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

Abstract

Rationale & Objective

To comprehensively summarize the efficacy of mineralocorticoid receptor antagonists (MRAs) to improve kidney and cardiovascular (CV) outcomes in patients with chronic kidney disease (CKD).

Study Design

Relevant studies were identified from Medline and Scopus databases from their inception up to August 2023.

Setting & Study Populations

Patients with nondialysis or dialysis CKD.

Selection Criteria for Studies

Systematic reviews and meta-analyses (SR-MAs) of randomized controlled trials (RCTs) that investigated the efficacy 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, and treatment effects were extracted.

Analytic Approach

Efficacy of MRAs was qualitatively summarized according to types of patients and MRAs.

Results

Forty SR-MAs were included. When compared with placebo/usual care, steroidal MRAs (sMRAs) provided significant benefit in decreasing all-cause (pooled RRs of 0.38 [0.22-0.65] to 0.87 [0.77-0.98]) 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 (nsMRAs) significantly lowered composite CV events in both nondialysis CKD (pooled RRs of 0.86 [0.79-0.94] to 0.92 [0.85-0.99]) and patients with diabetic kidney disease (DKD) (pooled RRs of 0.86 [0.78-0.95] to 0.88 [0.81-0.96]). In addition, nsMRAs showed significant benefit in reducing composite kidney outcomes in patients with either nondialysis CKD or DKD when compared with placebo. However, this efficacy was lower than sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with DKD. Moreover, both sMRAs and nsMRAs significantly 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 the advantages of SGLT2i over nsMRAs.

Conclusions

sMRAs offer benefits 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.

Plain Language Summary

Chronic kidney disease (CKD) can increase the risk of severe kidney problems and heart disease. A key factor in kidney decline and heart disease risk is the overactivation of mineralocorticoid receptors (MR). Medications called MR antagonists (MRAs) may lower heart disease risk. We performed a thorough review of all existing studies on both steroidal MRAs (sMRAs) and nonsteroidal MR antagonists (nsMRAs) to see how they might help reduce kidney and heart problems in different types of CKD. Our review found that sMRAs significantly lower the risk of death from all causes and heart issues in patients treated with dialysis, whereas nsMRAs reduce the chances of heart and kidney problems in patients not requiring dialysis. Both types of MRAs, however, do increase the risk of high potassium in patients requiring nondialysis.