How should finerenone be initiated, titrated, and monitored in an adult with type 2 diabetes mellitus and chronic kidney disease who has mild‑to‑moderate renal impairment (eGFR > 25 mL/min/1.73 m²) and normokalemia, and what are its contraindications and alternative therapies?

Finerenone Initiation, Titration, and Monitoring in Type 2 Diabetes with CKD

Patient Eligibility and Pre-Initiation Requirements

For an adult with type 2 diabetes, CKD (eGFR > 25 mL/min/1.73 m²), and normokalemia, finerenone should be initiated at 10 mg once daily after confirming persistent albuminuria (UACR ≥30 mg/g) despite maximum tolerated ACE inhibitor or ARB therapy, baseline serum potassium ≤4.8 mmol/L, and preferably after SGLT2 inhibitor therapy or if SGLT2i is contraindicated. 1, 2

Mandatory Pre-Treatment Criteria

• Confirm persistent albuminuria (UACR ≥30 mg/g) despite maximum tolerated RAS inhibitor (ACE inhibitor or ARB) therapy. 1, 2
• Verify baseline serum potassium ≤4.8 mmol/L—this is an absolute requirement before starting therapy. 1, 3, 2
• Document eGFR ≥25 mL/min/1.73 m²—patients below this threshold have no established dosing or safety data and were excluded from pivotal trials. 1, 2
• Ensure the patient is already on a maximally tolerated dose of ACE inhibitor or ARB as foundation therapy. 1, 2

Treatment Sequencing Hierarchy

The evidence-based treatment sequence for diabetic kidney disease follows a clear three-tier approach:

• First-line foundation: Maximum tolerated ACE inhibitor or ARB. 1, 2
• Second-line priority: SGLT2 inhibitor, which provides the largest effect on renal and cardiovascular outcomes. 1, 2
• Third-line consideration: Finerenone for patients with persistent albuminuria despite SGLT2 inhibitor therapy, or when SGLT2 inhibitor is contraindicated or not tolerated. 1, 2

This hierarchy is endorsed by KDIGO 2022 and ADA 2024 guidelines, reflecting the strength of evidence for each intervention. 1, 2

Initial Dosing Protocol

eGFR-Based Starting Dose

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

For your patient with mild-to-moderate renal impairment (eGFR > 25 mL/min/1.73 m²), the starting dose will be 10 mg once daily if eGFR is between 25–60 mL/min/1.73 m², or 20 mg once daily if eGFR exceeds 60 mL/min/1.73 m². 1, 2

This eGFR-based dosing strategy was applied in the FIDELIO-DKD and FIGARO-DKD trials to balance efficacy with hyperkalemia risk. 1

Dose Titration Strategy

One-Month Titration Protocol

After 1 month of treatment, increase the dose from 10 mg to 20 mg once daily if all three conditions are met: 1, 3, 2

• Serum potassium remains ≤4.8 mmol/L. 1, 2
• eGFR is stable (no clinically significant decline). 1
• The medication is well tolerated without adverse effects. 1

The 1-month interval captures the predictable early rise in potassium associated with mineralocorticoid receptor antagonism, allowing safe dose escalation. 1

Monitoring Protocol

Potassium Monitoring Schedule

• Pre-initiation: Confirm serum potassium ≤4.8 mmol/L. 1, 2
• At 1 month: Recheck potassium to assess for early hyperkalemia and guide dose titration. 1, 2
• Every 4 months: Monitor potassium during ongoing maintenance therapy. 1

Potassium-Based Management Algorithm

The following thresholds guide continuation, monitoring, or temporary discontinuation:

• Potassium ≤4.8 mmol/L: Continue current dose (10 mg or 20 mg daily) and maintain routine monitoring every 4 months. 1
• Potassium 4.9–5.5 mmol/L: Continue finerenone at current dose without adjustment; maintain monitoring every 4 months. 1
• 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
• Restart protocol: When potassium returns to ≤5.0 mmol/L, restart finerenone at 10 mg daily (regardless of prior dose). 1, 2

Additional Monitoring Parameters

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

Management of Creatinine Increases

A rise in serum creatinine up to 30% from baseline after starting finerenone is an anticipated hemodynamic effect reflecting reduced intraglomerular pressure, not acute kidney injury. 1

• Continue finerenone if creatinine rise is < 30% from baseline, no volume depletion is present, and the patient is clinically stable. 1
• Temporarily hold finerenone if creatinine increase exceeds 30% from baseline, or if volume depletion, hypotension, acute illness, or recent nephrotoxin exposure (NSAIDs, contrast, aminoglycosides) is identified. 1

This pattern mirrors that seen with ACE inhibitors and ARBs, where modest creatinine elevations support long-term kidney protection rather than signaling harm. 1

Absolute Contraindications

• eGFR < 25 mL/min/1.73 m² or end-stage renal disease—no established dosing or safety data exists for this population. 1, 2
• Baseline serum potassium > 4.8 mmol/L—excessive hyperkalemia risk precludes initiation. 1, 2

Relative Contraindications (Trial Exclusion Criteria)

• Heart failure with reduced ejection fraction was excluded from FIGARO-DKD, though finerenone is now recommended for HFpEF (EF ≥50%) or HFmrEF (EF 41–49%) with CKD per DCRM 2.0 (2024) guidelines. 1
• Uncontrolled hypertension was an exclusion criterion in FIGARO-DKD. 1

Expected Clinical Benefits

The evidence supporting finerenone is robust, derived from two large phase III trials (FIDELIO-DKD and FIGARO-DKD) and their pooled FIDELITY analysis:

• Kidney protection: 23% reduction in composite kidney outcome (kidney failure, ≥57% eGFR decline, or renal death). 1, 4
• Progression to end-stage kidney disease: 36% risk reduction. 1, 2
• Cardiovascular protection: 14% reduction in composite cardiovascular outcome (CV death, non-fatal MI, non-fatal stroke, or heart failure hospitalization). 1, 3, 2, 4
• Heart failure hospitalization: 29% risk reduction. 3, 2

These benefits were demonstrated over a median follow-up of 3.0 years in patients with eGFR ≥25 mL/min/1.73 m² and persistent albuminuria. 4

Safety Profile and Hyperkalemia Management

Hyperkalemia Incidence

• Hyperkalemia occurred in 10.8–14% of finerenone patients versus 5.3–6.9% with placebo in pooled trial data. 1, 3
• Severe hyperkalemia requiring permanent discontinuation occurred in only 1.2–1.7% of patients, with no deaths from hyperkalemia over 3 years. 1, 2

Risk Factors for Hyperkalemia

• Lower eGFR (particularly < 45 mL/min/1.73 m²) increases hyperkalemia risk. 1
• Beta-blocker use is an independent risk factor. 1
• SGLT2 inhibitor co-administration is protective and reduces hyperkalemia risk. 1, 5

Practical Hyperkalemia Prevention

• Consider new oral potassium binders (e.g., patiromer, sodium zirconium cyclosilicate) not to lower potassium per se, but to avoid discontinuing or allow dose escalation of RAS inhibitors or finerenone. 5
• 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 (10 mg daily) successfully manages most cases. 1

Alternative Therapies

If finerenone is contraindicated, not tolerated, or ineffective, consider:

• SGLT2 inhibitors (if not already prescribed)—these provide the largest effect on renal and cardiovascular outcomes and should be prioritized before finerenone. 1, 2
• GLP-1 receptor agonists—recommended by ADA guidelines as first-line for cardiorenal protection alongside SGLT2 inhibitors. 3
• Steroidal MRAs (spironolactone, eplerenone)—these have higher hyperkalemia risk and are less selective than finerenone, but may be considered in specific contexts. 5, 6

Nephrology Referral Triggers

Refer to nephrology when:

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

Common Pitfalls to Avoid

• Do not initiate finerenone before optimizing RAS inhibitor therapy—patients must be on maximum tolerated ACE inhibitor or ARB first. 1, 2
• Do not underdose finerenone out of fear of creatinine rise—pivotal trials used maximally tolerated doses (10–20 mg daily, adjusted for eGFR). 1
• Do not mistake hemodynamic creatinine changes for acute kidney injury—the absence of volume depletion, nephrotoxin exposure, and clinical instability argues against true AKI. 1
• Do not permanently discontinue for borderline potassium elevations—potassium measurements have inherent variability; consider repeating before making treatment decisions. 1
• Do not ignore the treatment hierarchy—SGLT2 inhibitors should be prioritized over finerenone as second-line therapy after RAS inhibition. 1, 2

Early Initiation Advantage

Starting finerenone early when eGFR is maintained reduces hyperkalemia risk and provides stronger clinical benefit, as demonstrated in the FIDELITY analysis. 5 The combination of RAS inhibitors, finerenone, and SGLT2 inhibitors appears to be the most promising treatment strategy for diabetic kidney disease. 5