Is spironolactone (aldosterone antagonist) safe to use in a patient with impaired renal function (eGFR 39) and reduced ejection fraction (EF 38%)?

Spironolactone Use in HFrEF with eGFR 39 and EF 38%

Spironolactone should be initiated cautiously at a reduced dose of 12.5 mg daily in this patient with HFrEF (EF 38%) and moderate renal impairment (eGFR 39 mL/min/1.73m²), as the mortality and hospitalization benefits are maintained—and potentially greater in absolute terms—in patients with reduced kidney function, provided potassium is <5.0 mEq/L and intensive monitoring is implemented. 1, 2

Rationale for Use Despite Renal Impairment

The evidence strongly supports spironolactone use in this clinical scenario:

• Patients with reduced baseline eGFR (30-60 mL/min/1.73m²) derive similar relative risk reductions but greater absolute risk reductions in mortality compared to those with normal renal function (10.3% vs 6.4% absolute risk reduction). 2

• The 2025 ESC Heart Failure Association guidelines explicitly recommend MRA initiation when eGFR >30 mL/min/1.73m² and potassium <5.0 mEq/L, which this patient meets. 3

• In the RALES trial, spironolactone reduced mortality from 46% to 35% (30% relative risk reduction) in patients with NYHA class III-IV heart failure, with the majority having creatinine ≤1.7 mg/dL (corresponding to eGFR approximately 35-45 mL/min/1.73m²). 3

Critical Pre-Initiation Requirements

Before starting spironolactone, verify the following:

• Baseline serum potassium must be <5.0 mEq/L 3, 1
• Confirm eGFR is >30 mL/min/1.73m² (this patient at 39 qualifies) 3, 1
• Discontinue all potassium supplements 3
• Review and minimize concomitant medications that increase hyperkalemia risk (NSAIDs, COX-2 inhibitors, high-dose ACE inhibitors/ARBs) 3

Dosing Strategy for eGFR 30-50 mL/min/1.73m²

Start with 12.5 mg daily (not 25 mg):

• The ACC/AHA guidelines recommend initiating at 12.5 mg daily or 25 mg every other day in patients with eGFR 30-50 mL/min/1.73m². 1, 3

• Do not attempt to reach the target dose of 25-50 mg daily if adverse effects occur—lower doses remain efficacious. In TOPCAT, patients with renal dysfunction received median doses of approximately 20 mg/day and still experienced benefit without significant heterogeneity in treatment effect. 4

• Dose escalation should only occur after 4-8 weeks if renal function and potassium remain stable. 3

Intensive Monitoring Protocol

This is non-negotiable for patient safety:

• Check potassium and renal function at 3 days and 1 week after initiation 3, 1
• Continue monthly monitoring for the first 3 months 3, 1
• Then monitor at 1,2,3, and 6 months after achieving maintenance dose, and every 6 months thereafter 3

Management of Complications

If potassium rises to 5.5-5.9 mEq/L:

• Reduce dose to 12.5 mg daily or 25 mg every other day 1
• Recheck potassium within 1 week 1

If potassium ≥6.0 mEq/L:

• Stop spironolactone immediately 3, 1
• Implement specific hyperkalemia treatment as needed 3

If creatinine rises to >2.5 mg/dL (or eGFR drops significantly):

• Halve the dose and monitor closely 3
• If creatinine exceeds 3.5 mg/dL, stop spironolactone immediately 3

Critical Caveats and Common Pitfalls

Serum creatinine underestimates renal dysfunction in elderly patients and those with low muscle mass—always use eGFR for assessment. 3, 1

The risk of hyperkalemia increases progressively as eGFR declines below 45 mL/min/1.73m²:

• In TOPCAT, patients with eGFR ≤60 mL/min/1.73m² had 30% discontinuation rates during the first year. 4
• However, discontinuation of spironolactone was associated with a 2-4 fold higher risk of subsequent adverse events, emphasizing the importance of maintaining therapy when possible. 3, 4

Avoid triple RAAS blockade (ACE inhibitor + ARB + spironolactone) due to extremely high hyperkalemia risk. 3, 1

Worsening renal function during spironolactone therapy:

• In RALES, 17% of spironolactone patients experienced worsening renal function (defined as 30% reduction in eGFR) versus 7% on placebo. 2
• Importantly, worsening renal function was associated with increased mortality in the placebo group (HR 1.9) but not in the spironolactone group (HR 1.1), suggesting spironolactone provides protection despite renal decline. 2

Net Clinical Benefit

Despite increased risks of hyperkalemia and renal dysfunction, the substantial net benefit of spironolactone therapy is maintained in patients with eGFR 30-45 mL/min/1.73m². 2 The absolute mortality benefit is actually greatest in those with reduced eGFR, making the risk-benefit ratio favorable when appropriate monitoring is implemented. 2, 5