Development of Diagnostic Methods for detecting Diabetic Nephropathy

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08717
• 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: National Center for Global Health and Medicine
• Principal Investigator: HIROYUKI KUBOTA (卯木浩之) 国立研究開発法人国立国際医療研究センター, その他部局等, 室長 (40323290)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 糖尿病性腎臓病 / 腎機能低下 / 尿プロテオーム

Outline of Final Research Achievements

We have previously performed a urinary proteomic analysis of patients with diabetic kidney disease (DKD) and identified the differentially excreted proteins in the patients with DKD. In this study, we evaluated the association of the differentially excreted proteins with an annual decline in estimated glomerular filtration (eGFR) in patients with type 2 diabetes (T2D) and preserved kidney function. We found that 9 proteins among them were significant independent predictors of annual decline in eGFR. In addition, urinary afamin levels, which have previously been found to be associated with changes in the urinary albumin-to-creatinine ratio, were increased in rapid decliner compared to that of slow decliner although the difference was not statistically significant. Our findings highlight the important effect of the identified urinary proteins including afamin as prognostic markers of early progressive renal decline in patients with T2D and preserved kidney function.

Free Research Field

糖尿病学

Academic Significance and Societal Importance of the Research Achievements

糖尿病性腎臓病患者における腎機能低下の危険因子である尿アルブミン・クレアチニン比やeGFRは、本研究で解析対象とする糖尿病性腎臓病を発症していない2型糖尿病患者における腎機能低下と明らかな関連を示さなかった。したがって本研究で新たに同定された尿中タンパク質の尿中濃度を用いた腎機能予後予測法を構築し、その有用性が示されれば、早期腎症期を的確に診断し、適切な治療介入により糖尿病性腎臓病の進展を阻止できる可能性がある。また、腎機能予後予測プログラムにて腎機能低下ハイリスク群と判定された2型糖尿病患者を対象として、腎機能低下をより効率的に予防する新たな治療法開発を進めることも可能となる。