What is finerenone?

What is Finerenone

Finerenone is a nonsteroidal, selective mineralocorticoid receptor antagonist (MRA) approved for adults with type 2 diabetes and chronic kidney disease who have persistent albuminuria despite maximum tolerated renin-angiotensin system inhibitor therapy, providing proven cardiovascular and kidney protection. 1

Drug Classification and Mechanism

Finerenone represents a distinct class of mineralocorticoid receptor antagonists—the nonsteroidal MRAs—which are not extrapolatable to traditional steroidal MRAs like spironolactone or eplerenone. 1 This selective antagonism of the mineralocorticoid receptor reduces inflammation and fibrosis in both cardiac and renal tissues. 2, 3

FDA-Approved Indication and Patient Selection

Finerenone is indicated for patients meeting ALL of the following criteria:

• Type 2 diabetes with chronic kidney disease 1, 4
• Persistent albuminuria (ACR ≥30 mg/g) despite maximum tolerated dose of ACE inhibitor or ARB 1, 4
• eGFR ≥25 mL/min/1.73 m² 1, 4
• Serum potassium ≤4.8 mmol/L at baseline 4

The KDIGO 2022 guidelines specifically note that finerenone is currently the only nonsteroidal MRA with proven clinical kidney and cardiovascular benefits. 1

Dosing Strategy

Initial dosing is eGFR-based: 4

• eGFR 25-60 mL/min/1.73 m²: Start 10 mg once daily
• eGFR >60 mL/min/1.73 m²: Start 20 mg once daily

Dose titration after 4 weeks: 4

• If serum potassium ≤4.8 mmol/L and eGFR stable, increase from 10 mg to 20 mg once daily

Clinical Benefits: Cardiovascular Outcomes

Finerenone provides substantial cardiovascular protection across two landmark trials (FIDELIO-DKD and FIGARO-DKD) and their pooled analysis (FIDELITY): 5

• 14% reduction in composite cardiovascular outcomes (cardiovascular death, nonfatal MI, nonfatal stroke, or hospitalization for heart failure): HR 0.86,95% CI 0.78-0.95 1, 5
• 29% reduction in heart failure hospitalization: HR 0.71,95% CI 0.56-0.90 1, 6
• 13% reduction in cardiovascular death, MI, stroke, or heart failure hospitalization in FIGARO-DKD: HR 0.87,95% CI 0.76-0.98 1

These benefits were demonstrated over a median follow-up of 3.0-3.4 years. 5, 3

Clinical Benefits: Kidney Outcomes

Finerenone significantly slows CKD progression: 1, 5

• 23% reduction in composite kidney outcomes (kidney failure, sustained ≥57% decrease in eGFR, or renal death): HR 0.77,95% CI 0.67-0.88 1, 5
• 20% reduction in kidney failure (chronic dialysis or transplantation): HR 0.80,95% CI 0.64-0.99 1
• 18% reduction in kidney disease progression in FIDELIO-DKD: HR 0.82,95% CI 0.73-0.93 1, 2

Therapeutic Positioning in Treatment Algorithm

The American Diabetes Association and KDIGO guidelines establish a clear hierarchy for cardiorenal protection: 6, 4

1. First-line: Maximize renin-angiotensin system inhibitor (ACE inhibitor or ARB)
2. Second-line: Add SGLT2 inhibitor (preferred due to larger effects on kidney and cardiovascular outcomes) 4
3. Third-line: Add finerenone if albuminuria persists (ACR ≥30 mg/g) despite SGLT2 inhibitor therapy 1, 4

Key positioning principle: Finerenone should be considered if a patient does not tolerate an SGLT2 inhibitor OR remains with persistent albuminuria despite being on an SGLT2 inhibitor. 4 The combination of RAS inhibitor + SGLT2 inhibitor + finerenone provides complementary cardiorenal protection. 4

Safety Profile and Hyperkalemia Management

Hyperkalemia is the primary adverse effect requiring vigilant monitoring: 6

• Incidence: 10.8-14% with finerenone vs. 5.3-6.9% with placebo 1, 6
• Permanent discontinuation due to hyperkalemia: 1.2-1.7% vs. 0.4-0.6% with placebo 1, 6
• No deaths attributed to hyperkalemia over 3 years of follow-up 1

Potassium monitoring protocol: 4

Timing	Action
Baseline	Check serum potassium (must be ≤4.8 mmol/L to initiate) [4]
4 weeks after initiation	Recheck potassium [6]
Maintenance	Monitor every 4 months [4]

Potassium-based dose adjustments: 4

• ≤4.8 mmol/L: Continue current dose or uptitrate to 20 mg if on 10 mg
• 4.9-5.5 mmol/L: Continue current dose, monitor every 4 months
• >5.5 mmol/L: Hold finerenone, adjust diet/medications, restart at 10 mg when potassium ≤5.0 mmol/L

Common Pitfalls to Avoid

Do not initiate finerenone if: 4

• Serum potassium >4.8 mmol/L at baseline
• eGFR <25 mL/min/1.73 m²
• Patient not on maximum tolerated dose of ACE inhibitor or ARB

Do not assume equivalence with steroidal MRAs: The nonsteroidal class (finerenone) has different pharmacology and clinical trial evidence compared to spironolactone or eplerenone, and results are not interchangeable. 1

Do not delay SGLT2 inhibitor therapy: SGLT2 inhibitors should generally be prioritized over finerenone due to larger magnitude of benefit on both kidney and cardiovascular outcomes. 4 Finerenone is positioned as add-on therapy when albuminuria persists.

Evidence Base

The recommendation for finerenone is based on high-quality evidence (Grade A) from two large phase III randomized controlled trials: 1

• FIDELIO-DKD (N=5,734): Focused on patients with more advanced CKD (eGFR 25-<60 or 25-<75 with higher albuminuria) 2
• FIGARO-DKD (N=7,437): Focused on patients with earlier CKD (eGFR 25-90 with moderate albuminuria or ≥60 with severe albuminuria) 3
• FIDELITY pooled analysis (N=13,026): Combined individual patient data across the full CKD spectrum 5

These trials demonstrated consistent benefits across diverse patient subgroups without significant heterogeneity. 1