Development of a new treatment method for acute kidney injury via erythropoietin receptor

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K17268
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Kurume University
• Principal Investigator: NAKAYAMA YOSUKE 久留米大学, 医学部, 助教 (00748486)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 急性腎障害 / 内皮障害 / ADMA / エリスロポエチン / 虚血 / HTS / SDMA / NO

Outline of Final Research Achievements

We have demonstrated that ADMA, an NO synthesis inhibitor, is involved in erythropoietin hyporesponsiveness in renal failure. In this study, we hypothesized that ADMA-induced erythropoietin hyporesponsiveness is also involved in anemia and renal damage during acute kidney injury. We aimed to develop a marker for acute kidney injury and a treatment method that involves erythropoietin hyporesponsiveness. As a result, we demonstrated that anemia correlates with renal dysfunction during acute kidney injury, and that SDMA, a structural isomer of ADMA, is a useful marker for predicting early renal failure, and we created an antibody for ADMA/SDMA ELISA. Furthermore, we constructed two types of HTS to search for compounds that metabolize ADMA, and found nine compounds from 1,234 known compounds.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

近年の患者の超高齢化と医療技術の目覚ましい発展に伴い，侵襲度の高い医療行為がハイリスク症例に適応されるようになりそれとともに急性腎障害の頻度は増加している。申請者は尿毒素物質の1つであるADMAがエリスロポエチン受容体低下を引き起こしEPO低反応性を誘導することを見出した。術後の急性腎不全や腎移植から生じる急性腎障害は不可避な医原性腎疾患であるが、障害発症が予想できるため予防可能な急性腎障害ともいえる。腎虚血を予見し、急性腎障害時のADMA抑制による腎虚血保護は急性腎障害の新たな治療戦略となり腎臓分野へ貢献ができると考えている。