Development of the measurement system of anti-erythropoietin receptor antibodies and the basic examination of these effect on renal outcome

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09608
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Kanazawa University
• Principal Investigator: Hara Akinori 金沢大学, 医学系, 准教授 (70507045)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 慢性腎臓病

Outline of Final Research Achievements

We developed the measurement system of autoantibodies to erythropoietin (EPO) receptor (EPOR) and performed the examination of these effect on renal outcome. Following lupus nephritis, we examined the effect of the antibodies in patients with type 2 diabetic nephropathy. A decrease in renal function was observed more frequently in patients with antibodies than in those without antibodies, and the presence of the antibodies together with well-known clinical parameters, including blood pressure and proteinuria, was a significant risk factor for end-stage renal disease. Pathologically, anti-EPOR antibodies were associated with increased levels of interstitial inflammation. Immunoglobulin G fractions containing anti-EPOR antibodies interfered the anti-inflammatory effect of EPO in a human tubular epithelial cells. Besides, we have improved the measurement system, and continued to examine the mechanism of organ protective effect of EPO using kidney disease models in mice.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

慢性腎臓病(CKD)において臨床的に有用なバイオマーカーの開発が求められている。近年、高齢化、肥満・糖尿病の増加など背景として末期腎不全のハイリスク者が増加している。末期腎不全は透析治療を余儀なくされるのみならず、高率に発症する心血管疾患による生命予後悪化およびそれに対する治療にかかる医療費負担が大きくなりやすい。したがって、患者予後改善および社会負担軽減のためCKDハイリスク群の診断法の向上および予後予測を可能とする方法の開発は重要な課題である。本研究で得られた成果である抗EPO受容体抗体の測定は、CKDにおける腎予後予測の補助を目的とした新たな臨床検査診断法となる可能性が考えられた。