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Updated: Jan 20, 2026
Ischemia-reperfusion Model of Acute Kidney Injury and Post Injury Fibrosis in Mice
Published on: August 9, 2013
Long-term outcomes in mouse models of ischemia-reperfusion-induced acute kidney injury
Lauren Scarfe1, Anna Menshikh1, Emily Newton1
1Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
Abstract:
Severe acute kidney injury has a high mortality and is a risk factor for progressive chronic kidney disease. None of the potential therapies that have been identified in preclinical studies have successfully improved clinical outcomes. This failure is partly because animal models rarely reflect the complexity of human disease: most preclinical studies are short term and are commonly performed in healthy, young, male mice. Therapies that are effective in preclinical models that share common clinical features seen in patients with acute kidney injury, including genetic diversity, different sexes, and comorbidities, and evaluate long-term outcomes are more likely to predict success in the clinic. Here, we evaluated susceptibility to chronic kidney disease after ischemia-reperfusion injury with delayed nephrectomy by monitoring long-term functional and histological responses to injury. We defined conditions required to induce long-term postinjury renal dysfunction and fibrosis without increased mortality in a reproducible way and evaluate effect of mouse strains, sexes, and preexisting diabetes on these responses.
Insights
Preclinical models for acute kidney injury often fail to predict clinical success. This study establishes a more relevant model using diverse mice to better assess long-term kidney disease risk and therapeutic potential.
Area of Science:
- Nephrology
- Translational Medicine
- Animal Models
Background:
- Severe acute kidney injury (AKI) leads to high mortality and chronic kidney disease (CKD).
- Existing preclinical AKI models often fail to translate to clinical success due to oversimplification.
- Current models rarely incorporate genetic diversity, sex differences, or comorbidities common in human AKI patients.
Purpose of the Study:
- To develop and validate a preclinical model of AKI that better reflects human disease complexity.
- To evaluate long-term susceptibility to CKD following AKI.
- To assess the impact of mouse strain, sex, and diabetes on AKI-induced CKD.
Main Methods:
- Induction of AKI via ischemia-reperfusion injury followed by delayed nephrectomy.
- Monitoring of long-term renal function and histology.
- Comparison of responses across different mouse strains, sexes, and in the presence of pre-existing diabetes.
Main Results:
- Established reproducible conditions for inducing long-term renal dysfunction and fibrosis post-AKI without increased mortality.
- Demonstrated that mouse strain, sex, and diabetes significantly influence long-term CKD susceptibility after AKI.
- Provided a more clinically relevant model for evaluating AKI therapies.
Conclusions:
- The developed AKI model offers a more robust platform for preclinical research.
- Understanding the influence of genetic background, sex, and comorbidities is crucial for predicting AKI-to-CKD progression.
- This model can improve the translation of AKI therapies from bench to bedside.
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