Aldosterone-targeted therapies: early implementation in resistant hypertension and chronic kidney disease

Area of Science:

• Cardiology
• Nephrology
• Pharmacology

Background:

• Treatment-resistant hypertension (TRH) frequently co-occurs with chronic kidney disease (CKD), elevating cardiovascular risk.
• Enhanced aldosterone and mineralocorticoid receptor activity in TRH and CKD patients drives cardiac and renal inflammation and fibrosis.
• Optimal blood pressure control and managing aldosterone-related risks are crucial for cardiorenal disease management.

Purpose of the Study:

• To review evidence for aldosterone-targeted therapies in patients with TRH and CKD.
• To re-evaluate current treatment strategies and clinical trial designs for TRH and CKD.

Main Methods:

• Review of existing clinical trial data and scientific literature on TRH, CKD, and aldosterone.
• Analysis of the role of mineralocorticoid receptor antagonists (MRAs) and emerging therapies.
• Consideration of safety profiles, particularly hyperkalemia risk in CKD patients.

Main Results:

• Mineralocorticoid receptor antagonists (MRAs) are recommended for TRH, but hyperkalemia risk limits their use in CKD.
• Non-steroidal MRAs and SGLT2 inhibitors demonstrate cardiorenal benefits and slow renal decline.
• Aldosterone synthase inhibitors represent a potential future therapeutic avenue for TRH.

Conclusions:

• Simply lowering blood pressure may be insufficient for preventing cardiorenal disease progression in TRH and CKD.
• Aldosterone-targeted therapies hold significant promise for improving cardiorenal outcomes in this patient population.
• Future clinical trials should incorporate aldosterone blockade as a primary or secondary endpoint.