Investigation of the mechanism and risk factors of encapsulating peritoneal sclerosis using peritoneal tissue pathological analysis

• Project/Area Number: 18K08205
• 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: Suzuki Yasuhiro 名古屋大学, 医学系研究科, 特任講師 (20584676)
• Co-Investigator(Kenkyū-buntansha): 水野 正司 名古屋大学, 医学系研究科, 特任教授 (20303638) ; 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
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 腹膜透析 / 被嚢性腹膜硬化症 / CAPD / EPS / vasculopathy

Outline of Final Research Achievements

In order to elucidate the mechanism of development and relapse of encapsulated peritoneal sclerosis (EPS) in peritoneal dialysis, we investigated the peritoneal damage pathologically focused on vasculopathy using 214 samples of peritoneal tissue obtained from EPS surgery cases. Comparing patients with acidic and neutral dialysate, the L/V ratio of the acidic group was significantly low which means severe vasculopathy, and vasculopathy progressed over time. There was no significant difference in the number of inflammatory cells and peritoneal thickeness. In the neutral fluid group, vasculopathy was milder than acidic group, and most of EPS progressed from peritonitis. The mechanism of EPS differed between the acidic and the neutral solution group. These results might indicate that vascular endothelial cell damage is caused by non-physiological factors especially with acidic dialysate, and that vascular damage promotes exudative lesions and triggered the onset of EPS.

Academic Significance and Societal Importance of the Research Achievements

腹膜透析療法において被嚢性腹膜硬化症(EPS)は最も重篤かつ長期施行の妨げとなっておりそのメカニズムの解明と予知・予防法の確立が求められているが、まれな疾患であり大規模に調査したものは世界的にもない。そこで、EPS手術症例が多数集積するあかね会土谷総合病院と共同して、200検体以上のEPSの腹膜組織検体を病理学的に解析した。その結果腹膜の血管内皮障害がEPS発症、再発の主要因子であることを同定した。特に酸性透析液による内皮細胞障害がEPSの引き金になるという発症のメカニズムを解明できた。今後、予知因子を同定し、EPSの予防や早期治療を可能にすることにつながる重要な成果と思われる。

Research Products

• [Journal Article] Vasculopathy plays an important role during the development and relapse of encapsulating peritoneal sclerosis with conventional peritoneal dialysis solutions (2020)
  • Author(s): Mitsuhiro Tawada, Yasuhiko Ito, Masataka Banshodani, Masahiro Yamashita, Sadanori Shintaku, Ting Sun, Yasuhiro Suzuki, Hiroshi Kinashi, Yoko Kubo, Masahiko Ando, Makoto Yamaguchi, Takayuki Katsuno, Masashi Mizuno, Hideki Kawanishi
  • Journal Title: Nephrol Dial Transplant Volume: ー Issue: 8 Pages: 1-9
  • DOI: 10.1093/ndt/gfaa073
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Peritoneal Pathological Differences In Conventional And PhNeutral Low- Gdp Solution (2021)
  • Author(s): Ito Yasuhiko, Tawada M, Suzuki Y, Mizuno M
  • Organizer: ISPD / EuroPD
  • Int'l Joint Research
• [Presentation] ヒト腹膜組織からみたEPSの病態 (2020)
  • Author(s): 伊藤恭彦
  • Organizer: 日本腹膜透析医学会学術集会
  • Invited