What is the role of Kerendia (finerenone) in managing chronic kidney disease (CKD) associated with type 2 diabetes?

Role of Kerendia (Finerenone) in Managing CKD Associated with Type 2 Diabetes

Finerenone is strongly recommended for adults with type 2 diabetes and chronic kidney disease who have persistent albuminuria despite maximum tolerated doses of renin-angiotensin system inhibitors, as it significantly reduces both kidney disease progression and cardiovascular events. 1, 2

Mechanism and Clinical Benefits

• Finerenone is a selective non-steroidal mineralocorticoid receptor antagonist (MRA) that provides cardiorenal protection through different mechanisms than SGLT2 inhibitors 1
• In the FIDELIO-DKD trial, finerenone demonstrated an 18% reduction in the primary composite kidney outcome (HR 0.82 [95% CI 0.73–0.93]; P = 0.001) and a 14% reduction in cardiovascular outcomes (HR 0.86 [95% CI 0.75–0.99]; P = 0.03) 1
• The FIGARO-DKD trial showed a 13% reduction in primary cardiovascular endpoints (HR 0.87 [95% CI 0.76–0.98]; P = 0.03), primarily driven by a 29% reduction in heart failure hospitalizations 1
• The FIDELITY pooled analysis of 13,026 patients demonstrated consistent benefits across the spectrum of CKD severity with a 14% reduction in composite cardiovascular outcomes (HR 0.86 [95% CI 0.78–0.95]; P = 0.0018) and a 23% reduction in composite kidney outcomes (HR 0.77 [95% CI 0.67–0.88]; P = 0.0002) 3, 4

Patient Selection Criteria

• Appropriate for adults with type 2 diabetes and CKD with:
  • Persistent albuminuria (UACR ≥30 mg/g) despite maximum tolerated RAS inhibitor doses 2
  • eGFR ≥25 mL/min/1.73 m² 1, 2
  • Normal serum potassium (<4.8 mmol/L) before initiation 1, 2
• Particularly beneficial for patients at high risk of CKD progression and cardiovascular events 3, 2

Dosing Recommendations

• For patients with eGFR 25-60 mL/min/1.73 m²: start with 10 mg once daily 1, 2
• For patients with eGFR >60 mL/min/1.73 m²: start with 20 mg once daily 3, 2
• Dose can be uptitrated from 10 mg to 20 mg daily after 1 month if serum potassium remains <4.8 mmol/L and eGFR is stable 1, 2

Safety Considerations and Monitoring

• Hyperkalemia is the most common adverse effect, occurring in 10.8% of patients on finerenone vs. 5.3% on placebo 1
• Treatment discontinuation due to hyperkalemia is relatively low (1.7% vs. 0.6% with placebo) 3, 4
• Regular monitoring of serum potassium is essential, especially during initiation and dose adjustments 2
• If potassium increases to >5.5 mmol/L, finerenone should be withheld and can be restarted at 10 mg daily when potassium is ≤5.0 mmol/L 2

Treatment Algorithm for CKD in Type 2 Diabetes

1. First-line therapy: Maximum tolerated dose of ACE inhibitor or ARB 1, 2
2. Second-line therapy: Add SGLT2 inhibitor (preferred) due to larger effects on reducing both kidney and cardiovascular outcomes 2
3. Third-line therapy: Add finerenone if:
   • Patient remains with albuminuria despite SGLT2 inhibitor therapy 2
   • Patient cannot tolerate an SGLT2 inhibitor 2
   • Additional cardiorenal protection is needed 3, 2

Mediation of Benefits

• Early albuminuria reduction accounts for a large proportion (84%) of finerenone's treatment effect against CKD progression and a modest proportion (37%) of the effect against cardiovascular outcomes 5
• A 30% or greater reduction in UACR was seen in 53.2% of patients in the finerenone group compared to 27.0% in the placebo group 5

Mortality Benefits

• Finerenone reduces all-cause mortality (8.5% vs. 9.4%) and cardiovascular mortality (4.9% vs. 5.6%) compared to placebo 6
• Significant reduction in sudden cardiac death was observed with finerenone versus placebo (1.3% vs. 1.8%; HR 0.75 [95% CI 0.57-0.996]; P = 0.046) 6

When to Consider Nephrology Referral

• Consider nephrology referral if the patient has continuously rising UACR levels and/or continuously declining eGFR 1
• Referral is particularly important when eGFR <30 mL/min/1.73 m² to discuss renal replacement therapy options 1, 3
• Consultation with a nephrologist when stage 4 CKD develops has been found to reduce cost, improve quality of care, and delay dialysis 1