Efficacy of Mineralocorticoid Receptor Antagonists on Kidney and Cardiovascular Outcomes in Patients With Chronic Kidney Disease: An Umbrella Review

Rationale , Objective: To comprehensively sum- marize the efficacy fi cacy of mineralocorticoid receptor antagonists (M RAs) to improve kidney , car- diovascular (CV) outcomes in patients with chronic kidney disease (CKD). Study Design: Relevant studies were identified fi ed from Medline and Scopus databases from their inception up to August 2023. Setting & Study Populations: Patients with non- dialysis or dialysis CKD. Selection Criteria for Studies: Systematic re- views and meta-analyses (SR-MAs) of randomized controlled trials (RCTs) that investigated the efficacy i cacy of MRAs on kidney and CV outcomes in patients with nondialysis or dialysis CKD were included in this study. Data Extraction: Characteristics of studies and participants , treatment effects were extracted. Analytic Approach: Efficacy i cacy of MRAs was quali- tatively summarized according to types of patients and MRAs. Results: Forty SR-MAs were included. When compared with placebo/usual care, steroidal MRAs (sM RAs) provided significant fi cant benefit fi t in decreasing all-cause (pooled RRs of 0.38 [0.22- 0.65] to 0.87 [0.77-0.9 8]) and CV mortality (pooled RRs of 0.34 [0.15-0.75] to 0.46 [0.28- 0.76]) only in patients treated with dialysis, when compared with placebo. Nonsteroidal MRAs (nsM RAs) significantly fi cantly lowered composite CV events in both nondialysis CKD (pooled RRs of 0.86 [0.79-0.9 4] to 0.92 [0.85-0.9 9]) and patients with diabetic kidney disease (DKD) (pooled RRs of 0.86 [0.78-0.95] to 0.88 [0.81- 0.9 6]). In addition, nsMRAs showed significant fi cant benefit fi t in reducing composite kidney outcomes in patients with either nondialysis CKD or DKD when compared with placebo. However, this efficacy i cacy was lower than sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with DKD. Moreover, both sMRAs and nsMRAs significantly fi cantly increased the risk of hyperkalemia in patients with nondialysis CKD and DKD. Limitations: The comparison between nsMRAs and SGLT2i is based on network meta-analyses. Consequently, additional head-to-head RCTs are necessary to confirm fi rm the advantages of SGLT2i over nsMRAs. Conclusions: sMRAs offer benefits fi ts in reducing all-cause and cardiovascular mortality and composite CV events in patients treated with dialysis. nsMRAs improve kidney outcomes in patients with nondialysis CKD and DKD but increase hyperkalemia risk.