Evaluating the risk of hyperkalaemia and acute kidney injury with cotrimoxazole: a retrospective observational study

Abstract

Objectives: Increasing antimicrobial resistance has renewed interest in older, less used antimicrobials. Cotrimoxazole shows promise; however, hyperkalaemia and acute kidney injury (AKI) are potential complications. Identifying risk factors for and quantification of these events is required for safe use. This study aimed to evaluate predictors of cotrimoxazole-associated AKI and hyperkalaemia in a clinical setting. Methods: Patients prescribed cotrimoxazole were identified using electronic healthcare records over 3 years (1 April 2016 to 31 March 2019. Individual risk factors were recognized. Serum creatinine and potassium trends were analysed over the subsequent 21 days. AKI and patients with hyperkalaemia were classified using Kidney Disease Improving Global Outcomes (KDIGO) and laboratory criteria. Univariate and multiple logistic regression analyses were performed. Results: Among 214 patients prescribed cotrimoxazole, 42 (19.6%, 95% confidence interval (CI) 14.6e25.7) met AKI criteria and 33 (15.4%, 95% CI 11.0e21.1) developed hyperkalaemia. Low baseline estimated glomerular filtration rate (<60 mL/min/1.73 m 2 , odds ratio (OR) 7.78, 95% CI 3.57e16.13, p < 0.0001) and cardiac disorders (OR 2.40, 95% CI 1.17e4.82, p 0.011) predicted AKI, while low baseline estimated glomerular filtration rate (<60 mL/min/1.73 m 2 , OR 6.80, 95% CI 3.09e15.06, p < 0.0001) and higher baseline serum potassium (p 0.001) predicted hyperkalaemia. Low-dose cotrimoxazole (<1920 mg/d) was associated with lower AKI and hyperkalaemia risk (p 0.007 and 0.019 respectively). Early (within the first 2e4 days of therapy) serum creatinine changes predicted AKI (OR 3.65, 95% CI 1.73e7.41, p 0.001), and early serum potassium changes predicted hyperkalaemia (>0.6 mmol/L, OR 2.47, 95% CI 1.14e5.27, p 0.0236). Conclusions: Cotrimoxazole-associated AKI and hyperkalaemia is frequent and dose dependent. Renal function, serum potassium and preexisting cardiac disorders should be evaluated before prescribing cotrimoxazole. Serum creatinine and potassium monitoring within first 2 to 4 days of treatment to identify susceptible patients is recommended, and the lowest effective dose ought to be prescribed.

Prevalence and risk factors of trimethoprim/sulfamethoxazole-related acute kidney injury in pediatric patients: an observational study from a public database

“…Our results indicated that 21.2% of the patients that received TMP/SMZ developed AKI, which is higher than the results from previous studies (19,20). Retrospective analysis of (20). However, both studies were based on adult populations, and AKI was diagnosed using the Kidney Disease Improving Global Outcomes classification system, which tests for an increase in serum creatinine and serum urea.…”

Characteristics of risk factors for acute kidney injury among inpatients administered sulfamethoxazole/trimethoprim: a retrospective observational study

“…Previous reports indicated hypertension, diabetes, low baseline eGFR, cardiac disorders, high-dose SMX/TMP, concomitant use of renin-angiotensin system blockers, potassium-sparing diuretics, and potassium supplements are risk factors for AKI associated with SMX/TMP [ 8 , 9 , 12 , 13 ]. However, our study examined whether loop diuretics could increase the risk of AKI.…”

“…In addition, AKI is a known prognostic factor regardless of the underlying disease [ 11 ]. Previous reports have identified various risk factors for developing AKI associated with SMX/TMP, such as the presence of hypertension, diabetes, low baseline estimated glomerular filtration rate (eGFR), cardiac disorders, administration of high-dose SMX/TMP, and concomitant use of renin-angiotensin system blockers, potassium-sparing diuretics, and potassium supplements [ 8 , 9 , 12 , 13 ]. However, it remains controversial about risk factors and no study has investigated the influence of loop diuretics on AKI associated with SMX/TMP.…”

Trimethoprim/sulfamethoxazole for nocardiosis in solid organ transplant recipients: Real‐life data from a multicentre retrospective study

“…Although the frequency of AEs does not seem to have been related to the eGFR at the start of TMP-SMX, we observed that the discontinuation rate for AEs was higher when the eGFR was <30 ml/min/1.73 m² (notably discontinuation because of increased SCr). In our study, no dose adjustment was made in patients with eGFR <30 ml/min/1.73 m² even though several studies 7,24,25 strongly support this approach. This factor may also partly explain the high rate of discontinuation for increased SCr in our patients.…”

“…Regarding safety, a retrospective study including 214 patients receiving short-course (median duration, 7 days) TMP-SMX, mostly for respiratory or skin and soft tissue infections, identified that 42 patients (19.6%) met acute kidney injury criteria and 33 (15.4%) experienced hyperkalemia. 7 However, SOT recipients with nocardiosis receive TMP-SMX at higher dose (10-20 mg of TMP/ kg/d) and longer duration (~6 months). Data in this specific context are therefore required.…”