In adults with type 2 diabetes and chronic kidney disease (eGFR 25–90 mL/min/1.73 m²) with albuminuria who are already on an ACE inhibitor or ARB, what are the efficacy and safety results of the finerenone phase III trials (FIDELIO‑DKD and FIGARO‑DKD) and what are the recommended dosing and monitoring guidelines?

Finerenone Phase III Trial Results and Clinical Implementation

FIDELIO-DKD and FIGARO-DKD: Landmark Efficacy Data

Finerenone reduces both kidney disease progression by 23% and major cardiovascular events by 14% in patients with type 2 diabetes and chronic kidney disease who have persistent albuminuria despite maximally tolerated RAS inhibitor therapy. 1

Kidney Outcomes

• FIDELIO-DKD (more advanced CKD population): Finerenone reduced the composite kidney outcome (kidney failure, sustained ≥40% eGFR decline, or renal death) by 18% (HR 0.82,95% CI 0.73–0.93) 1, 2
• Pooled FIDELITY analysis (13,026 patients, median 3.0 years follow-up): Finerenone achieved a 23% relative risk reduction in the composite kidney outcome (kidney failure, sustained ≥57% eGFR decrease, or renal death) (HR 0.77,95% CI 0.67–0.88) 1, 3
• End-stage kidney disease: Finerenone reduced progression to ESKD by 36% (HR 0.64,95% CI 0.41–0.995) 1, 4
• FIGARO-DKD (less advanced CKD): The ≥57% eGFR decline composite showed a 23% risk reduction (HR 0.77,95% CI 0.60–0.99) 5

Cardiovascular Outcomes

• Pooled FIDELITY data: Finerenone reduced the composite cardiovascular endpoint (CV death, non-fatal MI, non-fatal stroke, or heart failure hospitalization) by 14% (HR 0.86,95% CI 0.78–0.95) 1, 3
• FIGARO-DKD: Cardiovascular events were lowered by 13% (HR 0.87,95% CI 0.76–0.98) in patients with less advanced CKD 1
• Heart failure hospitalization: Finerenone reduced HF hospitalizations by 29% (HR 0.71) 4
• New-onset symptomatic heart failure: Finerenone reduced incident HF in patients without baseline HFrEF by approximately 25% (HR 0.75,95% CI 0.57–0.996) 1

Patient Selection Criteria

Finerenone is indicated for adults with type 2 diabetes, CKD stages 2–4 (eGFR 25–90 mL/min/1.73 m²), and persistent albuminuria (UACR ≥30 mg/g) despite maximally tolerated ACE inhibitor or ARB therapy. 1, 4

Eligibility Requirements

• Type 2 diabetes with chronic kidney disease 1
• eGFR 25–90 mL/min/1.73 m² (CKD stages 2–4) 1, 2
• Persistent albuminuria (UACR ≥30 mg/g) despite maximum tolerated RAS blockade 1, 4
• Serum potassium ≤4.8 mmol/L at baseline 1, 4
• Already on maximally tolerated ACE inhibitor or ARB 1, 2

Absolute Contraindications

• eGFR <25 mL/min/1.73 m² or end-stage renal disease (no established dosing or safety data) 2, 4
• Baseline serum potassium >4.8 mmol/L 2, 4

Dosing Protocol

Initial Dosing (eGFR-Based)

• eGFR 25–60 mL/min/1.73 m²: Start finerenone 10 mg once daily 1, 4
• eGFR >60 mL/min/1.73 m²: Start finerenone 20 mg once daily 1, 4

Dose Titration After 1 Month

Increase from 10 mg to 20 mg daily if:

• Serum potassium remains ≤4.8 mmol/L 1, 4
• eGFR is stable (no clinically significant decline) 1
• Medication is well tolerated 1

Monitoring Guidelines

Potassium Monitoring Schedule

• Pre-initiation: Verify serum potassium ≤4.8 mmol/L 1, 4
• At 1 month: Check potassium to capture the predictable early rise with MR antagonism 1
• Every 4 months: Ongoing maintenance monitoring 1

Potassium-Based Management Algorithm

• Potassium ≤4.8 mmol/L: Continue current dose; monitor every 4 months 1
• Potassium 4.9–5.5 mmol/L: Continue current dose without adjustment; maintain monitoring 1
• Potassium >5.5 mmol/L: Immediately hold finerenone; evaluate dietary potassium and concomitant medications; recheck potassium to confirm downtrend 1
• Restart protocol: Resume at 10 mg daily when potassium returns to ≤5.0 mmol/L 1, 4

Additional Monitoring Parameters

• eGFR: Assess at baseline, 1 month, then every 4 months 1
• UACR: Obtain at baseline and month 4 to evaluate albuminuria response 1

Safety Profile

Hyperkalemia Incidence

• Hyperkalemia rate: 14% with finerenone vs 6.9% with placebo in pooled trial data 1
• Permanent discontinuation: Only 1.7% vs 0.6% with placebo over median 3-year follow-up 1, 4
• Mortality: No deaths attributable to hyperkalemia were reported in pivotal trials 1

Expected Creatinine Changes

A rise in serum creatinine up to 30% from baseline after starting finerenone is an anticipated hemodynamic effect, not acute kidney injury; therapy may be continued provided serum potassium stays ≤5.5 mmol/L. 2

• Finerenone produces an acute eGFR decline of approximately 2.9 mL/min/1.73 m² during the first 3 months, reflecting reduced intraglomerular pressure rather than true renal injury 2
• Continue finerenone if creatinine rise is <30% from baseline, no volume depletion present, and patient is clinically stable 2
• Temporarily hold if creatinine increase exceeds 30% from baseline, volume depletion is present, or recent nephrotoxin exposure (NSAIDs, contrast, aminoglycosides) 2

Treatment Sequencing (Guideline-Based Hierarchy)

KDIGO 2022 and ADA 2024 recommend a clear treatment hierarchy for diabetic kidney disease: 1, 4

1. First-line foundation: Maximally tolerated ACE inhibitor or ARB 1, 4
2. Second-line priority: SGLT2 inhibitor (largest impact on renal and cardiovascular outcomes) 1, 4
3. Third-line consideration: Finerenone for patients with persistent albuminuria despite SGLT2 inhibitor therapy, or when SGLT2 inhibitors are contraindicated or not tolerated 1, 4

Complementary Therapy

• Finerenone and SGLT2 inhibitors have complementary mechanisms and can be combined for additive cardiorenal protection 1
• Do not consider them interchangeable; they work through different pathways 1

Critical Clinical Pitfalls to Avoid

• Do not start finerenone before optimizing RAS inhibitor therapy; patients must be on maximum tolerated dose of ACE inhibitor or ARB first 1
• Do not overlook the cardiovascular benefits; finerenone reduces major CV events, heart failure hospitalization, and sudden cardiac death beyond its antiproteinuric effect 1
• Do not permanently discontinue for a single potassium >5.5 mmol/L episode; temporary interruption with dose reduction upon restart (10 mg daily) successfully manages most cases 1
• Do not mistake hemodynamic creatinine changes for AKI; creatinine elevations <30% reflect beneficial reduction of intraglomerular pressure, not tubular damage 2
• Do not underdose out of fear of creatinine rise; pivotal trials used maximally tolerated doses (10–20 mg daily, adjusted for eGFR) 2

Nephrology Referral Triggers

• eGFR falls below 30 mL/min/1.73 m² (stage 4 CKD) to discuss renal replacement options 2
• Creatinine rise >30% from baseline that fails to stabilize after holding potential offending agents 2
• Persistent hyperkalemia despite dietary and medication adjustments 2