Investigation of new erythropoietin resistance factors and the mechanisms: with special attentions to associations between erythropoiesis and lipid metabolism

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07844
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: University of Fukui
• Principal Investigator: Kimura Hideki 福井大学, 学術研究院医学系部門(附属病院部), 准教授 (20283187)
• Co-Investigator(Kenkyū-buntansha): 丹羽 明 京都大学, iPS細胞研究所, 特定拠点助教 (20546999) ; 山内 高弘 福井大学, 学術研究院医学系部門, 教授 (90291377) ; 鳥居 国雄 福井大学, 学術研究院医学系部門(附属病院部), 主任臨床検査技師 (40534045)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 腎性腎血 / エリスロポエチン / 血液透析患者 / アシルカルニチン / 脂肪酸β酸化 / 血清脂質 / 網赤血球数

Outline of Final Research Achievements

Recent reports showed that division and proliferation of erythroid progenitor cells required an energy source shit from glucose to lipid. Therefore, some associations may occur between erythropoiesis and lipid metabolism including fatty acid β-oxidation. Here, various acylcarnitines (AC:C2-C18) were measured and analyzed for the correlation with erythropoiesis status in stable hemodialysis patients. TG and C18:1 were independently positively correlated with reticulocyte counts, and TC and a putative index for β-oxidation enhancement, C2/(C16+C18+C18:1) were independently negatively correlated with erythropoietin resistance (ERI). When the regression analysis was performed to investigate the impact of the number of acyl group carbons on the correlation coefficients between various ACs on ERI, a significant change from negative to positive correlation was observed with increasing carbon number. These suggest that lower fatty acid β-oxidation may be associated with higher ERI.

Free Research Field

腎臓内科学，臨床検査医学

Academic Significance and Societal Importance of the Research Achievements

保存期腎不全・透析患者の腎性貧血にエリスロポエチン(Epo)製剤が汎用され、世界的には7000億、本邦では約1000億の医療費となっている。本研究から、新たなEpo抵抗性の脂質関連マーカーが検出されれば、より適切なEpo製剤の使用法が計画できる。性別、新規の脂質指標を考慮してEpo、カルニチンを使い分け、医療費削減につながる。貧血の改善は、慢性腎臓病進展と心血管疾患発症の予防にも貢献する。