What are the recommended dosing, titration criteria, contraindications, and monitoring parameters for finerenone in an adult with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM)?

Finerenone Dosing, Titration, Contraindications, and Monitoring in Adults with CKD and Type 2 Diabetes

Initial Dosing Protocol

Start finerenone at 10 mg once daily if eGFR is 25–60 mL/min/1.73 m², or 20 mg once daily if eGFR is >60 mL/min/1.73 m². 1, 2

• Baseline serum potassium must be ≤4.8 mmol/L before initiating therapy 1, 2
• The patient must already be on maximum tolerated dose of an ACE inhibitor or ARB 1, 2
• Persistent albuminuria (UACR ≥30 mg/g) must be documented despite optimized RAS inhibitor therapy 1, 2

Dose Titration Strategy

After 1 month of treatment, increase the dose from 10 mg to 20 mg once daily if serum potassium remains ≤4.8 mmol/L and eGFR is stable. 1, 2

• The 1-month interval captures the predictable early rise in potassium associated with mineralocorticoid receptor antagonism 1
• Do not uptitrate if potassium exceeds 4.8 mmol/L or if eGFR has declined significantly 1

Absolute Contraindications

• eGFR <25 mL/min/1.73 m² or end-stage renal disease (no established dosing or safety data in this population) 1
• Baseline serum potassium >4.8 mmol/L 1, 2
• The landmark FIDELIO-DKD and FIGARO-DKD trials specifically excluded patients with eGFR <25 mL/min/1.73 m² 1

Monitoring Parameters

Potassium Monitoring Schedule

• Pre-initiation: Confirm serum potassium ≤4.8 mmol/L 1
• At 1 month: Check potassium to assess for early rise and determine eligibility for dose uptitration 1
• Every 4 months thereafter: Ongoing maintenance monitoring during continued therapy 1

Potassium-Based Management Algorithm

• Potassium ≤4.8 mmol/L: Continue current dose and monitor every 4 months 1
• Potassium 4.9–5.5 mmol/L: Continue finerenone without dose adjustment; maintain monitoring every 4 months 1
• Potassium >5.5 mmol/L: Immediately hold finerenone, evaluate dietary potassium and concomitant medications (NSAIDs, potassium-sparing diuretics), and recheck potassium 1
• Restarting after hyperkalemia: Resume at 10 mg daily when potassium returns to ≤5.0 mmol/L 1

Renal Function Monitoring

• Baseline, 1 month, then every 4 months: Measure serum creatinine and calculate eGFR 1
• Expected hemodynamic effect: An acute eGFR decline of approximately 2.9 mL/min/1.73 m² during the first 3 months is anticipated and reflects reduced intraglomerular pressure, not acute kidney injury 1
• Continue finerenone if creatinine rise is <30% from baseline in a clinically stable patient without volume depletion or nephrotoxin exposure 1
• Hold finerenone if creatinine increase exceeds 30% from baseline, or if volume depletion, hypotension, or acute illness is present 1

Albuminuria Monitoring

• Baseline and at 4 months: Obtain UACR to evaluate treatment response 1

Treatment Sequencing in Diabetic CKD

The American Diabetes Association and KDIGO guidelines establish a clear hierarchy: 3, 1

1. First-line foundation: Maximum tolerated ACE inhibitor or ARB 1
2. Second-line priority: SGLT2 inhibitor (provides largest effect on renal and cardiovascular outcomes) 1
3. Third-line consideration: Finerenone for persistent albuminuria despite ACE/ARB + SGLT2i, or when SGLT2i is contraindicated or not tolerated 1

Expected Clinical Benefits

Finerenone reduces kidney disease progression by 23% and major cardiovascular events by 14% in patients with type 2 diabetes and CKD. 2

• Kidney protection: 18% reduction in composite kidney outcome (kidney failure, sustained ≥40% eGFR decline, or renal death) 2
• End-stage kidney disease: 36% risk reduction 3, 2
• Cardiovascular protection: 13–14% reduction in composite cardiovascular outcomes (CV death, nonfatal MI, nonfatal stroke, or heart failure hospitalization) 3, 2
• Heart failure hospitalization: 29% reduction 4

Common Pitfalls to Avoid

• Do not start finerenone before optimizing RAS inhibitor therapy; patients must be on maximum tolerated ACE inhibitor or ARB first 2
• Do not permanently discontinue for a single potassium >5.5 mmol/L; temporary interruption with dose reduction upon restart (10 mg daily) successfully manages most cases 1
• Do not mistake hemodynamic creatinine changes for acute kidney injury; creatinine rises up to 30% reflect beneficial reduction of intraglomerular pressure, not tubular damage 1
• Do not underdose out of fear of creatinine rise; pivotal trials used maximally tolerated doses (10–20 mg daily, adjusted for eGFR) 1

Safety Profile

• Hyperkalemia incidence: 14% with finerenone versus 6.9% with placebo 2, 4
• Permanent discontinuation due to hyperkalemia: Only 1.7% versus 0.6% with placebo over 3 years 2
• No deaths attributed to hyperkalemia were reported in the FIDELIO-DKD or FIGARO-DKD trials 2
• Independent risk factors for hyperkalemia include lower eGFR (particularly <45 mL/min/1.73 m²) and beta-blocker use 1
• SGLT2 inhibitor co-administration reduces hyperkalemia risk 1

Nephrology Referral Triggers

• eGFR falls below 30 mL/min/1.73 m² (stage 4 CKD) to discuss renal replacement options 1
• Creatinine rise >30% from baseline that fails to stabilize after holding potential offending agents 1
• Persistent hyperkalemia despite dietary and medication adjustments 1