2021 Fiscal Year Final Research Report

Elucidation of the pathophysiology of secondary thrombotic microangiopathy (TMA) focusing on complement activity and glycan abnormalities

Research Project

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Project/Area Number	19K08692
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	Aichi Medical University
Principal Investigator	Katsuno Takayuki 愛知医科大学, 医学部, 准教授 (60642337)
Co-Investigator(Kenkyū-buntansha)	丸山彰一名古屋大学, 医学系研究科, 教授 (10362253) 坪井直毅藤田医科大学, 医学部, 教授 (50566958) 伊藤恭彦愛知医科大学, 医学部, 教授 (60402632) 三嶋秀行愛知医科大学, 医学部, 教授 (70520881)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	血栓性微小血管症
Outline of Final Research Achievements	In order to investigate the actual condition of TMA in Japan, we conducted a cross-sectional study using the data of the renal biopsy registry (J-RBR) by the Japanese Society of Nephrology. During the 10 years from 2007 to 2017, 38,495 renal biopsy cases were enrolled, of which 152 (0.39%) were diagnosed with TMA. The most common underlying diseases of TMA were hemolytic uremic syndrome (HUS) / thrombotic thrombocytopenic purpura (TTP) 16.4%, collagen disease 17.1%, and drug-induced 16.4%. A comparison of children, adults, and the elderly showed that renal function was significantly reduced in the elderly, suggesting that potential endothelial damage due to diabetes and hypertension may promote TMA pathology.
Free Research Field	膠原病関連腎障害
Academic Significance and Societal Importance of the Research Achievements	TMAの原因は多彩であり、その病態解明が必要である。研究では薬剤性や膠原病関連TMAが多く存在することが明らかとなった。近年、悪性腫瘍や膠原病の治療分野において分子標的薬は目覚ましい進歩を遂げ、適応疾患が拡大している。しかし使用頻度の増大を背景に、薬剤性TMAによる腎障害の報告が明らかに増加しており、治療レジメの変更を余儀なくされる症例も少なくない。二次性TMAのコホート研究では、腎予後および生命予後とも不良であった。二次性TMAの早期診断法や治療法の開発が今後も必要である。