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Bilateral Renal Ischemia-Reperfusion Model for Acute Kidney Injury in Mice
Published on: February 2, 2024
Magnetic Resonance Imaging of Contrast-Induced Acute Renal Injury and Related Pathological Alterations In Vivo
Yanfei Li1, Dafa Shi1, Haoran Zhang1
1Department of Radiology, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361102 Fujian, China.
Background:
The definitive mechanisms of CI-AKI include contrast medium (CM) nephrotoxicity and CM disturbances in renal blood flow, but how the immune system responds to CM has rarely been mentioned in previous studies, and different cell death pathways have not been clearly distinguished.
Aim:
To confirm whether MRI detect early CI-AKI and to investigate whether immunity-related responses, pyroptosis, and mitophagy participate in contrast-induced acute renal injury (CI-AKI).
Methods:
C57BL/6 mice with CI-AKI were established by tail vein injection of iodixanol 320. Magnetic resonance imaging of 9.4 T scanner and microscopic appearance of renal H&E staining were tools to test the occurrence of CI-AKI at different times. Immunohistochemistry and NGAL were used to examine the immune responses in the kidneys with CI-AKI. Transmission electron microscopy and western blot methods were used to distinguish various cell death pathways in CI-AKI. Key Results. The densitometry of T2WI, DTI, and BOLD presents CI-AKI in a regular way. The microscopic appearance presents the strongest renal damage in CI-AKI mice that existed between 12 h (P < 0.0001) and 24 h (P < 0.05) after contrast medium (CM) injection. Strong correlation may exist between MRI densitometry (T2WI, DTI, and BOLD) and pathology. Neutrophil and macrophage chemotaxis occurred in CI-AKI, and we observed that Ly6G was the strongest at 48 h (P < 0.0001). Pyroptosis (Nlrp3/caspase-1, P < 0.05), mitophagy (BNIP/Nix, P < 0.05), and apoptosis (Bax, P < 0.05) occurred in CI-AKI.
Conclusions:
fMRI can detect early CI-AKI immediately after CM injection. NLRP3 inflammasomes are involved in CI-AKI, and mitophagy may play a role in mitigating kidney injury. The mitochondrion is one of the key organelles in the tubular epithelium implicated in CI-AKI.
Insights
Magnetic resonance imaging detects early contrast-induced acute kidney injury (CI-AKI). This study reveals immune responses, pyroptosis, and mitophagy are involved in CI-AKI development and progression.
Area of Science:
- Nephrology
- Immunology
- Radiology
Background:
- Contrast-induced acute kidney injury (CI-AKI) mechanisms, including contrast medium (CM) nephrotoxicity and renal blood flow disturbances, are established.
- The role of the immune system and distinct cell death pathways in CI-AKI remains underexplored.
Purpose of the Study:
- To determine if magnetic resonance imaging (MRI) can detect early CI-AKI.
- To investigate the involvement of immunity-related responses, pyroptosis, and mitophagy in CI-AKI.
Main Methods:
- CI-AKI was induced in C57BL/6 mice using iodixanol 320.
- MRI (9.4 T scanner) and histological analysis (H&E staining) assessed CI-AKI.
- Immunohistochemistry, NGAL, transmission electron microscopy, and western blot analyzed immune responses and cell death pathways (pyroptosis, mitophagy, apoptosis).
Main Results:
- MRI (T2WI, DTI, BOLD) reliably detected CI-AKI, correlating with pathology.
- Peak renal damage occurred 12-24 hours post-CM injection.
- Immune cell infiltration (neutrophils, macrophages) and pyroptosis, mitophagy, and apoptosis were observed in CI-AKI kidneys.
Conclusions:
- Functional MRI can detect early CI-AKI shortly after CM administration.
- NLRP3 inflammasomes are implicated in CI-AKI pathogenesis.
- Mitophagy may offer protective effects against kidney injury, highlighting the mitochondrion's central role in CI-AKI.
Related Concept Videos
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Acute Kidney Injury I: Introduction
Acute Kidney Injury IV: Diagnostic Studies and Prevention
Imaging Studies VII: Vascular Imaging

