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.

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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. 


  1. Higashioka K, Niiro H, Yoshida K, et al. Renal Insufficiency in Concert With Renin-angiotensin aldosterone Inhibition is a Major Risk Factor for Hyperkalemia Associated With Low-dose Trimethoprim-sulfamethoxazole in Adults. Intern Med. doi:10.2169/internalmedicine.55.5697.