What is the role of Finerenone (Finerenone) in managing type 2 diabetes and chronic kidney disease (CKD)?

Finerenone in Type 2 Diabetes and Chronic Kidney Disease

Finerenone should be added to therapy in patients with type 2 diabetes and CKD who have persistent albuminuria (UACR ≥30 mg/g) despite maximum tolerated RAS inhibitor therapy, with eGFR ≥25 mL/min/1.73 m² and serum potassium ≤4.8 mmol/L, to reduce both cardiovascular events and kidney disease progression. 1, 2

Evidence for Cardiovascular and Renal Protection

Finerenone, a selective nonsteroidal mineralocorticoid receptor antagonist, demonstrates robust dual benefits across the spectrum of diabetic kidney disease:

Cardiovascular Outcomes

• Reduces composite cardiovascular events by 14% (cardiovascular death, nonfatal MI, nonfatal stroke, or heart failure hospitalization) in the pooled FIDELITY analysis of 13,026 patients (HR 0.86,95% CI 0.78-0.95) 1
• Decreases heart failure hospitalizations by 29% in the FIGARO-DKD trial, particularly benefiting patients without symptomatic heart failure with reduced ejection fraction 1
• The cardiovascular benefit is partially mediated by albuminuria reduction, accounting for approximately 37% of the treatment effect 3

Kidney Outcomes

• Reduces composite kidney outcome by 23% (kidney failure, sustained ≥57% eGFR decline, or renal death) in the pooled analysis (HR 0.77,95% CI 0.67-0.88) 1, 4
• Decreases progression to end-stage kidney disease by 36% in FIGARO-DKD 1
• Reduces kidney failure requiring dialysis or transplantation by 20% in FIDELIO-DKD 2
• Albuminuria reduction mediates 84% of the kidney protection effect, with 53% of finerenone-treated patients achieving ≥30% UACR reduction versus 27% with placebo 3

Clinical Implementation Algorithm

Patient Selection Criteria

Initiate finerenone if ALL of the following are met:

• Type 2 diabetes with CKD (eGFR 25-90 mL/min/1.73 m²) 1, 2, 5
• Persistent albuminuria (UACR ≥30 mg/g) despite standard therapy 1, 2, 5
• Already on maximum tolerated dose of ACE inhibitor or ARB 1, 2, 5
• Baseline serum potassium ≤4.8 mmol/L 1, 5

Do NOT initiate finerenone if:

• eGFR <25 mL/min/1.73 m² or on dialysis 5
• Baseline potassium >4.8 mmol/L 5
• Symptomatic heart failure with reduced ejection fraction 1

Treatment Sequencing

The optimal sequence for cardiorenal protection in diabetic CKD follows this hierarchy:

1. First-line foundation: Maximum tolerated RAS inhibitor (ACE inhibitor or ARB) 5
2. Second-line priority: SGLT2 inhibitor (larger magnitude of benefit on cardiovascular and kidney outcomes) 5
3. Third-line or alternative: Finerenone if:
   • SGLT2 inhibitor intolerance exists 5
   • Persistent albuminuria despite SGLT2 inhibitor therapy 5
   • Can be added to SGLT2 inhibitor for complementary protection 2, 6

This sequencing is endorsed by KDOQI guidelines, though both the American Diabetes Association and KDIGO support finerenone as an add-on to RAS inhibitors regardless of SGLT2 inhibitor use 1, 2, 5, 7

Dosing Protocol

Initial Dosing

• eGFR 25-60 mL/min/1.73 m²: Start 10 mg once daily 1, 5
• eGFR >60 mL/min/1.73 m²: Start 20 mg once daily 1, 5

Dose Titration

• After 1 month: Increase from 10 mg to 20 mg daily if serum potassium remains ≤4.8 mmol/L and eGFR is stable 1, 5

Ongoing Potassium Management

• Continue therapy: If potassium ≤5.5 mmol/L 5
• Withhold temporarily: If potassium >5.5 mmol/L 5
• Restart at 10 mg daily: When potassium returns to ≤5.0 mmol/L 5

Safety Profile and Monitoring

Hyperkalemia Risk

• Hyperkalemia occurs in 10.8% of finerenone patients versus 5.3% with placebo 1, 5
• Permanent discontinuation due to hyperkalemia is low at only 1.7% versus 0.6% with placebo over 3 years 2
• No deaths attributed to hyperkalemia in either FIDELIO-DKD or FIGARO-DKD trials 2
• The hyperkalemia risk is substantially lower than with steroidal mineralocorticoid receptor antagonists like spironolactone 8

Monitoring Requirements

• Verify serum potassium ≤4.8 mmol/L before initiation 5
• Monitor potassium regularly after starting therapy 5
• Check potassium at 1 month when considering dose uptitration 5

Common Pitfalls to Avoid

Critical Errors

• Do not use in eGFR <25 mL/min/1.73 m²: The landmark trials excluded these patients, and no safety or efficacy data exist for this population 5, 9
• Do not initiate without optimizing RAS inhibitor first: Finerenone is an add-on therapy, not a replacement for foundational RAS blockade 5
• Do not start if potassium >4.8 mmol/L: This increases hyperkalemia risk substantially 5

Practical Considerations

• Finerenone provides benefits across the entire CKD spectrum studied (eGFR 25-90 mL/min/1.73 m²), including patients with eGFR >60 mL/min/1.73 m² identified solely by albuminuria 4
• The medication works independently of baseline albuminuria levels and is effective regardless of concomitant SGLT2 inhibitor use 8
• Benefits emerge early, with median follow-up of 3.0 years in pooled analyses demonstrating sustained efficacy 4

Guideline Endorsements

Multiple major societies have incorporated finerenone into their recommendations:

• KDIGO 2022 (Grade 2A): Recommends finerenone for patients meeting the criteria outlined above 2, 7
• American Diabetes Association 2023-2024: Includes finerenone as a treatment option for reducing CKD progression and cardiovascular events in diabetic kidney disease 1, 7
• American College of Cardiology: Positions finerenone as add-on therapy for persistent albuminuria despite ACE inhibitor/ARB therapy 7

The strength of this recommendation is based on two large, well-designed phase 3 trials (FIDELIO-DKD with 5,734 patients and FIGARO-DKD with 7,437 patients) and their prespecified pooled analysis, representing Grade A evidence for both cardiovascular and kidney outcomes 1, 2, 4