2019 Fiscal Year Final Research Report

Search for new urinary biomarkers to detect early stage of CKD

Research Project

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Project/Area Number	17K09723
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Kidney internal medicine
Research Institution	独立行政法人国立病院機構新潟病院(臨床研究部)
Principal Investigator	Fujinaka Hidehiko 独立行政法人国立病院機構新潟病院(臨床研究部), 臨床研究部, 臨床研究部長 (20447642)
Co-Investigator(Kenkyū-buntansha)	矢尾板永信新潟大学, 医歯学系, 准教授 (00157950) 山本格新潟大学, 医歯学総合研究科, 特任教授 (30092737)
Project Period (FY)	2017-04-01 – 2020-03-31
Keywords	尿バイオマーカー / 慢性腎障害 / IgA腎症
Outline of Final Research Achievements	To discover new urinary biomarkers for early detection of CKD, 98 proteins were selected from our original kidney proteome database, and studied about their urinary excression in normal controls and IgA nephropathy patients. Four proteins (A-D) were confirmed significantly increased urinary excression in IgA nephropathy patients. Urinary proteins of A and C were originated from injured kidney glomerular podocytes, B was from interstitium, and D was from proximal tubule cells. Among these 4 proteins, urinary excretion of A was shown increased in many of IgA nephropathy patients of proteinuria negative (up/uCre<0.15). And urinary excression of most of the previously reported urinary biomarkers were positively correlated with the amount of proteinuria, although urinary KIM-1 tended to be higher in lower protenuria patients in IgA nephropathy. In conclusion, urinary proteins of A and KIM-1 were considered to be effective for detection of IgA nephropathy of early (lower proteinuric) stage.
Free Research Field	腎臓内科学
Academic Significance and Societal Importance of the Research Achievements	慢性腎障害（CKD）は通常の尿検査だけでは見逃される例がある。本研究の目的は、蛋白尿陰性でもCKDと診断しうる新規尿検査の開発である。尿蛋白質のうち血漿由来のアルブミン以外の成分は微量であり、多くが検討されていない。我々は尿蛋白質のうちアルブミン以外、特に腎臓由来の成分が新規尿バイオマーカーになる可能性を検討した。また既報の複数の尿バイオマーカーの比較検討も併せて行なった。結果、新規尿バイオマーカー候補蛋白質A、および既報の尿バイオマーカーKIM-1の尿中排泄が、蛋白尿の少ないIgA腎症患者の多くで増加することが確認できた。今後その測定がCKDの早期診断目的に組み込まれることが期待される。