The recent study by Alappan and colleagues [1] draws appropriate attention to the potential and perhaps little-known problem of hyperkalemia during treatment with trimethoprim-sulfamethoxazole in hospitalized patients. The authors attribute the observed impairment in potassium excretion primarily to the amiloride-like actions of trimethoprim in the distal tubule, and they note concurrent renal insufficiency as an associated risk factor. They fail to comment, however, on an important element of the pathogenesis of this disorder, that is, the influence of nutritional intake, obligate daily osmolar excretion, and urine volume on potassium excretion.

Acutely ill patients generally do not have adequate protein and total caloric intake [2] and therefore may have decreased obligate osmolar excretion. In addition, these patients commonly have relative hypovolemia or low extracellular fluid volume. The consequent increased reabsorption of urea and NaCl in more proximal portions of the nephron leads to decreased distal solute delivery and a low osmolar excretion rate. In patients with reduced fluid intake (due to illness) and an intact urinary-concentrating mechanism, the result is reduced urine volume and diminished flow through the cortical collecting duct. Although the transtubular potassium gradient is generally high in these patients [3], the ability to excrete potassium is limited by low urine flow. This pathophysiology certainly contributes to the observations made by Alappan and colleagues.

The authors describe the prescribed diets in their patients but do not provide information on actual intake, acuity and types of illness, or measured daily urine volumes. It would be of interest to know these details with regard to patient subgroups and their relation to observed hyperkalemia. Caution in the use of trimethoprim-sulfamethoxazole therapy might prove applicable only to certain groups of hospitalized patients.

Finally, although the authors clearly discuss only hospitalized patients, the casual reader might extrapolate these results to outpatient settings. This conclusion could be erroneous without specific study of trimethoprim-sulfamethoxazole in an ambulatory care setting, particularly in light of the nutritional considerations.