Roles of the complement system to develop peritoneal inures in PD

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08206
• 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: Nagoya University
• Principal Investigator: Mizuno Masashi 名古屋大学, 医学系研究科, 特任教授 (20303638)
• Co-Investigator(Kenkyū-buntansha): 鈴木 康弘 名古屋大学, 医学系研究科, 特任講師 (20584676) ; 伊藤 恭彦 愛知医科大学, 医学部, 教授 (60402632)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 人工透析 / 腹膜透析 / 補体活性化 / 補体制御 / 腹膜傷害 / 腹膜炎

Outline of Final Research Achievements

①We clarified the protective effects of C1 inhibitor, which is currently used as an anti-complement (C) in patients with HAE, on peritoneal injury in an animal model of peritoneal dialysis (PD)-related fungal peritonitis. We are also proceeding to investigate any roles of the C terminal pathway in the process from peritoneal injury to encapsulated peritoneal sclerosis (EPS) using genetically modified animals of C-related proteins and neutralizing antibodies in the animal model.
②Using human PD effluent, we reported increase of peritoneal eosinophils due to enhanced activation of the C system when PD was introduced with neutralized PD fluid. We also observed that the expression of membrane C regulatory proteins was at least increased during PD treatment 3 years periods in primary cultures of peritoneal mesothelial cells (HMPC) of PD effluent of PD patients.

Free Research Field

腎臓内科

Academic Significance and Societal Importance of the Research Achievements

PDとCの関連性の探求は、世界に先駆けて我々が開拓進めている研究分野である。今回の我々の研究成果は、PDが腹膜のC活性および制御系に与えることを証明し、腹膜炎による腹膜傷害に抗C薬が治療の選択肢となる可能性を示した。また、腹膜炎や腹膜傷害とEPS 発症進展に対して抗C薬の治療選択の糸口となり、更に腹膜傷害進展の証明や、腹膜傷害とEPS進展を予想するC関連のバイオマーカーの発見が、より長期に安全な PD の実現につながる可能性を示唆する。