Magnetic Resonance Imaging of Contrast-Induced Acute Renal Injury and Related Pathological Alterations In Vivo

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.

Automated summary

This study confirms that MRI can detect early CI-AKI and investigates the involvement of immune-related responses, pyroptosis, and mitophagy in contrast-induced acute renal injury. The findings suggest that NLRP3 inflammasomes and mitophagy may play a role in mitigating kidney injury in CI-AKI.