Review of Hyperkalemia Profile for Mineralocorticoid Receptor Antagonist in Patients with Chronic Kidney Disease and Type 2 Diabetes

BACKGROUND: Type 2 diabetes (T2D) frequently coexists with chronic kidney disease (CKD), magnifying the risk of both cardiovascular and renal complications. Although therapies targeting the renin-angiotensin-aldosterone system (RAAS) slow CKD progression and reduce cardiovascular events, they also raise the risk of hyperkalemia. Finerenone, a newer nonsteroidal mineralocorticoid receptor antagonist (MRA), offers potent cardiorenal protection with relatively low hyperkalemia risk. METHODS: We conducted a narrative review of randomized controlled trials (RCTs) published up to September 2024 which evaluated spironolactone, eplerenone, or finerenone in populations with T2D, CKD, or heart failure. Studies that reported explicit data on hyperkalemia incidence, severity, and management were included. The findings were synthesized narratively with the consideration of heterogeneity in study population and hyperkalemia definition. RESULTS: Evidence from spironolactone and eplerenone trials underscores the survival benefits of steroidal MRAs in heart failure patients but also demonstrates a notable hyperkalemia risk, especially in patients with advanced CKD. Finerenone, studied in FIDELIO-DKD, FIGARO-DKD, and subsequently pooled in FIDELITY, demonstrated robust efficacy in reducing cardiovascular and kidney outcomes. It was associated predominantly with mild-to-moderate hyperkalemia which stabilized with regular monitoring. The incidence of severe events and therapy discontinuations due to hyperkalemia were low. A risk-prediction model from FIDELITY further stratified patients by hyperkalemia risk, revealing consistent relative hyperkalemia risk of finerenone across all strata. CONCLUSIONS: Hyperkalemia remains a pivotal challenge when prescribing MRAs in patients with T2D and CKD, often leading to underutilization of these lifesaving agents. However, finerenone's safety profile, combined with diligent potassium surveillance and proactive management strategies (e.g., dietary guidance, potassium binders, use of diuretics), enables sustained cardiorenal benefits. Future research should explore real-world applicability of these trial findings and further refine risk-based treatment algorithms to optimize outcomes in this high-risk population.