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Updated: Jul 30, 2025
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A Large Animal Model for Acute Kidney Injury by Temporary Bilateral Renal Artery Occlusion
Published on: February 2, 2021
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Dynamic cellular changes in acute kidney injury caused by different ischemia time
Dan Shan1,2, Yin-Ying Wang3, Yuan Chang1,2
1Beijing Key Laboratory of Preclinical Research and Evaluation for Cardiovascular Implant Materials, Animal Experimental Centre, Fuwai Hospital, National Centre for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
Iscience
|May 11, 2023
Summary
Ischemia reperfusion injury causes acute kidney injury. Researchers found reduced isoleucine levels in mice and humans with acute kidney injury, suggesting it as a potential biomarker.
Area of Science:
- Nephrology
- Molecular Biology
- Biochemistry
Background:
- Ischemia reperfusion injury (IRI) is a major cause of acute kidney injury (AKI), particularly after surgical procedures.
- Understanding the dynamic cellular and molecular changes during IRI-induced AKI is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the dynamic process of AKI following prolonged ischemia using single-cell RNA sequencing.
- To identify specific cell types and molecular pathways involved in IRI-induced AKI.
- To explore potential biomarkers for acute kidney injury.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) was performed on a murine model of IRI with varying ischemic intervals.
- Mass spectrometry-based metabolomic analysis was used to profile plasma metabolites.
- Validation of metabolite changes in human patients with cardiac surgery-associated acute kidney injury (CSA-AKI).
Main Results:
- Slc5a2hi proximal tubular cells were identified as susceptible to AKI.
- The expression of the neutral amino acid transporter gene Slc6a19 significantly decreased over time in AKI models.
- Plasma levels of the neutral amino acid isoleucine were reduced in AKI mice and further confirmed in CSA-AKI patients.
Conclusions:
- The study elucidates the dynamic cellular responses during IRI-induced AKI.
- Reduced Slc6a19 expression in proximal tubular cells is linked to AKI development.
- Decreased plasma isoleucine presents a potential novel biomarker for diagnosing and monitoring CSA-AKI.
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