Predicting Cotrimoxazole-Associated Acute Kidney Injury and Hyperkalaemia

Increasing antimicrobial resistance has renewed interest in older, infrequently used antimicrobials. Cotrimoxazole shows future promise; however, acute kidney injury (AKI) and hyperkalaemia are potential complications. Recognising risk factors for cotrimoxazole-associated AKI and hyperkalaemia, and quantifying the impact, are required for safe use against future antimicrobial resistance.

A single-centre retrospective observational study using electronic-healthcare records of patients prescribed cotrimoxazole was conducted. Patient risk factors were identified, and serum creatinine and potassium levels were analysed over the subsequent 21-days from prescription. Univariate and multiple logistic regression analyses were performed. The project was registered locally with the clinical governance team as service evaluation [Ref: CSS033].

Of 214 patients, 42 (20%) developed AKI and 33 (15.4%) developed hyperkalaemia. Low baseline eGFR (<60mls/min/1,73m2, OR = 7.78, 95%CI 3.57-16.13, p<0.0001) and pre-existing cardiac disorders (OR = 2.40, 95%CI 1.17-4.82, p=0.011) significantly predicted AKI. Early serum creatinine increases within 2-4 days of therapy predicted future AKI (OR = 3.65, 95%CI 1.73-7.41, p = 0.001). A low baseline eGFR also significantly predicted future hyperkalaemia (<60mls/min/1.73m2, OR = 6.80, 95%CI 3.09-15.06, p<0.0001). Low-dose cotrimoxazole (<1920mg/day) was associated with lower AKI and hyperkalaemia risk (p = 0.007 and 0.019, respectively).

Cotrimoxazole-associated AKI and hyperkalaemia is frequent and dose-dependant. Renal function and pre-existing cardiac disorders should be carefully evaluated before prescribing cotrimoxazole. Serum creatinine should be monitored in the first 2-4 days of treatment to identify susceptible patients, and low-doses considered if AKI or hyperkalaemia is suspected.