Role of Finerenone in Medical Treatment
Finerenone is a nonsteroidal mineralocorticoid receptor antagonist (MRA) indicated for adults with type 2 diabetes and chronic kidney disease who have persistent albuminuria despite maximum tolerated doses of renin-angiotensin system inhibitors, with proven benefits in reducing kidney disease progression and cardiovascular events. 1
Mechanism and Classification
- Finerenone is a first-in-class, selective, nonsteroidal mineralocorticoid receptor antagonist that blocks sodium reabsorption through the mineralocorticoid receptor and reduces overactivation of this receptor in the kidney, heart, and blood vessels 1, 2
- Unlike steroidal MRAs (spironolactone, eplerenone), finerenone has a more favorable safety profile with lower rates of hyperkalemia and fewer endocrine side effects 3, 4
Clinical Indications
- Primary indication: Treatment of adults with type 2 diabetes and chronic kidney disease with persistent albuminuria (ACR ≥30 mg/g) despite maximum tolerated doses of renin-angiotensin system inhibitors 1, 5
- Eligible patients must have eGFR ≥25 mL/min/1.73 m² and normal serum potassium concentration before initiation 1, 5
- Positioned as "additional risk-based therapy" in current treatment algorithms for patients with diabetes and CKD 1
Clinical Benefits
Kidney Outcomes
- Reduces risk of kidney disease progression with a 18% reduction in composite kidney outcomes (HR: 0.82,95% CI: 0.73-0.93) 1, 6
- Significantly reduces albuminuria in patients with type 2 diabetes and CKD 7, 6
- Slows decline in estimated glomerular filtration rate (eGFR) 6
Cardiovascular Outcomes
- Reduces risk of cardiovascular events by 14% (HR: 0.86,95% CI: 0.75-0.99) 1
- Composite cardiovascular benefits include reduction in cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for heart failure 1, 5, 6
- Provides modest blood pressure lowering effects (2-3 mmHg systolic) 1, 7
Dosing and Administration
- Starting dose: 10 mg once daily for patients with eGFR 25-60 mL/min/1.73 m², and 20 mg once daily for patients with eGFR >60 mL/min/1.73 m² 1, 5
- Dose can be uptitrated to 20 mg daily if serum potassium remains <4.8 mmol/L after 4 weeks of treatment 5
- Should not be initiated if eGFR is <25 mL/min/1.73 m² 1, 5
Safety and Monitoring
- Hyperkalemia is the most common adverse effect (14% vs. 6.9% with placebo) 1
- Risk of severe hyperkalemia requiring drug discontinuation is relatively low (1.7% vs. 0.6%) 1
- Serum potassium should be <4.8 mmol/L before initiation and monitored regularly during treatment 1, 5
- If potassium increases to >5.5 mmol/L, finerenone should be withheld and can be restarted at 10 mg daily when potassium is ≤5.0 mmol/L 5
- No deaths due to hyperkalemia were reported in clinical trials over 3 years of follow-up 1, 7
Therapeutic Positioning in Treatment Algorithm
- SGLT2 inhibitors are prioritized over finerenone as the next step after baseline ACEi/ARB therapy due to larger effects on reducing both kidney and cardiovascular outcomes 1, 5
- Finerenone should be considered if a patient does not tolerate an SGLT2 inhibitor or remains with albuminuria despite being on an SGLT2 inhibitor 1, 5
- Finerenone may be added to a RASi and an SGLT2i for complementary cardiorenal protection 1, 5
- Current guidelines position finerenone after SGLT2 inhibitors and GLP-1 receptor agonists in the treatment algorithm for patients with type 2 diabetes and CKD 1
Clinical Pearls and Caveats
- Do not combine finerenone with other potassium-sparing diuretics or strong CYP3A4 inhibitors due to increased risk of hyperkalemia 1
- Contraindicated in patients with adrenal insufficiency 1
- Unlike steroidal MRAs, finerenone does not cause sexual dysfunction (gynecomastia, impotence) or menstrual irregularities 3, 4
- Patients with a history of hyperkalemia may require more frequent monitoring of serum potassium 1
- Benefits of finerenone were demonstrated across the spectrum of CKD severity and cardiovascular risk 8, 6