Development of a novel diagnosis marker for kidney diseases by metabolome analysis

• Project/Area Number: 15K21364
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine; General physiology
• Research Institution: Keio University
• Principal Investigator: HIRAYAMA Akiyoshi 慶應義塾大学, 政策・メディア研究科(藤沢), 特任講師 (00572405)
• Research Collaborator: MARUYAMA Shoichi ; AKIYAMA Shinichi
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 腎疾患 / マーカー / CE-MS / 尿 / 血漿 / ネフローゼ / メタボロミクス / バイオマーカー

Outline of Final Research Achievements

In this study, a comprehensive analysis of urine and plasma metabolites from nephrotic disease patients was conducted by capillary electrophoresis-mass spectrometry (CE-MS) in order to discover biomarkers specific to the type of disease. As a result, it was possible to create a model to distinguish from seven types of nephrotic diseases by combining two to five types of metabolites. With respect to unknown peaks, it was possible to perform a fractionation operation using LC-MS to identify new biomarker candidates.

Research Products

• [Journal Article] Efficacy of Indigo Naturalis in a Multicenter Randomized Controlled Trial of Patients With Ulcerative Colitis (2018)
  • Author(s): Naganuma M et al.
  • Journal Title: Gastroenterology Volume: 154 Pages: 935-947
  • DOI: 10.1053/j.gastro.2017.11.024
  • Peer Reviewed / Open Access
• [Journal Article] Changes of liver metabolites following hepatectomy with ischemia reperfusion towards liver regeneration (2018)
  • Author(s): Y Saito, Y Morine, S Iwahashi, T Ikemoto, S Imura, H Yamanaka-Okumura, A Hirayama, T Soga, M Tomita, M Shimada
  • Journal Title: Annals of Gastroenterological Surgery Volume: - Pages: 1-8
  • DOI: 10.1002/ags3.12058
  • Peer Reviewed
• [Journal Article] Reliability of plasma polar metabolite concentrations in a large-scale cohort study using capillary electrophoresis-mass spectrometry. (2018)
  • Author(s): Harada Sei、Hirayama Akiyoshi、Chan Queenie、Kurihara Ayako、Fukai Kota、Iida Miho、Kato Suzuka、Sugiyama Daisuke、Kuwabara Kazuyo、Takeuchi Ayano、Akiyama Miki、Okamura Tomonori、Ebbels Timothy M. D.、Elliott Paul、Tomita Masaru、Sato Asako、Suzuki Chizuru、Sugimoto Masahiro、Soga Tomoyoshi、Takebayashi Toru
  • Journal Title: PLOS One Volume: 13
  • DOI: 10.1371/journal.pone.0191230
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Comparative analysis of cerebrospinal fluid metabolites in Alzheimer’s disease and idiopathic normal pressure hydrocephalus in a Japanese cohort (2018)
  • Author(s): 1)Nagata Y, Hirayama A, Ikeda S, Shirahata A, Shoji F, Maruyama M, Kayano M, Bundo M, Hattori K, Yoshida S, Goto Y, Urakami K, Soga T, Ozaki K and Niida S.
  • Journal Title: Biomarker Research Volume: 6 Pages: 1-11
  • DOI: 10.1186/s40364-018-0119-x
  • Peer Reviewed / Open Access
• [Journal Article] Development of a sheathless CE-ESI-MS interface (2018)
  • Author(s): Hirayama A, Abe H, Yamaguchi N, Tabata S, Tomita M, Soga T.
  • Journal Title: Electrophoresis Volume: 印刷中
  • DOI: 10.1002/elps.201800017
  • Peer Reviewed
• [Journal Article] Thymidine Catabolism as a Metabolic Strategy for Cancer Survival. (2017)
  • Author(s): Tabata S, Yamamoto M, Goto H, Hirayama A, Ohishi M, Kuramoto T, Mitsuhashi A, Ikeda R, Haraguchi M, Kawahara K, Shinsato Y, Minami K, Saijo A, Hanibuchi M, Nishioka Y, Sone S, Esumi H, Tomita M, Soga T, Furukawa T, Akiyama SI
  • Journal Title: Cell Rep. Volume: 19 Pages: 1313-1321
  • DOI: 10.1016/j.celrep.2017.04.061
  • Peer Reviewed / Open Access
• [Journal Article] Global metabolic reprogramming of colorectal cancer occurs at adenoma stage and is induced by MYC (2017)
  • Author(s): Satoh K, Yachida S, Sugimoto M, Oshima M, Nakagawa T, Akamoto S, Tabata S, Saitoh K, Kato K, Sato S, Igarashi K, Aizawa Y, Kajino-Sakamoto R, Kojima Y, Fujishita T, Enomoto A, Hirayama A, Ishikawa T, Taketo MM, Kushida Y, Haba R, Okano K, Tomita M, Suzuki Y, Fukuda S, Aoki M, Soga T.
  • Journal Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 114
  • DOI: 10.1073/pnas.1710366114
  • Peer Reviewed
• [Journal Article] Dynamic Metabolomics Reveals that Insulin Primes the Adipocyte for Glucose Metabolism (2017)
  • Author(s): James R. Krycer, Satoshi Ohnoら全21名
  • Journal Title: Cell Reports Volume: 21 Pages: 3536-3547
  • DOI: 10.1016/j.celrep.2017.11.085
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 陰イオン性代謝物に特化した新規メタボローム分析法の開発 (2017)
  • Author(s): 平山明由、田畑祥、曽我朋義
  • Organizer: 第5回 がんと代謝研究会
• [Presentation] 疫学研究に必要なメタボローム解析の精度管理 (2017)
  • Author(s): 平山明由
  • Organizer: 第45回 産業中毒・生物学的モニタリング研究会
  • Invited
• [Presentation] Development of anionic metabolome analysis method using capillary ion chromatography-mass spectrometry (2017)
  • Author(s): Hirayama Akiyoshi、Tomita Masaru、Soga Tomoyoshi
  • Organizer: 13th Annual International Conference of the Metabolomics Society
  • Int'l Joint Research
• [Presentation] メタボロミクスを用いた新たな尿検査の可能性 (2016)
  • Author(s): 平山明由、湯澤由紀夫
  • Organizer: 日本臨床検査自動化学会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-09-22
  • Invited
• [Presentation] メタボローム解析技術を用いたCKDの尿中バイオマーカー探索 (2015)
  • Author(s): 平山明由、秋山真一、尾崎武徳、松尾清一、曽我朋義、丸山彰一
  • Organizer: 日本腎臓学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県）
  • Year and Date: 2015-06-05
  • Invited