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Neointimal hyperplasia in the inferior vena cava of adenine-induced chronic kidney disease rats with aortocaval fistulas

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The failure of autologous arteriovenous fistulas (AVFs) occurs primarily due to stenosis in the anastomotic site, which is mainly related to the development of neointimal hyperplasia (NIH). Therefore, we conducted… Click to show full abstract

The failure of autologous arteriovenous fistulas (AVFs) occurs primarily due to stenosis in the anastomotic site, which is mainly related to the development of neointimal hyperplasia (NIH). Therefore, we conducted a study to establish a novel approach to create aortocaval fistulas (ACFs) in adenine-induced (AD) chronic kidney disease (CKD) rats to study the NIH in the inferior vena cava. Ten adult female rats received a 0.75% adenine-rich diet for 4 weeks to induce CKD and underwent ACF surgery. Ten healthy rats served as controls. A 5–10-mm segment of a vein immediately adjacent to that the portion of the vein used for creating the fistula was surgically removed at the time of creating the fistula, and reconstruction of the failed fistula from the same patient was used as controls. ACF was assessed using duplex scans and histopathological analyses. At the end of the experiment, AD rats showed higher serum creatinine and urea nitrogen than those of vehicle-treated rats. Remarkable histological changes in kidney tissues demonstrated successful CKD models. Sections of the ACF in AD rats and veins removed at the time of the reconstruction of the failed fistula of the patient demonstrated that the eccentric neointima formation is irregularly thickened, with several small vessels within a more cellular region of the neointima. Immunohistochemistry demonstrated the presence of myofibroblasts, contractile smooth muscle cells and macrophages within the neointima. Our rat models with ACFs showed typical features of NIH in the formation of fistula stenosis, which can resemble clinical findings in uremic patients.

Keywords: chronic kidney; adenine induced; aortocaval fistulas; induced chronic; neointimal hyperplasia; kidney disease

Journal Title: Clinical and Experimental Nephrology
Year Published: 2020

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