2021 Fiscal Year Final Research Report

Pathophysiological Role of Heparin Cofactor II in Diabetic Kidney Diseases

Research Project

PDF

Project/Area Number	19K08680
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 53040:Nephrology-related
Research Institution	The University of Tokushima
Principal Investigator	AIHARA Ken-ichi 徳島大学, 大学院医歯薬学研究部(医学域), 特任教授 (70372711)
Co-Investigator(Kenkyū-buntansha)	八木秀介徳島大学, 大学院医歯薬学研究部(医学域), 特任教授 (00507650) 吉田守美子徳島大学, 大学院医歯薬学研究部(医学域), 准教授 (40510904) 池田康将徳島大学, 大学院医歯薬学研究部(医学域), 教授 (60432754)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	トロンビン / ヘパリン・コファクターII / 糖尿病性腎臓病 / 尿中アルブミン / L-FABP
Outline of Final Research Achievements	Thrombin promotes renal injuries. Heparin cofactor II (HCII) specifically inactivates thrombin; thus, we hypothesized that low plasma HCII activity correlates with diabetic kidney diseases. Plasma HCII activity and urine biomarkers, including albumin and liver-type fatty acid-binding protein (L-FABP), were determined as the urine albumin-to-creatinine ratio (uACR) and the urine L-FABP-to-creatinine ratio (uL-FABPCR) in 310 Japanese patients with diabetes. The relationships between HCII and those DKD urine biomarkers were evaluated. In addition, the relationship between HCII and annual uACR changes was evaluated. Multivariate-regression analysis showed that plasma HCII activity contributed to the suppression of the uACR and log-transformed uACR values but not uL-FABPCR. In addition, plasma HCII inversely correlated with annual uACR and log-transformed uACR increments.Taken together, the plasma HCII activity was inversely associated with glomerular injury in patients with diabetes.
Free Research Field	内分泌代謝内科学
Academic Significance and Societal Importance of the Research Achievements	糖尿病患者の腎合併症の進展によって、我が国でも多くの患者が血液透析治療を受けていることは、患者予後や医療コストの両面で、解消すべき大きな臨床課題である。本研究結果から、糖尿病性腎臓病、特に尿中アルブミン排泄の増加で表現される糸球体障害について、血漿HCIIは、病態進展抑制的に働くことが示唆された。このことから、血漿HCII活性の測定が、糖尿病患者における糸球体障害をきたすハイリスク個体の層別化に寄与する可能性がある。また血漿HCII活性を高める薬剤探索が今後進めば、糖尿病性糸球体障害の発症や進展予防に貢献する新薬開発につながる可能性がある。