Clinical Characteristics and Outcomes of Drug-Induced Acute Kidney Injury Cases

Zaid K. Yousif, Jejo D. Koola, Etienne Macedo, Jorge Cerda, Stuart L. Goldstein, Rajasekara Chakravarthi, Andrew Lewington, David Selewski, Michael Zappitelli, Dinna Cruz, Ashita Tolwani, Melanie S. Joy, Vivekanand Jha, Raja Ramachandran, Marlies Ostermann, Bhavna Pandya, Anjali Acharya, Patrick Brophy, Daniela Ponce, Julia SteinkeJosee Bouchard, Carlos E. Irarrazabal, Romina Irarrazabal, Andrés Boltansky, David Askenazi, Nitin Kolhe, Rolando Claure-Del Granado, Nadine Benador, Clare Castledine, Andrew Davenport, Jonathan Barratt, Sunil Bhandari, Alyssa A. Riley, T. K. Davis, Christopher Farmer, Michael Hogarth, Mark Thomas, Patrick T. Murray, Cassianne Robinson-Cohen, Paola Nicoletti, Sucheta Vaingankar, Ravindra Mehta, Linda Awdishu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Introduction: Drug-induced acute kidney injury (DI-AKI) is a frequent adverse event. The identification of DI-AKI is challenged by competing etiologies, clinical heterogeneity among patients, and a lack of accurate diagnostic tools. Our research aims to describe the clinical characteristics and predictive variables of DI-AKI. Methods: We analyzed data from the Drug-Induced Renal Injury Consortium (DIRECT) study (NCT02159209), an international, multicenter, observational cohort study of enriched clinically adjudicated DI-AKI cases. Cases met the primary inclusion criteria if the patient was exposed to at least 1 nephrotoxic drug for a minimum of 24 hours prior to AKI onset. Cases were clinically adjudicated, and inter-rater reliability (IRR) was measured using Krippendorff's alpha. Variables associated with DI-AKI were identified using L1 regularized multivariable logistic regression. Model performance was assessed using the area under the receiver operating characteristic curve (ROC AUC). Results: A total of 314 AKI cases met the eligibility criteria for this analysis, and 271 (86%) cases were adjudicated as DI-AKI. The majority of the AKI cases were recruited from the United States (68%). The most frequent causal nephrotoxic drugs were vancomycin (48.7%), nonsteroidal antiinflammatory drugs (18.2%), and piperacillin/tazobactam (17.8%). The IRR for DI-AKI adjudication was 0.309. The multivariable model identified age, vascular capacity, hyperglycemia, infections, pyuria, serum creatinine (SCr) trends, and contrast media as significant predictors of DI-AKI with good performance (ROC AUC 0.86). Conclusion: The identification of DI-AKI is challenging even with comprehensive adjudication by experienced nephrologists. Our analysis identified key clinical characteristics and outcomes of DI-AKI compared to other AKI etiologies.

Original languageEnglish
Pages (from-to)2333-2344
Number of pages12
JournalKidney International Reports
Issue number11
StatePublished - Nov 2023

Bibliographical note

© 2023 International Society of Nephrology. Published by Elsevier Inc.


  • drug-induced acute kidney injury
  • nephrotoxicity


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