Safety and efficacy of steroidal mineralocorticoid receptor antagonists in patients with kidney failure requiring dialysis: a systematic review and meta-analysis of randomised controlled trials.

Background: Mineralocorticoid receptor antagonists can prevent cardiovascular events in patients with heart failure and non-severe chronic kidney disease, but their effects in patients with kidney failure requiring dialysis are uncertain. We aimed to assess the efficacy and safety of mineralocorticoid receptor antagonists in this patient population.

Methods: In this systematic review and meta-analysis, we updated our previous systematic review by searching MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and the Cumulative Index to Nursing and Allied Health Literature for randomised controlled trials published between database inception and March 18, 2025. Trials comparing a mineralocorticoid receptor antagonist with placebo or standard of care in adults (aged ≥18 years) receiving maintenance dialysis were eligible. Studies that did not report an outcome of interest (cardiovascular mortality, heart failure hospitalisation, all-cause mortality, all-cause hospitalisation, hyperkalaemia, gynaecomastia or breast pain, or hypotension) were excluded. Two reviewers independently identified studies, extracted data, and assessed the risk of bias using the Cochrane risk-of-bias tool. The main outcome was cardiovascular mortality assessed using the empirical Bayes random-effects models, stratified by risk-of-bias. The protocol is registered with PROSPERO (CRD420251008119).

Findings: 19 trials of steroidal mineralocorticoid receptor antagonists including 4675 participants met eligibility criteria. Effect estimates differed trials with low and high risk of bias. In four trials with a low risk of bias (n=3562), 264 cardiovascular deaths occurred in 1785 patients in the mineralocorticoid receptor antagonist group compared with 276 of 1777 patients in the control group (odds ratio 0·98 [95% CI 0·80-1·20]; I²=0·0%; τ²=0·0; moderate certainty) resulting in an absolute risk reduction of 1 fewer event per 1000 patients per year (95% CI 14 fewer to 11 more).

Interpretation: Our findings suggest that steroidal mineralocorticoid receptor antagonists have little to no effect on cardiovascular mortality in patients requiring dialysis. There is insufficient information on the effects of steroidal mineralocorticoid receptor antagonists in subgroups of patients requiring dialysis and no information on non-steroidal mineralocorticoid receptor antagonists. Future trials would need to consider the likelihood of only smaller effects or effects limited to patients or events with pathophysiology that is more clearly driven by aldosterone in their design.

Funding: None.