For a patient with type 2 diabetes mellitus and chronic kidney disease (eGFR ≥ 25 mL/min/1.73 m²) with persistent albuminuria despite maximally tolerated ACE inhibitor or ARB, how should finerenone be initiated, what is the dosing and titration schedule, what monitoring is required, and what are its contraindications and additional renal‑protective strategies?

Finerenone Initiation and Management in Type 2 Diabetes with CKD

Patient Eligibility and Prerequisites

Finerenone should be initiated only after confirming the patient is on a maximally tolerated ACE inhibitor or ARB, has persistent albuminuria (UACR ≥30 mg/g), eGFR ≥25 mL/min/1.73 m², and serum potassium ≤4.8 mmol/L. 1, 2

• The patient must have type 2 diabetes with CKD stages 2–4 (eGFR 25–90 mL/min/1.73 m²) 1, 2
• Persistent albuminuria must be documented despite maximum tolerated RAS inhibitor therapy 1, 2, 3
• Baseline serum potassium must be verified at ≤4.8 mmol/L before starting therapy 1, 2
• The patient must already be receiving the maximum tolerated dose of an ACE inhibitor or ARB—this is an absolute prerequisite 1, 2

Treatment Sequencing Algorithm

SGLT2 inhibitors should be prioritized as second-line therapy after RAS inhibition, with finerenone reserved as third-line for patients with persistent albuminuria despite SGLT2 inhibitor therapy or when SGLT2 inhibitors are contraindicated or not tolerated. 1, 2, 3

The evidence-based treatment hierarchy is:

1. First-line foundation: Maximize ACE inhibitor or ARB dose to the highest tolerated amount 1, 2
2. Second-line priority: Add an SGLT2 inhibitor, which provides the largest incremental cardiorenal benefit 1, 2
3. Third-line consideration: Introduce finerenone when albuminuria remains elevated (UACR ≥30 mg/g) despite SGLT2 inhibitor therapy, or when SGLT2 inhibitors cannot be used 1, 2, 3

This hierarchy reflects KDIGO 2022 and ADA 2024 guideline recommendations, which prioritize SGLT2 inhibitors due to their superior magnitude of renal and cardiovascular benefit 1, 2.

Dosing Protocol

Initial Dosing Based on eGFR

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

Baseline eGFR	Starting Dose
25–60 mL/min/1.73 m²	10 mg once daily
>60 mL/min/1.73 m²	20 mg once daily

This eGFR-stratified dosing was established in the FIDELIO-DKD and FIGARO-DKD trials to balance efficacy with hyperkalemia risk 1, 4, 5.

Dose Titration After 1 Month

Increase the dose from 10 mg to 20 mg daily after 1 month 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, 2
• The medication must be well tolerated without adverse effects 1

Monitoring Requirements

Potassium Monitoring Schedule

Check serum potassium before initiation, at 1 month, then every 4 months during maintenance therapy. 1, 2

• Pre-initiation: Verify potassium ≤4.8 mmol/L 1, 2
• 1 month after starting: Assess for early potassium rise 1, 2
• Every 4 months thereafter: Ongoing surveillance during continued therapy 1, 2

Potassium-Based Management Algorithm

Serum Potassium (mmol/L)	Action
≤4.8	Continue current dose (10 or 20 mg); monitor every 4 months [1,2]
4.9–5.5	Continue current dose without adjustment; maintain monitoring every 4 months [1,2]
>5.5	Immediately hold finerenone; evaluate dietary potassium, review concomitant medications, recheck potassium; restart at 10 mg daily when potassium returns to ≤5.0 mmol/L [1,2]

Do not permanently discontinue finerenone for a single episode of potassium >5.5 mmol/L—temporary interruption with dose reduction upon restart successfully manages most cases. 1

Additional Monitoring Parameters

• eGFR: Assess at baseline, 1 month, then every 4 months 1, 2
• UACR: Obtain at baseline and month 4 to evaluate albuminuria response 1
• Creatinine rise up to 30% from baseline is an expected hemodynamic effect and does not require discontinuation, provided potassium remains ≤5.5 mmol/L and the patient is clinically stable 1

Absolute Contraindications

Finerenone must not be initiated in the following circumstances: 1, 2

• eGFR <25 mL/min/1.73 m² or end-stage renal disease (no established dosing or safety data) 1
• Baseline serum potassium >4.8 mmol/L 1, 2
• Patient not receiving a maximally tolerated RAS inhibitor (ACE inhibitor or ARB) 2
• Patient on dialysis 1

Relative Contraindications (Trial Exclusion Criteria)

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

Expected Clinical Benefits

Finerenone provides dual cardiorenal protection with a 23% reduction in kidney disease progression and a 14% reduction in major cardiovascular events. 1, 3

Kidney Outcomes

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

Cardiovascular Outcomes

• 14% reduction in composite cardiovascular endpoint (CV death, non-fatal MI, non-fatal stroke, or heart failure hospitalization) in pooled FIDELITY analysis 1, 3
• 13% reduction in cardiovascular events in FIGARO-DKD 3, 5
• 29% reduction in heart failure hospitalization 3, 6, 5
• 25% reduction in new-onset symptomatic heart failure in patients without baseline HFrEF 3, 6

These benefits were demonstrated in the phase 3 FIDELIO-DKD and FIGARO-DKD trials, representing high-quality (Level A) evidence 1, 3, 4, 5.

Safety Profile

Hyperkalemia is the primary safety concern, occurring in 14% of finerenone-treated patients versus 6.9% with placebo, but permanent discontinuation remains low at 1.7% versus 0.6% over 3 years. 1, 2, 3

• No deaths were attributed to hyperkalemia during a median 3-year follow-up in the pivotal trials 1, 2, 3
• Hyperkalemia leading to hospitalization or study drug discontinuation was low across all treatment groups 7

Risk Factors for Hyperkalemia

• Higher risk: Lower eGFR, particularly <45 mL/min/1.73 m² 1
• Protective factors: Concomitant SGLT2 inhibitor use 1; concomitant diuretic use 7

Additional Renal-Protective Strategies

Finerenone should be combined with other evidence-based cardiorenal therapies for maximal protection. 1, 2, 3

• Continue maximally tolerated ACE inhibitor or ARB therapy 1, 2
• Add or continue SGLT2 inhibitor when tolerated—these agents have complementary mechanisms and can be safely combined 1, 3
• Optimize blood pressure control and glycemic management 1
• Implement dietary potassium restriction when potassium levels rise 1, 2
• Review and adjust concomitant medications that may contribute to hyperkalemia (NSAIDs, potassium-sparing diuretics, potassium supplements) 1

Nephrology Referral Thresholds

Refer to nephrology when eGFR falls below 30 mL/min/1.73 m² (stage 4 CKD) for discussion of renal replacement therapy. 1

• Also refer if creatinine rise >30% from baseline fails to stabilize after holding potential offending agents 1
• Refer for persistent hyperkalemia despite dietary and medication adjustments 1

Common Pitfalls 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
• Do not permanently discontinue for a single potassium reading >5.5 mmol/L—temporary interruption with dose reduction upon restart 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 1
• Do not overlook the cardiovascular benefits—finerenone reduces major cardiovascular events, heart failure hospitalization, and sudden cardiac death beyond its antiproteinuric effect 3
• Do not consider SGLT2 inhibitors and finerenone interchangeable—they have complementary mechanisms and should be sequenced appropriately 3
• Do not underdose finerenone out of fear of creatinine rise—pivotal trials used the maximally tolerated dose (10–20 mg daily, adjusted for eGFR) 1