Challenges in Pharmacovigilance: Variability in the Criteria for Determining Drug-Associated Acute Kidney Injury in Retrospective, Observational Studies

Background: Drug-associated acute kidney injury (D-AKI) accounts for 19–26% of acute kidney injury (AKI) events in hospitalized patients and results in outcomes similar to patients with AKI from other etiologies. Diagnosing D-AKI is complex and various criteria have been used. Summary: To highlight the variability in D-AKI determination, a review was conducted between January 2017 and December 2022 using PubMed. Search terms included adaptations of “drug associated kidney injury” to identify a sampling of literature discussing definitions and criteria for D-AKI evaluation. The search yielded 291 articles that were uploaded to Rayyan, a software tool used to screen and select studies. Retrospective, observational electronic health record (EHR) studies conducted in hospitalized patients were included. The final sample contained 16 studies for data extraction, representing mostly adult populations (n = 13, 81.3%) in noncritical or unspecified inpatient settings (n = 12, 75%). Nine studies (56.3%) utilized the recommended Kidney Disease: Improving Global Outcome guidelines (KDIGO) criteria to define AKI. Baseline creatinine or laboratory criteria for kidney function were provided in 10 studies (62.5%). Eleven studies (68.8%) established a temporal sequence assessment linking nephrotoxin drug exposure to an AKI event, but these criteria were inconsistent among studies using time frames as soon as 3 months prior to AKI. Conclusion: This review highlights the substantial variability in D-AKI criteria in select studies. Minimum expectations about what should be reported and criteria for the elements reported are needed to assure transparency, consistency, and standardization of pharmacovigilance strategies.