Aldosterone in Chronic Kidney Disease

Area of Science:

• Nephrology
• Cardiology
• Endocrinology

Background:

• Chronic kidney disease (CKD) poses a global health burden with significant morbidity and mortality.
• Existing treatments like RAS inhibitors and SGLT2 inhibitors leave a substantial residual risk.
• Aldosterone overactivation is a key factor in CKD progression, causing renal inflammation and fibrosis.

Purpose of the Study:

• To review the pathophysiology of aldosterone in CKD.
• To explore emerging therapeutic strategies targeting the mineralocorticoid receptor pathway.
• To address the unmet need in managing residual risk in CKD patients.

Main Methods:

• Review of physiological regulation of aldosterone synthesis and secretion.
• Analysis of aldosterone breakthrough under RAS blockade.
• Evaluation of mechanisms of aldosterone-mediated kidney damage.
• Assessment of novel therapeutic agents, including non-steroidal MRAs and aldosterone synthase inhibitors.

Main Results:

• Finerenone, a novel non-steroidal MRA, demonstrates improved safety and efficacy in reducing renal and cardiovascular outcomes.
• Aldosterone synthase inhibitors offer an upstream approach to decrease aldosterone production.
• These agents show potential in mitigating residual cardiovascular and renal risks in CKD.

Conclusions:

• Targeting aldosterone overactivation is crucial for managing CKD progression.
• Novel therapeutics like finerenone and aldosterone synthase inhibitors represent promising strategies.
• These advancements may significantly improve long-term outcomes for CKD patients by reducing residual risk.