How should finerenone be started, dosed, titrated, and monitored in an adult with type 2 diabetes mellitus, diabetic kidney disease, estimated glomerular filtration rate ≥25 mL/min/1.73 m² and persistent albuminuria (urinary albumin‑to‑creatinine ratio ≥30 mg/g) despite maximally tolerated angiotensin‑converting enzyme inhibitor or angiotensin receptor blocker therapy?

Finerenone Initiation, Dosing, Titration, and Monitoring in Diabetic Kidney Disease

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, after confirming serum potassium is ≤4.8 mmol/L, and uptitrate to 20 mg daily after 1 month if potassium remains ≤4.8 mmol/L and eGFR is stable. 1

Patient Selection Criteria

Before initiating finerenone, verify the following eligibility criteria:

• Type 2 diabetes with persistent albuminuria (UACR ≥30 mg/g) despite maximally tolerated ACE inhibitor or ARB therapy 1, 2
• eGFR ≥25 mL/min/1.73 m² (CKD stages 2–4) 1, 2
• Serum potassium ≤4.8 mmol/L at baseline 1
• Already on maximum tolerated dose of RAS inhibitor (ACE inhibitor or ARB) 2, 3

Critical pitfall to avoid: Do not start finerenone before optimizing RAS inhibitor therapy—patients must be on the maximum tolerated dose of an ACE inhibitor or ARB first. 3 Starting finerenone prematurely undermines the evidence-based treatment sequence and may expose patients to unnecessary hyperkalemia risk.

Treatment Sequencing Algorithm

The evidence-based treatment hierarchy for diabetic kidney disease is:

1. First-line foundation: Maximum tolerated dose of ACE inhibitor or ARB 2
2. Second-line priority: SGLT2 inhibitor (larger effects on kidney and cardiovascular outcomes) 2
3. Third-line consideration: Finerenone for persistent albuminuria despite SGLT2 inhibitor, or as an alternative when SGLT2 inhibitors are contraindicated or not tolerated 2, 3

The KDIGO 2022 guidelines and American College of Cardiology position finerenone as add-on therapy after RAS inhibition and, when tolerated, SGLT2 inhibitor therapy. 2, 3 However, finerenone can be used as an alternative when SGLT2 inhibitors cannot be used. 3

Initial Dosing Protocol

Dose selection is based solely on baseline eGFR:

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

This eGFR-based dosing strategy was used in both FIDELIO-DKD and FIGARO-DKD trials and reflects the need to balance efficacy with hyperkalemia risk in patients with more advanced kidney disease. 1

Dose Titration Strategy

After 1 month of treatment, uptitrate from 10 mg to 20 mg once daily if:

• Serum potassium remains ≤4.8 mmol/L 1
• eGFR is stable (no significant decline) 1
• The medication is well-tolerated 2

The 1-month timepoint captures the predictable initial rise in potassium that occurs with mineralocorticoid receptor antagonism and allows assessment of eGFR stability before dose escalation. 2

Potassium Monitoring Protocol

Pre-Initiation Requirements

• Verify serum potassium ≤4.8 mmol/L before starting finerenone 1, 2
• Patients with baseline potassium >4.8 mmol/L should not initiate therapy due to excessive hyperkalemia risk 2

Initial Monitoring Phase

• Check serum potassium at 1 month after starting finerenone to capture the initial potassium rise 2

Maintenance Monitoring Schedule

• Monitor serum potassium every 4 months during ongoing therapy 2

This schedule allows early detection of hyperkalemia while minimizing unnecessary testing burden. 2

Potassium-Based Management Algorithm

For potassium ≤4.8 mmol/L:

• Continue current finerenone dose (10 mg or 20 mg daily) 2
• Continue monitoring every 4 months 2

For potassium 4.9–5.5 mmol/L:

• Continue finerenone at current dose without adjustment 2
• Maintain monitoring every 4 months 2

For potassium >5.5 mmol/L:

• Immediately hold finerenone 2
• Evaluate and adjust dietary potassium intake 2
• Review concomitant medications that may contribute to hyperkalemia (NSAIDs, potassium supplements, potassium-sparing diuretics) 2
• Recheck potassium levels to confirm downtrend 2
• Restart finerenone at 10 mg daily when potassium returns to ≤5.0 mmol/L 2

Critical pitfall to avoid: Do not permanently discontinue finerenone for a single episode of potassium >5.5 mmol/L unless other interventions fail. 2 Temporary interruption with dose reduction upon restart (10 mg daily) successfully manages most cases. 2

Safety Profile and Hyperkalemia Context

The pooled FIDELITY analysis (13,026 patients) demonstrated that hyperkalemia occurred in 14% of finerenone patients versus 6.9% with placebo, yet permanent discontinuation due to hyperkalemia was rare (1.7% vs 0.6%). 2, 4 No deaths were attributed to hyperkalemia in either FIDELIO-DKD or FIGARO-DKD trials over a median 3-year follow-up. 1, 3

Risk factors for hyperkalemia include:

• Lower eGFR (particularly <45 mL/min/1.73 m²) 2
• Beta-blocker use 2

Protective factors that reduce hyperkalemia risk:

• SGLT2 inhibitor co-administration 2

Real-world data from Japan (120 patients with DKD) confirmed that symptomatic hypotension, acute kidney injury, and hyperkalemia leading to drug discontinuation were uncommon in clinical practice. 5

Additional Monitoring Parameters

Beyond potassium, monitor:

• eGFR at baseline, 1 month, then every 4 months to assess kidney function stability 2
• UACR at baseline and month 4 to assess albuminuria response 1
• Blood pressure as finerenone causes a small reduction in systolic blood pressure 6

Clinical Benefits to Expect

Finerenone provides dual cardiorenal protection:

• 23% reduction in composite kidney outcome (kidney failure, sustained ≥57% eGFR decrease, or renal death) in the pooled FIDELITY analysis 1, 3, 4
• 14% reduction in composite cardiovascular outcome (cardiovascular death, nonfatal MI, nonfatal stroke, or heart failure hospitalization) 1, 3, 4
• 36% reduction in progression to end-stage kidney disease in FIDELIO-DKD 1, 2
• 29% reduction in heart failure hospitalizations in FIGARO-DKD 3

Real-world analysis demonstrated that finerenone significantly improved the rate of eGFR decline from -4.99 to -0.59 mL/min/1.73 m²/year (P <0.0001) and reduced UACR from 908 to 487 mg/gCr (P <0.0001). 5

Combination Therapy Considerations

Finerenone can be safely combined with SGLT2 inhibitors for complementary cardiorenal protection. 3, 7 The mechanisms are additive: SGLT2 inhibitors reduce intraglomerular pressure and provide metabolic benefits, while finerenone blocks mineralocorticoid receptor-mediated inflammation and fibrosis. 7, 6 Real-world data suggest that the eGFR slope improves regardless of whether SGLT2 inhibitor therapy is used concomitantly. 5

Do not consider SGLT2 inhibitors and finerenone interchangeable—they have complementary mechanisms and should be layered sequentially according to the treatment algorithm. 3

When NOT to Use Finerenone

Absolute contraindications:

• eGFR <25 mL/min/1.73 m² or end-stage renal disease (no established dosing or safety data) 2
• Baseline potassium >4.8 mmol/L 1, 2
• Not on maximum tolerated RAS inhibitor therapy 2, 3

Relative contraindications (trial exclusion criteria):

• Heart failure with reduced ejection fraction (excluded from FIGARO-DKD) 1
• Uncontrolled hypertension (excluded from FIGARO-DKD) 1

The landmark trials (FIDELIO-DKD and FIGARO-DKD) specifically excluded patients with eGFR <25 mL/min/1.73 m², and there is no established dosing or safety data for this population. 2