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Analyzing the Pathophysiological Mechanisms of Nephrotic Syndrome using 23Na-MRI

Research Project

Project/Area Number 20K08586
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53040:Nephrology-related
Research InstitutionNiigata University

Principal Investigator

Kaseda Ryohei  新潟大学, 医歯学総合病院, 助教 (20737697)

Co-Investigator(Kenkyū-buntansha) 成田 一衛  新潟大学, 医歯学系, 教授 (20272817)
細島 康宏  新潟大学, 医歯学総合研究科, 特任准教授 (50464003)
斎藤 亮彦  新潟大学, 医歯学総合研究科, 特任教授 (80293207)
寺田 康彦  筑波大学, 数理物質系, 准教授 (20400640)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsMRI / 23Na MRI / 糖尿病性腎臓病 / ナトリウム / 対向流増幅系 / ネフローゼ症候群 / Nephrotic syndrome / diabetic model mouse / Na / 23Na-MRI
Outline of Research at the Start

ネフローゼ症候群では、Na+の貯留と浮腫の成因として、underfillingとoverfillingの機序が提唱されているが、腎臓内のNa+の全体像を明らかにする方法は今までなかった。申請者らは、マウスのごく小さな腎臓に対し、23Na-MRI(磁気共鳴映像法)を用いて23Naをもとにした画像化に成功し、水の効率的な再吸収が可能となる対向流増幅系のNa+の濃度勾配・Na+の貯留の状態を可視化した。23Na-MRI画像をもとに、ネフローゼ症候群における「腎臓全体のNa+のハンドリング・Na+の貯留」と「Na+の再吸収に関わるチャネル・トランスポーター」の関係を明らかにし、病態生理の解明を試みる。

Outline of Final Research Achievements

Using 23Na-MRI (sodium magnetic resonance imaging), successful imaging based on 23Na was achieved for the tiny kidneys of mice, visualizing the concentration gradient of Na+ in the countercurrent amplication system, which enables efficient water reabsorption, and the state of Na+ retention.
A new detection coil was created, obtaining 23Na-MRI images that matched the existing 1H proton MRI images.
In the nephrotic mouse model, no changes were observed in the cortical Na+ concentration. However, in the study involving a diabetes mouse model, changes in the countercurrent multiplier system were detected at a very early stage, specifically at 6 weeks of age. Together with the measurement of urinary albumin, the possibility of early diagnosis of tubular abnormalities in diabetic kidney disease was suggested. These findings were published in Kidney360 journal.

Academic Significance and Societal Importance of the Research Achievements

23Na MRIでは、腎傷害を反映した血中・尿中マーカーと異なり、ナトリウムの代謝機能の変化をみることで、尿中アルブミンの測定とともに、糖尿病性腎臓病での尿細管の異常を早期診断して、治療につなげられる可能性がある。
23Na MRIでは、今までわからなかった腎臓内のナトリウムの代謝変化を明らかにでき、糖尿病性腎臓病にとどまらず、他のナトリウム代謝に関わる脱水や一部の高血圧のより詳細な病態の把握できる可能性がある。また、マウスのごく小さな腎臓の詳細な可視化成功から、対象臓器拡大の可能性も考えられる。これらの知見の積み重ねにより、23Na MRIの臨床応用も期待できる。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (3 results)

All 2023 2022 2021

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

  • [Journal Article] Sodium magnetic resonance imaging shows impairment of the counter-current multiplication system in diabetic mice kidney2023

    • Author(s)
      Nakagawa Yusuke、Kaseda Ryohei、Suzuki Yuya、Watanabe Hirofumi、Otsuka Tadashi、Yamamoto Suguru、Kaneko Yoshikatsu、Goto Shin、Terada Yasuhiko、Haishi Tomoyuki、Sasaki Susumu、Narita Ichiei
    • Journal Title

      Kidney360

      Volume: Publish Ahead of Print Pages: 0-0

    • DOI

      10.34067/kid.0000000000000072

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Sodium Magnetic Resonance Imaging Shows Impairment of the Counter-Current Multiplication System in the Diabetic Model Mice Kidney2022

    • Author(s)
      Yusuke Nakagawa,Ryohei Kaseda,Yuya Suzuki,Yasuhiko Terada,Tomoyuki Haishi,Susumu Sasaki,Ichiei Narita
    • Organizer
      American Society of Nephrology Kidney Week 2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 23Na-MRIを用いた2型糖尿病マウスにおける腎臓内Na+濃度勾配の検討2021

    • Author(s)
      中川裕介
    • Organizer
      第64回日本腎臓学会学術総会
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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