Management of Spironolactone in Acute Kidney Injury
Continue spironolactone in mild AKI unless creatinine exceeds 2.5 mg/dL in men or 2.0 mg/dL in women (eGFR <30 mL/min/1.73 m²), or potassium exceeds 5.0 mEq/L, as discontinuation is associated with 2-4 fold higher risk of adverse cardiovascular events. 1, 2
Evidence-Based Decision Algorithm
Continue Spironolactone If:
- Creatinine ≤2.5 mg/dL (men) or ≤2.0 mg/dL (women) AND eGFR >30 mL/min/1.73 m² AND potassium <5.0 mEq/L 1
- Small to moderate worsening of renal function during AKI does not represent true contraindication to continuation, as oral guideline-directed medical therapy should not be withheld for mild deteriorations 1
- Spironolactone and beta-blockers may actually be protective in heart failure patients with worsening renal function 1
Reduce Spironolactone Dose If:
- Potassium 5.0-5.5 mEq/L: Reduce to 12.5 mg every other day 3, 2
- Creatinine >220 μmol/L (2.5 mg/dL): Halve dose to 25 mg on alternate days 4, 3
- eGFR 30-49 mL/min/1.73 m²: Reduce to 12.5 mg once daily or every other day 3
Discontinue Spironolactone If:
- Potassium ≥6.0 mEq/L despite dose reduction 4, 3
- Creatinine >310 μmol/L (3.5 mg/dL) 4
- eGFR <30 mL/min/1.73 m² with concurrent hyperkalemia 2
Critical Monitoring Protocol
Check potassium and creatinine within 2-3 days after recognizing AKI, then again at 7 days, and monitor at least monthly for the first 3 months 1
- Recheck at 1 week and 4 weeks after any dose adjustment 3
- Continue monitoring at 8 weeks and 12 weeks 3
- Any increase in ACE inhibitor or ARB dosing triggers a new monitoring cycle 1
Rationale for Continuation Strategy
The 2025 European Society of Cardiology consensus statement emphasizes that discontinuing mineralocorticoid receptor antagonists during hospitalization is associated with worse outcomes 2, 1. This recommendation is based on compelling evidence:
- Continuation during hospitalization was associated with lower 30-day mortality and heart failure rehospitalization in the COACH study 1
- Spironolactone discontinuation increases risk of subsequent adverse events by 2-4 fold, even when stopped for hyperkalemia or low glomerular filtration rate 2, 1
- Analysis from the Stockholm SCREAM project showed that stopping an MRA after hyperkalemia reduced recurrent hyperkalemia risk but increased risk of death or cardiovascular events 2
Common Pitfalls to Avoid
Do not use relative changes in creatinine as discontinuation criteria—use absolute threshold values instead 1. A rise in creatinine during AKI does not automatically warrant discontinuation if it remains below the absolute thresholds.
Do not assume AKI is caused by spironolactone alone—investigate volume depletion, as high-dose loop diuretics combined with spironolactone can cause pre-renal azotemia that is reversible with volume optimization 3, 4
Do not discontinue based on eGFR alone without considering potassium levels and clinical context 3, 2. The mortality benefit of spironolactone persists even in advanced chronic kidney disease despite increased adverse event risk 3.
Balancing Risk and Benefit
While spironolactone increases risk of hyperkalemia (incidence 2.9 events per 1000 person-months) and AKI (10.1 events per 1000 person-months) 5, these risks are amplified primarily in patients with baseline eGFR <30 mL/min/1.73 m² 6. However, the consistent efficacy across all eGFR categories supports continuation with intensified monitoring rather than automatic discontinuation 6.
Real-world data shows that 7.2% of patients require discontinuation due to hyperkalemia or renal failure 7, but this must be weighed against the substantial mortality benefit. The key is using absolute threshold values combined with intensified monitoring rather than reflexive discontinuation 1.