Association of the modality of iron administration and vascular calcification in renal anemia treatment

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K09742
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Hyogo Medical University
• Principal Investigator: Nakanishi Takeshi 兵庫医科大学, 医学部, 教授 (70217769)
• Co-Investigator(Kenkyū-buntansha): 長澤 康行 兵庫医科大学, 医学部, 講師 (10379167) ; 倉賀野 隆裕 兵庫医科大学, 医学部, 教授 (60411998)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 血管石灰化 / 慢性腎臓病 / 鉄 / リン / 酸化ストレス

Outline of Final Research Achievements

In chronic kidney disease (CKD), vascular calcification (VC) is one of the major factors accelerating cardiovascular events. Although hyperphosphatemia has been established to be the major determinant of VC, we cannot prevent the progression of VC due to several modulators of VC including oxidative stress. In the present study, we tested the effect of iron, the promotor of the oxidative stress, on the VC of aorta from CKD rats, as we previously demonstrated that iron overload accelerated the calcification of cultured vascular cells and iron. We could demonstrate the close relation between iron and calcium content in aorta of these animals. In addition, factor attenuating oxidative stress, ferritin H, was also increased. Thus, iron could accelerate the vascular calcification while it also could attenuate oxidative stress. From these observations, we suspected these conflicting interactions of iron on VC might cause the complicated results.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

慢性腎臓病の有病率は成人の約1/8とされているが、腎機能低下に伴い心血管系事象も増加する。血管石灰化は循環器系合併症の重要な促進因子であり、リンの排泄低下に伴い血管石灰化が促進することが報告されているが、他の多くの因子も石灰化に影響するため適切な予防法がない。慢性腎臓病の進行に伴い貧血および慢性炎症が進行し、それに伴い鉄利用が減少しさらに鉄代謝障害が発生するが、鉄自体が酸化ストレスを促進するため石灰化への影響を検討した。今回の研究から、鉄代謝と石灰化の関連性が示唆され、貧血の管理や鉄剤投与の適正化とともに炎症状態を鎮静化する必要性が明らかとなった。