Impact of nonsteroidal mineralocorticoid receptor antagonism on cardiorenal outcomes in diabetic kidney disease: a systematic review

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PURPOSE: Diabetic kidney disease (DKD) is a major complication of type 2 diabetes and a leading cause of kidney failure and cardiovascular death. This review evaluated the cardiorenal effects and safety of nonsteroidal mineralocorticoid receptor antagonists (MRAs), particularly finerenone, in DKD. METHODS: PubMed, Scopus, Embase, Web of Science, and ClinicalTrials.gov were searched through October 2024 for randomized controlled trials and prospective studies in adults with DKD. Two reviewers independently performed study selection, data extraction, and risk-of-bias assessment. Because eligible analyses were derived predominantly from the same two parent trials, quantitative pooling was avoided to prevent double-counting of participants. RESULTS: Seven analyses from the FIDELITY programme (FIDELIO-DKD and FIGARO-DKD), representing 13,026 unique participants, were included. Finerenone reduced composite renal outcomes by 23% (HR 0.77, 95% CI 0.67-0.88) and cardiovascular outcomes by 14% (HR 0.86, 95% CI 0.78-0.95). Over approximately three years, absolute risk reductions were 1.6% for the kidney composite (5.5% vs 7.1%; NNT ≈60) and 1.7% for the cardiovascular composite (12.7% vs 14.4%). Benefits were generally consistent across subgroups and accompanied by reduced albuminuria and slower eGFR decline. Hyperkalemia was more frequent with finerenone (14.0% vs 6.9%) but rarely resulted in discontinuation (1.7% vs 0.6%). CONCLUSION: Finerenone provides meaningful cardiorenal protection in DKD with a manageable safety profile. However, evidence is largely limited to finerenone within a single trial programme; therefore, these findings should not be generalized to the entire nonsteroidal MRA class.

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