What is the role of finerenone (Mineralocorticoid Receptor Antagonist) in the management of patients with Chronic Kidney Disease (CKD)?

Finerenone in Chronic Kidney Disease: Evidence from Major Trials

Finerenone is a nonsteroidal mineralocorticoid receptor antagonist (MRA) that significantly reduces both kidney disease progression and cardiovascular events in patients with type 2 diabetes and CKD, supported by Grade A evidence from the FIDELIO-DKD and FIGARO-DKD trials. 1

Key Clinical Trial Evidence

FIDELIO-DKD Trial (Advanced CKD Population)

This landmark trial enrolled 5,734 patients with type 2 diabetes and more advanced kidney disease 2:

Patient Eligibility Criteria:

• UACR 30-300 mg/g with eGFR 25-60 mL/min/1.73 m² plus diabetic retinopathy, OR
• UACR 300-5,000 mg/g with eGFR 25-75 mL/min/1.73 m² 1, 2
• All patients on maximum tolerated RAS inhibitor therapy 2
• Normal serum potassium (≤4.8 mmol/L) required 1

Primary Kidney Outcome Results:

• 18% relative risk reduction in composite kidney outcome (kidney failure, sustained ≥40% eGFR decline, or renal death): HR 0.82 (95% CI 0.73-0.93, P=0.001) 1, 2
• 20% reduction in kidney failure requiring dialysis or transplantation: HR 0.80 (95% CI 0.64-0.99) 1

Secondary Cardiovascular Outcome Results:

• 14% reduction in cardiovascular composite (CV death, MI, stroke, heart failure hospitalization): HR 0.86 (95% CI 0.75-0.99, P=0.03) 1, 2

FIGARO-DKD Trial (Earlier CKD Population)

This trial studied 7,437 patients with less advanced kidney disease 3:

Patient Eligibility Criteria:

• UACR 30-300 mg/g with eGFR 25-90 mL/min/1.73 m² (stage 2-4 CKD), OR
• UACR 300-5,000 mg/g with eGFR ≥60 mL/min/1.73 m² (stage 1-2 CKD) 1, 3

Primary Cardiovascular Outcome Results:

• 13% reduction in cardiovascular composite: HR 0.87 (95% CI 0.76-0.98, P=0.03) 1, 3
• Benefit primarily driven by 29% reduction in heart failure hospitalizations: HR 0.71 (95% CI 0.56-0.90) 4, 3

Secondary Kidney Outcome Results:

• 36% reduction in end-stage kidney disease: HR 0.64 (95% CI 0.41-0.995) 1, 4

FIDELITY Pooled Analysis

Combined analysis of both trials (12,512 patients) demonstrated consistent benefits across the CKD spectrum 1, 5:

• 14% reduction in cardiovascular outcomes: HR 0.86 (95% CI 0.78-0.95) 1
• 23% reduction in kidney composite outcomes: HR 0.77 (95% CI 0.67-0.88) 1, 4
• Benefits observed regardless of baseline eGFR, albuminuria level, or concomitant SGLT2 inhibitor use 5

Guideline-Based Recommendations

KDIGO 2022 Guidelines

Recommend finerenone (Grade 2A) for patients with: 1

• Type 2 diabetes AND
• eGFR >25 mL/min/1.73 m² AND
• Albuminuria (UACR >30 mg/g) AND
• Normal serum potassium AND
• Already on maximum tolerated RAS inhibitor dose

The KDIGO Work Group specifically notes that finerenone is currently the only nonsteroidal MRA with proven clinical kidney and cardiovascular benefits. 1

American Diabetes Association 2025 Standards

Recommend finerenone for patients with: 1

• Type 2 diabetes and CKD
• eGFR ≥20 mL/min/1.73 m² (updated from prior ≥25 threshold)
• UACR ≥30 mg/g despite standard therapy
• Can be added to SGLT2 inhibitors for complementary protection 4

KDOQI 2025 Commentary

The KDOQI Work Group prioritizes SGLT2 inhibitors over finerenone as the next step after RAS inhibitor therapy because SGLT2 inhibitors demonstrate larger effects on both kidney and cardiovascular outcomes 1. However, finerenone should be considered if:

• Patient does not tolerate SGLT2 inhibitor, OR
• Patient remains with albuminuria despite SGLT2 inhibitor therapy 1

Practical Dosing Algorithm

Initial Dose Selection 1, 6

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

Dose Titration Protocol 6

After 1 month, increase from 10 mg to 20 mg daily if ALL of the following are met:

• Serum potassium ≤4.8 mmol/L
• eGFR remains stable
• Medication well-tolerated

Ongoing Potassium Monitoring 6

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

Safety Profile and Hyperkalemia Management

Hyperkalemia Incidence

Hyperkalemia occurred more frequently with finerenone but discontinuation rates remained low: 1

• Hyperkalemia incidence: 14% vs 6.9% with placebo (FIDELIO-DKD) 1
• Hyperkalemia incidence: 10.8% vs 5.3% with placebo (FIGARO-DKD) 1
• Permanent discontinuation due to hyperkalemia: only 1.7% vs 0.6% over 3 years 1
• No deaths attributed to hyperkalemia in either trial 1

Critical Safety Considerations

Finerenone demonstrates lower hyperkalemia risk compared to steroidal MRAs (spironolactone), but potassium monitoring remains essential. 1, 5 The American Heart Association emphasizes verifying serum potassium ≤4.8 mmol/L before initiation and monitoring regularly throughout treatment 6.

Mechanism of Benefit: Albuminuria Reduction

A mediation analysis from the FIDELITY pooled data revealed that early albuminuria reduction accounted for a substantial proportion of finerenone's treatment effects 7:

• 84% of kidney outcome benefit mediated by UACR reduction (analyzed as continuous variable) 7
• 37% of cardiovascular outcome benefit mediated by UACR reduction 7
• When using the guideline-recommended 30% UACR reduction threshold, proportions mediated were 64% for kidney outcomes and 26% for cardiovascular outcomes 7

Clinical Implementation Considerations

Patient Selection Priorities 1, 4

Finerenone is most appropriate for patients at high risk of CKD progression and cardiovascular events, demonstrated by:

• Persistent albuminuria despite RAS inhibitor therapy
• Type 2 diabetes with stage 2-4 CKD
• Normal baseline potassium levels

Combination Therapy Strategy 1, 4

Finerenone can be safely added to SGLT2 inhibitors for complementary cardiorenal protection, though definitive data on combined benefits remain limited 1. The FIDELIO-DKD and FIGARO-DKD trials had only 4.5% of participants on SGLT2 inhibitors at baseline 1, representing a knowledge gap in contemporary practice where SGLT2 inhibitors are now standard of care.

Common Pitfalls to Avoid

• Do not initiate finerenone in patients with elevated baseline potassium (>4.8 mmol/L) 6
• Do not combine with other MRAs (spironolactone, eplerenone) due to excessive hyperkalemia risk 1
• Exercise caution when combining with ACE inhibitors or ARBs, though this combination was standard in the trials 4
• Monitor potassium more frequently in patients with eGFR 25-45 mL/min/1.73 m² 6

Nephrology Referral Thresholds

Consider nephrology consultation when eGFR <30 mL/min/1.73 m² for management of advanced kidney disease and discussion of renal replacement therapy 1, 4.