Identification of nephrotoxic trigger proteins of uremic toxins for advocacy of CKD prevention and treatment methods

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19372
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 47:Pharmaceutical sciences and related fields
• Research Institution: Kanazawa University
• Principal Investigator: Arakawa Hiroshi 金沢大学, 薬学系, 准教授 (40709028)
• Co-Investigator(Kenkyū-buntansha): 藤田 光 金沢大学, 薬学系, 助教 (40782850)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: 腎臓 / トランスポーター / 尿毒症物質 / 尿中排泄 / 炎症 / CD38 / NPT4

Outline of Final Research Achievements

This study searched for binding proteins of uric acid, a uremic substance, and found that it binds to an NAD+-degrading enzyme CD38, indicating that uric acid modulates the immune-inflammatory response through inhibition of CD38 in macrophages. This study also found that NPT4, an organic anion transporter, transports indoxyl sulfate as a physiological substrate, and that a decrease in NPT4 function causes an increase in the blood concentration of indoxyl sulfate.

Free Research Field

薬物動態学

Academic Significance and Societal Importance of the Research Achievements

尿酸の生理的意義は抗酸化作用以外不明であったが、本研究により尿酸はNAD+の細胞内濃度の調節に関与し、急性炎症反応を抑制する働きがあることが示された。またインドキシル硫酸の尿中排泄に関わる輸送機構を明らかとしたことで、尿毒症物質の体内蓄積を低下させる治療・予防手法へ発展させられる可能性を示すことができた。