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Biopathological analysis and novel therapy development for pediatric severe acute kidney injury

Research Project

Project/Area Number 19K08277
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52050:Embryonic medicine and pediatrics-related
Research InstitutionOkayama University

Principal Investigator

Tsukahara Hirokazu  岡山大学, 医歯薬学域, 教授 (90207340)

Co-Investigator(Kenkyū-buntansha) 宮原 宏幸  岡山大学, 大学病院, 医員 (00807654)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2021: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords活性酸素 / 活性窒素 / 急性腎障害 / 細胞機能修飾薬 / 酸化ストレス / 集中治療 / 多臓器障害 / レドックス / 内因性NO合成酵素阻害因子 / 病態解析 / 補助治療 / 生体応答 / 生体マーカー
Outline of Research at the Start

小児ICUで管理される重症患者は容易に急性腎障害(Acute kidney injury: AKI)あるいは急性腎不全(Acute renal failure: ARF)を発症する。AKI / ARFへの既存の薬剤治療が予後を改善させるエビデンスは決して高いものではない。そこで、本申請者らは、細胞・組織機能の保持と再生を目指した有効な補助治療(adjunctive therapy)を開発したいと考えている。
今回、“生体マーカー”を橋渡しにして臨床研究と実験研究の両結果を双方向性にリンクさせながら、この危急疾患の適正管理の方向付け、および、新規の効果的治療法の開発を目指したい。

Outline of Final Research Achievements

Critically ill pediatric patients are likely to present with acute kidney injury (AKI) or acute renal failure (ARF). In this project, we have obtained data on the use of specific biomarkers of oxidative/nitrosative stress and endothelial function in the pathogenetic mechanisms involved in multiple organ failure, cardiac defects, respiratory/allergic diseases, Kawasaki disease, IgA vasculitis, and renal stone disease. AKI/ARF might develop in these diseases. Reactive oxygen/nitrogen species contribute to the progression and amplification of the pathophysiological responses related to the diseases. Future breakthroughs in this field may provide a promising therapeutic strategy for the prevention and treatment of AKI/ARF in the pediatric patients.

Academic Significance and Societal Importance of the Research Achievements

感染性、炎症性、腫瘍性疾患はいうに及ばず、呼吸器、消化器、腎血管、内分泌、代謝性疾患などにおいても,“酸化ストレス”は基本病態である。各疾患は急速進行性でも、慢性遷延性でも組織・臓器を廃絶に導く危険性を伴うが、これを防ぐ有効な手段として酸化ストレスの制御は重要である。一方、病状悪化を抑えながら組織・臓器を保護し再生させるためには,“血管内皮機能”を保持することも必要である。今回の3年間の研究では、この方面に特化した研究成果として一定の進展が見られた。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (19 results)

All 2022 2021 2020 2019

All Journal Article (19 results) (of which Peer Reviewed: 16 results,  Open Access: 7 results)

  • [Journal Article] 253. 低カルシウム血症・低マグネシウム血症2022

    • Author(s)
      長谷川高誠, 塚原宏一
    • Journal Title

      周産期医学必修知識 第9版

      Volume: 51巻増刊号 Pages: 880-882

    • Related Report
      2021 Annual Research Report
  • [Journal Article] 254. 血中リン異常2022

    • Author(s)
      塚原宏一, 宮原宏幸, 馬場健児
    • Journal Title

      周産期医学必修知識 第9版

      Volume: 51巻増刊号 Pages: 883-885

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Anti-high mobility group box 1 monoclonal antibody suppressed hyper-permeability and cytokine production in human pulmonary endothelial cells infected with influenza A virus2021

    • Author(s)
      Namba T, Tsuge M, Yashiro M, Saito Y, Liu K, Nishibori M, Morishima T, Tsukahara H
    • Journal Title

      Inflamm Res

      Volume: 70(10-12) Issue: 10-12 Pages: 1101-1111

    • DOI

      10.1007/s00011-021-01496-5

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Current Insights into Atopic March2021

    • Author(s)
      Tsuge M, Ikeda M, Matsumoto N, Yorifuji T, Tsukahara H
    • Journal Title

      Children (Basel)

      Volume: 19;8(11) Issue: 11 Pages: 1067-1067

    • DOI

      10.3390/children8111067

    • NAID

      120007180266

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Preterm birth and Kawasaki disease: a nationwide Japanese population-based study2021

    • Author(s)
      Takeuchi A, Namba T, Matsumoto N, Tamai K, Nakamura K, Nakamura M, Kageyama M, Kubo T, Tsukahara H, Yorifuji T
    • Journal Title

      Pediatr Res

      Volume: Oct 8 Issue: 2 Pages: 557-562

    • DOI

      10.1038/s41390-021-01780-4

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reactive Oxygen Species and Antioxidative Defense in Chronic Obstructive Pulmonary Disease2021

    • Author(s)
      Taniguchi A, Tsuge M, Miyahara N, Tsukahara H
    • Journal Title

      Antioxidants (Basel)

      Volume: 28;10(10) Issue: 10 Pages: 1537-1537

    • DOI

      10.3390/antiox10101537

    • NAID

      120007170512

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association Between Eosinophilia and Late-onset Circulatory Collapse in Preterm Infants: A case-Control Study2021

    • Author(s)
      Okamura T, Washio Y, Watanabe H, Nakanishi H, Uchiyama A, Tsukahara H, Kusuda S
    • Journal Title

      Acta Medica Okayama

      Volume: 75 Issue: 4 Pages: 505-509

    • DOI

      10.18926/AMO/62403

    • NAID

      120007146046

    • URL

      https://ousar.lib.okayama-u.ac.jp/62403

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 23. 腎・尿路結石2021

    • Author(s)
      宮原宏幸, 塚原宏一
    • Journal Title

      小児内科 小児疾患診療のための病態生理2 改訂第6版

      Volume: 第53巻増刊号 Pages: 598-600

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Breastfeeding and risk of food allergy: A nationwide birth cohort in Japan2020

    • Author(s)
      Matsumoto N, Yorifuji T, Nakamura K, Ikeda M, Tsukahara H, Doi H
    • Journal Title

      Allergology International

      Volume: 69 Issue: 1 Pages: 91-97

    • DOI

      10.1016/j.alit.2019.08.007

    • NAID

      130007788684

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Associations of Birth Weight for Gestational Age with Child Health and Neurodevelopment among Term Infants: A Nationwide Japanese Population-Based Study2020

    • Author(s)
      Tamai K, Yorifuji T, Takeuchi A, Fukushima Y, Nakamura M, Matsumoto N, Washio Y, Kageyama M, Tsukahara H
    • Journal Title

      J Pediatr

      Volume: 20 Pages: 30829-5

    • DOI

      10.1016/j.jpeds.2020.06.075

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Laboratory changes during ACTH therapy associated with renal calcified lesions.2020

    • Author(s)
      Miyahara H, Akiyama T, Hasegawa K, Akiyama M, Oka M, Kobayashi K, Tsukahara H.
    • Journal Title

      Pediatr Int.

      Volume: - Issue: 5 Pages: 587-592

    • DOI

      10.1111/ped.14158

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hemophagocytic lymphohistiocytosis complicating invasive pneumococcal disease: a pediatric case report.2020

    • Author(s)
      Tsuge M, Miyamoto M, Miyawaki R, Kondo Y, Tsukahara H.
    • Journal Title

      BMC Pediatr.

      Volume: 20 Issue: 1 Pages: 15-15

    • DOI

      10.1186/s12887-020-1915-7

    • NAID

      120006839437

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Head circumference in infants with non-opiate-induced neonatal abstinence syndrome2020

    • Author(s)
      Morimoto D, Washio Y, Hatayama K, Okamura T, Watanabe H, Yoshimoto J, Tsukahara H
    • Journal Title

      CNS Spectr

      Volume: 1 Issue: 5 Pages: 1-17

    • DOI

      10.1017/s1092852920001522

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical Factors Affecting the Dose Conversion Ratio from Intravenous to Oral Tacrolimus Formulation among Pediatric Hematopoietic Stem Cell Transplantation Recipients2020

    • Author(s)
      Kanamitsu K, Yorifuji T, Ishida H, Fujiwara K, Washio K, Shimada A, Tsukahara H
    • Journal Title

      Ther Drug Monit

      Volume: 42(6) Issue: 6 Pages: 803-810

    • DOI

      10.1097/ftd.0000000000000793

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] 酸化ストレスと酸化ストレスマーカーの知識2020

    • Author(s)
      塚原宏一、馬場健児、鷲尾洋介、大野直幹.
    • Journal Title

      Medical Technology

      Volume: -

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Lupus anticoagulant-hypoprothrombinemia syndrome and immunoglobulin-A vasculitis: a report of Japanese sibling cases and review of the literature.2019

    • Author(s)
      Fujiwara K, Shimizu J, Tsukahara H, Shimada A.
    • Journal Title

      Rheumatol Int.

      Volume: 39 Issue: 10 Pages: 1811-1819

    • DOI

      10.1007/s00296-019-04404-7

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Balloon atrial septostomy in hypoplastic left heart syndrome with restrictive atrial septum.2019

    • Author(s)
      Fukushima Y, Baba K, Kondo M, Kurita Y, Eitoku T, Shigemitsu Y, Hirai K, Tsukahara H, Iwasaki T, Kasahara S, Kotani Y, Otsuki S.
    • Journal Title

      Pediatr Int.

      Volume: 61 Issue: 4 Pages: 339-344

    • DOI

      10.1111/ped.13716

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical outcomes after the endovascular treatments of pulmonary vein stenosis in patients with congenital heart disease.2019

    • Author(s)
      Kurita Y, Baba K, Kondo M, Eitoku T, Kasahara S, Iwasaki T, Ohtsuki S, Tsukahara H.
    • Journal Title

      Cardiol Young.

      Volume: 29 Issue: 8 Pages: 1057-1065

    • DOI

      10.1017/s1047951119001495

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Long-stay pediatric patients in Japanese intensive care units: their significant presence and a newly developed, simple predictive score.2019

    • Author(s)
      Knaup E, Nosaka N, Yorifuji T, Tsukahara K, Naito H, Tsukahara H, Nakao A; JaRPAC Study Group.
    • Journal Title

      J Intensive Care.

      Volume: 7 Issue: 1 Pages: 38-38

    • DOI

      10.1186/s40560-019-0392-2

    • NAID

      120006816636

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access

URL: 

Published: 2019-04-18   Modified: 2023-01-30  

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