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Clinical application of nephron number and nephron parameters

Research Project

Project/Area Number 21K08238
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53040:Nephrology-related
Research InstitutionJikei University School of Medicine

Principal Investigator

Tsuboi Nobuo  東京慈恵会医科大学, 医学部, 准教授 (40408422)

Co-Investigator(Kenkyū-buntansha) 清水 章  日本医科大学, 大学院医学研究科, 大学院教授 (00256942)
春原 浩太郎  東京慈恵会医科大学, 医学部, 助教 (20827034)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsネフロン / ポソサイト / ポドサイト / 単一ネフロンGFR / 単一ネフロンパラメーター
Outline of Research at the Start

本研究では、非造影CT腎立体像と腎生検標本を組み合わせた方法を用いて、3,000例以上の腎疾患患者の総ネフロン数(/腎)を計測する。本法によって、これまで剖検解析に依存してきたヒトネフロン数の計測が初めて臨床応用される。また、ネフロン数および単一ネフロン指標をもとに、高リスク群をより高い精度で早期に同定する腎予後予測モデルの構築を目指す。本研究の成果によって、積極的介入を要する対象がこれまでよりも明確となり、腎障害の進展および腎不全発症を効果的に抑制することが期待できる。

Outline of Final Research Achievements

In this study, we have analyzed the number of nephrons and nephron-related parameters in various progressive kidney diseases and reported them in academic conferences and journals (245 patients with IgA nephropathy, 106 patients with membranous nephropathy, 48 patients with obesity-related glomerulopathy, and 80 patients with diabetic nephropathy). In addition, we are measuring the number and volume of glomerular podocytes (podometric analysis) in various disease groups. We found that podometric parameters are closely related to nephron parameters and closely related to the progression of various kidney diseases. These are the first findings from a clinical approach using imaging data and biopsy specimens. Analysis is underway for clinical application.

Academic Significance and Societal Importance of the Research Achievements

腎臓の構造と機能の維持に必須の解剖学的単位であるネフロン数やポドサイト数を臨床的に定量化することはこれまで技術的に困難であった。我々はこれまでに臨床的アプローチによりネフロン数とポドサイト数を定量化する方法を確立し、各種腎疾患の病態との関連について検討を行ってきた。この方法を応用することで、各個人のネフロン数と疾患病態や予後との解析、腎疾患患者における単一ネフロンGFRをはじめとした単一ネフロン指標の解析が初めて可能となった。また、同一対象においてネフロン数、単一ネフロン指標とポドサイト数を計測した既報研究はなく、相互の関連についての初めての知見となった。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (27 results)

All 2024 2023 2022 2021 Other

All Int'l Joint Research (4 results) Journal Article (13 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 10 results,  Open Access: 10 results) Presentation (10 results) (of which Int'l Joint Research: 6 results,  Invited: 1 results)

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

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] Colombia University(米国)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] Monash University(オーストラリア)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] Colombia University(米国)

    • Related Report
      2022 Research-status Report
  • [Journal Article] Single-nephron assessment of urate excretion in patients with IgA nephropathy2024

    • Author(s)
      Marumoto Hirokazu、Tsuboi Nobuo、Sasaki Takaya、Okabayashi Yusuke、Haruhara Kotaro、Kanzaki Go、Ichida Kimiyoshi、Yokoo Takashi
    • Journal Title

      Clinical Kidney Journal

      Volume: 17 Issue: 3

    • DOI

      10.1093/ckj/sfae036

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Single-Nephron GFR in Different Glomerular Basement Membrane Stages of Membranous Nephropathy2023

    • Author(s)
      Okabayashi Yusuke、Tsuboi Nobuo、Marumoto Hirokazu、Sasaki Takaya、Haruhara Kotaro、Kanzaki Go、Koike Kentaro、Ueda Hiroyuki、Shimizu Akira、Puelles Victor G.、D'Agati Vivette、Yokoo Takashi
    • Journal Title

      Kidney360

      Volume: 4 Issue: 6 Pages: e777-e786

    • DOI

      10.34067/kid.0000000000000142

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Single-Nephron GFR in Different GBM Stages of Membranous Nephropathy2023

    • Author(s)
      Yusuke Okabayashi, Nobuo Tsuboi, Hirokazu Marumoto, Takaya Sasaki, Kotaro Haruhara, Go Kanzaki, Kentaro Koike, Hiroyuki Ueda, Akira Shimizu, Victor G. Puelles, Vivette D’Agati and Takashi Yokoo.
    • Journal Title

      Kidney 360 (in press)

      Volume: -

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Associations between nephron number and podometrics in human kidneys2022

    • Author(s)
      Haruhara Kotaro、Kanzaki Go、Sasaki Takaya、Hatanaka Saeko、Okabayashi Yusuke、Puelles Victor G.、Harper Ian S.、Shimizu Akira、Cullen-McEwen Luise A.、Tsuboi Nobuo、Yokoo Takashi、Bertram John F.
    • Journal Title

      Kidney International

      Volume: 102 Issue: 5 Pages: 1127-1135

    • DOI

      10.1016/j.kint.2022.07.028

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Nephrons, podocytes and chronic kidney disease: Strategic antihypertensive therapy for renoprotection2022

    • Author(s)
      Haruhara Kotaro、Kanzaki Go、Tsuboi Nobuo
    • Journal Title

      Hypertension Research

      Volume: 46 Issue: 2 Pages: 299-310

    • DOI

      10.1038/s41440-022-01061-5

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 予防医学から見た腎疾患診療 肥満:腎血行動態・形態学的変化と腎障害2022

    • Author(s)
      坪井伸夫 岡林祐典
    • Journal Title

      腎と透析

      Volume: 92 (5) Pages: 838-842

    • Related Report
      2022 Research-status Report
  • [Journal Article] IgA腎症-最新の知見 総ネフロン数と単一ネフロンGFR2022

    • Author(s)
      坪井伸夫 丸本裕和
    • Journal Title

      腎と透析

      Volume: 92 (6) Pages: 993-997

    • Related Report
      2022 Research-status Report
  • [Journal Article] ネフロン数と高血圧・腎機能連関2022

    • Author(s)
      坪井伸夫
    • Journal Title

      腎臓内科

      Volume: 16 (5) Pages: 611-617

    • Related Report
      2022 Research-status Report
  • [Journal Article] Total Nephron Number and Single-Nephron Parameters in Patients with IgA Nephropathy2021

    • Author(s)
      Marumoto Hirokazu、Tsuboi Nobuo、D’Agati Vivette D.、Sasaki Takaya、Okabayashi Yusuke、Haruhara Kotaro、Kanzaki Go、Koike Kentaro、Shimizu Akira、Kawamura Tetsuya、Rule Andrew D.、Bertram John F.、Yokoo Takashi
    • Journal Title

      Kidney360

      Volume: 2 Issue: 5 Pages: 828-841

    • DOI

      10.34067/kid.0006972020

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Renal Pathology of Obesity: Structure-Function Correlations2021

    • Author(s)
      Tsuboi Nobuo、Okabayashi Yusuke
    • Journal Title

      Seminars in Nephrology

      Volume: 41 Issue: 4 Pages: 296-306

    • DOI

      10.1016/j.semnephrol.2021.06.002

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Determinants of the Glomerular Maximal Size Threshold2021

    • Author(s)
      Tsuboi Nobuo
    • Journal Title

      Kidney and Blood Pressure Research

      Volume: 46 Issue: 4 Pages: 393-395

    • DOI

      10.1159/000516612

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Podometrics in Japanese Living Donor Kidneys: Associations with Nephron Number, Age, and Hypertension2021

    • Author(s)
      Haruhara Kotaro、Sasaki Takaya、de Zoysa Natasha、Okabayashi Yusuke、Kanzaki Go、Yamamoto Izumi、Harper Ian S.、Puelles Victor G.、Shimizu Akira、Cullen-McEwen Luise A.、Tsuboi Nobuo、Yokoo Takashi、Bertram John F.
    • Journal Title

      Journal of the American Society of Nephrology

      Volume: 32 Issue: 5 Pages: 1187-1199

    • DOI

      10.1681/asn.2020101486

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Assessment of nephron number and single-nephron glomerular filtration rate in a clinical setting2021

    • Author(s)
      Tsuboi Nobuo、Sasaki Takaya、Okabayashi Yusuke、Haruhara Kotaro、Kanzaki Go、Yokoo Takashi
    • Journal Title

      Hypertension Research

      Volume: 44 Issue: 6 Pages: 605-617

    • DOI

      10.1038/s41440-020-00612-y

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Podocyte density, rather than podocyte number per glomerulus, is associated with kidney outcomes in obesity-related glomerulopathy2023

    • Author(s)
      Kotaro Haruhara, Yusuke Okabayashi, Takaya Sasaki, Eisuke Kubo, Vivette D. D'Agati, John F. Bertram, Nobuo Tsuboi and Takashi Yokoo
    • Organizer
      Annual Meeting of the American Society of Nephrology 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Single-nephron dynamics in patients with overt diabetic nephropathy2023

    • Author(s)
      Akane Miura, Masahiro Okabe, Kotaro Haruhara, Takaya Sasaki, Nobuo Tsuboi, Takashi Yokoo
    • Organizer
      Annual Meeting of the American Society of Nephrology 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Podometrics in different cortical zones of the human kidney: The effect of age and hypertension.2022

    • Author(s)
      Haruhara K, Kanzaki G, Sasaki T, Hatanaka S, Okabayashi Y, Shimizu A, Tsuboi N, Yokoo T.
    • Organizer
      The 29th Scientific Meeting of the International Society of Hypertension
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] 単一ネフロンあたりの塩分排泄量の推算と腎臓病診療への臨床応用2022

    • Author(s)
      坪井伸夫
    • Organizer
      第 34 回ソルトサイエンス研究財団助成研究発表会
    • Related Report
      2022 Research-status Report
  • [Presentation] 顕性糖尿病性腎症におけるネフロン数と単一ネフロン動態2022

    • Author(s)
      三浦茜 岡部匡裕 佐々木峻也 春原浩太郎 坪井伸夫 横尾隆
    • Organizer
      第33回日本糖尿病生腎症研究会
    • Related Report
      2022 Research-status Report
  • [Presentation] Total number of functional glomeruli at the biopsy diagnosis and disease outcomes in patients with IgA nephropathy: A retrospective observational study2021

    • Author(s)
      Nobuo Tsuboi, Hirokazu Marumoto, Takaya Sasaki, Yusuke Okabayashi, Kotaro Haruhara, Go Kanzaki, Kentaro Koike, Hiroyuki Ueda, Tetsuya Kawamura, Takashi Yokoo
    • Organizer
      International IgA nephropathy symposium
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Single-nephron salt excretion and nighttime hypertension: A cross-sectional study in patients with IgA nephropathy2021

    • Author(s)
      Nobuo Tsuboi, Hirokazu Marumoto, Kotaro Haruhara, Takaya Sasaki, Yusuke Okabayashi, Go Kanzaki, Kentaro Koike, Takashi Yokoo
    • Organizer
      Annual meeting of the American Society of Nephrology
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Podometrics in different cortical zones and associations with the number of non-sclerotic glomeruli2021

    • Author(s)
      Kotaro Haruhara1, 2, Go Kanzaki2, Yusuke Okabayashi2, Takaya Sasaki2, Saeko Hatanaka2, Akira Shimizu3, Luise A. Cullen-McEwen1, Nobuo Tsuboi2, Takashi Yokoo2 and John F. Bertram*1
    • Organizer
      nnual meeting of the American Society of Nephrology
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] 慢性腎臓病の病態とネフロン数2021

    • Author(s)
      坪井伸夫
    • Organizer
      日本腎臓学会総会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] ポドサイト数と大きさの腎皮質領域別解析:剖検腎の検討2021

    • Author(s)
      春原浩太郎 神崎剛 畑中彩恵子 佐々木峻也 岡林佑典 清水章 坪井伸夫 横尾隆
    • Organizer
      日本腎臓学会総会
    • Related Report
      2021 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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