Aldosterone synthase inhibition in chronic kidney disease

Abstract

Purpose: Chronic kidney disease (CKD) is associated with elevated cardiovascular risk and progression to kidney failure, despite advances in therapy with renin-angiotensin system inhibitors and sodium-glucose-co-transporter-2 inhibitors. Overactivation of the aldosterone pathway contributes to residual cardiorenal risk. Nonsteroidal mineralocorticoid receptor antagonists (MRAs) have shown efficacy in reducing cardiorenal outcomes in patients with albuminuric diabetic kidney disease, providing a rationale to explore broader aldosterone pathway inhibition in CKD.

Recent findings: While steroidal MRAs are effective, their use is often limited by hormonal side effects and risk of hyperkalemia. Finerenone, a selective nonsteroidal MRA, showed cardiovascular and renal benefit in CKD patients with diabetes, although with only modest BP-lowering effects. Its role in nondiabetic populations and in those with lower levels of albuminuria remains to be determined. More recently, aldosterone synthase inhibitors (ASIs) have emerged as promising agents that directly suppress aldosterone production. Early-phase studies in patients with CKD, with or without diabetes, have shown reductions in albuminuria and BP, with a favorable safety profile.

Summary: Direct inhibition of aldosterone synthesis may provide a novel and complementary strategy to reduce residual cardiorenal risk in CKD. Ongoing phase 3 trials will be key to defining the clinical utility of ASIs and their integration into future treatment paradigms.

Keywords: albuminuria; aldosterone; aldosterone synthase inhibitors; chronic kidney disease.