What is the role of finerenone in the management of diabetic kidney disease?

Finerenone in Diabetic Kidney Disease

Finerenone is a highly effective second-line therapy for patients with type 2 diabetes and chronic kidney disease who have persistent albuminuria (UACR ≥30 mg/g) despite maximum tolerated RAS inhibitor therapy, with eGFR ≥25 mL/min/1.73 m² and serum potassium ≤4.8 mmol/L, providing significant reductions in both kidney disease progression (18% relative risk reduction) and cardiovascular events (13-14% reduction). 1

Patient Selection Criteria

Finerenone should be initiated when ALL of the following criteria are met:

• Type 2 diabetes with CKD and persistent albuminuria (UACR ≥30 mg/g) 1, 2
• Already on maximum tolerated dose of RAS inhibitor (ACE inhibitor or ARB) as foundation therapy 1, 2
• eGFR ≥25 mL/min/1.73 m² (do not use in ESRD or dialysis patients) 2
• Serum potassium ≤4.8 mmol/L at baseline 1, 2
• Normal baseline potassium levels verified before initiation 1

Treatment Sequencing Algorithm

The evidence-based treatment hierarchy for diabetic kidney disease is:

1. First-line foundation: RAS inhibitor at maximum tolerated dose 2
2. Second-line priority: SGLT2 inhibitor (larger effects on kidney and cardiovascular outcomes) 1, 2
3. Third-line or alternative to SGLT2i: Finerenone if:
   • SGLT2 inhibitor intolerance 2
   • Persistent albuminuria despite SGLT2 inhibitor therapy 1, 2
   • Patient preference or contraindication to SGLT2i 2

Finerenone can be safely combined with SGLT2 inhibitors for complementary cardiorenal protection, though definitive data on combined benefits remain limited 1, 3

Dosing Protocol

Initial dose based on eGFR:

• eGFR 25-60 mL/min/1.73 m²: Start 10 mg once daily 2, 3
• eGFR >60 mL/min/1.73 m²: Start 20 mg once daily 2, 3

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

Clinical Benefits Demonstrated

Kidney outcomes (FIDELIO-DKD trial):

• 18% relative risk reduction in composite kidney outcome (kidney failure, sustained ≥40% eGFR decline, or renal death) 1
• 20% reduction in kidney failure requiring dialysis or transplantation 1
• 36% reduction in progression to end-stage kidney disease 2

Cardiovascular outcomes (FIGARO-DKD trial):

• 13-14% reduction in composite cardiovascular events (CV death, MI, stroke, heart failure hospitalization) 1, 3
• 29% reduction in heart failure hospitalizations 1, 3

Albuminuria reduction:

• 53.2% of patients achieved ≥30% reduction in UACR (vs 27.0% with placebo) 4
• Albuminuria reduction mediated 84% of the treatment effect on kidney outcomes and 37% on cardiovascular outcomes 4

Potassium Monitoring and Management

Monitoring schedule:

• Verify potassium ≤4.8 mmol/L before starting 2, 3
• Check potassium at 4 weeks after initiation 3
• Monitor regularly throughout treatment 2

Management algorithm for hyperkalemia:

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

Safety Profile

Hyperkalemia risk is manageable:

• Hyperkalemia occurs in 10.8-14% with finerenone vs 5.3-6.9% with placebo 3
• Severe hyperkalemia requiring permanent discontinuation occurs in only 1.2-1.7% of patients 1, 3
• No deaths attributed to hyperkalemia in major trials 1
• Discontinuation rates remain low overall (1.7% vs 0.6% over 3 years) 1

Critical Contraindications

Do NOT initiate finerenone if:

• eGFR <25 mL/min/1.73 m² 2
• Patient is on dialysis or has ESRD 2
• Baseline potassium >4.8 mmol/L 2
• Patient not yet optimized on maximum tolerated RAS inhibitor 2

Common Pitfalls to Avoid

• Do not skip RAS inhibitor optimization first - finerenone is not a replacement for ACE inhibitor/ARB therapy 2
• Do not prioritize finerenone over SGLT2 inhibitors - SGLT2i should be the next step after RAS inhibitor unless contraindicated or not tolerated 1, 2
• Do not use in advanced CKD (eGFR <25) - no safety or efficacy data exists for this population 2
• Do not neglect potassium monitoring - while hyperkalemia risk is lower than steroidal MRAs, vigilant monitoring remains essential 3, 5

Mechanism of Action

Finerenone is a highly selective nonsteroidal mineralocorticoid receptor antagonist that directly reduces inflammation and fibrosis in both kidney and cardiac tissue, offering complementary mechanisms to current hemodynamic and metabolic therapies 6, 5, 7