What is the role of finerenone (generic name) and what are its expected benefits in patients with chronic kidney disease (CKD) and type 2 diabetes?

Role and Expected Benefits of Finerenone

Finerenone is a nonsteroidal mineralocorticoid receptor antagonist indicated for patients with type 2 diabetes and chronic kidney disease (CKD stages 2-4 with eGFR 25-90 mL/min/1.73 m²) who have persistent albuminuria (UACR ≥30 mg/g) despite maximum tolerated RAS inhibitor therapy, providing significant reductions in both cardiovascular events and kidney disease progression. 1, 2

Patient Selection Criteria

Finerenone should be initiated when all of the following conditions are met:

• Type 2 diabetes with CKD (eGFR 25-90 mL/min/1.73 m²) and persistent albuminuria (UACR ≥30 mg/g) 2, 3
• Already on maximum tolerated dose of ACE inhibitor or ARB 2, 4
• Serum potassium ≤4.8 mmol/L at baseline 2
• No end-stage renal disease (eGFR must be ≥25 mL/min/1.73 m²) 2

Treatment Sequencing Algorithm

The recommended treatment sequence follows a stepwise approach:

1. First-line: RAS inhibitor (ACE inhibitor or ARB) at maximum tolerated dose 2
2. Second-line: SGLT2 inhibitor (prioritized over finerenone due to larger effects on kidney and cardiovascular outcomes) 2
3. Third-line: Finerenone for patients with SGLT2 inhibitor intolerance or persistent albuminuria despite SGLT2 inhibitor 2

Importantly, finerenone provides cardiovascular and kidney benefits regardless of concurrent SGLT2 inhibitor use, with no interaction between the two therapies (P-interaction = 0.46 for cardiovascular outcomes and 0.29 for kidney outcomes) 5

Expected Cardiovascular Benefits

Finerenone delivers substantial cardiovascular protection across multiple endpoints:

• 13% reduction in composite cardiovascular outcomes (cardiovascular death, nonfatal MI, nonfatal stroke, or heart failure hospitalization) with HR 0.87 (95% CI 0.76-0.98) 1, 3
• 29% reduction in heart failure hospitalizations with HR 0.71 (95% CI 0.56-0.90) 3
• 18% reduction in all-cause mortality during on-treatment analysis with HR 0.82 (95% CI 0.70-0.96) 6
• 25% reduction in sudden cardiac death with HR 0.75 (95% CI 0.57-0.996) 6
• Prevention of progression from asymptomatic stage A heart failure to symptomatic incident heart failure 1, 4

These benefits were demonstrated in the FIGARO-DKD trial with 7,437 patients over a median follow-up of 3.0 years 3, 7

Expected Kidney Benefits

Finerenone provides robust kidney protection:

• 36% reduction in end-stage kidney disease with HR 0.64 (95% CI 0.41-0.995) 3
• 23% reduction in composite kidney outcomes (kidney failure, sustained ≥57% eGFR decline, or renal death) with HR 0.77 (95% CI 0.67-0.88) 7
• Reduction in albuminuria progression across the spectrum of CKD stages 2, 7

The kidney benefits were established in the FIDELIO-DKD trial, which specifically enrolled patients with more advanced diabetic kidney disease 1, 4

Dosing Protocol

Initial dosing based on eGFR:

• eGFR 25-60 mL/min/1.73 m²: Start 10 mg once daily 2
• eGFR >60 mL/min/1.73 m²: Start 20 mg once daily 2

Dose uptitration:

• After 1 month, increase from 10 mg to 20 mg daily if serum potassium remains ≤4.8 mmol/L and eGFR is stable 2

Potassium Monitoring and Management

Hyperkalemia is the primary safety concern requiring systematic monitoring:

• Baseline requirement: Potassium ≤4.8 mmol/L before initiation 2, 3
• Incidence: 10.8% with finerenone vs 5.3% with placebo 2, 3
• Discontinuation rate: Only 1.2-2.3% discontinued due to hyperkalemia 3, 4
• No deaths related to hyperkalemia occurred in clinical trials 3

Management algorithm for hyperkalemia:

• Potassium ≤5.5 mmol/L: Continue finerenone 2
• Potassium >5.5 mmol/L: Withhold finerenone 2
• Restart criteria: When potassium returns to ≤5.0 mmol/L, restart at 10 mg daily 2

Critical Contraindications and Limitations

Do not initiate finerenone if:

• eGFR <25 mL/min/1.73 m² or patient is on dialysis (no established dosing or safety data for ESRD) 2
• Baseline potassium >4.8 mmol/L 2
• Patient has not been optimized on maximum tolerated RAS inhibitor first 2

The landmark trials (FIDELIO-DKD and FIGARO-DKD) specifically excluded patients with eGFR <25 mL/min/1.73 m², making evidence-based recommendations impossible for this population 2

Blood Pressure Effects

Finerenone provides modest blood pressure reduction that contributes to its cardiorenal benefits:

• Office systolic blood pressure reductions occur across all baseline blood pressure quartiles 8
• Only 13.8% of kidney benefit and 12.6% of cardiovascular benefit are attributed to blood pressure reduction, indicating blood pressure-independent mechanisms of action 8
• Cardiorenal outcomes improve with finerenone regardless of baseline blood pressure (P-interaction 0.87 for kidney outcomes and 0.78 for cardiovascular outcomes) 8

Clinical Context and Positioning

Finerenone represents the first nonsteroidal mineralocorticoid receptor antagonist with proven cardiovascular and kidney benefits in type 2 diabetes with CKD 1, 4. It is now incorporated into major guidelines including KDIGO 2022, American Diabetes Association 2024, and American College of Cardiology recommendations as add-on therapy for patients with persistent albuminuria despite standard care 2, 4. The combined evidence from FIDELIO-DKD and FIGARO-DKD (pooled as FIDELITY analysis with 13,026 patients) provides robust support for its use across a broad spectrum of CKD stages 7.