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Updated: Mar 14, 2026
Bilateral Renal Ischemia-Reperfusion Model for Acute Kidney Injury in Mice
Published on: February 2, 2024
A mouse model of alcoholic liver fibrosis-associated acute kidney injury identifies key molecular pathways
Shinji Furuya1, Grace A Chappell1, Yasuhiro Iwata1
1Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, USA.
Abstract:
Clinical data strongly indicate that acute kidney injury (AKI) is a critical complication in alcoholic hepatitis, an acute-on-chronic form of liver failure in patients with advanced alcoholic fibrosis. Development of targeted therapies for AKI in this setting is hampered by the lack of an animal model. To enable research into molecular drivers and novel therapies for fibrosis- and alcohol-associated AKI, we aimed to combine carbon tetrachloride (CCl4)-induced fibrosis with chronic intra-gastric alcohol feeding. Male C57BL/6J mice were administered a low dose of CCl4 (0.2ml/kg 2× week/6weeks) followed by alcohol intragastrically (up to 25g/kg/day for 3weeks) and with continued CCl4. We observed that combined treatment with CCl4 and alcohol resulted in severe liver injury, more pronounced than using each treatment alone. Importantly, severe kidney injury was evident only in the combined treatment group. This mouse model reproduced distinct pathological features consistent with AKI in human alcoholic hepatitis. Transcriptomic analysis of kidneys revealed profound effects in the combined treatment group, with enrichment for damage-associated pathways, such as apoptosis, inflammation, immune-response and hypoxia. Interestingly, Havcr1 and Lcn2, biomarkers of AKI, were markedly up-regulated. Overall, this study established a novel mouse model of fibrosis- and alcohol-associated AKI and identified key mechanistic pathways.
Insights
Researchers developed a new mouse model for studying alcohol-related liver and kidney injury. This model mimics human alcoholic hepatitis with acute kidney injury (AKI), aiding the search for new treatments.
Area of Science:
- Nephrology
- Hepatology
- Toxicology
Background:
- Acute kidney injury (AKI) is a significant complication in alcoholic hepatitis.
- Current research into AKI associated with alcoholic hepatitis is limited by the absence of a suitable animal model.
Purpose of the Study:
- To develop and validate a novel mouse model for studying fibrosis- and alcohol-associated AKI.
- To investigate the molecular mechanisms underlying AKI in the context of alcoholic liver disease.
Main Methods:
- Induction of liver fibrosis using carbon tetrachloride (CCl4) in male C57BL/6J mice.
- Chronic intra-gastric administration of alcohol concurrently with CCl4 treatment.
- Assessment of liver and kidney injury, including pathological examination and transcriptomic analysis of kidney tissue.
Main Results:
- Combined CCl4 and alcohol treatment induced severe liver injury, exceeding the effects of individual treatments.
- Significant kidney injury, characteristic of AKI, was observed exclusively in the combined treatment group.
- Transcriptomic analysis revealed upregulated damage-associated pathways (apoptosis, inflammation, hypoxia) and AKI biomarkers (Havcr1, Lcn2) in the kidneys.
Conclusions:
- A novel mouse model accurately recapitulates key features of fibrosis- and alcohol-associated AKI seen in human alcoholic hepatitis.
- This model provides a valuable platform for exploring the molecular drivers of AKI in this clinical setting.
- The study identified critical mechanistic pathways involved in the development of AKI.
