Does taking spironolactone (a potassium-sparing diuretic) affect liver and kidney function?

Effects of Spironolactone on Liver and Kidney Function

Spironolactone can significantly affect kidney function by causing hyperkalemia and potential acute renal function decline, while liver effects are minimal in patients with normal hepatic function. 1

Kidney Effects

Immediate Effects on Kidney Function

• Spironolactone typically causes an initial acute decline in estimated glomerular filtration rate (eGFR) during the first month of treatment 2, 3
• This initial decline (averaging 5.1 mL/min/1.73 m²) is usually followed by stabilization of kidney function if the medication is continued 2
• Interestingly, a larger initial eGFR drop may predict better long-term kidney function stability 2

Long-term Kidney Effects

• After the initial decline, kidney function typically remains stable with continued treatment 2
• In patients with chronic kidney disease, spironolactone may actually slow the monthly rate of eGFR decline compared to controls (0.323 vs 0.474 mL/min/1.73 m²) 3
• In kidney transplant patients, spironolactone reduces measured GFR but does not affect the progression of interstitial fibrosis 4

Electrolyte Abnormalities

• The most significant kidney-related effect is hyperkalemia, with serum potassium typically increasing by 0.8 mEq/L on average 3, 1
• Even at low doses (25 mg daily), spironolactone causes significant elevation in serum potassium, though usually within clinically acceptable ranges in patients with normal renal function 5
• Hyponatremia can occur but is less common than hyperkalemia 1

Liver Effects

• Spironolactone has minimal direct hepatotoxic effects in patients with normal liver function 1
• Very rare cases of mixed cholestatic/hepatocellular toxicity have been reported, with one reported fatality 1
• In patients with pre-existing liver disease, especially cirrhosis with ascites, spironolactone requires special consideration:
  • It can cause sudden alterations in fluid and electrolyte balance
  • These changes may precipitate impaired neurological function or worsen hepatic encephalopathy 1

Monitoring Recommendations

Kidney Function Monitoring

• Check renal function and serum electrolytes before starting treatment 6
• Recheck at 1 week and 4 weeks after initiation 6
• After dose changes, recheck at 1 and 4 weeks 6
• Once on maintenance dose, monitor at 1,2,3, and 6 months, then every 6 months if stable 6

When to Adjust Dose or Discontinue

• If potassium rises to >5.5 mmol/L: reduce dose by half 7
• If potassium rises to ≥6.0 mmol/L: stop spironolactone immediately 7, 6
• If creatinine rises to >220 μmol/L (2.5 mg/dL): reduce dose by half 7
• If creatinine rises to >310 μmol/L (3.5 mg/dL): stop spironolactone immediately 7

Special Considerations

High-Risk Populations

• Elderly patients: Higher risk of adverse effects due to decreased renal function 6, 1
• Patients with diabetes: Higher risk of hyperkalemia 7
• Patients on concomitant ACE inhibitors or ARBs: Significantly increased risk of hyperkalemia 6
• Patients with baseline renal impairment: Require lower doses and more frequent monitoring 6

Contraindications

• Avoid in patients with:
  • Serum creatinine >2.5 mg/dL in men or >2.0 mg/dL in women 7
  • eGFR <30 mL/min 7, 6
  • Serum potassium >5.0 mmol/L 7, 6
  • Concomitant use of potassium supplements or other potassium-sparing diuretics 1

Practical Approach

1. Before starting spironolactone:

   • Check baseline renal function and electrolytes
   • Ensure eGFR >30 mL/min and potassium <5.0 mmol/L

2. Start with low dose:

   • 25 mg daily for normal renal function
   • 25 mg every other day for eGFR 30-50 mL/min

3. Monitor closely:

   • Check potassium and renal function at 1 week and 4 weeks
   • Be vigilant for hyperkalemia, especially in patients also taking ACE inhibitors or ARBs

4. Adjust based on monitoring:

   • If stable and well-tolerated, continue with regular monitoring
   • If hyperkalemia or significant renal function decline occurs, reduce dose or discontinue

By following these guidelines, the risks of adverse kidney and liver effects from spironolactone can be minimized while maintaining its therapeutic benefits.