Involvements of advanced glycation end products on the developments of peripheral arterial disease in CKD patients

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08251
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Juntendo University
• Principal Investigator: Seiji Ueda 順天堂大学, 医学部, 准教授 (80322593)
• Co-Investigator(Kenkyū-buntansha): 山岸 昌一 久留米大学, 医学部, 教授 (40281026)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 慢性腎臓病 / 動脈硬化 / 内皮障害 / 血管石灰化 / 糖化蛋白

Outline of Final Research Achievements

In the present study, we investigated the roles of AGEs in the development of vascular injury especially focusing in CKD patients with peripheral vascular disease (PAD). Serum levels of AGEs were markedly higher in CKD patients with PAD. Further, elevated AGEs levels were significantly associated with surrogate makers for atherosclerosis such as ABI and vascular calcification index in these patients. Interestingly, AGEs levels were also corelated to the incidence of sarcopenia and the severity of frail in hemodialysis patients. AGE accumulated in the gastrocnemius muscle of 5/6 nephrectomy mice in association with morphological abnormalities, capillary rarefaction, and mitochondrial dysfunction, all of which were completely inhibited by DNA-aptamer raised against AGE. Our present findings may suggest the pathological role of AGE in sarcopenia and frailty in CKD. We are now investigating the impacts of AGEs on vascular calcification using adenine-induced nephropathy model.

Free Research Field

腎臓内科

Academic Significance and Societal Importance of the Research Achievements

本研究では、尿毒素物質であるAGEsの血管障害における役割を検討した。大血管障害に関する影響はまだ検討中ではあるが、末梢血管の内皮障害がサルコペニア・フレイルの発症に寄与していることをはじめて明らかとし、世界に先駆けて報告した。さらには、AGEsのアプタマーの治療薬としての可能性も見出している。CKDやまたサルコペニア患者で心血管病が多発し、その生命予後も不良であることはよく知られているが、本研究の知見により新たな病態があきらかとなり、また新たな治療戦略の確立にも寄与できる可能性が高く社会的意義も高いと考える。