Regulation of arteriovenous fistula maturation in high-risk groups of occlusion

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K24006
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0905:Surgery of the organs maintaining homeostasis and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Isaji Toshihiko 東京大学, 医学部附属病院, 助教 (40779790)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: 動静脈瘻 / 内膜肥厚 / 内皮機能 / eNOS / 糖尿病 / 性差 / Sildenafil

Outline of Final Research Achievements

Diabetes mellitus is a known risk factor for occlusion of arteriovenous fistulas for dialysis due to intimal thickening. We focused on vascular endothelial damage in diabetic patients and compared postoperative maturation of arteriovenous fistulas with and without sildenafil, which enhances eNOS, in a mouse model. Although there was no difference in arteriovenous fistula patency and degree of intimal thickening at 6 weeks postoperatively, the diameter of shunted vena cava tended to be dilated in the sildenafil-treated group. We attempted to create an arteriovenous fistula model in mice with type I diabetes mellitus by administering streptozotocin, but the mortality rate during the postoperative course made it difficult to conduct a comparative study with the control group. We also created an ovariectomy model in mice, but the postoperative mortality rate was so high that we were unable to create an arteriovenous fistula model.

Free Research Field

血管外科学

Academic Significance and Societal Importance of the Research Achievements

人工透析を要する慢性腎不全患者におけるブラッドアクセスの長期開存の確保は喫緊の課題である。これまで我々は動静脈瘻造設術後の成熟と不全を司るいくつかの分子に着目してきたが、いずれも動物実験段階から実臨床への応用の道のりには数多くのプロセスを経る必要がある。シルデナフィルは勃起不全症に対する治療薬として薬事承認を受けた薬剤であり、本研究を発展させて動静脈瘻に対する内膜肥厚制御効果さらに長期開存率改善効果が認められれば、比較的早期の臨床応用が期待できる。