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

Abstract

Trimethoprim-sulfamethoxazole (TMP-SMX) can cause hyperkalemia by reducing renal potassium excretion. We assessed the risk of hyperkalemia after initiating TMP-SMX versus amoxicillin and determined if this risk is modified by a patient's baseline kidney function [estimated glomerular filtration rate (eGFR)]. We conducted a population-based cohort study in Ontario, Canada involving adults ≥66years of age newly treated with TMP-SMX (n=58999) matched 1:1 with those newly treated with amoxicillin (2008-2020). The primary outcome was a hospital encounter with hyperkalemia defined by a laboratory serum potassium value ≥5.5mmol/L within 14days of antibiotic treatment. Secondary outcomes included a hospital encounter with acute kidney injury (AKI) and all-cause hospitalization. Risk ratios (RRs) were obtained using a modified Poisson regression. A hospital encounter with hyperkalemia occurred in 269/58999 (0.46%) patients treated with TMP-SMX versus 80/58999 (0.14%) in those treated with amoxicillin {RR 3.36 [95% confidence interval (CI) 2.62-4.31]}. The absolute risk of hyperkalemia in patients treated with TMP-SMX versus amoxicillin increased progressively with decreasing eGFR (risk difference of 0.12% for an eGFR ≥60ml/min/1.73m2, 0.42% for eGFR 45-59, 0.85% for eGFR 30-44 and 1.45% for eGFR <30; additive interaction P<.001). TMP-SMX versus amoxicillin was associated with a higher risk of a hospital encounter with AKI [RR 3.15 (95% CI 2.82-3.51)] and all-cause hospitalization [RR 1.43 (95% CI 1.34-1.53)]. The 14-day risk of a hospital encounter with hyperkalemia was higher in patients newly treated with TMP-SMX versus amoxicillin and the risk was highest in patients with a low eGFR.