Does aldactone (spironolactone) increase serum creatinine levels?

Does Aldactone (Spironolactone) Raise Creatinine Levels?

Yes, spironolactone can cause serum creatinine to rise, though this elevation is typically modest (not exceeding 30-50% from baseline in most patients) and represents hemodynamically-mediated changes in renal perfusion rather than true kidney damage. 1

Mechanism of Creatinine Elevation

The creatinine increase occurs through aldosterone blockade effects on renal hemodynamics, reducing glomerular filtration rate by altering intrarenal blood flow dynamics rather than causing direct nephrotoxicity. 1 This is an expected pharmacologic effect, not necessarily a sign of kidney injury.

Clinical Evidence

Landmark Trial Data

• In the RALES trial, rising creatinine occurred more commonly in the spironolactone group compared to placebo, though patients with baseline creatinine >2.5 mg/dL were excluded from enrollment. 2, 1
• Research studies confirm this effect: one study showed serum creatinine increased from 1.35 to 1.56 mg/dL (p=0.006) after spironolactone addition to ACE inhibitor/ARB therapy in diabetic patients. 3

Real-World Experience

• A 2021 study of 60 patients with severe heart failure found no significant increase in serum creatinine (p>0.05) with 25 mg daily spironolactone over 3 months when renal function was intact at baseline. 4
• Population-based analysis from Scotland showed that despite tripling of spironolactone prescriptions after RALES publication, careful monitoring prevented increases in adverse renal outcomes. 5

Critical Baseline Thresholds

Do not initiate spironolactone if: 2, 1

• Baseline creatinine >2.5 mg/dL in men or >2.0 mg/dL in women
• Estimated creatinine clearance <30 mL/min
• Baseline potassium >5.0 mEq/L

Management Algorithm for Rising Creatinine

When creatinine rises during therapy: 6, 1

• Creatinine rises to >220 μmol/L (2.5 mg/dL): Halve the dose to 25 mg on alternate days
• Creatinine rises to >310 μmol/L (3.5 mg/dL): Discontinue spironolactone completely
• Creatinine decreasing or stable: Continue current dose without adjustment

Risk Factors for Greater Creatinine Elevation

The following factors predict larger increases in creatinine: 2, 1

• Elderly patients with age-related renal decline (serum creatinine underestimates dysfunction in low muscle mass)
• Concomitant ACE inhibitor or ARB use, especially at higher doses (captopril ≥75 mg daily; enalapril or lisinopril ≥10 mg daily)
• Dehydration or volume depletion states
• Concurrent NSAID or COX-2 inhibitor use (should be avoided entirely)

Monitoring Protocol

ACC/AHA guidelines mandate: 2, 1

• Check potassium and creatinine at 3 days after initiation
• Recheck at 1 week
• Then monitor at least monthly for the first 3 months
• Continue monitoring every 6 months thereafter if stable

For patients with eGFR 30-50 mL/min: 6

• Start with reduced dose of 12.5 mg daily
• Monitor more frequently

The Hyperkalemia-Creatinine Connection

While creatinine elevation is important, hyperkalemia is the primary safety concern and often occurs before significant creatinine changes: 2

• Clinical trials reported 2% hyperkalemia incidence
• Real-world practice shows 15-24% incidence
• One series reported up to 24% hyperkalemia rate with half having potassium >6 mEq/L

Even if creatinine is stable or improving, if potassium rises to >5.5 mEq/L, halve the spironolactone dose. 6, 7

Common Pitfalls to Avoid

• Never combine ACE inhibitor + ARB + aldosterone antagonist routinely - this dramatically increases both hyperkalemia and renal dysfunction risk. 2
• Don't ignore low muscle mass in elderly - serum creatinine underestimates true renal dysfunction; calculate creatinine clearance or eGFR. 2
• Instruct patients to stop spironolactone during diarrhea, dehydration, or when loop diuretics are interrupted. 2
• Discontinue or reduce potassium supplements when starting spironolactone. 2

Long-Term Renal Protection

Paradoxically, despite initial creatinine increases, long-term data suggests potential renal protection: 8

• After initial 1-month decrease in eGFR, the monthly rate of eGFR decline over 1 year was lower in spironolactone-treated patients (0.323 vs 0.474 mL/min/1.73 m²/month, p<0.01)
• A 2025 study showed modest eGFR improvement (p=0.042) and significant creatinine reduction (p=0.003) with low-dose spironolactone in diabetic kidney disease. 9