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Trimethoprim-sulfamethoxazole and the risk of a hospital encounter with hyperkalemia: a matched population-based cohort study


Background — Trimethoprim-sulfamethoxazole (TMP-SMX) can cause hyperkalemia by reducing renal potassium excretion. We assessed the risk of hyperkalemia after initiating TMP-SMX vs amoxicillin and determined if this risk is modified by a patient's baseline kidney function (estimated glomerular filtration rate [eGFR]).

Methods — We conducted a population-based cohort study in Ontario, Canada involving adults aged ≥66 years newly treated with TMP-SMX (n = 58,999) matched 1:1 with those newly treated with amoxicillin (2008–2020). The primary outcome was a hospital encounter with hyperkalemia defined by laboratory serum potassium value ≥5.5 mmol/L within 14 days of antibiotic treatment. Secondary outcomes included a hospital encounter with acute kidney injury and all-cause hospitalization. Risk ratios (RRs) were obtained using modified Poisson regression.

Results — A hospital encounter with hyperkalemia occurred in 269/58,999 (0.46%) patients treated with TMP-SMX vs 80/58,999 (0.14%) in those treated with amoxicillin (RR, 3.36 [95% CI, 2.62 to 4.31]). The absolute risk of hyperkalemia in patients treated with TMP-SMX vs amoxicillin increased progressively with decreasing eGFR (risk difference of 0.12% for eGFR ≥60 mL/min/1.73 m2, 0.42% for eGFR 45–59, 0.85% for eGFR 30–44, and 1.45% for eGFR <30; additive interaction P <0.001). TMP-SMX vs amoxicillin was associated with a higher risk of a hospital encounter with acute kidney injury (RR, 3.15 [CI, 2.82 to 3.51]) and all-cause hospitalization (RR, 1.43 [95% CI, 1.34 to 1.53]).

Conclusions — The 14-day risk of a hospital encounter with hyperkalemia was higher in patients newly treated with TMP-SMX vs amoxicillin, and the risk was highest in patients with a low eGFR.



Hwang YJ, Muanda FT, McArthur E, Weir MA, Sontrop JM, Lam NN, Garg AX. Nephrol Dial Transplant. 2023; 38(6):1459-68. Epub 2022 Oct 7.

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