Can spironolactone cause metabolic acidosis or metabolic alkalosis?

Spironolactone's Effect on Acid-Base Balance

Spironolactone primarily causes metabolic acidosis, specifically a hyperchloremic normal anion gap metabolic acidosis, due to its inhibition of aldosterone action in the distal tubule.

Mechanism of Action and Acid-Base Effects

Spironolactone is an aldosterone antagonist that acts on the distal tubules to increase natriuresis and conserve potassium 1. Its effects on acid-base balance occur through several mechanisms:

1. Primary Effect - Metabolic Acidosis:

   • Spironolactone blocks aldosterone-dependent sodium reabsorption and potassium/hydrogen ion secretion in the distal tubule
   • This impairs renal hydrogen ion secretion, leading to hyperchloremic normal anion gap metabolic acidosis 2
   • Research demonstrates that spironolactone administration results in decreased serum bicarbonate levels 3, 4

2. Secondary Effects:

   • Hyperkalemia commonly occurs alongside the acidosis due to decreased potassium excretion 5
   • In some cases, spironolactone can increase endogenous acid production through effects on protein catabolism 3, 6

Evidence from Clinical Studies

Research clearly demonstrates spironolactone's acidosis-inducing properties:

• In patients with cirrhosis, spironolactone therapy (100-200 mg/day) significantly decreased serum bicarbonate from 18.2 to 10.9 mEq/L, which reversed upon discontinuation 4
• In a study of normal subjects with induced chronic metabolic acidosis, spironolactone exacerbated the acidosis by decreasing plasma bicarbonate from 19.8 to 17.7 mmol/L 3
• In adrenalectomized dogs, spironolactone administration resulted in sustained metabolic acidosis due to impaired renal secretion of hydrogen and potassium 6

Clinical Implications and Management

The acid-base disturbances caused by spironolactone have important clinical implications:

1. Monitoring Requirements:

   • Regular monitoring of serum electrolytes is mandatory when using spironolactone 1
   • Guidelines recommend checking renal function and electrolytes at 1 and 4 weeks after starting treatment and after dose increases 1

2. Risk Factors for Acid-Base Disturbances:

   • Patients with cirrhosis are particularly susceptible to spironolactone-induced metabolic acidosis 4
   • Patients with pre-existing renal impairment are at higher risk 5
   • Concomitant use of ACE inhibitors or ARBs increases risk of electrolyte abnormalities 5

3. Management of Acidosis:

   • If significant acidosis develops, consider dose reduction or discontinuation of spironolactone 4
   • In patients with cirrhosis, combination therapy with low-dose furosemide may help ameliorate the dilutional hyperchloremic acidosis 7

Special Considerations

• When spironolactone is used with loop diuretics like furosemide, the metabolic alkalosis typically caused by loop diuretics may partially offset spironolactone's acidosis-inducing effects 1, 7
• Spironolactone can cause multiple electrolyte abnormalities beyond acidosis, including hyponatremia, hypomagnesemia, and hypocalcemia 5
• The FDA label specifically warns that spironolactone can cause hypochloremic alkalosis when used with other medications, particularly cholestyramine 5

Conclusion

When prescribing spironolactone, clinicians should be vigilant about potential acid-base disturbances, particularly hyperchloremic metabolic acidosis. Regular monitoring of electrolytes and renal function is essential, with special attention to patients with pre-existing renal impairment or liver disease.