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Definitive molecules for pathogenesis of glomerulonephritis

Research Project

Project/Area Number 16K08698
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Human pathology
Research InstitutionKyorin University (2017-2018)
Nippon Medical School (2016)

Principal Investigator

Nagahama Kiyotaka  杏林大学, 医学部, 講師 (00336538)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords糸球体腎炎 / 質量分析 / アミロイドーシス / 代謝異常 / 糸球体沈着症 / apoE / 人体病理学
Outline of Final Research Achievements

Some cases of glomerulonephritis pose problems in accurate typing of glomerulonephritis due to lack of approproate tool for dissecting molecules responsible for glomerular lesions. We thus utlized technique of laser microdissection (LMD) and tandem mass spectrometry-based proteomic analysis (LC-MS/MS)as a sensitive and specific tool for the diagnosis of glomerulonephriatis. Using kidney specimens, we successfully diagnose accurately the type of amyloid deposited in the glomeruli while immunofluorescence or immunohistochemistry failed to reveal amyloid precursors. Especially, our system was very useful for amyloid cases diagnosed solely at autopsy because serum or urine samples of autopsy cases were generally unavailable for further testing of precursors such as free light chains. In addition, we successfully determined non-amyloid depositions such as apoE and fibrinogen using renal biopsy specimens with LMD and LC-MS/MS.

Academic Significance and Societal Importance of the Research Achievements

糸球体腎炎の診断は糸球体の光学顕微鏡を用いた形態変化に基づいてなされるが、軽微な形態変化である場合、観察者間のばらつきが大きく診断の確定が困難である症例がしばしば経験される。今回、形態以外の客観的指標を確立するため質量分析を用いた解析を行った。結果、アミロイドーシスのみならず、apoEやfibrinogenの沈着による糸球体病変を証明することができ、適切な治療法の提案、開発につなげることができた。従来の沈着症の概念が大きく変わる可能性が示唆された。

Report

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

    (19 results)

All 2019 2018 2017 2016

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 3 results) Presentation (12 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results) Book (1 results)

  • [Journal Article] Rapid progression to end‐stage renal disease in a young female with mixed immunopathological features of lupus and ANCA‐associated vasculitis2019

    • Author(s)
      Fukue Ryosuke、Takeno Mitsuhiro、Miyamoto Daisuke、Shirai Yuichiro、Nagahama Kiyotaka、Shimizu Akira、Kuwana Masataka
    • Journal Title

      International Journal of Rheumatic Diseases

      Volume: in print Issue: 5 Pages: 956-958

    • DOI

      10.1111/1756-185x.13573

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Membranous Nephropathy-Like Apolipoprotein E Deposition Disease with Apolipoprotein E Toyonaka (Ser197Cys) and a Homozygous Apolipoprotein E2/2.2018

    • Author(s)
      Fukunaga M, Nagahama K, Aoki M, Shimizu A, Hara S, Matsunaga A, Muso E, Saito T.
    • Journal Title

      Case Rep Nephrol Dial.

      Volume: 20 Issue: 1 Pages: 45-55

    • DOI

      10.1159/000487919

    • NAID

      120006473637

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dysregulated heme oxygenase-1low M2-like macrophages augment lupus nephritis via Bach1 induced by type I interferons2018

    • Author(s)
      Kishimoto Daiga、Kirino Yohei、Tamura Maasa、Takeno Mitsuhiro、Kunishita Yosuke、Takase-Minegishi Kaoru、Nakano Hiroto、Kato Ikuma、Nagahama Kiyotaka、Yoshimi Ryusuke、Igarashi Kazuhiko、Aoki Ichiro、Nakajima Hideaki
    • Journal Title

      Arthritis Research & Therapy

      Volume: 20 Issue: 1 Pages: 64-64

    • DOI

      10.1186/s13075-018-1568-1

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ruptured infected aneurysm of the thoracic aorta associated with tunneled dialysis catheter-related methicillin-resistant Staphylococcus aureus bacteremia in a hemodialysis patient2018

    • Author(s)
      Katsuragawa Fumiko、Nagahama Kiyotaka、Naito Shotaro、Tsuura Yukio、Otani Megumi、Koide Takaaki、Nishiyama Sakino、Yanagi Tomoki、Nanamatsu Azuma、Aki Shota、Aoyagi Makoto、Tanaka Hiroyuki、Rai Tatemitsu、Uchida Shinichi
    • Journal Title

      CEN Case Reports

      Volume: 7 Issue: 2 Pages: 325-329

    • DOI

      10.1007/s13730-018-0352-z

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Idiopathic collapsing focal segmental glomerulosclerosis in an 81-year-old Japanese woman: a case report and review of the literature2016

    • Author(s)
      Yamazaki J, Kanehisa E, Yamaguchi W, Kumagai J, Nagahama K, Fujisawa H
    • Journal Title

      CEN Case Rep

      Volume: 5 Issue: 2 Pages: 197-202

    • DOI

      10.1007/s13730-016-0224-3

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Impact of anti-glomerular basement membrane antibodies and glomerular neutrophil activation on glomerulonephritis in experimental myeloperoxidase-antineutrophil cytoplasmic antibody vasculitis.2016

    • Author(s)
      Kanzaki G, Nagasaka S, Higo S, Kajimoto Y, Kanemitsu T, Aoki M, Nagahama K, Natori Y, Tsuboi N, Yokoo T, Shimizu A
    • Journal Title

      Nephrol Dial Transplant

      Volume: 4 Issue: 4 Pages: 574-585

    • DOI

      10.1093/ndt/gfv384

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] Membranous Nephropathy-like Deposition of Apolipoprotein E in a patient with Apolipoprotein E Toyonaka (Ser197Cys) and a Homozygous Apolipoprotein E2/22018

    • Author(s)
      Fukunaga Megumu、Nagahama Kiyotaka、Aoki Michiko、Shimizu Akira、Hara Shigeo、Matsunaga Akira、Muso Eri、Saito Takao
    • Organizer
      ISN FRONTIERS 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Light chain proximal tubulopathy without crystal formation疑いの1例2018

    • Author(s)
      山室 めぐみ、村木 直弘、中野 雄太、杉田 行平、石原 早織、大橋 敦希、熊谷 二郎、長濱 清隆、藤澤 一
    • Organizer
      第48回日本腎臓学会東部学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Membranous Nephropathy-like Deposition of Apolipoprotein E in a patient with Apolipoprotein E Toyonaka (Ser197Cys) and a Homozygous Apolipoprotein E2/22018

    • Author(s)
      Megumu Fukunaga, Kiyotaka Nagahama, Michiko Aoki, Akira Shimizu, Shigeo Hara, Akira Matsunaga, Eri Muso, Takao Saito.
    • Organizer
      ISN FRONTIERS 2018
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] ANCA関連血管炎に続発するTMAを発症し、免疫抑制剤と血漿交換療法にて透析を離脱した1例2017

    • Author(s)
      山室めぐみ、中野雄太、大橋敦希、金久恵理子、山口若葉、熊谷二郎、長濱清隆、藤澤一
    • Organizer
      第47回日本腎臓学会東部学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] ネフローゼ症候群を呈し腎生検を施行した妊娠16週の一例2017

    • Author(s)
      桂川史子、西山早乃、小出高彰、大谷恵、柳智貴、七松東、安藝昇太、青柳誠、田中啓之、長濱清隆
    • Organizer
      第47回日本腎臓学会東部学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 緩徐な経過を辿った抗糸球体基底膜(GBM)抗体型糸球体腎炎の1例2017

    • Author(s)
      柳智貴、大谷恵、小出高彰、西山早乃、桂川史子、七松東、安藝昇太、青柳誠、田中啓之、長濱清隆
    • Organizer
      第47回日本腎臓学会東部学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 高齢女性に発症したTINU症候群に対し経口ステロイド投与で加療した一例2017

    • Author(s)
      源馬拓、大石真理子、平井俊行、西田秀範、藤井徹郎、長濱清隆
    • Organizer
      第47回日本腎臓学会東部学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 液体クロマトグラフ質量分析法を用いた重鎮と軽鎖アミロイドーシスの臨床病理学的比較2016

    • Author(s)
      青木 路子, 康 徳東, 新井 考司, 寺崎 美佳, 桑原 尚美, 金光 剛史, 岡林 佑典, 梶本 雄介, 長濱 清隆, 清水 章
    • Organizer
      第59回日本腎臓学会総会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2016 Research-status Report
  • [Presentation] 菲薄基底膜病における糸球体係蹄障害を含めた臨床病理学的検討2016

    • Author(s)
      梶本 雄介, 益田 幸成, 肥後 清一郎, 神崎 剛, 永坂 真也, 長濱 清隆, 清水 章
    • Organizer
      第105回日本病理学会総会
    • Place of Presentation
      仙台国際センター会議棟
    • Related Report
      2016 Research-status Report
  • [Presentation] 液体クロマトグラフ質量分析法により腎生検の糸球体に蓄積されたアミロイド前駆蛋白の発現2016

    • Author(s)
      康 徳東, 青木 路子, 新井 孝司, 寺崎 美佳, 桑原 尚美, 金光 剛史, 岡林 佑典, 長濱,, 清水 章
    • Organizer
      第105回日本病理学会総会
    • Place of Presentation
      仙台国際センター会議棟
    • Related Report
      2016 Research-status Report
  • [Presentation] 腎生検病理診断コンサルテーション・アンド・レビュー2016

    • Author(s)
      長濱 清隆
    • Organizer
      第59回日本腎臓学会総会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 長濱 清隆2016

    • Author(s)
      質量分析の腎生検への応用
    • Organizer
      第46回日本腎臓学会東部学術大会
    • Place of Presentation
      東京京王プラザホテル
    • Related Report
      2016 Research-status Report
    • Invited
  • [Book] ANCA関連血管炎診療ガイドライン20172017

    • Author(s)
      有村義宏、丸山彰一、本間栄 ほか
    • Total Pages
      180
    • Publisher
      診断と治療社
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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