Iranian Journal of Basic Medical Sciences

Iranian Journal of Basic Medical Sciences

Rat renal ischemia-reperfusion model: From mechanistic insights to translational applications in acute kidney injury

Articles in Press

Document Type : Review Article

Authors
Maryam Ghaffari Rahbar 1
Soroush - Taherkhani 2
Farshid - Haghverdi 3
Ali Zarei 4
Saeed Changizi-Ashtiyani 2
1 Department of Internal Medicine, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
2 Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
3 Department of Internal Medicine, School of Medicine, Arak University of Medical Sciences, Arak, Iran
4 Department of Physiology, Estahban School of Paramedical Sciences, School of Nursing, Hazrat Zahra (P.B.U.H), Abadeh, Shiraz University of Medical Sciences, Shiraz, Iran
10.22038/ijbms.2026.94856.20463
Abstract
The renal ischemia-reperfusion (IR) injury model in rats is an indispensable experimental cornerstone for advancing our understanding of acute kidney injury (AKI). This model replicates the complex pathophysiology observed in critical human clinical scenarios such as renal transplantation, cardiovascular surgery, and septic shock, providing an unparalleled platform for mechanistic discovery and therapeutic screening. This review provides a critical analysis from a kidney physiology perspective, detailing the established surgical protocols—including bilateral clamping, unilateral clamping with and without contralateral nephrectomy, and advanced minimally invasive techniques. We dissect the phased pathophysiological cascade, from the initial ischemic metabolic crisis to the reperfusion-driven onslaught of oxidative stress, endothelial dysfunction, and inflammation, and correlate these events with functional and histological outcomes across different models. A rigorous appraisal of the model’s strategic advantages, such as high physiological relevance and experimental control, is balanced against its inherent limitations, including species-specific differences and challenges in modeling chronicity. Finally, we present standardized frameworks for comprehensive diagnostic evaluation and robust preclinical therapeutic testing, cementing the rat IR model’s role as a vital bridge between basic molecular research and clinical application in nephrology. Furthermore, this review highlights how recent refinements—such as modeling clinical comorbidities, applying multi-omics technologies, and incorporating novel biomarkers and imaging endpoints—are reshaping this foundational model’s predictive utility for bridging the translational gap in AKI therapeutics.
Keywords
Acute kidney injury
IR model
Nephrectomy
Rat
Renal ischemia-reperfusion
Subjects
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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 17 October 2026