What is the role of finerenone in managing chronic kidney disease and heart failure in adults with hypertension and diabetes?

Finerenone: A Comprehensive Overview

What is Finerenone?

Finerenone is a selective, nonsteroidal mineralocorticoid receptor antagonist (MRA) indicated for adults with type 2 diabetes and chronic kidney disease (eGFR ≥25 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 and kidney disease progression. 1, 2

Patient Selection Criteria

Who Should Receive Finerenone?

• Type 2 diabetes with CKD stages 2-4 (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 1, 2
• Serum potassium ≤4.8 mmol/L at baseline 1, 2

Who Should NOT Receive Finerenone?

• End-stage renal disease (eGFR <25 mL/min/1.73 m²) - no established dosing or safety data 2
• Patients on dialysis or with kidney transplant 2
• Baseline potassium >4.8 mmol/L - excessive hyperkalemia risk 2
• Symptomatic heart failure with reduced ejection fraction - excluded from landmark trials 2

Treatment Sequencing Algorithm

The KDIGO 2022 Recommended Hierarchy:

1. First-line foundation: RAS inhibitor (ACE-I or ARB) at maximum tolerated dose 1, 2
2. Second-line priority: SGLT2 inhibitor - larger effects on kidney and cardiovascular outcomes 1, 2
3. Third-line consideration: Finerenone for persistent albuminuria despite SGLT2i, or if SGLT2i intolerance 1, 2

This sequencing is critical - finerenone should not be initiated in patients who have not been optimized on maximum tolerated RAS inhibitor first. 2 SGLT2 inhibitors are prioritized over finerenone due to larger magnitude of benefit, but finerenone provides additive benefits when combined with SGLT2 inhibitors. 2, 3

Dosing Protocol

Initial Dose Selection Based on eGFR:

• eGFR 25-60 mL/min/1.73 m²: Start 10 mg once daily 2, 3
• eGFR >60 mL/min/1.73 m²: Start 20 mg once daily 2, 3

Dose Uptitration:

• After 1 month: Increase from 10 mg to 20 mg daily if serum potassium remains ≤4.8 mmol/L, eGFR is stable, and medication is well-tolerated 2

Potassium Monitoring and Management

Pre-Initiation:

• Verify serum potassium ≤4.8 mmol/L before starting therapy 2, 3

Monitoring Schedule:

• At 1 month after initiation to capture predictable initial potassium rise 2
• Every 4 months during maintenance therapy 2

Potassium-Based Management Algorithm:

• 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 levels 2
• Restart criteria: When potassium returns to ≤5.0 mmol/L, restart at 10 mg daily 2

Risk Factors for Hyperkalemia:

• Lower eGFR (particularly <45 mL/min/1.73 m²) increases risk 2
• Beta-blocker use increases risk 2
• SGLT2 inhibitor co-administration reduces hyperkalemia risk 2

Clinical Benefits

Cardiovascular Outcomes:

• 14% reduction in composite cardiovascular outcomes (cardiovascular death, nonfatal MI, nonfatal stroke, or heart failure hospitalization): HR 0.86 (95% CI 0.78-0.95) 1, 4
• 29% reduction in heart failure hospitalization: HR 0.71 (95% CI 0.56-0.90) 3, 5
• 32% reduction in new-onset heart failure: HR 0.68 (95% CI 0.50-0.93) in patients without baseline HF 5
• 18% reduction in sudden cardiac death: HR 0.75 (95% CI 0.57-0.996) 6

Kidney Outcomes:

• 18% reduction in composite kidney outcomes (kidney failure, sustained ≥40% eGFR decrease, or kidney death): HR 0.82 (95% CI 0.73-0.93) 1
• 23% reduction in kidney failure, sustained ≥57% eGFR decrease, or renal death: HR 0.77 (95% CI 0.67-0.88) 1, 4
• 36% reduction in end-stage kidney disease: HR 0.64 (95% CI 0.41-0.995) 2, 7

These benefits are consistent across the entire spectrum of CKD severity (eGFR 25-90 mL/min/1.73 m²) and albuminuria levels (UACR ≥30 mg/g). 1, 4, 8

Safety Profile

Hyperkalemia:

• Incidence: 14% with finerenone vs 6.9% with placebo in pooled trial data 1
• Permanent discontinuation: Only 1.7% vs 0.6% with placebo 1, 2
• No deaths from hyperkalemia over 3 years of follow-up 1

Hyperkalemia is manageable with proper monitoring and dose adjustments - temporary interruption with dose reduction upon restart successfully manages most cases. 2

Overall Safety:

• Treatment-emergent adverse events were balanced between finerenone and placebo groups 5
• Finerenone has significantly lower hyperkalemia risk compared to steroidal MRAs like spironolactone while providing equivalent or superior cardiovascular and renal protection 2

Evidence Base

Landmark Trials:

• FIDELIO-DKD: Enrolled patients with more advanced diabetic kidney disease (mean eGFR 57.6 mL/min/1.73 m², 67% with severe albuminuria) 1
• FIGARO-DKD: Enrolled 7,437 patients with earlier-stage CKD 1, 5
• FIDELITY: Pooled analysis of 13,026 patients with median 3.0-year follow-up 4

All trials required patients to be on maximum tolerated RAS inhibitor therapy at baseline, with 99.8% on RAS inhibitors. 6

Combination Therapy

With SGLT2 Inhibitors:

• Additive benefits when combined with SGLT2 inhibitors 3
• SGLT2 inhibitors reduce hyperkalemia risk when co-administered with finerenone 2
• Consider finerenone as second-line therapy for patients with persistent albuminuria already on SGLT2 inhibitors 3

With GLP-1 Receptor Agonists:

• Can be used in combination for patients needing additional glycemic control 1

Common Pitfalls to Avoid

• Do not permanently discontinue finerenone for a single episode of potassium >5.5 mmol/L unless other interventions fail - temporary interruption with dose reduction upon restart successfully manages most cases 2
• Do not initiate finerenone in patients not optimized on maximum tolerated RAS inhibitor first 2
• Do not use in end-stage renal disease (eGFR <25 mL/min/1.73 m²) - no established dosing or safety data 2
• Be aware of potassium measurement variability - consider repeating borderline values before making treatment decisions 2

Guideline Incorporation

Finerenone is now incorporated into major guidelines including KDIGO 2022, American Diabetes Association 2024, and American College of Cardiology recommendations as add-on therapy for patients with persistent albuminuria despite standard care. 2 The KDIGO 2022 guideline specifically identifies finerenone as "currently the only nonsteroidal mineralocorticoid receptor antagonist with proven clinical kidney and cardiovascular benefits." 1

Special Populations

Type 1 Diabetes:

• Currently under investigation in the FINE-ONE trial 7
• Could become the first registered treatment for CKD associated with type 1 diabetes in almost 30 years if efficacy is demonstrated 7
• Current evidence base is exclusively in type 2 diabetes 1, 4

Patients with History of Heart Failure:

• Benefits are consistent irrespective of baseline heart failure history 5, 8
• Symptomatic HF with reduced ejection fraction was excluded from landmark trials 2