Does spironolactone cause alkalosis or acidosis?

From the Guidelines

Spironolactone causes hyperkalemia, which can lead to metabolic acidosis, but it is more commonly associated with causing hypokalemic alkalosis is not supported, instead, it is more likely to cause a metabolic acidosis due to the hyperkalemia.

Mechanism of Action

• Spironolactone is an aldosterone antagonist that acts on the distal tubules to increase natriuresis and conserve potassium 1.
• This mechanism can lead to hyperkalemia, a significant complication that frequently limits the use of spironolactone in the treatment of ascites 1.

Side Effects

• The most common side effects of spironolactone include hyperkalemia, gynecomastia, mastalgia, hyposexuality, and erectile dysfunction 1.
• Hyperkalemia can cause metabolic acidosis, and spironolactone should be reduced or stopped in case of hyperkalemia 1.

Clinical Use

• Spironolactone is the drug of choice in the initial treatment of ascites due to cirrhosis, and it is initiated at a dose of 50–100 mg/day, with a maximum dose of 400 mg/day 1.
• The use of spironolactone should be monitored by repeated measurements of serum creatinine and potassium, and it should be reduced or stopped in case of hyperkalemia 1.

From the FDA Drug Label

In addition to causing hyperkalemia, spironolactone can cause hyponatremia, hypomagnesemia, hypocalcemia, hypochloremic alkalosis, and hyperglycemia. Hyperkalemic metabolic acidosis has been reported in patients given spironolactone concurrently with cholestyramine.

Spironolactone can cause alkalosis, specifically hypochloremic alkalosis. However, it can also cause metabolic acidosis when given concurrently with cholestyramine, resulting in hyperkalemic metabolic acidosis 2 2.

From the Research

Effect of Spironolactone on Acid-Base Balance

• Spironolactone can cause metabolic acidosis, as evidenced by a study where it resulted in exacerbation of acidosis in patients with chronic metabolic acidosis 3.
• The mechanism of spironolactone-induced acidosis is thought to be related to an increase in endogenous acid production, as well as a decrease in renal acid excretion 3.
• Type 4 renal tubular acidosis, a condition characterized by hyperkalemia and metabolic acidosis, has been reported in patients taking spironolactone 4, 5.

Clinical Implications

• Spironolactone may be safe to initiate in hospitalized patients with heart failure and chronic kidney disease, but careful monitoring of potassium levels and acid-base balance is necessary 6.
• In patients with liver cirrhosis, spironolactone in combination with low-dose furosemide may have a beneficial effect on acid-base disorders, including respiratory alkalosis and dilutional hyperchloremic acidosis 7.

Key Findings

• Spironolactone can cause metabolic acidosis, rather than alkalosis, in certain patient populations 3, 4, 5.
• The risk of hyperkalemia and acidosis associated with spironolactone therapy should be carefully considered in patients with chronic kidney disease or liver cirrhosis 6, 7.