Neointimal hyperplasia in the inferior vena cava of adenine-induced chronic kidney disease rats with aortocaval fistulas
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ORIGINAL ARTICLE
Neointimal hyperplasia in the inferior vena cava of adenine‑induced chronic kidney disease rats with aortocaval fistulas Jing Du1,2 · Liming Liang1,3 · Shuai Liu4 · Xiaoqing Yang5 · Shujuan Cao6 · Hui Zhang7 · Hong Su1 · Xiaojie Gong1 · Qinlan Chen1 · Xianglei Kong1,3 · Dongmei Xu1,3,8,9 Received: 25 October 2019 / Accepted: 4 July 2020 © Japanese Society of Nephrology 2020
Abstract Background 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. Methods 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. Results 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. Conclusions 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 Fistula · Neointimal hyperplasia · Adenine · Chronic kidney disease · Rat
Jing Du and Liming Liang contributed equally to this work. 5
Department of Pathology, Shandong Provincial Qianfoshan Hospital, Shandong University, No.16766, Jingshi Road, Jinan, People’s Republic of China
6
Department of Nephrology, Shandong Provincial Qianfoshan Hospital, Shandong University, No.16766, Jingshi Road, Jinan 250014, People’s Republic of China
Department of Imaging Ultrasound, Shandong Provincial Qianfoshan Hospital, Shandong University, No.16766, Jingshi Road, Jinan, People’s Republic of China
7
Department of Blood Purification Center, Weifang People’s Hospital, No.151, Guangwen Street, Kuiwen District, Weifang, People’s Republic of China
Department of Pathology, Shandong University Qilu Hospital, No.107, Wenhua West Road, Jinan, People’s Republic of China
8
Department of Nephrology, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital o
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