In a patient with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) with estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m², who is at risk for or has a history of heart‑failure hospitalization and has no baseline hyperkalaemia, how should finerenone be initiated, including starting dose, titration criteria, monitoring schedule, and contraindications?

Finerenone Initiation in Heart Failure with Type 2 Diabetes and CKD

For a patient with T2DM, CKD (eGFR ≥30 mL/min/1.73 m²), and heart failure risk or history, initiate finerenone at 10 mg once daily (since eGFR is 30–60 range), uptitrate to 20 mg after 1 month if serum potassium remains ≤4.8 mmol/L, and monitor potassium at 1 month then every 4 months thereafter. 1, 2

Patient Eligibility Criteria

Before starting finerenone, verify the following prerequisites:

• Type 2 diabetes with CKD stages 2–4 (eGFR 25–90 mL/min/1.73 m²) 3, 1
• Persistent albuminuria (UACR ≥30 mg/g) despite maximally tolerated RAS inhibitor (ACE inhibitor or ARB) 3, 1, 2
• Baseline serum potassium ≤4.8 mmol/L (absolute requirement before initiation) 3, 1, 2
• Already on maximum tolerated dose of ACE inhibitor or ARB (foundation therapy must be optimized first) 3, 1, 2

The KDIGO 2024 and ADA 2024 guidelines give a strong recommendation (Grade 2A) for adding finerenone in this clinical scenario, independent of heart failure status. 3, 1

Treatment Sequencing Algorithm

Follow this hierarchical approach for diabetic kidney disease management:

1. First-line foundation: Maximize ACE inhibitor or ARB dose 3, 1
2. Second-line priority: Add SGLT2 inhibitor (provides largest cardiorenal benefit) 3, 1
3. Third-line consideration: Add finerenone if persistent albuminuria despite SGLT2 inhibitor, or when SGLT2 inhibitor is contraindicated/not tolerated 3, 1, 2

Finerenone can be safely combined with SGLT2 inhibitors for complementary cardiorenal protection, and this triple therapy (RAS inhibitor + SGLT2i + finerenone) appears promising. 1, 4

Starting Dose Protocol

The eGFR-based dosing strategy from the FIDELIO-DKD and FIGARO-DKD trials:

• eGFR 25–60 mL/min/1.73 m²: Start finerenone 10 mg once daily 3, 1, 2
• eGFR >60 mL/min/1.73 m²: Start finerenone 20 mg once daily 3, 1, 2

This eGFR-stratified dosing balances efficacy against hyperkalemia risk in patients with reduced kidney function. 1

Dose Titration Criteria

After 1 month of treatment, increase from 10 mg to 20 mg daily only if all three conditions are met:

• Serum potassium remains ≤4.8 mmol/L 1, 2
• eGFR is stable (no clinically significant decline) 1
• Medication is well-tolerated (no symptomatic hypotension or adverse effects) 1

The 1-month interval captures the predictable early rise in potassium associated with mineralocorticoid receptor antagonism. 1

Monitoring Schedule

Pre-Initiation

• Confirm serum potassium ≤4.8 mmol/L 1, 2
• Document baseline eGFR and UACR 1

Initial Phase (First Month)

• Check serum potassium at 1 month after starting finerenone 1, 2
• Assess eGFR at 1 month to ensure stability 1

Maintenance Phase

• Monitor serum potassium every 4 months during ongoing therapy 1, 2
• Monitor eGFR every 4 months 1
• Reassess UACR at month 4 to evaluate albuminuria response 1

Potassium Management Algorithm

Use this threshold-based approach for ongoing potassium monitoring:

• Potassium ≤4.8 mmol/L: Continue current finerenone dose; proceed with uptitration if at 1-month mark 1, 2
• Potassium 4.9–5.5 mmol/L: Continue finerenone at current dose without adjustment; maintain monitoring every 4 months 1, 2
• Potassium >5.5 mmol/L: Immediately hold finerenone, evaluate dietary potassium intake, review concomitant medications (NSAIDs, potassium supplements, other potassium-sparing agents), and recheck potassium to confirm downtrend 1, 2
• Restart protocol: When potassium returns to ≤5.0 mmol/L, restart finerenone at 10 mg daily (regardless of prior dose) 1, 2

Important Nuance on Hyperkalemia Risk

Hyperkalemia occurs in 14% of finerenone-treated patients versus 6.9% with placebo, yet permanent discontinuation is rare (1.7% vs 0.6% over 3 years), and no deaths from hyperkalemia occurred in the pivotal trials. 2, 5 The risk is higher with lower eGFR (<45 mL/min/1.73 m²) and beta-blocker use, but is reduced when SGLT2 inhibitors are co-administered. 1

Absolute Contraindications

Do not initiate finerenone if:

• eGFR <25 mL/min/1.73 m² or end-stage renal disease (no established dosing or safety data for this population) 1, 2
• Baseline serum potassium >4.8 mmol/L 3, 1, 2
• Patient is on dialysis or has ESRD 1

Relative Contraindications (Trial Exclusion Criteria)

• Heart failure with reduced ejection fraction (HFrEF) was excluded from FIGARO-DKD, though the 2024 DCRM guideline now recommends finerenone for HFpEF/HFmrEF with CKD 1, 6
• Uncontrolled hypertension (excluded from FIGARO-DKD) 1

Expected Clinical Benefits

Finerenone provides dual cardiorenal protection with robust trial evidence:

Kidney Protection

• 23% reduction in composite kidney outcome (kidney failure, ≥57% eGFR decline, or renal death) in pooled FIDELITY analysis 1, 2
• 36% reduction in progression to end-stage kidney disease in FIDELIO-DKD 3, 1, 5
• 18% reduction in composite kidney outcome (kidney failure, ≥40% eGFR decline, or kidney death) 1, 2

Cardiovascular Protection

• 14% reduction in major cardiovascular events (CV death, nonfatal MI, nonfatal stroke, or heart failure hospitalization) 1, 2, 5
• 29% reduction in heart failure hospitalizations 5
• 25% reduction in new-onset symptomatic heart failure in patients without baseline HFrEF 2
• 29% reduction in new-onset atrial fibrillation 7

These benefits apply across the broad spectrum of patients, including those with baseline heart failure or atherosclerotic cardiovascular disease. 8

Management of Creatinine Rise

An acute eGFR decline of approximately 2.9 mL/min/1.73 m² during the first 3 months is an expected hemodynamic effect, not acute kidney injury. 1

Continue finerenone if:

• Serum creatinine rise is <30% from baseline 1
• No evidence of volume depletion or nephrotoxin exposure (NSAIDs, contrast, aminoglycosides) 1
• Patient is clinically stable without acute illness 1

Temporarily hold finerenone if:

• Serum creatinine increase exceeds 30% from baseline 1
• Volume depletion, hypotension, or acute illness is present 1
• Recent nephrotoxin exposure occurred 1

This creatinine pattern mirrors that of ACE inhibitors/ARBs and reflects beneficial hemodynamic reduction of intraglomerular pressure, not tubular damage. 1

Common Pitfalls to Avoid

• Do not start finerenone before optimizing RAS inhibitor therapy—patients must be on maximum tolerated ACE inhibitor or ARB dose first 2
• 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, 2
• Do not mistake hemodynamic creatinine changes for AKI—creatinine rises <30% without volume depletion or nephrotoxin exposure support long-term kidney protection 1
• Do not consider SGLT2 inhibitors and finerenone interchangeable—they have complementary mechanisms and can be combined for additive cardiorenal protection 2
• Do not overlook the cardiovascular benefits—finerenone reduces major cardiovascular events, heart failure hospitalization, and sudden cardiac death beyond its antiproteinuric effect 2

Nephrology Referral Triggers

Refer to nephrology when:

• eGFR falls below 30 mL/min/1.73 m² (stage 4 CKD) to discuss renal replacement therapy 1
• Creatinine rise >30% from baseline persists despite holding potential offending agents 1
• Persistent hyperkalemia despite dietary and medication adjustments 1
• Etiology of kidney disease is uncertain 1