Greenberg and colleagues [1] ascribed the hyperkalemia found in some human immunodeficiency virus (HIV)-infected patients treated with high-dose trimethoprim to the drug's similarity to amiloride [2]. Recently, we saw a patient without the acquired immunodeficiency syndrome (AIDS) who developed hyperkalemia while receiving standard doses of trimethoprim.

This patient, a healthy, active 72-year-old woman with a history of nonprogressive sarcoidosis not requiring medication and mild reactive airway disease treated as needed with an albuterol inhaler was hospitalized with tracheobronchitis and worsening of her reactive airway disease. Laboratory findings at admission were normal, with normal electrolytes (potassium, 4.8 mmol/L), normal renal function (blood urea nitrogen, 8 mg/dL; creatinine, 0.6 mg/dL), and a pH of 7.4. She was given trimethoprim, 160 mg, and sulfamethoxazole, 800 mg (one double-strength tablet), twice daily, and inhaled albuterol. After 2 days, albuterol treatment was discontinued. Her potassium level was then found to be 5.7 mmol/L and remained between 5.7 and 6.0 mmol/L for 4 more days while on a diet that did not include excessive potassium and despite vigorous hydration with intravenous normal saline. Her urinary sediment remained normal, as did her other electrolytes and renal function. The day after therapy with trimethoprim-sulfamethoxazole was discontinued, her potassium level returned to 4.4 mmol/L. During the next week, her potassium level remained at 4.8 mmol/L.

The temporal association of trimethoprim use with hyperkalemia in this patient strongly suggests a causal role. As noted, hyperkalemia could not be explained by volume depletion, renal failure, interstitial nephritis, acidosis, diet, or other medications. It would be interesting to see if this association is confirmed in a large clinical trial, especially in older persons with some degree of age-related renal insufficiency.