Background and Aims Patients with CKD have high risk of AKI. Quantifying the contribution of drugs to the occurrence of AKI in this population and assessing its risk factors is important to design preventive interventions. We sought to comprehensively describe drug-related components associated with AKI in patients with CKD. We documented the incidence of drug-related AKI, the proportion of preventable AKI, identified the various drugs potentially associated with it, explored the risk factors, and assessed the one-year incidences of the recurrence of drug-related AKI, kidney failure, and death. Method The CKD-REIN study is a national prospective cohort of 3,033 nephrology outpatients with a confirmed diagnosis of CKD (eGFR <60 mL/min/1.73 m²) in France. AKIs and adverse drug reactions (ADRs) were prospectively identified from hospital charts, medical records, and patient interviews. Nephrologists used the Kidney Disease: Improving Global Outcomes criteria to adjudicate all stages of AKI, and expert pharmacologists used validated tools to adjudicate ADRs (including drug-related AKIs). A drug-related AKI was considered serious when the outcome is death, a life-threatening situation, hospital admission, disability, permanent damage, or another important medical event. We used cause-specific Cox proportional hazard models to investigate the patients’ baseline clinical characteristics associated with the risk of drug-related AKI. Results Over a median [interquartile range] period of 4.9 [3.4-5.1] years, 832 cases of AKI were reported in 639 (21%) of the 3,033 study participants. Over a quarter of the AKI events were drug-related (n = 236, 28%); from those, 47% were hospital- and 53% community-acquired AKI. From the 168 serious drug-related AKI events, 28% were considered preventable or potentially preventable. The three most frequently implicated drug classes were diuretics, renin-angiotensin system inhibitors, and contrast agents. At least two concomitant medications were implicated in more than half of the AKIs with a drug-related component, RASis and diuretics, two diuretics, and diuretics and antibiotics were the 3 most frequent associations (Figure). A history of cardiovascular events, and the presence of diabetes, lower levels of hemoglobin and eGFR, poor medication adherence, and ≥5 drugs being taken daily were associated with a greater risk of drug-related AKI. The one-year cumulative incidences of recurrent drug-related AKI, kidney replacement therapy, and death were 7%, 15%, and 11%, respectively, after the first drug-related AKI. Conclusion Drug-related AKI is prevalent among patients with CKD. Further training in drug management for both CKD patients and healthcare professionals involved in their care might mitigate the incidence of drug-related AKI.