Renal impairment plus TMP-SMX boosts hyperkalemia risk

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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 Dr Kazuhiko Hiashioka, of Matsuyama Red Cross Hospital, in Japan and colleagues found. 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.

Objective: Low-dose trimethoprim-sulfamethoxazole (TMP-SMX) is commonly used to prevent pneumocystis pneumonia in daily practice. Previous reports have shown a relationship between high- or standard-dose of TMP-SMX and hyperkalemia, however it remains unclear whether this is true for low-dose TMP-SMX. In this study we sought to determine the risk factors for hyperkalemia associated with low-dose TMP-SMX.
Methods: In this retrospective cohort study, 186 consecutive adult patients who received TMP-SMX as prophylaxis for pneumocystis pneumonia from January 2014 to January 2015 were evaluated. Data on the patients’ age, gender, baseline estimated glomerular filtration rate (eGFR), baseline serum potassium, maximum serum potassium, duration reaching the maximal serum potassium level, dosage, and concomitant use of angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB), β-blockers, non-steroidal anti-inflammatory drugs and potassium-sparing diuretics were retrospectively collected. Hyperkalemia was defined as a serum potassium level ≥5 mEq/L. Univariate and multivariate analyses were performed.
Results: The median age of the patients was 66 years and 51.1% were men. Hyperkalemia associated with low-dose TMP-SMX was observed in 32 patients (17.2%). The median duration to reach the maximal serum potassium level was 12 days. The multivariate logistic regression analysis identified renal insufficiency to be a major risk factor for hyperkalemia associated with low-dose TMP-SMX (eGFR Conclusion: Renal insufficiency in concert with ACEi/ARB use is a major risk factor for hyperkalemia induced by low-dose TMP-SMX.

Infectious Disease Advisor material
Internal Medicine abstract

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