Association of Ibuprofen Prescription With Acute Kidney Injury Among Hospitalized Children in China

IMPORTANCE: Ibuprofen is widely used in children worldwide, especially in those with cancer, fever, or trauma. However, large and high-quality studies of the association between ibuprofen and acute kidney injury (AKI) in children have been lacking. OBJECTIVE: To examine the association between the use of ibuprofen and the risk of hospital-acquired AKI in hospitalized children in China. DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed the cohort of the Epidemiology of AKI in Chinese Hospitalized Patients (EACH) study, a large, multicenter retrospective study of 3 044 023 patients who were admitted to 1 of 25 academic medical centers in China between January 1, 2013, and December 31, 2015. Patient-level data were obtained from the electronic health record system of the participating centers. Hospitalized children aged 1 month to 18 years who had prescriptions and a certain number of serum creatinine (SCr) tests were included. Children with end-stage renal disease, community-acquired AKI, low baseline SCr level (<10 μmol/L), high standardized baseline SCr level (>4 times the sex- and age-specific reference value), or missing diagnosis code were excluded. Data analysis was conducted from January 1, 2020, to August 30, 2020. EXPOSURES: Exposure to ibuprofen was coded as a time-dependent dichotomous variable. MAIN OUTCOMES AND MEASURES: Baseline SCr level was calculated for each patient as the mean of all available SCr values between the 30 days prior to admission and the first SCr testing within the first 3 days of hospitalization. Acute kidney injury was defined as an increase in SCr level of 26.5 μmol/L or higher within 48 hours or by 50% or more over the baseline value, according to the Kidney Disease: Improving Global Outcomes guidelines. RESULTS: Among the 50 420 children (mean [SD] age, 5.0 [5.2] years; 30 640 boys [60.8%]) included in this study, 5526 (11.0%) used ibuprofen and 3476 (6.9%) developed hospital-acquired AKI during hospitalization. Ibuprofen use was associated with a statistically significantly increased risk of hospital-acquired AKI (hazard ratio [HR], 1.23; 95% CI, 1.14-1.34) after adjusting for confounders. Ibuprofen use was associated with a greater hazard in children who had chronic kidney disease vs those without (HR, 2.31 [95% CI, 1.73-3.10] vs 1.19 [95% CI, 1.09-1.29]), required intensive care vs those without this need (HR, 1.47 [95% CI, 1.24-1.75] vs 1.18 [95% CI, 1.07-1.29]), or were older vs younger (>10 years and >1 year to 10 years vs 1 month to 1 year) (HR, 1.64 [95% CI, 1.32-2.05]; 1.36 [95% CI, 1.23-1.52] vs 0.99 [95% CI, 0.86-1.13]). Dose-response analysis suggested that the association of ibuprofen with the risk of hospital-acquired AKI was dose-dependent. CONCLUSIONS AND RELEVANCE: This study found that ibuprofen was widely used and associated with an increased risk of hospital-acquired AKI in hospitalized children in China. The judicious use of ibuprofen and close monitoring of kidney function in children are needed.