Mechanism of Action of Finerenone
Finerenone is a non-steroidal mineralocorticoid receptor antagonist (MRA) that selectively blocks the mineralocorticoid receptor to reduce inflammation and fibrosis in the kidneys and heart, providing cardiorenal protection in patients with chronic kidney disease and type 2 diabetes. 1
Molecular Mechanism
- Finerenone has higher selectivity toward the mineralocorticoid receptor compared to steroidal MRAs like spironolactone and stronger binding affinity than eplerenone 2
- Unlike steroidal MRAs, finerenone targets specific inflammatory and fibrotic pathways that drive disease progression and organ damage in diabetic kidney disease 1
- Finerenone blocks the overactivation of mineralocorticoid receptors in both kidney and cardiac tissues 1
- The drug has a short plasma half-life and unique tissue distribution pattern that contributes to its favorable clinical profile 3
Clinical Effects
- Finerenone reduces albuminuria in patients with type 2 diabetes and chronic kidney disease 4
- It provides modest blood pressure lowering effects (2-3 mmHg systolic) 4
- Finerenone significantly reduces the risk of kidney failure progression (HR: 0.82,95% CI: 0.73-0.93) 4
- It also reduces cardiovascular events including death from cardiovascular causes, nonfatal MI, nonfatal stroke, and hospitalization for heart failure 4
Differences from Steroidal MRAs
- Finerenone has a more favorable benefit-risk profile compared to steroidal MRAs like spironolactone and eplerenone 1
- While it can cause hyperkalemia (14% vs. 6.9% with placebo), the risk of severe hyperkalemia requiring drug discontinuation is relatively low (1.7% vs. 0.6%) 4
- No deaths due to hyperkalemia were reported in clinical trials over 3 years of follow-up 4
- Finerenone can be used in patients with reduced kidney function (eGFR ≥25 ml/min/1.73m²) with appropriate monitoring 4
Preclinical Effects
- In animal models, finerenone has been shown to reduce cardiac fibrosis and improve left ventricular diastolic function 5
- It increases endothelial nitric oxide synthase phosphorylation and improves cardiac perfusion in preclinical models 5
- These effects occur independently from changes in kidney function, suggesting direct cardiac benefits 5
Clinical Applications
- Finerenone is indicated for patients with type 2 diabetes and chronic kidney disease with persistent albuminuria (ACR ≥30 mg/g) despite maximum tolerated doses of renin-angiotensin system inhibitors 4
- It should be initiated at 10 mg daily for patients with eGFR 25-60 ml/min/1.73m² and 20 mg daily for those with eGFR >60 ml/min/1.73m² 4
- Serum potassium should be <4.8 mmol/L before initiation and monitored regularly during treatment 4
Therapeutic Positioning
- Finerenone complements other treatments for diabetic kidney disease, including SGLT2 inhibitors, by targeting different pathophysiological mechanisms 6
- It represents an additional pillar in the comprehensive management of patients with type 2 diabetes and chronic kidney disease 6
- Current guidelines position finerenone as an "additional risk-based therapy" for patients with persistent albuminuria despite standard treatment 4