The Evolving Role of Nonsteroidal MRAs in Cardiorenal Disease
The Evolving Role of Nonsteroidal MRAs in Cardiorenal Disease
Source: ReachMD CME Transcript – “Expert Perspectives on Nonsteroidal MRAs and Cardiorenal Protection”
(Published 3 days ago)
Cardiorenal Disease Overview
Cardiovascular and kidney diseases often coexist (Cardiorenal Syndrome), with studies showing that up to 40–50% of patients with chronic heart failure also have chronic kidney disease (CKD).
MRAs may be considered to reduce hospitalizations in patients with HFpEF and HFmrEF (i.e., mildly reduced ejection fraction), with a Class IIb recommendation—particularly in those with elevated natriuretic peptides, clinical congestion, and a history of prior hospitalization.
New Biomarker Mechanism Identified
A recent study published in the Journal of the American Society of Nephrology (June 19, 2025) identified a novel molecular mechanism:
• The cardiac LIM protein (CSRP3) is released into the bloodstream after acute cardiorenal injury (e.g., post–cardiac arrest).
• It is absorbed by the kidneys via megalin-mediated endocytosis, promoting fibrosis and vascular remodeling.
Why Nonsteroidal MRAs Matter
1. Mechanism & Safety Profile
• Selectively inhibit mineralocorticoid receptors without binding to steroid hormone receptors.
• This leads to targeted cardiorenal protection with fewer endocrine side effects.
2. Clinical Benefits in T2D & CKD
• Trials such as FIDELIO-DKD and FIGARO-DKD show significant reductions in:
• Albuminuria
• CKD progression
• Heart failure hospitalizations
• Cardiovascular events
3. Expanded Role in Heart Failure
• Nonsteroidal MRAs also improve:
• Cardiac remodeling
• Inflammation
• Myocardial fibrosis
• Supporting better cardiac function in heart failure patients.
4. Emerging Evidence in Type 1 Diabetes
• The ongoing FINE-ONE trial is assessing finerenone in T1D with albuminuria, potentially expanding its indication in CKD.
5. Future Pipeline
• Novel agents in development include:
• Ocedurenone (Phase III for CKD-related hypertension)
• Exaserone (next-generation MRA)
• Both aim to improve safety and tolerability profiles.
6. Clinical Implementation
• CME guidance now emphasizes:
• Initiation strategies
• Dose titration
• Monitoring protocols
• Hyperkalemia management in real-world practice
Conclusion
MRAs—especially nonsteroidal agents like finerenone—are transforming the management of cardiorenal disease by offering dual organ protection with a well-tolerated safety profile.
As evidence continues to grow, especially in CKD-only and T1D populations, these agents are becoming essential therapeutic partners alongside SGLT2 inhibitors and RAS blockers in the evolving CKM care landscape.