2022 Fiscal Year Final Research Report

A clinical study of non-immunological factors affecting allograft survival focusing on AGEs.

Research Project

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Project/Area Number	20K08969
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55010:General surgery and pediatric surgery-related
Research Institution	Tokai University
Principal Investigator	Nakamura Michio 東海大学, 医学部, 教授 (00246547)
Co-Investigator(Kenkyū-buntansha)	深川雅史東海大学, 医学部, 教授 (00211516) 永井竜児東海大学, 農学部, 教授 (20315295) 山中幹宏東海大学, 農学部, 特任准教授 (70767946) 豊田雅夫東海大学, 医学部, 准教授 (00349383)
Project Period (FY)	2020-04-01 – 2023-03-31
Keywords	腎移植 / 終末糖化産物 / AGEs / AGEsセンサ
Outline of Final Research Achievements	With a focus on advanced glycation products (AGEs), which are closely related to non-immunological mechanisms of allograft failure, we analyzed the relationship between measurement of tissue and blood levels of AGEs and background factors in kidney transplant recipients. Skin tissue AGEs were measured by a AGEs sensor developed in Japan, and two types of blood AGEs, CML and MG-H1, were measured by LC-MS/MS. In a cross-sectional study, both tissue and blood AGEs in kidney recipients were found to be significantly higher than in healthy subjects, and this was more pronounced in patients with concomitant diabetes and dyslipidemia. Multiple regression analysis showed that patient dialysis history and blood AGEs levels affected significantly skin AGEs levels. In the longitudinal study, a divergence was observed, with high blood AGEs levels quickly decreasing with improvement in allograft function after transplantation, while tissue AGEs levels changed influenced by background factors.
Free Research Field	臓器移植　腎移植
Academic Significance and Societal Importance of the Research Achievements	臓器不足が課題の移植医療において、移植腎廃絶原因を明らかにし、移植腎の長期生着達成は重要事項である。本研究では非免疫学的機序と関連深い終末糖化産物（AGEs）に着目した。対象を腎移植患者とする研究は稀有であり、さらに血中AGEsレベル測定が難しい中、比較的測定容易な皮膚組織中AGEsを本邦で開発されたAGEsセンサーで測定し、血中AGEsとの関連性や腎移植後の推移とともに解析した研究は初めてである。今後、皮膚組織AGEs測定を中長期に及んで継続解析することで、移植腎の長期予後改善へ向けた患者管理の一方法を提供できる可能性があり、本研究の研究成果は学術的とともに社会的意義があると考えている。