Bridging translation for acute kidney injury with better preclinical modeling of human disease
Open accessAbstract
The current lack of effective therapeutics for patients with acute kidney injury (AKI) represents an important and unmet medical need. Given the importance of the clinical problem, it is time for us to take a few steps back and reexamine current practices. The focus of this review is to explore the extent to which failure of therapeutic translation from animal studies to human studies stems from deficiencies in the preclinical models of AKI. We will evaluate whether the preclinical models of AKI that are commonly used recapitulate the known pathophysiologies of AKI that are being modeled in humans, focusing on four common scenarios that are studied in clinical therapeutic intervention trials: cardiac surgery-induced AKI; contrast-induced AKI; cisplatin-induced AKI; and sepsis associated AKI. Based on our observations, we have identified a number of common limitations in current preclinical modeling of AKI that could be addressed. In the long term, we suggest that progress in developing better preclinical models of AKI will depend on developing a better understanding of human AKI. To this this end, we suggest that there is a need to develop greater in-depth molecular analyses of kidney biopsy tissues coupled with improved clinical and molecular classification of patients with AKI.
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Previous research on renal I/R injury has primarily used animal models.
“Previous research on renal I/R injury has primarily used animal models”
From Material-dependent oxygen transport governs ischemia-reperfusion injury and drug response in a kidney microphysiological system (2026) · cites this paper as Skrypnyk et al., 2016
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Kutsuzawa, N., Nakamura, H., Shinha, K., & Kimura, H. (2026) · Frontiers in Toxicology · doi:10.3389/ftox.2026.1854389
- Authors
- Skrypnyk, N. I., Siskind, L. J., Faubel, S., & de Caestecker, M. P.
- Affiliations
- Vanderbilt University Medical Center (US)
- University of Louisville (US)
- Denver VA Medical Center (US)
- Division of Nephology and Hypertension, Vanderbilt University Medical Center, Nashville, Tennessee;
- Venue
- American Journal of Physiology-Renal Physiology
- Publisher
- American Physiological Society
- Published
- 2016-05-15
- Volume
- 310
- Issue
- 10
- Pages
- F972-F984
- ISSN
- 1522-1466 (ISSN-L)
- 1931-857X
- PMC
- PMC4889323
- OpenAlex
- W2301240993
- Cited by
- 61
- References
- 4
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 6 · 2023: 2 · 2022: 6 · 2021: 6 · 2020: 6 · 2019: 7 · 2018: 6 · 2017: 9
- FWCI
- 0.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal of Physiology-Renal Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (U24DK076169, RC4DK090770, R01DK069403, P30DK079307, R01DK093462)
- Topics
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Keywords
- acute kidney injury, preclinical animal models, translational research, contrast-induced nephropathy, cisplatin nephrotoxicity, sepsis-associated acute kidney injury, AKI pathophysiology
- MeSH terms
- Animals, Antineoplastic Agents, Cisplatin, Contrast Media, Disease Models, Animal, Cardiac Surgical Procedures, Humans, Sepsis, Translational Research, Biomedical, Acute Kidney Injury
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