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

Kerendia (Finerenone) in Type 2 Diabetes and Chronic Kidney Disease

Finerenone is a nonsteroidal mineralocorticoid receptor antagonist indicated for patients with type 2 diabetes and chronic kidney disease (stages 2-4, eGFR 25-90 mL/min/1.73 m²) who have persistent albuminuria (UACR ≥30 mg/g) despite maximum tolerated RAS inhibitor therapy, providing significant reductions in both cardiovascular events (13% relative risk reduction) and kidney disease progression (23% relative risk reduction). 1, 2

Patient Selection Criteria

Initiate finerenone when ALL of the following criteria are met:

• Type 2 diabetes with chronic kidney disease (eGFR 25-90 mL/min/1.73 m²) 1, 2
• Persistent albuminuria (UACR ≥30 mg/g) despite optimal therapy 1, 2
• Already on maximum tolerated dose of ACE inhibitor or ARB 2, 3
• Serum potassium ≤4.8 mmol/L 2, 4

Do NOT initiate finerenone if:

• eGFR <25 mL/min/1.73 m² or patient is on dialysis (no safety or efficacy data in this population) 2
• Baseline potassium >4.8 mmol/L (excessive hyperkalemia risk) 2, 4
• Heart failure with reduced ejection fraction (excluded from trials) 2

Treatment Sequencing Algorithm

The American Diabetes Association and KDIGO guidelines recommend the following stepwise approach for patients with type 2 diabetes and CKD: 1, 2, 3

1. First-line foundation: RAS inhibitor (ACE inhibitor or ARB) at maximum tolerated dose 2, 3
2. Second-line priority: SGLT2 inhibitor (larger effects on kidney and cardiovascular outcomes than finerenone) 2
3. Third-line add-on: Finerenone if persistent albuminuria despite above therapies, or if SGLT2 inhibitor intolerance 2, 3

Dosing Protocol

Initial dosing based on eGFR: 2

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

Dose uptitration: 2

• After 1 month, if serum potassium remains ≤4.8 mmol/L and eGFR is stable, uptitrate from 10 mg to 20 mg daily 2

Potassium Monitoring and Management

Pre-initiation: Verify serum potassium ≤4.8 mmol/L 2, 4

Monitoring schedule: 2

• Check potassium at 1 month after initiation (captures predictable initial rise) 2
• Then every 4 months during maintenance therapy 2

Potassium-based management algorithm: 2

• Potassium ≤4.8 mmol/L: Continue current dose, monitor every 4 months 2
• Potassium 4.9-5.5 mmol/L: Continue current dose without adjustment, maintain monitoring every 4 months 2
• Potassium >5.5 mmol/L: Immediately hold finerenone, evaluate dietary potassium and concomitant medications, recheck potassium to confirm downtrend 2
• Restart criteria: When potassium returns to ≤5.0 mmol/L, restart at 10 mg daily 2

Clinical Benefits

Cardiovascular outcomes: 1, 4

• 13% reduction in composite cardiovascular endpoint (cardiovascular death, nonfatal MI, nonfatal stroke, or heart failure hospitalization) with HR 0.87 (95% CI 0.76-0.98) 1, 4
• 29% reduction in heart failure hospitalizations with HR 0.71 (95% CI 0.56-0.90) 4
• Prevents progression from asymptomatic to symptomatic heart failure 1, 3
• Significant on-treatment reduction in cardiovascular mortality with HR 0.82 (95% CI 0.67-0.99) 5

Kidney outcomes: 1, 4, 6

• 23% reduction in composite kidney outcome (kidney failure, sustained ≥57% decrease in eGFR, or renal death) with HR 0.77 (95% CI 0.67-0.88) 6
• 36% reduction in end-stage kidney disease with HR 0.64 (95% CI 0.41-0.995) 4
• Benefits occur across all CKD stages (eGFR 25-90 mL/min/1.73 m²) and albuminuria levels 6, 5

Safety Profile and Common Pitfalls

Hyperkalemia risk: 4, 6

• Incidence: 10.8% with finerenone vs 5.3% with placebo 4
• Discontinuation rate due to hyperkalemia: only 1.2% 4
• No deaths related to hyperkalemia in clinical trials 4
• Lower hyperkalemia risk than steroidal MRAs like spironolactone 6

Risk factors for hyperkalemia: 2

• Lower eGFR (particularly <45 mL/min/1.73 m²) 2
• Concurrent beta-blocker use 2

Protective factors: 2

• Concurrent SGLT2 inhibitor use reduces hyperkalemia risk 2

Critical pitfall to avoid: 2

• Do NOT permanently discontinue finerenone for a single episode of potassium >5.5 mmol/L 2
• Temporary interruption with dose reduction upon restart (10 mg daily) successfully manages most cases 2
• Consider repeating borderline potassium measurements before making treatment decisions due to inherent variability 2

Evidence Base

The recommendation is based on two landmark trials: 1, 3, 4

• FIDELIO-DKD: 5,734 patients with more advanced diabetic kidney disease (eGFR 25-75 mL/min/1.73 m²), demonstrated significant kidney outcome benefits 1, 7
• FIGARO-DKD: 7,437 patients with earlier-stage CKD, demonstrated significant cardiovascular outcome benefits 1, 4
• FIDELITY pooled analysis: 13,026 patients, confirmed benefits across the full CKD spectrum 6, 5

All patients in these trials were on maximum tolerated RAS inhibitor therapy at baseline (99.8%), establishing finerenone as add-on therapy rather than monotherapy. 5