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.

Impact of hypokalemia on peritonitis in peritoneal dialysis patients: a systematic review

“…Each domain was rated on a maximum of one star, except comparability, which can be given up to two stars. 0, high risk of bias or no description; 1 or 2, low risk of bias several surveys [17,19,20]; however, serum potassium levels were not influenced by spironolactone in two studies [17,19]. Ito, et al [20] showed that serum potassium levels were increased in patients with spironolactone, but the prevalence of hypokalemia and peritonitis were comparable between patients with and without spironolactone.…”

“…0, high risk of bias or no description; 1 or 2, low risk of bias several surveys [17,19,20]; however, serum potassium levels were not influenced by spironolactone in two studies [17,19]. Ito, et al [20] showed that serum potassium levels were increased in patients with spironolactone, but the prevalence of hypokalemia and peritonitis were comparable between patients with and without spironolactone. Yi et al [21] showed the effect of glucose-free icodextrin on the improvement of hypokalemia compared with conventional glucose-containing dialysate, possibly through an enhanced nutritional status and an intracellular potassium shift.…”

Cardiac hypertrophy in chronic kidney disease—role of Aldosterone and FGF23

“…Alternatively, aldosterone blockade with spironolactone elicited a regression of LV hypertrophy despite no changes in systemic blood pressure in diabetic patients with microalbuminuria [10] (Table 1). Furthermore, spironolactone treatment significantly ameliorated LV mass index and/or cardiac function not only in patients with early stage CKD [45,46] but also in patients with advanced CKD on hemodialysis [47][48][49] or peritoneal dialysis [50][51][52]. More importantly, Matsumoto et al [53] elegantly demonstrated that 3-year treatment with spironolactone reduced the death rate from cardiovascular or cerebrovascular events in patients on hemodialysis in Dialysis Outcomes Heart Failure Aldactone Study (DOHAS).…”

“…As indicated above, aldosterone blockade reduces cardiac hypertrophy and improves cardiac function in patients on hemodialysis [47][48][49] and peritoneal dialysis [50][51][52] (Table 1). Furthermore, DOHAS trial clearly demonstrates that aldosterone blockade by spironolactone prevents cardiovascular events and ameliorates the survival rate in hemodialysis patients [53].…”

“…Indeed, several studies have reported that the administration of spironolactone is associated with increased incidence of hyperkalemia in patients on maintenance hemodialysis therapy [63][64][65] although pronounced hyperkalemia (serum potassium ≥ 6 mEq/L) does not occur commonly [66]. Notably, there are also reported a substantial number of studies showing that spironolactone does not cause significantly higher levels of serum potassium in patients on hemodialysis [47][48][49] or peritoneal dialysis therapy [50,51,67,68], when compared with placebo (Table 1). Taken together, the use of aldosterone blockers is teleologically reasonable in terms of cardiovascular protection, although the adverse effect of these blockers might hamper the wide-spread use of this type of agents in patients with CKD.…”