Generation of a drug-induced renal injury list to facilitate the development of new approach methodologies for nephrotoxicity
Open accessAbstract
Drug-induced renal injury (DIRI) causes >1.5 million adverse events annually in the USA alone. Although standard biomarkers exist for DIRI, they lack the sensitivity or specificity to detect nephrotoxicity before the significant loss of renal function. In this study, we describe the creation of DIRIL - a list of drugs associated with DIRI and nephrotoxicity - from two literature datasets with DIRI annotation, confirmed using FDA drug labeling. DIRIL comprises 317 orally administered drugs covering all 14 anatomical, therapeutic and chemical (ATC) classification categories. Of the 317 drugs, 171 were DIRI-positive and 146 were DIRI-negative. DIRIL will be a relevant and invaluable resource for discovery of new approach methods (NAMs) to predict the occurrence and possible severity of DIRI earlier in drug development.
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The NCTR has produced drug-induced toxicity benchmark datasets by manually reading and analyzing drug labeling documents, such as DILI, DICT, and DIRIL.
“during the past two decades, the research team at the NCTR has produced several drug-induced toxicity benchmark datasets by manually reading and analyzing drug labeling documents, such as those for drug-induced liver injury (DILI) [9–11], drug-induced cardiotoxicity (DICT) [12], drug-induced renal injury list (DIRIL) [13], and others”
From Leveraging FDA Labeling Documents and Large Language Model to Enhance Annotation, Profiling, and Classification of Drug Adverse Events with AskFDALabel (2025) · cites this paper as [13]
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- Authors
- Connor, S., Li, T., Qu, Y., Roberts, R. A., & Tong, W.
- Affiliations
- National Center for Toxicological Research (US)
- University of Birmingham (GB)
- Corresponding author
- Tong, Weida
- Venue
- Drug Discovery Today
- Publisher
- Elsevier BV
- Published
- 2024-04
- Volume
- 29
- Issue
- 4
- Pages
- 103938
- ISSN
- 1359-6446 (ISSN-L)
- OpenAlex
- W4392388062
- Cited by
- 21
- References
- 34
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 5
- FWCI
- 6.01
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Drug Discovery Today (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Nephrotoxicity and Medicinal Plants
- Keywords
- drug-induced nephrotoxicity, nephrotoxicity, adverse drug reactions, FDA drug labeling, new approach methodologies, oral medication, ATC classification, drug development
- MeSH terms
- Humans, Kidney, Biomarkers, Acute Kidney Injury, Drug-Related Side Effects and Adverse Reactions
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