What to do with a patient with heart failure (HF) on spironolactone with impaired renal function, specifically an estimated glomerular filtration rate (eGFR) of 28?

Management of Spironolactone in Heart Failure with eGFR 28 mL/min/1.73 m²

Continue spironolactone at a reduced dose of 12.5 mg once daily or every other day, with close monitoring of potassium and renal function, as the mortality benefit persists even in advanced chronic kidney disease despite increased risk of adverse events. 1

Rationale for Continuation

The 2013 ACC/AHA guidelines explicitly provide dosing recommendations for spironolactone in patients with eGFR 30-49 mL/min/1.73 m², recommending an initial dose of 12.5 mg once daily or every other day, with maintenance dosing of 12.5-25 mg once daily. 1 While your patient's eGFR of 28 falls just below the 30 threshold, the evidence strongly supports continuation rather than discontinuation:

• Spironolactone discontinuation is associated with 2-4 fold higher risk of subsequent adverse cardiovascular events, even when stopped for hyperkalemia or renal dysfunction. 1
• In propensity-matched studies of HF patients with renal dysfunction (mean eGFR 46 mL/min/1.73 m²), spironolactone was associated with improved 2-year survival (84% vs 73%, HR 0.59) despite causing worsening renal function and increased potassium. 2
• The absolute mortality benefit of spironolactone is actually greatest in patients with reduced eGFR (10.3% absolute risk reduction vs 6.4% in those with eGFR >60). 3

Specific Dosing Algorithm for eGFR 28

Step 1: Check current potassium level immediately 1, 4

• If K⁺ ≤5.0 mEq/L: Reduce to 12.5 mg once daily 1
• If K⁺ 5.0-5.5 mEq/L: Reduce to 12.5 mg every other day 1
• If K⁺ 5.5-6.0 mEq/L: Reduce to 12.5 mg every other day and recheck in 72 hours 1
• If K⁺ >6.0 mEq/L: Hold spironolactone temporarily until K⁺ <5.0, then restart at 12.5 mg every other day 1

Step 2: Eliminate other potassium-raising medications 1, 4

• Discontinue potassium supplements (KCl) 1
• Avoid NSAIDs (including over-the-counter ibuprofen) 1
• Counsel patient to avoid "low salt" substitutes with high potassium content 1
• Review for combination diuretic preparations containing amiloride or triamterene 1

Intensive Monitoring Protocol

The FDA label and guidelines mandate more frequent monitoring in this eGFR range: 4

First month:

• Check potassium and creatinine at 1 week after dose adjustment 1
• Recheck at 4 weeks 1

Months 2-3:

• Check at 8 weeks and 12 weeks 1

Months 4-12:

• Check at 6 months, 9 months, and 12 months 1

After first year:

• Check every 6 months 1

Critical Thresholds for Discontinuation

Hold spironolactone if: 1

• Creatinine rises to >220 μmol/L (2.5 mg/dL): Reduce to 12.5 mg every other day
• Creatinine rises to >310 μmol/L (3.5 mg/dL): Stop immediately
• Potassium >6.0 mEq/L: Stop immediately until K⁺ <5.0, then consider restarting at lower dose

Permanently discontinue only if: 4

• Recurrent hyperkalemia >6.0 mEq/L despite dose reduction and elimination of other contributing factors
• Progressive renal decline to eGFR <20 mL/min/1.73 m² 1
• Patient develops acute kidney injury requiring dialysis

Common Pitfalls to Avoid

Do not automatically discontinue based on eGFR alone. The 2025 ESC consensus statement emphasizes that MRAs should be continued whenever possible, as discontinuation carries higher mortality risk than the adverse events themselves. 1 The eGFR of 28 is close to the guideline threshold, and the mortality benefit persists in this range. 2, 3

Do not ignore concurrent volume depletion. High-dose loop diuretics combined with spironolactone can cause hypovolemia and pre-renal azotemia, which may be reversible with volume optimization rather than spironolactone discontinuation. 1

Do not fail to counsel about diarrhea/vomiting. Instruct the patient to temporarily stop spironolactone during acute illness with volume loss and contact you immediately. 1

Do not overlook drug interactions. The incidence of hyperkalemia and renal insufficiency is higher in current practice (7.2%) than in the original RALES trial (2%) due to more frequent concurrent use of beta-blockers, ACE inhibitors, and ARBs. 5 Review the entire medication list for interactions.

Evidence Quality Considerations

The 2013 ACC/AHA guidelines provide the most authoritative dosing table for this specific clinical scenario (eGFR 30-49), though your patient falls just below this range. 1 The 2025 ESC consensus statement provides the most recent evidence emphasizing continuation over discontinuation in borderline cases. 1 The RALES post-hoc analysis demonstrates that worsening renal function on spironolactone does not eliminate the mortality benefit (interaction p=0.009), meaning the drug remains protective even when causing mild renal decline. 3

The TOPCAT-Americas analysis showed that while adverse events increase with declining eGFR, the efficacy of spironolactone remains consistent across all eGFR categories, supporting use in advanced CKD "when close laboratory surveillance is possible." 6 Your monitoring protocol above provides this surveillance framework.