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Early and minimally invasive diagnosis of kidney failure using chiral amino acid metabolomics

Research Project

Project/Area Number 16H05080
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Physical pharmacy
Research InstitutionKyushu University

Principal Investigator

Kenji Hamase  九州大学, 薬学研究院, 教授 (10284522)

Co-Investigator(Kenkyū-buntansha) 猪阪 善隆  大阪大学, 医学系研究科, 教授 (00379166)
井手 友美  九州大学, 医学研究院, 准教授 (90380625)
Research Collaborator Mita Masashi  
Lindner Wolfgang  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2018: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Keywords分析化学 / メタボロミクス / 光学分割 / アミノ酸
Outline of Final Research Achievements

For the early and minimally invasive diagnosis of kidney failure, LC/LC/MS three-dimensional system, LC/LC/LC three-dimensional system and LC/LC/MS/MS four-dimensional analysis system have been developed. As the analytes, various chiral amino acids, hydroxy acids and peptides were selected, and the analytical systems were designed using the real clinical samples. Using the human plasma with chronic kidney diseases, the chiral amino acids were analyzed. As a result, the present system could be applicable to all samples including the patients with high eGFR, indicating that the proposed method is effective for the early stage diagnosis of CKD.

Academic Significance and Societal Importance of the Research Achievements

腎不全は様々な原因で腎機能が低下した状態である。罹患人口は増加の一途をたどり、予備軍を含めた慢性腎不全患者数は日本で2000万人と推定されている。腎不全は原因疾患、病変部位共に多岐に亘るが、臨床症状が類似する場合もあり、確定診断・鑑別には腎生検が必要とされる。また、治療や予防の観点から軽度腎不全での診断法開発が切望されている。本研究では高い選択性を有する血中キラルアミノ酸分析システムを開発し、実際の腎不全検体を用いて早期の低侵襲診断を可能とした。この研究成果は、腎不全罹患者の生涯QOL改善に貢献するものであり、社会的有用性が高い。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (41 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (10 results) Journal Article (6 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 6 results,  Open Access: 4 results) Presentation (22 results) (of which Int'l Joint Research: 16 results,  Invited: 16 results) Remarks (3 results)

  • [Int'l Joint Research] ウィーン大学/ザルツブルグ大学(オーストリア)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] 台北医学大学(台湾)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] マヒドン大学(タイ)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] ウィーン大学/ザルツブルグ大学(オーストリア)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] 台北医学大学(台湾)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] マヒドン大学(タイ)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] ウィーン大学/ザルツブルグ大学(オーストリア)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] チュービンゲン大学(ドイツ)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] 台北医学大学(台湾)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] マヒドン大学(タイ)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Development of a Three-Dimensional HPLC System for the Simultaneous Determination of Lactate and 3-Hydroxybutyrate Enantiomers in Mammalian Urine2019

    • Author(s)
      Chin-Ling HSIEH, Po-Yeh LIN, Takeyuki AKITA, Masashi MITA, Tomomi IDE, Jen-Ai LEE, Kenji HAMASE
    • Journal Title

      CHROMATOGRAPHY

      Volume: 40 Issue: 1 Pages: 25-32

    • DOI

      10.15583/jpchrom.2018.021

    • NAID

      130007612989

    • ISSN
      1342-8284, 1348-3315
    • Year and Date
      2019-02-20
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Multi-Dimensional HPLC Analysis of Serine Containing Chiral Dipeptides in Japanese Traditional Amber Rice Vinegar2018

    • Author(s)
      SEREEKITTIKUL Nutchaya、KOGA Reiko、AKITA Takeyuki、FURUSHO Aogu、REISCHL Roland、MITA Masashi、FUJII Akira、HASHIGUCHI Kazunori、NAGANO Masanobu、LINDNER Wolfgang、HAMASE Kenji
    • Journal Title

      CHROMATOGRAPHY

      Volume: 39 Issue: 2 Pages: 59-66

    • DOI

      10.15583/jpchrom.2018.002

    • NAID

      130007403307

    • ISSN
      1342-8284, 1348-3315
    • Year and Date
      2018-06-20
    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Development of a Highly-Sensitive Two-Dimensional HPLC System with Narrowbore Reversed-Phase and Microbore Enantioselective Columns and Application to the Chiral Amino Acid Analysis of the Mammalian Brain2018

    • Author(s)
      FURUSHO Aogu、KOGA Reiko、AKITA Takeyuki、MIYOSHI Yurika、MITA Masashi、HAMASE Kenji
    • Journal Title

      CHROMATOGRAPHY

      Volume: 39 Issue: 2 Pages: 83-90

    • DOI

      10.15583/jpchrom.2018.007

    • NAID

      130007403273

    • ISSN
      1342-8284, 1348-3315
    • Year and Date
      2018-06-20
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of an online two-dimensional high-performance liquid chromatographic system in combination with tandem mass spectrometric detection for enantiomeric analysis of free amino acids in human physiological fluid2018

    • Author(s)
      Ishii Chiharu、Akita Takeyuki、Mita Masashi、Ide Tomomi、Hamase Kenji
    • Journal Title

      Journal of Chromatography A

      Volume: 1570 Pages: 91-98

    • DOI

      10.1016/j.chroma.2018.07.076

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enantioselective and simultaneous determination of lactate and 3-hydroxybutyrate in human plasma and urine using a narrow-bore online two-dimensional high-performance liquid chromatography system2018

    • Author(s)
      C.-L. Hsieh, R. Koga, A. Furusho, T. Akita, M. Mita, T. Ide, J.-A. Lee, K. Hamase
    • Journal Title

      Journal of Separation Science

      Volume: 41 Issue: 6 Pages: 1-9

    • DOI

      10.1002/jssc.201701283

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Two-Dimensional HPLC-MS/MS Determination of Multiple D-Amino Acid Residues in the Proteins Stored Under Various pH Conditions2017

    • Author(s)
      Ishii Chiharu、Miyamoto Tetsuya、Ishigo Shoto、Miyoshi Yurika、Mita Masashi、Homma Hiroshi、Ueda Tadashi、Hamase Kenji
    • Journal Title

      CHROMATOGRAPHY

      Volume: 38 Issue: 2 Pages: 65-72

    • DOI

      10.15583/jpchrom.2017.009

    • NAID

      130007040478

    • ISSN
      1342-8284, 1348-3315
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Enantioselective multi-dimensional HPLC analysis of amino acids and related compounds in complex matrices; Application to food and extraterrestrial samples2019

    • Author(s)
      Kenji HAMASE
    • Organizer
      35th International Annual Meeting in Pharmaceutical Sciences (IAMPS35) and CU-MPU International Collaborative Research Conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Chiral amino acid analysis using 2D/3D-HPLC for the screening of functional molecules and biomarkers2019

    • Author(s)
      Kenji HAMASE
    • Organizer
      9th Federation of the Asian and Oceanian Physiological Societies Congress
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Multi-dimensional HPLC with fluorescence detection as a promising method for trace analysis of chiral amino acids and hydroxy acids in clinical, food and extraterrestrial samples2018

    • Author(s)
      Kenji HAMASE
    • Organizer
      XVIII International Symposium on Luminescence Spectrometry
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Multi-dimensional chiral HPLC: A promising approach to expand the frontier of amino acid, peptide and protein research2018

    • Author(s)
      Kenji HAMASE
    • Organizer
      2018 Sino-Japanese Joint Symposium on Separation Sciences
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Three-dimensional chiral HPLC analysis of amino acids and related compounds in complex biological matrices including human clinical samples2018

    • Author(s)
      Kenji HAMASE, Reiko KOGA, Aogu FURUSHO, Chin-Ling HSIEH, Nutchaya SEREEKITTIKUL, Takeyuki AKITA, Masashi MITA, Tomomi IDE, Jen-Ai LEE, Wolfgang LINDNER
    • Organizer
      47th International Symposium on High Performance Liquid Phase Separations and Related Techniques
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Chiral amino acid metabolomics studies using two/three-dimensional HPLC for the screening of new biomarkers and designing functional foods/beverages2018

    • Author(s)
      Kenji HAMASE, Chiharu ISHII, Aogu FURUSHO, Reiko KOGA, Takeyuki AKITA, Masashi MITA, Masanobu NAGANO, Tomomi IDE, Tomonori KIMURA, Wolfgang LINDNER
    • Organizer
      The 11th International Symposium on Drug Analysis & The 29th International Symposium on Pharmaceutical and Biomedical Analysis
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Chiral amino acid analysis using multi-dimensional HPLC: A new frontier of the amino acid and protein research2018

    • Author(s)
      Kenji HAMASE
    • Organizer
      15th Conference of the International Society of Tryptophan Research
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Multi-dimensional HPLC analysis of chiral amino acids for drug discovery and diagnosis2017

    • Author(s)
      Kenji HAMASE
    • Organizer
      The JSPS-NRCT Follow-Up Seminar 2017 and 33rd International Annual Meeting in Pharmaceutical Sciences
    • Place of Presentation
      Bangkok, Thailand
    • Year and Date
      2017-03-02
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 多次元HPLCによるキラルアミノ酸分析と医療応用2017

    • Author(s)
      浜瀬健司
    • Organizer
      第77回分析化学討論会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Three-dimensional HPLC analysis of amino acid enantiomers in complicated real world samples2017

    • Author(s)
      Kenji HAMASE, Reiko KOGA, Yurika MIYOSHI, Masashi MITA, Wolfgang LINDNER
    • Organizer
      45th International Symposium on High Performance Liquid Phase Separations and Related Techniques
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Multi-dimensional HPLC analysis of D-amino acids and related compounds in complicated biological matrices and its clinical applications2017

    • Author(s)
      Kenji HAMASE, Reiko KOGA, Yurika MIYOSHI, Masashi MITA, Jen-Ai LEE, Wolfgang LINDNER
    • Organizer
      The 3rd International Conference of D-Amino Acid Research
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Development of the multi-dimensional HPLC system for serine containing chiral dipeptides and application to clinical/food samples2017

    • Author(s)
      Nutchaya SEREEKITTIKUL, Reiko KOGA, Aogu FURUSHO, Roland REISCHL, Masashi MITA, Wolfgang LINDNER, Kenji HAMASE
    • Organizer
      第35回九州分析化学若手の会夏季セミナー
    • Related Report
      2017 Annual Research Report
  • [Presentation] 多次元HPLCによるキラルアミノ酸・ヒドロキシ酸分析とアプリケーション2017

    • Author(s)
      浜瀬健司
    • Organizer
      日本分析化学会第66年会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Multi-dimensional HPLC analysis of serine containing chiral depeptides in human physiological fluids and fermented products2017

    • Author(s)
      Nutchaya SEREEKITTIKUL, Reiko KOGA, Aogu FURUSHO, Roland REISCHL, Masashi MITA, Masanobu NAGANO, Tomomi IDE, Wolfgang LINDNER, Kenji HAMASE
    • Organizer
      The 46th International Symposium on High Performance Liquid Phase Separations and Related Techniques
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Multi-dimensional chiral HPLC analysis of amino acids in clinical samples and extraterrestrial materials2017

    • Author(s)
      Kenji HAMASE, Takeyuki AKITA, Masashi MITA, Hiroshi NARAOKA, Wolfgang LINDNER
    • Organizer
      The 46th International Symposium on High Performance Liquid Phase Separations and Related Techniques
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Chiral amino acid metabolomics using multi-dimensional HPLC2016

    • Author(s)
      Kenji HAMASE, Reiko KOGA, Takeyuki AKITA, Yurika MIYOSHI, Masashi MITA, Hiroshi NARAOKA, Wolfgang LINDNER
    • Organizer
      XVII International Symposium on Luminescence Spectrometry
    • Place of Presentation
      Taipei, Taiwan
    • Year and Date
      2016-11-24
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Chiral amino acid analysis: New frontier of drug discovery and diagnosis2016

    • Author(s)
      Kenji HAMASE, Reiko KOGA, Yurika MIYOSHI, Masashi MITA, Wolfgang LINDNER
    • Organizer
      27th International Symposium on Pharmaceutical and Biomedical Analysis
    • Place of Presentation
      Guangzhou, China
    • Year and Date
      2016-11-14
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] キラルアミノ酸分析が拓く未来の医療2016

    • Author(s)
      浜瀬健司
    • Organizer
      第47回中部化学関係学協会支部連合秋季大会
    • Place of Presentation
      豊橋
    • Year and Date
      2016-11-05
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 多次元分析による生体・食品・宇宙試料中のキラルアミノ酸精密定量2016

    • Author(s)
      浜瀬健司,古賀鈴依子,三次百合香,三田真史,奈良岡 浩
    • Organizer
      第12回D-アミノ酸学会学術講演会
    • Place of Presentation
      高知
    • Year and Date
      2016-09-14
    • Related Report
      2016 Annual Research Report
  • [Presentation] 多次元HPLCを用いるキラルアミノ酸メタボロミクスによる創薬・診断・機能性プロダクト開発2016

    • Author(s)
      浜瀬健司
    • Organizer
      第29回バイオメディカル分析科学シンポジウム
    • Place of Presentation
      京都
    • Year and Date
      2016-09-03
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Chiral amino acid targeted metabolomics as a new strategy for biomarker screening and designing functional foods/beverages2016

    • Author(s)
      Kenji HAMASE, Yurika MIYOSHI, Masashi MITA, Wolfgang LINDNER
    • Organizer
      44th International Symposium on High-Performance Liquid Phase Separations and Related Techniques
    • Place of Presentation
      San Francisco, CA, USA
    • Year and Date
      2016-06-23
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Enantioselective 2D-HPLC determination of citrulline and ornithine in the urine of D-amino acid oxidase deficient mice2016

    • Author(s)
      Reiko KOGA, Yurika MIYOSHI, Yu SATO, Masashi MITA, Ryuichi KONNO, Wolfgang LINDNER, Kenji HAMASE
    • Organizer
      44th International Symposium on High-Performance Liquid Phase Separations and Related Techniques
    • Place of Presentation
      San Francisco, CA, USA
    • Year and Date
      2016-06-21
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Remarks] 創薬育薬産学官連携分野ホームページ

    • URL

      http://soyaku.phar.kyushu-u.ac.jp/

    • Related Report
      2018 Annual Research Report
  • [Remarks] http://soyaku.phar.kyushu-u.ac.jp/

    • Related Report
      2017 Annual Research Report
  • [Remarks]

    • URL

      http://soyaku.phar.kyushu-u.ac.jp/

    • Related Report
      2016 Annual Research Report

URL: 

Published: 2016-04-21   Modified: 2022-08-19  

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