ABSTRACT: BACKGROUND AND OBJECTIVES:Pediatric CKD management focuses on limiting kidney injury, including avoiding nephrotoxic medications. Nephrotoxic medication prescription practices for children with CKD are unknown. Our objective was to determine the prevalence and rates of primary care prescriptions for potentially nephrotoxic medications in children with CKD versus without CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:We conducted a retrospective, matched population-based cohort study of patients aged <18 years, registered at a general practice participating in the UK Clinical Practice Research Datalink (CPRD) from 1997 to 2017. Children with a clinical code indicating an incident diagnosis of CKD were matched 1:4 to patients without CKD on CKD diagnosis date, sex, age, CPRD practice, and number of general practitioner visits in the year before cohort entry. We calculated the prevalence and the rate of potentially nephrotoxic medication prescriptions throughout the follow-up period in patients with versus without CKD. Primary analyses included the following medication classes: aminoglycosides, antivirals, nonsteroidal anti-inflammatory drugs, salicylates, proton pump inhibitors, and immunomodulators. Secondary analyses used an expanded nephrotoxicity definition that also included, among others, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Adjusted prescription rates were calculated using multivariable binomial regression. RESULTS:From 1,535,816 eligible patients, we identified 1018 incident CKD and 4072 non-CKD matches (mean age, 9.8 years [range, 1.1-17.9 years]; 52% male; mean follow-up time, 3.3 years). Overall, 26% of patients with and 15% of patients without CKD were prescribed one or more potentially nephrotoxic medication during follow-up. The overall rate of nephrotoxic medication prescriptions was 71 (95% confidence interval [95% CI], 55 to 93) prescriptions per 100 person-years in patients with CKD and eight (95% CI, 7 to 9) prescriptions per 100 person-years in patients without CKD (adjusted rate ratio, 4.1; 95% CI, 2.7 to 6.1). CONCLUSIONS:Potentially nephrotoxic medications are prescribed at high rates to children with CKD.