Journal article
Heterogeneity of Nephrotoxic Risk Across Medication Classes and Combinations in Hospitalized Adults
Kidney360
09/01/2026
DOI: 10.34067/KID.0000001346
PMID: 42678799
Abstract
Drug-associated acute kidney injury (DA-AKI) is common among hospitalized patients receiving multiple medications. Nephrotoxicity is often treated as a binary categorization, but AKI risk likely varies across medication classes and combinations. We sought to characterize class-specific AKI associations and evaluate whether medication-class interactions associate with DA-AKI prediction.
This retrospective observational study included adults admitted to the University of Iowa from 2014-2023 who met high nephrotoxin exposure criteria, defined as receipt of ≥3 concurrent potentially nephrotoxic medications. The primary outcome was stage 2/3 AKI within 7 days of initial high-nephrotoxin exposure. Models adjusted for demographics, comorbidities, admission diagnosis, laboratory values, and vital signs at index exposure. Generalized estimating equation logistic models were used to estimate medication-class associations and test 66 two-way class interactions. XGBoost models were used to explore nonlinear and higher-order exposure patterns.
We evaluated 66,977 admissions with high-nephrotoxin exposure from 42,558 patients, with stage 2/3 AKI developing in 3,309 (5%). Adjusted odds ratios ranged from 0.74 (95% CI 0.64-0.87) for NSAID exposure to 1.71 (95% CI 1.55-1.88) for piperacillin-tazobactam, indicating substantial heterogeneity in class-specific associations with AKI. Among 66 medication-class pairs tested, 9 (14%) remained statistically significant after multiple-comparison adjustment. Inclusion of medication class and pairwise terms was associated with increased GEE discrimination from ROC-AUC 0.73 to 0.76 and PR-AUC 0.16 to 0.17. XGBoost achieved ROC-AUC 0.78 and PR-AUC 0.20, suggesting additional nonlinear or higher-order exposure patterns.
Among hospitalized adults with high nephrotoxin exposure, medication class composition and pairwise exposure patterns were associated with subsequent stage 2/3 AKI. These findings support evaluation of weighted nephrotoxin surveillance frameworks incorporating medication class, combinations, and clinical context.
Details
- Title: Subtitle
- Heterogeneity of Nephrotoxic Risk Across Medication Classes and Combinations in Hospitalized Adults
- Creators
- Yaohua Wang - University of IowaCasey G Hardin - University of IowaMary Vaughan-Sarrazin - University of IowaMelissa Swee - University of IowaMasaaki Yamada - University of IowaMichael Tabet - Duke UniversityJason Misurac - University of Iowa Stead Family Children’s HospitalBrian C Lund - Iowa City VA Health Care SystemW Nick Street - University of IowaDiana I Jalal - University of IowaBenjamin R Griffin - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Kidney360
- DOI
- 10.34067/KID.0000001346
- PMID
- 42678799
- NLM abbreviation
- Kidney360
- ISSN
- 2641-7650
- eISSN
- 2641-7650
- Language
- English
- Electronic publication date
- 09/01/2026
- Academic Unit
- Bus Admin College; Nephrology, Dialysis and Transplantation; Health Management and Policy; Stead Family Department of Pediatrics; Epidemiology; Nursing; Computer Science; Nephrology; Business Analytics; General Internal Medicine; Internal Medicine
- Record Identifier
- 9985221943202771
Metrics
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