Pathogenesis of FSGS in CNI toxicity in renal allograft

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07418
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: Taneda Sekiko 東京女子医科大学, 医学部, 准教授 (40408472)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 移植腎生検 / 腎臓移植 / 巣状分節性糸球体硬化症 / 成因 / Banff分類 / 足細胞 / 糸球体内皮細胞 / カルシニューリン阻害剤

Outline of Final Research Achievements

The FSGS cases were classified into the 4 groups depending on the etiologies: CNIs-FSGS group, recurrent-FSGS group, ABMR-FSGS group, and unknown etiology (UE)-FSGS group, and compared. FSGS lesions were evaluated according to the Columbia classification. The most of CNI-FSGS cases were the NOS variant with endothelial injury, but COL variants which had strong epithelial cell proliferation were also found. The recurrent-FSGS group showed the highest ratio of the COL variant among the groups, but the COL variant of recurrent-FSGS group had a least endothelial injury. The ABMR-FSGS group had little pathological similarity to the CNI-FSGS group. The UE-FSGS group included significantly more cases of T cell-mediated rejection or reflux nephropathy, which were the NOS variant. The clinicopathologic features of post-transplant FSGS differ depending on the etiology. Morphological assessment of FSGS lesions may help in the diagnosis and clinical management of FSGS during renal transplantation.

Free Research Field

腎臓病理

Academic Significance and Societal Importance of the Research Achievements

FSGSは糸球体傷害の形態的なカテゴリーである。腎移植はCNIを含む免疫抑制剤や拒絶反応の影響を受ける。過去の報告では、腎移植におけるFSGSは、臨床的特徴に関連する形態学的特徴に基づき、CNIによる血管毒性、ABMR、ネフロン喪失/過剰濾過に病因分類されている。本研究では、CNIの影響を対象群（再発性FSGS群、ABMR-FSGS群、いずれの群にも属していない病因不明なFSGS群）と比較した。その結果、移植後FSGSの臨床学的特徴は病因によって異なり、同一の病理亜型であっても、電顕上傷害部位は異なっていた。腎移植のFSGS病変の形態学的評価は、FSGSの診断と臨床管理に役立つと考えられた。