How does finerenone help with diabetic kidney disease?

Mechanism of Finerenone in Diabetic Kidney Disease

Finerenone, a nonsteroidal mineralocorticoid receptor antagonist (MRA), reduces kidney disease progression by 23%, cardiovascular events by 14%, and hospitalization for heart failure by 29% in patients with type 2 diabetes and chronic kidney disease through its anti-inflammatory and anti-fibrotic effects. 1

Mechanism of Action

Finerenone works through several key mechanisms:

1. Selective Mineralocorticoid Receptor Antagonism

   • Unlike steroidal MRAs, finerenone has a more balanced tissue distribution between heart and kidney
   • Provides more potent anti-inflammatory and anti-fibrotic effects than steroidal MRAs
   • Has minimal hormonal side effects compared to steroidal MRAs 1

2. Reduction in Albuminuria

   • Significantly reduces urinary albumin-to-creatinine ratio (UACR)
   • This reduction in albuminuria mediates 84% of finerenone's treatment effect on kidney outcomes and 37% of its effect on cardiovascular outcomes 2
   • A 30% or greater reduction in UACR was achieved in 53.2% of patients on finerenone compared to 27.0% on placebo 2

3. Cardiorenal Protection

   • Reduces risk of kidney failure, sustained decrease in eGFR, and renal death
   • Decreases cardiovascular mortality, with particular benefit in reducing sudden cardiac death (HR 0.75; 95% CI 0.57-0.996) 3
   • Reduces new-onset atrial fibrillation or flutter by 29% (HR 0.71; 95% CI 0.53-0.94) 4

Clinical Application

Patient Selection

• Indicated for patients with:
  • Type 2 diabetes and chronic kidney disease
  • Persistent albuminuria (>30 mg/g) despite maximum tolerated RAS inhibitor therapy
  • eGFR ≥25 mL/min/1.73 m²
  • Baseline serum potassium ≤4.8 mmol/L 1

Dosing

• 10 mg once daily for patients with eGFR 25-59 ml/min/1.73 m²
• 20 mg once daily for patients with eGFR ≥60 ml/min/1.73 m² 1

Monitoring

• Check serum potassium at:
  • Baseline
  • 1 month after initiation
  • Every 4 months thereafter
• Target potassium level ≤4.8 mmol/L
• Hold finerenone if serum potassium >5.5 mmol/L 1

Efficacy Across Patient Subgroups

Finerenone's benefits are consistent regardless of:

• Baseline HbA1c levels (both <7.5% and ≥7.5%)
• Insulin use
• Baseline kidney function across all KDIGO risk groups 5, 3

Safety Considerations

Hyperkalemia Risk

• Incidence of hyperkalemia: 10.8% with finerenone vs. 5.3% with placebo in FIGARO-DKD
• Discontinuation due to hyperkalemia: 2.3% with finerenone vs. 0.9% with placebo in FIDELIO-DKD 1
• Lower risk of hyperkalemia compared to steroidal MRAs

Contraindications

• Adrenal insufficiency
• eGFR <25 mL/min/1.73 m²
• Serum potassium >4.8 mmol/L 1

Combination Therapy

Finerenone can be effectively combined with:

• SGLT2 inhibitors (without dose adjustment)
• GLP-1 receptor agonists
• Metformin (if eGFR >30 ml/min/1.73 m²) 1

These combinations provide additive cardiorenal protection in patients with type 2 diabetes and CKD.

Clinical Pearls

• Finerenone should be considered after optimizing RAS inhibitor therapy in patients with persistent albuminuria
• The medication's benefits extend beyond kidney protection to include significant cardiovascular protection
• Careful potassium monitoring is essential but hyperkalemia risk is lower than with steroidal MRAs
• Early albuminuria reduction (within first 4 months) is a strong predictor of long-term kidney and cardiovascular benefits