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Fundamental research on the construction of an acute kidney injury warning system and reversibility indicators of renal function in the area of severe heart failure.

Research Project

Project/Area Number 20K07819
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52010:General internal medicine-related
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

Yoshihara Fumiki  国立研究開発法人国立循環器病研究センター, 病院, 部長 (70393220)

Co-Investigator(Kenkyū-buntansha) 福嶌 教偉  国立研究開発法人国立循環器病研究センター, 病院, 客員部長 (30263247)
細田 洋司  国立研究開発法人国立循環器病研究センター, 研究所, 客員研究員 (40359807)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords急性腎障害 / バンコマイシン腎症 / 重症心不全 / フローサイトメトリー / エクソソーム解析
Outline of Research at the Start

わが国の重症心不全患者の治療における喫緊の課題のひとつは、高度腎障害を合併した心不全患者における腎機能の可逆性指標の同定である。わが国では欧米と異なり心腎同時移植が実施されておらず、重症心不全患者が高度腎障害を合併した場合、その後の補助人工心臓の装着や心移植の適応判断に難渋している。本研究の目的は、重症心不全患者・心移植患者を対象に急性腎障害発症の警告システムを構築し、腎機能の可逆性指標を同定するための基盤的研究を行うことである。目標が達成されれば、重症心不全患者の治療戦略を立てる上でひとつの大きな目安を提案することが可能となる。

Outline of Final Research Achievements

(1) The usefulness of urinary shedding tubular epithelial cells for the diagnosis of acute kidney injury (AKI) was investigated in mice with vancomycin-induced AKI. As adrenomedullin (AM) has organ-protective effects in AKI models, AM was administered to rats with chronic kidney injury, a risk factor for AKI, to investigate the clinical application of AM.
(2) A clinical study 'Study on the establishment of an acute kidney injury warning system (vancomycin-induced kidney injury)' was initiated. Urine samples are collected over time from vancomycin-treated patients to identify the characteristics of urinary findings and to study their relationship to clinical findings, including renal function, renal prognosis and vancomycin blood levels.

Academic Significance and Societal Importance of the Research Achievements

日本人の急性腎障害の頻度は251人/100,000人・年と報告されている。急性腎障害の内、その後7日~90日間に渡り腎機能低下が持続する場合を急性腎臓病と称するが、急性腎臓病は生命予後の悪化と関連することが知られている。急性腎障害、急性腎臓病の薬物治療は確立されていないため、本研究は診断ツールや精度の向上および治療方法開発への基盤的知見を深めることに寄与し得る。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (21 results)

All 2023 2022 2021 2020 2019

All Journal Article (11 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 11 results,  Open Access: 3 results) Presentation (8 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Book (2 results)

  • [Journal Article] Association between oral frailty and cystatin C-related indices?A questionnaire (OFI-8) study in general internal medicine practice2023

    • Author(s)
      Kusunoki Hiroshi、Ekawa Kazumi、Kato Nozomi、Yamasaki Keita、Motone Masaharu、Shinmura Ken、Yoshihara Fumiki、Shimizu Hideo
    • Journal Title

      PLOS ONE

      Volume: 18 Issue: 4 Pages: e0283803-e0283803

    • DOI

      10.1371/journal.pone.0283803

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Acute Calcineurin Inhibitor Nephrotoxicity Diagnosed Using Kidney Doppler Ultrasonography After Heart Transplant: A Case Report2022

    • Author(s)
      Hada Tasuku、Seguchi Osamu、Mochizuki Hiroki、Watanabe Takuya、Yoshihara Fumiki、Fukushima Satsuki、Fujita Tomoyuki、Tsukamoto Yasumasa
    • Journal Title

      Transplantation Proceedings

      Volume: 54 Issue: 10 Pages: 2722-2726

    • DOI

      10.1016/j.transproceed.2022.10.027

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Plasma Clearance of Intravenously Infused Adrenomedullin in Rats with Acute Renal Failure2022

    • Author(s)
      Hosoda Hiroshi、Nakamura Tsutomu、Yoshihara Fumiki
    • Journal Title

      Biomolecules

      Volume: 12 Issue: 9 Pages: 1281-1281

    • DOI

      10.3390/biom12091281

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Renin-angiotensin system blocker and the COVID-19 aggravation in patients with hypertension, diabetes, renal failure, Cerebro-cardiovascular disease, or pulmonary disease: Report by the COVID-19 Registry Japan2022

    • Author(s)
      Yoshihara Fumiki、Ohtsu Hiroshi、Nakai Michikazu、Tsuzuki Shinya、Hayakawa Kayoko、Terada Mari、Matsunaga Nobuaki、Yasuda Satoshi、Ogawa Hisao、Ohmagari Norio
    • Journal Title

      Journal of Cardiology

      Volume: 80 Issue: 4 Pages: 292-297

    • DOI

      10.1016/j.jjcc.2022.04.001

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Kinetics of atrial and brain natriuretic peptides during hemodialysis are regulated in association with different cardiac functional changes2022

    • Author(s)
      Horio Takeshi、Ito Shogo、Fujimoto Kohei、Izumiya Yasuhiro、Yoshiyama Minoru、Iwashima Yoshio、Nakamura Satoko、Yoshihara Fumiki
    • Journal Title

      Heart and Vessels

      Volume: 37 Issue: 7 Pages: 1146-1152

    • DOI

      10.1007/s00380-021-02011-w

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Catheter-based ultrasound renal denervation in patients with resistant hypertension: the randomized, controlled REQUIRE trial2021

    • Author(s)
      Kario K、Yokoi Y、Okamura K、Fujihara M、Ogoyama Y、Yamamoto E、Urata H、Cho Jin-Man、Kim Chong-Jin、Choi Seung-Hyuk、Shinohara K、Mukai Y、Ikemoto T、Nakamura M、Seki S、Matoba S、Shibata Y、Sugawara S、Yumoto K、Tamura K、Yoshihara F、Nakamura S et al.
    • Journal Title

      Hypertension Research

      Volume: 45 Issue: 2 Pages: 221-231

    • DOI

      10.1038/s41440-021-00754-7

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hypocholesterolemia is a risk factor for reduced systemic vascular resistance reactivity during hemodialysis2021

    • Author(s)
      Matsuo Miki、Kojima Shiori、Arisato Tetsuya、Matsubara Masaki、Koezuka Ryo、Kishida Masatsugu、Ogawa Koji、Inoue Hiroshi、Yoshihara Fumiki
    • Journal Title

      Hypertension Research

      Volume: 44 Issue: 8 Pages: 988-995

    • DOI

      10.1038/s41440-021-00640-2

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Combined evaluation of plasma B-type natriuretic peptide and urinary liver-type fatty acid-binding protein/creatinine ratio is related to worsening renal function in patients undergoing elective percutaneous coronary intervention2021

    • Author(s)
      Yoshihara Fumiki、Hosoda Hiroshi、Doi Takahito、Yoshida Morikatsu、Kitamura Kazuo、Yamamoto Haruko、Asaumi Yasuhide、Ishibashi-Ueda Hatsue、Kishida Masatsugu、Arisato Tetsuya、Matsuo Miki、Miyazato Mikiya、Yasuda Satoshi
    • Journal Title

      Clinical and Experimental Nephrology

      Volume: 25 Issue: 12 Pages: 1319-1328

    • DOI

      10.1007/s10157-021-02113-9

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Associations between arterial stiffness indices and chronic kidney disease categories in essential hypertensive patients2020

    • Author(s)
      Kusunoki H、Hayashi S他
    • Journal Title

      American Journal of Hypertension

      Volume: 34 Issue: 5 Pages: 484

    • DOI

      10.1093/ajh/hpaa163

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Impact of Percutaneous Revascularization on Left Ventricular Mass and Its Relationship to Outcome in Hypertensive Patients with Renal Artery Stenosis2020

    • Author(s)
      Iwashima Yoshio、Fukuda Tetsuya、Horio Takeshi、Kusunoki Hiroshi、Hayashi Shin-ichiro、Kamide Kei、Kawano Yuhei、Ishimitsu Toshihiko、Yoshihara Fumiki
    • Journal Title

      American Journal of Hypertension

      Volume: 33 Issue: 6 Pages: 570

    • DOI

      10.1093/ajh/hpaa036

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Genetic factors associated with elevation of uric acid after treatment with thiazide-like diuretic in patients with essential hypertension2019

    • Author(s)
      Ohta Yuko、Kamide Kei、Hanada Hironori、et al. (37人中31番目)
    • Journal Title

      Hypertension Research

      Volume: 43 Issue: 3 Pages: 220

    • DOI

      10.1038/s41440-019-0356-x

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] Renin-Angiotensin System Blocker and the COVID-19 Aggravation: Report by the COVID-19 REGISTRY JAPAN2022

    • Author(s)
      Fumiki Yoshihara, Hiroshi Ohtsu, Michikazu Nakai, Shinya Tsuzuki, Kayoko Hayakawa, Mari Terada, Nobuaki Matsunaga, Satoshi Yasuda, Hisao Ogawa, Norio Ohmagari
    • Organizer
      International Society of Hypertension
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] 心腎連関症候群の病態と治療2022

    • Author(s)
      吉原史樹 岸田真嗣 有里哲哉 松尾実紀
    • Organizer
      日本腎臓学会西部
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 透析低血圧における全身血管抵抗の意義と関連因子の検討2021

    • Author(s)
      松尾実紀、肥塚諒、岸田真嗣、有里哲哉、小川浩司、井上裕之、中村敏子、吉原史樹
    • Organizer
      第9回臨床高血圧フォーラム
    • Related Report
      2021 Research-status Report
  • [Presentation] 血中および尿中バイオマーカーによる冠動脈形成術後の腎機能障害の予測性に関する2021

    • Author(s)
      吉原史樹、細田洋司、岸田真嗣、有里哲哉、松尾実紀、小島詩織
    • Organizer
      第64回日本腎臓学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 心移植後にタクロリムス腎障害を来たしエベロリムスへの変更にて維持透析を離脱し得た一例2021

    • Author(s)
      小島詩織、松尾実紀、有里哲哉、岸田真嗣、瀬口 理、福嶌教偉、吉原史樹
    • Organizer
      第51回日本腎臓学会・西部
    • Related Report
      2021 Research-status Report
  • [Presentation] シンポジウム8「CKD・DKD診療の新展開」  CKD領域の新規薬物治療2021

    • Author(s)
      吉原史樹、岸田真嗣、有里哲哉、松尾実紀、細田洋司
    • Organizer
      第51回日本腎臓学会・東部
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 尿細管に著明な赤血球漏出を伴う 顕微鏡的多発血管炎に血漿交換併用ステロイド治療奏功後、ステロイド治療離脱できた一例2020

    • Author(s)
      岸田真嗣 菱田 藍 石塚 梓 楠 博 小島詩織 肥塚 諒 松原正樹 松尾実紀 有里哲哉 中村敏子 吉原史樹
    • Organizer
      日本透析医学会
    • Related Report
      2020 Research-status Report
  • [Presentation] An Elevated Urinary Liver-Type Fatty Acid-Binding Protein/Creatinine Ratio One Day after Percutaneous Coronary Intervention is Relat ed to Worsening Renal Function2020

    • Author(s)
      Fumiki Yoshihara, Hiroshi Hosoda, Toshimitsu Hamasaki, Kazuo Kitamura, Haruko Yamamoto, Yasuhide Asaumi, Hatsue Ishibashi-Ueda, Masatsugu Kishida, Tetsuya Arisato, Satoshi Yasuda
    • Organizer
      日本循環器学会
    • Related Report
      2020 Research-status Report
  • [Book] 内科 心腎連関の応用:心不全治療薬2020

    • Author(s)
      松尾実紀 吉原史樹
    • Total Pages
      6
    • Publisher
      南江堂
    • Related Report
      2020 Research-status Report
  • [Book] 薬局 CKD合併心不全とβ遮断薬2020

    • Author(s)
      岸田真嗣 吉原史樹
    • Total Pages
      6
    • Publisher
      南山堂
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2025-01-30  

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