Renal insufficiency is a risk factor for hyperkalemia associated with low-dose trimethoprim-sulfamethoxazole (TMP-SMX), a drug prescribed to prevent pneumocystis pneumonia, a new Japanese study concludes.
Additional risk factors include use of ACE inhibitors (ACEis) or angiotensin receptor blockers (ARBs). These medications potentially lead to hyperkalemia because of inhibition of the renin-aldosterone system, impaired potassium disposition, and a reduced potassium excretion.
“Taken together, our current findings indicate that renal dysfunction greatly puts patients at risk for hyperkalemia irrespective of the dosage of TMP-SMX,” lead investigator Kazuhiko Hiashioka, MD, of Matsuyama Red Cross Hospital, in Japan, and colleagues wrote in Internal Medicine. Previous research has linked standard-dose and high-dose TMP-SMX with hyperkalemia.
For the study, the investigators examined outcomes among 186 Japanese patients (median age 66 years) who received low-dose TMP-SMX (TMP 80 mg/day or less) as prophylaxis for pneumocystis pneumonia during 2014–2015. Hemodialysis patients were excluded. Hyperkalemia was defined as a serum potassium level of 5 mEq/L or above.
Hyperkalemia developed in 17.2% of patients over a median 12 days. Multivariable analysis identified renal insufficiency, defined as an estimated glomerular filtration rate less than 60 mL/min/1.73m2, as a major risk factor for hyperkalemia associated with low-dose TMP-SMX. ACEi/ARB use was another major risk factor.
The current findings also suggested that male gender may be a risk factor for hyperkalemia. Male hormones, such as testosterone, may enhance the potassium-sparing effects of low-dose TMP-SMX, according to Dr Hiashioka and colleagues.
The investigators suggest that patients with renal insufficiency be monitored closely for hyperkalemia when receiving TMP-SMX, especially if they are also taking an ACEi or ARB.
As this study included only Japanese patients, future research involving other populations are needed to confirm the results.