How should I manage an increase in serum creatinine in a patient receiving finerenone?

Managing Finerenone-Associated Creatinine Rise

A modest rise in serum creatinine up to 30% from baseline with finerenone should not prompt discontinuation, as this represents an expected hemodynamic effect rather than acute kidney injury, and continuation of therapy is appropriate when potassium remains ≤5.5 mmol/L. 1, 2

Understanding the Creatinine Rise

• Finerenone causes a predictable acute decline in eGFR of approximately 2.9 mL/min/1.73 m² during the first 3 months of therapy, which is hemodynamic in nature and does not represent true kidney injury 3
• This initial eGFR decline is similar to the well-characterized effect seen with RAS inhibitors (ACE inhibitors and ARBs), where creatinine increases up to 30% are expected and do not indicate acute kidney injury 1
• The ACCORD BP trial demonstrated that patients with up to 30% creatinine increases from intensive blood pressure lowering had no increase in mortality or progressive kidney disease, and markers of actual kidney injury were not elevated 1

Management Algorithm for Creatinine Changes

Continue finerenone if:

• Serum creatinine rise is <30% from baseline 1
• Serum potassium remains ≤5.5 mmol/L 2, 4
• No evidence of volume depletion or concurrent nephrotoxic exposures 1
• Patient is clinically stable without signs of acute illness 1

Temporarily hold finerenone and investigate if:

• Serum creatinine rise exceeds 30% from baseline 1
• Concurrent volume depletion, hypotension, or acute illness is present 1
• Serum potassium exceeds 5.5 mmol/L (hold for hyperkalemia, not creatinine) 2, 4
• Patient has been exposed to nephrotoxins (NSAIDs, iodinated contrast, aminoglycosides) 1

Monitoring Protocol

• Check serum creatinine and eGFR at baseline, 1 month after initiation, then every 4 months during maintenance therapy 2, 4
• Simultaneously monitor serum potassium at these intervals, as hyperkalemia is the primary safety concern, not creatinine changes 2, 4
• Measure UACR at baseline and month 4 to assess therapeutic response 2
• Expect the acute eGFR decline to stabilize after 3 months, with no significant difference in chronic eGFR slope thereafter 3

Key Distinctions from True AKI

• Nonsteroidal mineralocorticoid receptor antagonists like finerenone do not increase the risk of acute kidney injury when used appropriately 1
• The creatinine rise with finerenone reflects reduced intraglomerular pressure (a beneficial hemodynamic effect) rather than tubular injury 1, 3
• In the FIDELIO-DKD and FIGARO-DKD trials, finerenone demonstrated a 36% reduction in progression to end-stage kidney disease despite causing initial eGFR declines 2

Common Pitfalls to Avoid

• Do not discontinue finerenone for modest creatinine elevations <30%, as this mirrors the well-established pattern with RAS inhibitors where continuation provides long-term kidney protection 1, 2
• Do not confuse hemodynamic creatinine changes with acute kidney injury—the absence of volume depletion, nephrotoxin exposure, and clinical instability argues against true AKI 1
• Do not underdose finerenone due to fear of creatinine rise—the clinical trials demonstrating efficacy used maximally tolerated doses (10-20 mg daily based on eGFR), not conservative low doses 1, 2
• Do not restart finerenone at the same dose if it was held for potassium >5.5 mmol/L—resume at 10 mg daily once potassium returns to ≤5.0 mmol/L 2, 4

When to Refer to Nephrology

• eGFR falls below 30 mL/min/1.73 m² (stage 4 CKD) for discussion of renal replacement therapy planning 2
• Creatinine rise exceeds 30% from baseline and does not stabilize after holding potential offending agents 1
• Recurrent hyperkalemia (>5.5 mmol/L) despite dietary modification and medication review 2, 4