Treatment approach against cardiovascular disease in hemodialysis patients through improvement of uremic toxins

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461250
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Osaka City University
• Principal Investigator: Mori Katsuhito 大阪市立大学, 大学院医学研究科, 講師 (60382040)
• Co-Investigator(Kenkyū-buntansha): SHOJI Tetsuo 大阪市立大学, 大学院医学研究科, 准教授 (40271192)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: fetuin-A / インドキシル硫酸 / 心血管イベント / 血液透析 / CKD / 尿毒症 / 血管石灰化 / 培養肝細胞

Outline of Final Research Achievements

Fetuin-A is a liver-derived circulating protein that has potent calcification-inhibitory activity. Uremic patients exhibit decreased serum fetuin-A levels, increased vascular calcification and elevated cardiovascular mortality. Because the mechanisms for fetuin-A deficiency are unknown, we hypothesised that some uremic toxins suppressed hepatic fetuin-A production, which resulted in accelerated vascular calcification and poor outcome. Among these potential candidates, indoxyl sulfate (IS) has highly toxic properties. We examined the direct effects of IS on hepatic fetuin-A expression using the human hepatoma HepG2 cell line. IS suppressed hepatic fetuin-A expression by activating the aryl hydrocarbon receptor, suggesting a relationship among uremia, fetuin-A deficiency and cardiovascular mortality.

Free Research Field

代謝・腎臓内科学