Abstract
Effects of Nephrotoxic Medication Combinations on Rates of Stage 2/3 AKI: SA-OR008
Journal of the American Society of Nephrology, Vol.36(10S)
10/2025
DOI: 10.1681/ASN.2025mwpxgmyj
Abstract
Background:
Acute kidney injury (AKI) is common in hospitalized patients and significantly affects clinical outcomes. Previous studies suggest higher nephrotoxin exposure is associated with higher rates of AKI, which may be exacerbated by possible synergistic nephrotoxicity between drug classes. We analyzed AKI rates following exposure to different combinations of nephrotoxins to explore relative rates of nephrotoxicity with combinations of pharmacologic classes.
Methods:
This single-center retrospective analysis included 9,226 adults admitted from 2014-2022 with a high-nephrotoxin exposure, defined per the current Nephrotoxic Injury Negated by Just-in-Time (NINJA) definition. Combinations of pharmacologic classes were analyzed by sequentially evaluating 2-way interaction terms in a generalized estimating equation (GEE) along with 26 other clinical variables, with stage 2/3 AKI development within 7 days of high-nephrotoxin exposure as the primary outcome.
Results:
Multiple statistically significant interactions were identified, including angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB) with or without antibiotics (OR 2.16, 95% CI 1.07-4.37, p=0.03), non-steroidal anti-inflammatory drugs (NSAIDs) with or without antibiotics (OR 2.65, 95% CI 1.12-6.23, p=0.03), and contrast dye with or without NSAIDs (OR 0.45, 95% CI 0.26-0.79, p=0.01), among others. Odds ratios for combinations of medications are shown in Figure 1.
Conclusion:
Within a database of high-risk patients with simultaneous exposure to multiple nephrotoxins, risks of stage 2/3 AKI associated with a particular drug class differed significantly depending on the presence or absence of other specific medication classes. Synergistic nephrotoxicity is not currently considered in nephrotoxic AKI prevention programs such as NINJA, and future research should examine whether factoring in these interactions improves predictive accuracy.
Details
- Title: Subtitle
- Effects of Nephrotoxic Medication Combinations on Rates of Stage 2/3 AKI: SA-OR008
- Creators
- Casey G. Hardin - University of Iowa Hospitals and Clinics, Iowa City, Iowa, United StatesMary Vaughan Sarrazin - University of Iowa Hospitals and Clinics, Iowa City, Iowa, United StatesMichael I. Tabet - University of IowaYaohua Wang - University of Iowa Hospitals and ClinicsJason Misurac - University of Iowa Hospitals and ClinicsDiana I. Jalal - University of IowaBenjamin R. Griffin - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Journal of the American Society of Nephrology, Vol.36(10S)
- DOI
- 10.1681/ASN.2025mwpxgmyj
- ISSN
- 1046-6673
- eISSN
- 1533-3450
- Publisher
- American Society of Nephrology
- Language
- English
- Date published
- 10/2025
- Academic Unit
- Nephrology, Dialysis and Transplantation; Health Management and Policy; Stead Family Department of Pediatrics; Nephrology; General Internal Medicine; Internal Medicine
- Record Identifier
- 9985019040802771
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