Association between mineralocorticoid receptor antagonists and kidney harm: A systematic review and meta‐analysis of randomized controlled trials

Abstract Conflicting data have been reported on the association between mineralocorticoid receptor antagonists (MRAs) and acute kidney injury (AKI). This systematic review and meta‐analysis aimed to evaluate whether MRAs affect the risk of AKI. MEDLINE via PubMed, the Cochrane Central Register of Controlled Trials, and the ClinicalTrials.gov website were comprehensively searched to extract all relevant studies. Randomized controlled trials (RCTs) were selected that compared MRA versus placebo or no treatment and had study populations consisting of patients with heart or kidney disease. The primary outcome was AKI. The secondary outcome was kidney injury, including AKI and non‐AKI. Thirty‐three studies were included in the meta‐analysis. MRAs were not associated with an increased risk of AKI (risk ratio [RR] 1.13, 95% confidence interval [CI] 0.88–1.46, p = 0.29, I 2 = 15%, 18,065 patients, 13 RCTs, moderate certainty). For the secondary outcome, MRAs were associated with an increased risk of kidney injury (RR 1.52, 95% CI 1.24–1.87, p < 0.01, I 2 = 48%, 27,492 patients, 33 RCTs, low certainty). In particular, only canrenone (RR 5.39, 95% CI 2.17–13.37, p < 0.01) and spironolactone (RR 1.78, 95% CI 1.48–2.14, p < 0.01) were associated with an increased risk of kidney injury. However, eplerenone and finerenone seem not to increase the risk of kidney injury in patients with heart or kidney disease. The selection of MRAs might influence the risk of kidney‐associated events. Further studies focusing on individual MRAs may be needed to clarify these differences.