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Objective: To determine the effect of standard-dose trimethoprim-sulfamethoxazole on serum potassium concentration in hospitalized patients., Design: Prospective chart review., Setting: Community-based teaching hospital., Patients: 105 patients with various infections were hospitalized and treated. Eighty patients treated with standard-dose trimethoprim-sulfamethoxazole (trimethoprim, < or = 320 mg/d; sulfamethoxazole, < or = 1600 mg/d) composed the treatment group; 25 patients treated with other antibiotic agents served as the control group., Measurements: Serum sodium, potassium, and chloride concentrations; serum carbon dioxide content; anion gap; blood urea nitrogen level; and serum creatinine level., Results: The serum potassium concentration in the treatment group (mean +/- SD) was 3.89 +/- 0.46 mmol/L (95% CI, 3.79 to 3.99 mmol/L), and it increased by 1.21 mmol/L (CI, 1.09 to 1.32 mmol/L) 4.6 +/- 2.2 days after trimethoprim-sulfamethoxazole therapy was initiated. Blood urea nitrogen levels increased from 7.92 +/- 5.7 mmol/L (CI, 6.67 to 9.16 mmol/L) to 9.2 +/- 5.8 mmol/L (CI, 7.9 to 10.5 mmol/L), and serum creatinine levels increased from 102.5 +/- 49.5 mumol/L (CI, 91.4 to 113.6 mumol/L) to 126.1 +/- 70.7 mumol/L (CI, 110.3 to 141.9 mumol/L). Patients with a serum creatinine level of 106 mumol/L (1.2 mg/dL) or more developed a higher peak potassium concentration (5.37 +/- 0.59 mmol/L [CI, 5.15 to 5.59 mmol/L]) than patients with a serum creatinine level of less than 106 mumol/L (4.95 +/- 0.48 mmol/L [CI, 4.80 to 5.08 mmol/L]). Patients with diabetes had a slightly higher peak potassium concentration (5.14 +/- 0.45 mmol/L [CI, 4.93 to 5.39 mmol/L]) than did patients without diabetes (5.08 +/- 0.59 mmol/L [CI, 4.93 to 5.23 mmol/L]), but the difference was not statistically significant. The serum potassium concentration in the control group was 4.33 +/- 0.45 mmol/L (CI, 4.15 to 4.51 mmol/L), and it decreased nonsignificantly over 5 days of therapy., Conclusions: Standard-dose trimethoprim-sulfamethoxazole therapy used to treat various infections leads to an increase in serum potassium concentration. A peak serum potassium concentration greater than 5.0 mmol/L developed in 62.5% of patients; severe hyperkalemia (peak serum potassium concentration > or = 5.5 mmol/L) occurred in 21.2% of patients. Patients treated with standard-dose trimethoprim-sulfamethoxazole should be monitored closely for the development of hyperkalemia, especially if they have concurrent renal insufficiency (serum creatinine level > or = 106 mumol/L).

Objectives: 1) To determine the incidence and severity of hyperkalemia during trimethoprim therapy. 2) To test the hypothesis that trimethoprim inhibits renal potassium excretion by blocking sodium channels in the mammalian distal nephron., Patients: Thirty consecutive patients who were treated with trimethoprim-containing drugs. All patients included in the study had the acquired immunodeficiency syndrome (AIDS)., Experimental Animals: Thirty-nine male Sprague-Dawley rats receiving normal rat chow and tap water (allowed free access)., Intervention: Humans: high dose (20 mg/kg per day) of trimethoprim therapy. Rats: trimethoprim (9.6 mg/h per kg body weight) was infused intravenously or into the renal distal tubules (1 mmol/L)., Measurements: Humans: Serum and urine electrolyte levels, serum creatinine, renin, aldosterone, and cortisol levels were measured, and the transtubular potassium gradient was calculated. Rats: The effects of trimethoprim infusion on urinary sodium, chloride, and potassium concentration and urine volume were measured. Sodium, chloride, potassium, and inulin concentrations were measured in fluid samples obtained from kidney distal tubules. The voltage across the wall of the distal tubule was measured., Results: Humans: Trimethoprim increased the serum potassium concentration by 0.6 mmol/L (95% Cl, 0.29 to 0.95 mmol/L) despite normal adrenocortical function and glomerular filtration rate. Serum potassium levels greater than 5 mmol/L were observed during trimethoprim treatment in 15 of 30 patients. Rats: Intravenous trimethoprim inhibited renal potassium excretion by 40% (Cl, 21% to 60%) and increased renal sodium excretion by 46% (Cl, 9% to 83%). Trimethoprim (1 mmol/L) in tubule fluid inhibited distal tubule potassium secretion by 59% (Cl, 26% to 92%) and depolarized the lumen-negative transepithelial voltage by 66% (Cl, 46% to 85%)., Conclusions: Trimethoprim (an organic cation) acts like amiloride and blocks apical membrane sodium channels in the mammalian distal nephron. As a consequence, the transepithelial voltage is reduced and potassium secretion is inhibited. Decreased renal potassium excretion secondary to these direct effects on kidney tubules leads to hyperkalemia in a substantial number of patients being treated with trimethoprim-containing drugs.