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Mechanisms of development and progression of chronic kidney disease due to reduced renal nephron numbers

Research Project

Project/Area Number 18K15987
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53040:Nephrology-related
Research InstitutionJikei University School of Medicine

Principal Investigator

Kanzaki Go  東京慈恵会医科大学, 医学部, 助教 (00816473)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsネフロン数 / 慢性腎臓病 / 高血圧 / 糸球体過剰濾過 / 糖尿病 / 高血圧性腎硬化症 / 糖尿病性腎症 / 糸球体肥大
Outline of Final Research Achievements

We have reported that the number of nephrons (glomeruli) in the Japanese population is low compared to other ethnic groups, and that the number of nephrons is further reduced in hypertension and chronic kidney disease (CKD). However, the detailed mechanisms by which low nephron numbers contribute to glomerular hyperfiltration and glomerular hypertrophy, and to the development and progression of hypertension and CKD, remain to be fully elucidated.
In this study, we will elucidate the mechanism of glomerular hyperfiltration by analyzing the molecular biology of glomerular compensatory changes induced by nephron depletion using urine samples from a low nephron count rat model (HGN rat) and Aborigines. The aim of this study was to reconsider the concept of glomerular hypertrophy and to apply it to the actual treatment of kidney disease.

Academic Significance and Societal Importance of the Research Achievements

ネフロン数の減少は、残存糸球体に代償性の糸球体過剰濾過および肥大を生じ、その後、糸球体硬化に至らせ、更なるネフロン減少を引き起こすことが唱えられている。しかしながら、低ネフロン数のみでは腎疾患の感受性に差がないとの報告もある。また低ネフロン数は高血圧およびCKDの病態と関わるとされているが、その因果関係、詳細な機序については未だ十分に解明されていない。日本では8人に1人がCKDに罹患しているとされ、世界的にもその罹患率は高い。申請者は日本人のネフロン数は他人種と比較し少ないことを報告してきたが、日本人の低ネフロン数と高血圧およびCKD発症の機序を解明し日本人CKD診療の貢献を目指す。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (18 results)

All 2020 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (13 results) (of which Int'l Joint Research: 4 results,  Invited: 3 results) Remarks (2 results)

  • [Int'l Joint Research] Monash University(オーストラリア)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Dietary Protein Intake and Single-Nephron Glomerular Filtration Rate2020

    • Author(s)
      Oba Rina、Kanzaki Go、Sasaki Takaya、Okabayashi Yusuke、Haruhara Kotaro、Koike Kentaro、Kobayashi Akimitsu、Yamamoto Izumi、Tsuboi Nobuo、Yokoo Takashi
    • Journal Title

      Nutrients

      Volume: 12 Issue: 9 Pages: 2549-2549

    • DOI

      10.3390/nu12092549

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human Nephron Number, Hypertension, and Renal Pathology2019

    • Author(s)
      Go Kanzaki, Nobuo Tsuboi, Akira Shimizu, Takashi Yokoo
    • Journal Title

      Anat Rec (Hoboken)

      Volume: 15 Issue: 10 Pages: 24302-24302

    • DOI

      10.1002/ar.24302

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] Glomerular Blood Flow in Living Donor Kidney Transplant Recipients2020

    • Author(s)
      Go Kanzaki, Takaya Sasaki, Kotaro Haruhara, Rina Oba, Yusuke Okabayashi, Kentaro Koike, Akimitsu Kobayashi, Izumi Yamamoto, Nobuo Tsuboi, and Takashi Yokoo
    • Organizer
      Kidney Week 2020 米国腎臓病学会 (ASN2020)
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 移植腎における糸球体内血行動態の変化2020

    • Author(s)
      神崎 剛、佐々木 峻也、坪井 伸夫、小林 賛光、山本 泉、占部 文彦、小池 祐介、三木 淳、山田 裕紀、木村 高弘、丹野 有道、山本 裕康、横尾 隆
    • Organizer
      日本腎臓学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] キャリア・ストラテジーとしての海外留学2020

    • Author(s)
      神崎 剛、坪井 伸夫、横尾 隆
    • Organizer
      日本腎臓学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Racial differences in nephron number: role of body size, kidney weight and cortical volume in adult subjects among five populations.2019

    • Author(s)
      Go Kanzaki, Victor G. Puelles, Luise A. Cullen-McEwen, Wendy E. Hoy, Yusuke Okabayashi, Nobuo Tsuboi, Akira Shimizu, Michael D. Hughson, Takashi Yokoo, and John F. Bertram
    • Organizer
      国際DOaD学会
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Total nephron number and single nephron glomerular filtration rate in Japanese subjects2019

    • Author(s)
      Go Kanzaki, Victor G. Puelles, Luise A. Cullen-McEwen, Wendy E. Hoy, Yusuke Okabayashi, Nobuo Tsuboi, Akira Shimizu, Michael D. Hughson, Takashi Yokoo, and John F. Bertram
    • Organizer
      国際DOaD学会
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 日本人ネフロン数の特徴と人種間比較2019

    • Author(s)
      神崎 剛、坪井 伸夫、岡林 佑典、清水 章、 John Bertram、横尾 隆
    • Organizer
      日本腎臓学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 人種間比較からみた日本人ネフロン数の特徴2019

    • Author(s)
      神崎 剛、坪井 伸夫、岡林 佑典、清水 章、 John Bertram、横尾 隆
    • Organizer
      日本腎臓学会
    • Related Report
      2019 Research-status Report
  • [Presentation] TOTAL NEPHRON NUMBER AND SINGLE NEPHRON GFR IN CKD SUBJECTS2018

    • Author(s)
      Go Kanzaki, Victor Puelles, Luise Cullen-McEwen, Yusuke Okabayashi, Nobuo Tsuboi, Akira shimizu, Takashi Yokoo, John Bertram
    • Organizer
      55th ERA-EDTA Congress
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 慢性腎臓病患者におけるネフロン数と単一糸球体過濾過量(SNeGFR)2018

    • Author(s)
      神崎 剛, 坪井 伸夫, 岡林 佑典, 小倉 誠, 清水 章, John Bertram, 横尾 隆
    • Organizer
      第107回日本病理学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 日本人のネフロン数と欧米人のネフロン数の差異をどう考えるか?2018

    • Author(s)
      神崎 剛
    • Organizer
      第7回日本DOHaD学会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Single Nephron GFR から見たタンパク質摂取量と糸球体過剰濾過の関連性2018

    • Author(s)
      神崎 剛、大庭梨菜、佐々木峻也、岡林佑輔、春原浩太郎、小池健太郎、小林賛光、山本 泉、坪井伸夫、横尾 隆
    • Organizer
      第22回日本病態栄養学会年次学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 日本人のネフロン数からみた慢性腎臓病の病態解析2018

    • Author(s)
      神崎 剛, 坪井 伸夫, 岡林 佑典, 小倉 誠, 清水 章, 横尾 隆
    • Organizer
      第115回日本内科学会講演会
    • Related Report
      2018 Research-status Report
  • [Presentation] 日本人ネフロン数の特徴2018

    • Author(s)
      神崎 剛, 坪井 伸夫, 岡林 佑典, 小倉 誠, 清水 章, 横尾 隆
    • Organizer
      第115回日本内科学会講演会
    • Related Report
      2018 Research-status Report
  • [Remarks] Anatomy and Developmental Biology

    • URL

      http://www.med.monash.edu.au/anatomy/research/kidney-development-disease-regeneration-group.html

    • Related Report
      2018 Research-status Report
  • [Remarks] 東京慈恵会医科大学腎臓・高血圧内科

    • URL

      http://www.jikei-kidneyht.jp/

    • Related Report
      2018 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

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