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Establishment and elucidation of the mechanisms of new renal pathological entity "IgM-positive plasma cell tubulointerstitial nephritis''

Research Project

Project/Area Number 17K09692
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Kidney internal medicine
Research InstitutionUniversity of Fukui

Principal Investigator

Takahashi Naoki  福井大学, 学術研究院医学系部門(附属病院部), 助教 (30377460)

Co-Investigator(Kenkyū-buntansha) 岩野 正之  福井大学, 学術研究院医学系部門, 教授 (20275324)
木村 秀樹  福井大学, 学術研究院医学系部門(附属病院部), 准教授 (20283187)
糟野 健司  福井大学, 学術研究院医学系部門, 准教授 (60455243)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsIgM / 形質細胞 / 尿細管性アシドーシス / 原発性胆汁性胆管炎 / 尿細管間質性腎炎 / ファンコニー症候群 / 腎病理 / Fancnoni症候群
Outline of Final Research Achievements

In 2017, we reported the clinical and histological features of tubulointerstitial nephritis with IgM-positive plasma cells (IgMPC-TIN) in J Am Soc Nephrol. The clinical features were 100% distal renal tubular acidosis, 92% urinary glucose (Fanconi syndrome), 82% anti-mitochondrial antibody positivity, and 46% primary biliary cholangitis. The histological features were marked infiltration of IgMPC into the interstitium and tubulitis with CD3-positive T lymphocytes in the proximal tubules and collecting ducts. In order to establish the diagnostic criteria for IgMPC-TIN, we have started a multi center clinical study in which more than 20 institutions newly parrticipated and we are currently analyzing the data.

Academic Significance and Societal Importance of the Research Achievements

本研究成果として、IgM陽性形質細胞が腎臓に多く存在している腎炎 (IgMPC-TIN) を発見し、この病気の症状や顕微鏡所見の特徴を明らかにし、我が国から先行して世界に報告することができた。これは学術的に非常に意義の高いことである。また、この病気は全国では腎生検の0.06%と頻度は多くないが、われわれの施設では0.7%と10倍以上の頻度で認めており、原因不明の腎炎として見逃されてきた可能性が高い。これまで原因不明とされていた病気が新たに見いだされ、その病気の病態解明が進めば、次のステップとして副作用の少ない新しい治療の開発の道が開けるため、社会的意義も高いと考えられる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (20 results)

All 2020 2019 2018 2017 Other

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 2 results) Presentation (9 results) (of which Int'l Joint Research: 6 results,  Invited: 1 results) Book (2 results) Remarks (3 results)

  • [Journal Article] IgA Vasculitis Developed as an Adverse Effect of Tofacitinib Taken for Rheumatoid Arthritis2020

    • Author(s)
      Itoh I, Kasuno K, Yamamoto C, Takahashi N, Shimizu H, Ojima T, Hayashi S, Kimura H, Iwano M.
    • Journal Title

      Internal Medicine

      Volume: 59 Issue: 6 Pages: 817-821

    • DOI

      10.2169/internalmedicine.3668-19

    • NAID

      130007808723

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2020-03-15
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Analytical and clinical validation of rapid chemiluminescence enzyme immunoassay for urinary thioredoxin, an oxidative stress-dependent early biomarker of acute kidney injury.2020

    • Author(s)
      Yokoi S, Kasuno K, Nishimori K, Nishikawa S, Nishikawa Y, Morita S, Kobayashi M, Fukushima S, Mikami D, Takahashi N, Oota Y, Kimura H, Soya Y, Kimata S, Nishimura K, Ono T, Muso E, Yoshida H, Yodoi J, Iwano M.
    • Journal Title

      Clin Chim Acta.

      Volume: 507 Pages: 271-279

    • DOI

      10.1016/j.cca.2020.04.025

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chronic hypoxia exacerbates diabetic glomerulosclerosis through mesangiolysis and podocyte injury in db/db mice2020

    • Author(s)
      Naoki Takahashi, Haruyoshi Yoshida, Hideki Kimura, Kazuko Kamiyama, Tomomi Kurose, Hidehiro Sugimoto, Toshio Imura, Seiji Yokoi, Daisuke Mikami, Kenji Kasuno, Hiroyuki Kurosawa, Yoshiaki Hirayama, Hironobu Naiki, Masanori Hara, Masayuki Iwano.
    • Journal Title

      Nephrol Dial Transplant

      Volume: - Issue: 10 Pages: 1678-1688

    • DOI

      10.1093/ndt/gfaa074

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Elevated Levels of Urinary Extracellular Vesicle Fibroblast-Specific Protein 1 in Patients with Active Crescentic Glomerulonephritis.2019

    • Author(s)
      Morikawa Y, Takahashi N, Kamiyama K, Nishimori K, Nishikawa Y, Morita S, Kobayashi M, Fukushima S, Yokoi S, Mikami D, Kimura H, Kasuno K, Yashiki T, Naiki H, Hara M, Iwano M.
    • Journal Title

      Nephron

      Volume: 141 Issue: 3 Pages: 177-187

    • DOI

      10.1159/000495217

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] β-Hydroxybutyrate, a ketone body, reduces the cytotoxic effect of cisplatin via activation of HDAC5 in human renal cortical epithelial cells.2019

    • Author(s)
      Mikami D, Kobayashi M, Uwada J, Yazawa T, Kamiyama K, Nishimori K, Nishikawa Y, Morikawa Y, Yokoi S, Takahashi N, Kasuno K, Taniguchi T, Iwano M.
    • Journal Title

      Life Sci

      Volume: 222 Pages: 125-132

    • DOI

      10.1016/j.lfs.2019.03.008

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tubulointerstitial Nephritis with IgM-Positive Plasma Cells.2017

    • Author(s)
      Takahashi N, Kimura H et al
    • Journal Title

      J Am Soc Nephrol.

      Volume: 28 Issue: 12 Pages: 3688-3698

    • DOI

      10.1681/asn.2016101074

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Difference between urinary vesicle fibroblast specific protein1 and urinary soluble CD 163 as a marker of crescent formation2019

    • Author(s)
      Yukie Morikawa, Naoki Takahashi, Kazuko Kamiyama, Sho Nishikawa, Kazuhisa Nishimori, Yudai Nishikawa, Sayu Morita, Mamiko Kobayashi, Sachiko Fukushima, Seiji Yokoi, Daisuke Mikami, Hideki Kimura, Kenji Kasuno, Masayuki Iwano
    • Organizer
      ASN Kidney Week 2019 Annual Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Fanconi syndrome in an elderly patient with membranous nephropathy during treatment with immunosuppressant mizoribine2019

    • Author(s)
      Sho Nishikawa, Naoki Takahashi, Yudai Nishikawa, Sayu Morita, Kazuhisa Nishimori, Mamiko Kobayashi, Sachiko Fukushima, Seiji Yokoi, Daisuke Mikami, Hideki Kimura, Kenji Kasuno, Masayuki Iwano
    • Organizer
      ASN Kidney Week 2019 Annual Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 免疫グロブリン沈着症 IgM陽性形質細胞浸潤を伴った尿細管間質性腎炎(IgMPC-TIN)の発見2019

    • Author(s)
      髙橋直生、岩野正之
    • Organizer
      日本腎臓学会東部学術大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] PLA2R陽性膜性腎症はPLA2R陰性膜性腎症に比べ尿蛋白選択性が低い2019

    • Author(s)
      髙橋 直生, 西川 翔, 西森 一久, 福島 佐知子, 森川 幸恵, 西川 雄大, 小林 麻美子, 横井 靖二, 三上 大輔, 木村 秀樹, 糟野 健司, 岩野 正之
    • Organizer
      日本腎臓学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 腎組織の特徴的線維化が乏しいIgG4関連腎臓病(IgG4-RKD)の一例2019

    • Author(s)
      福島 佐知子, 髙橋 直生, 西川 翔, 横井 靖二, 西森 一久, 小林 麻美子, 森田 紗由, 西川 雄大, 三上 大輔, 木村 秀樹, 糟野 健司, 岩野 正之
    • Organizer
      日本腎臓学会西部学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] A unique form of tubulointerstitial nephritis with IgM-positive plasma cells2018

    • Author(s)
      Naoki Takahashi, Takako Saeki, Atsushi Komatsuda, Chishio Munemura, Tsuguru Hatta, Ken-ichi Samejima, Yudai Nishikawa, Mamiko Kobayashi, Daisuke Mikami, Kenji Kasuno, Hideki Kimura, Hironobu Naiki, Haruyoshi Yoshida, Ichiei Narita and Masayuki Iwano
    • Organizer
      ISN Frontier 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Elevated levels of urinary extracellular vesicle fibroblast-specific protein 1 in patients with active crescentic glomerulonephritis2018

    • Author(s)
      Yukie Morikawa, Naoki Takahashi, Kazuko Kamiyama, Kazuhisa Nishimori, Yudai Nishikawa, Mamiko Kobayashi, Sachiko Fukushima, Seiji Yokoi, Daisuke Mikami, Hideki Kimura, Kenji Kasuno, Masanori Hara and Masayuki Iwano
    • Organizer
      ASN Kidney Week 2018 Annual Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] A unique form of tubulointerstitial nephritis with IgM-positive plasma cells2018

    • Author(s)
      Naoki Takahashi, Takako Saeki, Atsushi Komatsuda, Chishio Munemura, Tsuguru Hatta, Ken-ichi Samejima, Yudai Nishikawa, Mamiko Kobayashi, Daisuke Mikami, Kenji Kasuno, Hideki Kimura, Hironobu Naiki, Haruyoshi Yoshida, Ichiei Narita and Masayuki Iwano
    • Organizer
      ISN Frontier Meeting 2018
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Tubulointerstitial nephritis with IgM-positive plasma cells2017

    • Author(s)
      Naoki Takahashi, Takako Saeki, Atsushi Komatsuda, Ken-ichi Samejima, Yudai Nishikawa, Kazuhisa Nishimori, Sayu Morita, Mamiko Kobayashi, Yukie Morikawa, Sachiko Fukushima, Seiji Yokoi, Daisuke Mikami, Kenji Kasuno, Hideki Kimura, Ichiei Narita and Masayuki Iwano
    • Organizer
      American Society of Nephrology 2017 Annual Meeting
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Book] 腎と透析2019

    • Author(s)
      髙橋直生、岩野正之
    • Total Pages
      6
    • Publisher
      東京医学社
    • Related Report
      2019 Annual Research Report
  • [Book] Hospitalist2018

    • Author(s)
      高橋直生 岩野正之
    • Total Pages
      10
    • Publisher
      メディカル・サイエンス・インターナショナル
    • ISBN
      9784895929530
    • Related Report
      2018 Research-status Report
  • [Remarks] 髙橋直生先生「これまで見逃されてきた新しいタイプの腎炎を発見」JASNに掲載

    • URL

      http://www-n.med.u-fukui.ac.jp/information/2266/

    • Related Report
      2017 Research-status Report
  • [Remarks] 新タイプの腎炎発見、福井大など研究チーム「治療法確立を目指す」

    • URL

      http://www.fukuishimbun.co.jp/articles/-/235952

    • Related Report
      2017 Research-status Report
  • [Remarks] 福井大 新たな腎炎発見 見逃された発掘も

    • URL

      https://mainichi.jp/articles/20170919/k00/00e/040/152000c

    • Related Report
      2017 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2021-02-19  

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