What are the benefits and dosing of finerenone (Mineralocorticoid receptor antagonist) in patients with Chronic Kidney Disease (CKD)?

Finerenone Benefits and Dosing in Chronic Kidney Disease

Finerenone, a nonsteroidal mineralocorticoid receptor antagonist (MRA), should be initiated at 10 mg daily for patients with eGFR 25-59 ml/min/1.73 m² and 20 mg daily for those with eGFR ≥60 ml/min/1.73 m², with significant benefits in reducing kidney disease progression by 23% and cardiovascular events by 14% in patients with CKD. 1

Benefits of Finerenone in CKD

Finerenone offers several important benefits for patients with CKD:

1. Cardiorenal Protection:

   • Reduces kidney disease progression by 23% (HR 0.77,95% CI: 0.67-0.88) 1
   • Decreases cardiovascular events by 14% (HR 0.86,95% CI: 0.78-0.95) 1
   • Reduces hospitalization for heart failure by 29% (HR 0.71,95% CI: 0.56-0.90) 1
   • Lowers risk of sudden cardiac death (1.3% vs 1.8%; HR 0.75,95% CI: 0.57-0.996) 2

2. Albuminuria Reduction:

   • Achieves ≥30% reduction in urine albumin-to-creatinine ratio (UACR) in 53.2% of patients (vs 27.0% with placebo) 3
   • This reduction mediates 84% of the treatment effect on kidney outcomes and 37% on cardiovascular outcomes 3

3. Advantages over Steroidal MRAs:

   • More balanced tissue distribution between heart and kidney
   • More potent anti-inflammatory and anti-fibrotic effects
   • Lower risk of hyperkalemia
   • Minimal hormonal side effects 1

4. Heart Failure Benefits:

   • Reduces new-onset heart failure by 32% (HR 0.68,95% CI: 0.50-0.93) 4
   • Decreases first hospitalization for heart failure by 29% (HR 0.71,95% CI: 0.56-0.90) 4
   • Improves left ventricular diastolic function 5

Dosing and Administration

Initial Dosing

• eGFR 25-59 ml/min/1.73 m²: 10 mg once daily 6, 1
• eGFR ≥60 ml/min/1.73 m²: 20 mg once daily 6, 1

Prerequisites for Initiation

• Serum potassium must be ≤4.8 mmol/L 6, 1
• eGFR must be ≥25 ml/min/1.73 m² 6, 1

Dose Titration

• Consider increasing from 10 mg to 20 mg daily after 1 month if:
  • Serum potassium remains ≤4.8 mmol/L
  • eGFR is stable 1

Monitoring Protocol

1. Initial follow-up: Check serum potassium at 1 month after initiation
2. Ongoing monitoring: Check serum potassium every 4 months 6, 1

Dose Adjustment Based on Serum Potassium

• K+ ≤4.8 mmol/L: Continue current dose
• K+ 4.9-5.5 mmol/L: Continue current dose with monitoring every 4 months
• K+ >5.5 mmol/L: Hold finerenone, adjust diet/medications, recheck K+, consider reinitiating when K+ ≤5.0 mmol/L 6

Patient Selection

Finerenone is most appropriate for:

1. Primary Indication: Patients with CKD and type 2 diabetes with:

   • Persistent albuminuria (>30 mg/g) despite maximum tolerated RAS inhibitor therapy 6
   • eGFR ≥25 ml/min/1.73 m² 6, 1
   • Normal serum potassium (≤4.8 mmol/L) 6, 1

2. Combination Therapy: Can be safely combined with:

   • SGLT2 inhibitors for additive cardiorenal protection
   • GLP-1 receptor agonists
   • Metformin (if eGFR >30 ml/min/1.73 m²) 1

Potential Adverse Effects

1. Hyperkalemia:

   • Incidence: 10.8% with finerenone vs. 5.3% with placebo 1
   • Discontinuation due to hyperkalemia: 2.3% with finerenone vs. 0.9% with placebo 1

2. Contraindications:

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

Clinical Pearls

1. Combination with SGLT2i: Consider adding finerenone to SGLT2 inhibitor therapy for additive cardiorenal protection in patients with type 2 diabetes and CKD 6, 1

2. Monitoring Approach: Regular potassium monitoring is essential, but the risk of severe hyperkalemia is lower than with steroidal MRAs 1

3. Albuminuria as Surrogate Marker: Early reduction in albuminuria correlates strongly with long-term kidney and cardiovascular benefits 3

4. Benefits across CKD Spectrum: Effects on mortality are consistent across all KDIGO risk groups 2