Identifying High-Risk Medications Associated with Acute Kidney Injury in Critically Ill Patients: A Pharmacoepidemiologic Evaluation

Background: Nephrotoxic medications are a common cause of acute kidney injury (AKI). Critically ill children receive more medication than other inpatients; however, the risk of nephrotoxic medication-induced AKI in these children is not well understood. Objective: The aim of this study was to determine the association between exposure to nephrotoxic medications in the intensive care unit (ICU) and the development of AKI amongst critically ill children, adjusting for differences in underlying risk. Methods: We conducted a nested case–control study among a cohort of patients admitted to a paediatric intensive care unit between January 2006 and June 2009. Cases were identified according to the RIFLE criteria. Using incidence density sampling, controls were matched 1:1 according to pre-ICU nephrotoxic drug exposure. Administration of nephrotoxic medications and other known risk factors of AKI were evaluated during the ICU stay prior to the diagnosis of AKI. Results: A total of 914 patients in the cohort developed AKI and had an identifiable matched control. Eighty-seven percent of cases and 74% of controls were exposed to one or more nephrotoxic medications in the ICU during the study period. Furosemide (administered to 67.8% of patients), vancomycin (28.7%), and gentamicin (21.4%) were the most frequently administered nephrotoxic drugs. Patients who developed AKI were more likely to be exposed to at least one nephrotoxic medication and risk increased with increasing number of nephrotoxic medications. Ganciclovir (adjusted odds ratio [AOR] 4.7; 95% CI 1.7–13.0), furosemide (AOR 1.9; 95% CI 1.4–2.4), and gentamicin (AOR 1.8; 95% CI 1.4–2.4) significantly increased the odds of developing AKI after adjusting for underlying differences in risk factors of AKI. Conclusion: This is the first study to assess the association between risk-adjusted nephrotoxic medication exposure and the development of AKI in critically ill children. Nephrotoxic medication exposure was common amongst children in the ICU and we found AKI was associated with the administration of specific drugs after adjustment for important risk factors.