Abstract
Contrast-induced acute kidney injury (CI-AKI) is a serious and common complication in patients receiving intravenous iodinated contrast medium (CM). Clinically, congestive heart failure is the most critical risk factor for CI-AKI and always leads to renal congestion for increased central venous pressure and fluid overload. Here, we aimed to investigate a novel CI-AKI rat model based on renal congestion. After the exploratory testing phase, we successfully constructed a CI-AKI rat model by inducing renal congestion by clamping the unilateral renal vein, removing the contralateral kidney, and a single tail vein injection of iohexol. This novel CI-AKI rat model showed elevated serum creatinine, urea nitrogen, and released tubular injury biomarkers (KIM-1 and NGAL), reduced glomerular filtration rate, and typical pathologic features of CM-induced tubular injury with extensive foamy degeneration, tubular edema, and necrosis. Electron microscopy and confocal laser scanning revealed excessive mitochondrial fission and increased translocation of Drp1 from the cytoplasm to the mitochondrial surface in tubular epithelial cells. As a Drp1 inhibitor, Mdivi-1 attenuated excessive mitochondrial fission and exerted reno-protection against CM injury. Simultaneously, Mdivi-1 alleviated oxidative stress, apoptosis, and inflammatory responses induced by CM toxicity. We concluded that renal congestion exacerbated CM toxicity and presented a novel CI-AKI rat model. Excessive mitochondrial fission plays a crucial role in CM reno-toxicity and is a promising target for preventing and treating CI-AKI.
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