What are the indications for Kerendia (finerenone)?

Indications for Kerendia (Finerenone)

Kerendia (finerenone) is indicated to reduce the risk of sustained estimated glomerular filtration rate (eGFR) decline, end-stage kidney disease, cardiovascular death, nonfatal myocardial infarction, and hospitalization for heart failure in adults with chronic kidney disease (CKD) associated with type 2 diabetes. 1, 2

Patient Selection Criteria

Finerenone is specifically indicated for patients with the following characteristics:

• Type 2 diabetes with established chronic kidney disease
• Albuminuria with either:
  • UACR 30 to <300 mg/g with eGFR 25 to <60 mL/min/1.73 m² and diabetic retinopathy, OR
  • UACR 300-5,000 mg/g with eGFR 25 to <75 mL/min/1.73 m² 1

Dosing Algorithm

1. Initial dosing based on baseline eGFR:

   • eGFR 25-60 mL/min/1.73 m²: 10 mg once daily
   • eGFR ≥60 mL/min/1.73 m²: 20 mg once daily 1

2. Dose titration:

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

Clinical Benefits

Finerenone has demonstrated significant benefits in two major clinical trials:

1. FIDELIO-DKD trial:

   • 18% reduction in primary composite kidney outcome (HR 0.82,95% CI 0.73-0.93; P=0.001)
   • 14% reduction in key secondary cardiovascular outcome (HR 0.86,95% CI 0.75-0.99; P=0.03) 1, 3

2. FIGARO-DKD trial:

   • 13% reduction in primary cardiovascular outcome (HR 0.87,95% CI 0.76-0.98; P=0.03)
   • 36% reduction in end-stage kidney disease (HR 0.64,95% CI 0.41-0.995) 1

3. FIDELITY pooled analysis (combining both trials):

   • 14% reduction in composite cardiovascular outcomes (HR 0.86,95% CI 0.78-0.95; P=0.0018)
   • 23% reduction in composite kidney outcomes (HR 0.77,95% CI 0.67-0.88; P=0.0002) 1, 4

Safety Considerations and Monitoring

1. Hyperkalemia risk:

   • Higher incidence compared to placebo (10.8% vs 5.3%)
   • Treatment discontinuation due to hyperkalemia: 1.2-2.3% 1
   • Less pronounced than with steroidal MRAs like spironolactone 4

2. Required monitoring:

   • Check serum potassium before initiating therapy (must be ≤4.8 mmol/L)
   • Monitor potassium levels regularly during treatment
   • Evaluate eGFR stability 1, 5

Placement in Treatment Algorithm

According to current guidelines, finerenone should be positioned as:

1. Additional risk-based therapy after first-line treatments:

   • Can be added if ACR ≥30 mg/g and normal potassium levels 1
   • Used in conjunction with RAS inhibitors at maximum tolerated dose 1

2. Complementary to other kidney-protective therapies:

   • Can be used alongside SGLT2 inhibitors for additive benefit
   • Only 4.5% of patients in clinical trials were on SGLT2 inhibitors, but benefit was maintained 1, 6

Important Clinical Pearls

• Finerenone is the first nonsteroidal, selective mineralocorticoid receptor antagonist approved for CKD in type 2 diabetes 5
• Unlike steroidal MRAs (spironolactone), finerenone does not cause gynecomastia 6
• Benefits are observed across the spectrum of CKD severity, regardless of baseline ASCVD history 1
• Finerenone should be used as part of a comprehensive approach to reducing cardiorenal risk in patients with type 2 diabetes and CKD 1

By targeting the mineralocorticoid receptor through a novel mechanism, finerenone addresses a key pathophysiological pathway in diabetic kidney disease progression that complements other therapeutic approaches.