed as part of the study. HD, hemodialysis; SAH, subarachnoid hemorrhage; UCG, echocardiography; UF, ultrafiltration.

Figure 2.

Spironolactone prevented cardiac hypertrophy and decreases in LVEF in patients on PD. Effects of spironolactone are clear in men and in patients with reduced residual renal function. Effects of spironolactone on LVMI and function in patients undergoing PD. LVMI in all patients (A), in men with LVMI≤50 g/m^2.7 (B) or >50 g/m^2.7 (C), and in PD patients with renal Kt/V<0.49 (D). Ejection fraction in all patients (E) and in patients with renal Kt/V<0.49 (F). 95% C.I., 95% confidence interval; Spiro (−), control group; Spiro (+), spironolactone treatment group.

Figure 3.

Both urine volume and renal Kt/V decreased with time, but rate of change did not significantly differ between the treatment and control groups. Effects of spironolactone on residual renal function and peritoneal membrane function. (A) Changes in urine volume. Rate of change in urine volume was significantly higher in both groups after 18 months compared with baseline values but did not significantly differ between groups during the observation period. (B) Changes in residual renal function Kt/V. Changes in renal Kt/V were not significantly different compared with baseline values and did not significantly differ between groups during the observation period. (C) Peritoneal membrane function assessed by D/P Cr. Rate of change in D/P Cr did not differ between groups. 95% C.I., 95% confidence interval; Spiro (−), control group; Spiro (+), spironolactone treatment group.