Chiral amino acids in pathogenesis diabetic nephropathy/diabetic kidney disease and their perspectives for biomarker candidates

2022 Fiscal Year Final Research Report

• Project/Area Number: 19H03557
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Kanazawa University
• Principal Investigator: Wada Takashi 金沢大学, その他部局等, その他 (40334784)
• Co-Investigator(Kenkyū-buntansha): 古市 賢吾 金沢医科大学, 医学部, 教授 (50432125) ; 坂井 宣彦 金沢大学, 附属病院, 准教授 (60377421) ; 岩田 恭宜 金沢大学, 附属病院, 特任教授 (90432137)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 腎臓 / 糖尿病性腎症 / 糖尿病性腎臓病 / キラルアミノ酸 / バイオマーカー

Outline of Final Research Achievements

This study was aimed to determine D-amino acid (AA) profile and associated bacteria in patients with chronic kidney disease (CKD) with and without diabetes mellitus (DM). Detailed D-AA profile has not been studied in CKD patients with DM so far. We examined the chiral AA levels of salivary, stool, plasma, and urine and related bacteria in patients examined. 16S rRNA gene sequencing analysis of the oral and gut microbiota were also performed to determine bacterial species responsible for D-AA levels. Plasma D-alanine and D-serine levels were higher in patients with CKD than in healthy adults. In addition, plasma D-alanine levels were significantly higher in CKD patients with DM as compared to those without DM. D-alanine was produced by salivary Streptococcus, which positively correlated with plasma D-alanine levels. Collectively, D-alanine might be a biomarker candidate for CKD patients with DM.

Free Research Field

腎臓学、内科学、臨床検査医学

Academic Significance and Societal Importance of the Research Achievements

糖尿病性腎臓病・糖尿病性腎症（腎症）は透析導入原疾患の第1位である。そのため、腎症の病態解明と病態を反映するバイオマーカー開発は重要な課題である。本研究の学術的な特色は、技術革新により分析可能となったキラルアミノ酸に着目し、１）腎症の病態の解明と病態・予後を反映するD-アミノ酸の同定と病態への役割の検討、２）特定のD-アミノ酸の産生微生物の同定、３）腎臨床・病理所見とD-アミノ酸の突合を行い、その分子機序、病態・予後など臨床的意義を反映することである。本研究はキラルアミノ酸により腎症の病態解明とバイオマーカー開発を目指すものであり、学術的意義ならびに社会的意義が深い。