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Reno-protective mechanism by therapeutic intervention of metabolic acidosis on chronic kidney disease

Research Project

Project/Area Number 16K08487
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General physiology
Research InstitutionTohoku University

Principal Investigator

Abe Michiaki  東北大学, 大学病院, 准教授 (40400246)

Co-Investigator(Kenkyū-buntansha) 小柴 生造  東北大学, 東北メディカル・メガバンク機構, 教授 (70332301)
三枝 大輔  東北大学, 東北メディカル・メガバンク機構, 講師 (90545237)
Research Collaborator Shoji Mutsumi  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords慢性腎臓病 / 酸性尿 / アルカリ性化剤 / 経口アルカリ性化剤 / 尿毒症物質 / クエン酸 / 重炭酸 / 腎 / 体液 / 酸塩基平衡
Outline of Final Research Achievements

The main findings of this study are described below;
1. As a result of quantitative metabolomic analysis of uremic toxins by LC-MS/MS of plasma and early-morning urine before and after alkalinizing agent intervention, urinary excretions of indoxyl sulfate, paracresyl sulfate and argininosuccinic acid were increased in Na/K citrate administration. And plasma levels of indoxyl sulfate was decreased.
2. The improvement of aciduria was observed by the administration of Na/K citrate, the renal function tended to be better as seen in the pH improvement of the spot urine was larger than that of early-morning urine. Na/K citric could be expected different mechanisms on renal protection effect other than alkalization from Na bicarbonate. It is considered this would be a new main stream of therapeutic strategies for chronic kidney disease.

Academic Significance and Societal Importance of the Research Achievements

本研究は、アルカリ性化剤は比較的軽症の慢性腎臓病・経度腎機能障害から腎保護効果を期待できるということを実証する目的で行われた。しかしながら、現時点では軽症の腎障害を鋭敏かつ適切に評価できる検査指標はない。本研究ではそのような腎障害マーカの探索も行っている。サンプル保存を維持するため単施設で進められたので、昨年12月で登録患者の検査データの収集が終了した。全研究データはモニタリング・クリーニングなどを経て3月31日に固定された。現在解析中。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (16 results)

All 2019 2018 2017 2016

All Journal Article (6 results) (of which Peer Reviewed: 5 results,  Open Access: 1 results) Presentation (5 results) (of which Int'l Joint Research: 3 results) Patent(Industrial Property Rights) (5 results) (of which Overseas: 1 results)

  • [Journal Article] A 29-year-old Woman with Recurrent Pregnancy-induced Hypertension Based on Vascular Compression of the Medulla Oblongata2019

    • Author(s)
      Akaishi Tetsuya、Kiyomoto Hideyasu、Abe Michiaki、Okuda Hiroshi、Ishizawa Kota、Endo Toshiki、Miyata Masahiro、Nakayama Keisuke、Ito Sadayoshi、Tominaga Teiji、Ishii Tadashi
    • Journal Title

      Internal Medicine

      Volume: 58 Issue: 15 Pages: 2257-2261

    • DOI

      10.2169/internalmedicine.2382-18

    • NAID

      130007686858

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2019-08-01
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High glucose level and angiotensin II type 1 receptor stimulation synergistically amplify oxidative stress in renal mesangial cells2019

    • Author(s)
      Akaishi Tetsuya、Abe Michiaki、Okuda Hiroshi、Ishizawa Kota、Abe Takaaki、Ishii Tadashi、Ito Sadayoshi
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 5214-5220

    • DOI

      10.1038/s41598-019-41536-z

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Long-term Assessment of Intrarenal Blood Flow with Doppler Ultrasonography for Hypertensive Patients after Percutaneous Transluminal Renal Angioplasty.2019

    • Author(s)
      Abe M, Araya K, Akaishi T, Miki T, Miki M, Sugawara A, Abe T, Ishii T, Ito S
    • Journal Title

      Hypertension Research

      Volume: 0000 Pages: 0000-0000

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Low frequency of cervicocranial artery involvement in Japanese with renal artery fibromuscular dysplasia compared with that of Caucasians2018

    • Author(s)
      Eikan Mishima, Shu Umezawa, Takehiro Suzuki, Miki Fujimura, Michiaki Abe, Junichiro Hashimoto, Takaaki Abe, Sadayoshi Ito
    • Journal Title

      Clin Exp Nephrol

      Volume: 印刷中 Issue: 6 Pages: 1294-1299

    • DOI

      10.1007/s10157-018-1575-1

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 大学病院総合診療科初診患者のうつ状態を評価するためのハミルトンうつ病評価尺度の有用性2018

    • Author(s)
      阿部 倫明, 野崎 裕之, 中川 高, 八木橋 真央, 石沢 興太, 奥田 拓史, 赤石 哲也, 田中 淳一, 大澤 稔, 沼田 健裕, 菊地 章子, 高山 真, 奈良 正之, 小野寺 浩, 富田 博秋, 石井 正
    • Journal Title

      日本病院総合診療医学会雑誌

      Volume: 14 Pages: 556-563

    • NAID

      40021754601

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 座談会:酸塩基平衡と生活習慣病2016

    • Author(s)
      富野 康日己,原 茂子, 丸中良典, 阿部倫明, 鶴岡秀一
    • Journal Title

      腎・高血圧の最新治療

      Volume: 5 Pages: 193-203

    • NAID

      40020981197

    • Related Report
      2016 Research-status Report
  • [Presentation] Oral alkali supplementation to reduce uremic toxin in early stage CKD patients2018

    • Author(s)
      Abe M, Saigusa D, Koshiba S, Tanabe O, Satoh F, Sato H, Ishii T, Ito S and CKOALA study group
    • Organizer
      ISN Frontiers meetings
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Oral alkali supplementation to reduce uremic toxin in early stage CKD patients.2018

    • Author(s)
      Michiaki Abe, Daisuke Saigusa, Seizo Koshiba, Fumitoshi Satoh, Hiroshi Sato, Tadashi Ishii, Sadayoshi Ito and CKOALA study group.
    • Organizer
      ISN Frontiers Meeting 2018
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 経口アルカリ性化剤により薬物的血液浄化される尿毒症物質の検討2017

    • Author(s)
      阿部倫明,三枝大輔,小柴生造,鈴木洋一,田邊修,安田純,佐藤文俊,工藤正孝,佐藤博,森本玲,中道崇,小川晋,清元秀泰,三木俊,高山真,宮崎真理子,石井正,伊藤貞嘉,CKOALA 研究グループ
    • Organizer
      第60回日本腎臓学会学術総会
    • Place of Presentation
      仙台,仙台国際センター
    • Year and Date
      2017-05-26
    • Related Report
      2016 Research-status Report
  • [Presentation] 経口アルカリ性化剤により薬物的血液浄化される尿毒症物質の検討2017

    • Author(s)
      阿部倫明,三枝大輔,小柴生造,鈴木洋一,田邊修,安田純,佐藤文俊,工藤正孝,佐藤博,森本玲,中道崇,小川晋,清元秀泰,三木俊,高山真,宮崎真理子,石井正,伊藤貞嘉,CKOALA 研究グループ
    • Organizer
      第60回日本腎臓学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Oral alkali supplementation to reduce uremic toxin in early stage CKD patients.2017

    • Author(s)
      Michiaki Abe, Daisuke Saigusa, Tomokazu Souma, Hiroshi Sato, Sadayoshi Ito and CKOALA study group.
    • Organizer
      Kidney Week 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Patent(Industrial Property Rights)] 腎機能維持又は改善剤2019

    • Inventor(s)
      阿部倫明,小柴生造,西岡浩一郎,川口和彦,山崎里美,寺中康行
    • Industrial Property Rights Holder
      阿部倫明,小柴生造,西岡浩一郎,川口和彦,山崎里美,寺中康行
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] アルカリ性化剤による血液浄化2018

    • Inventor(s)
      阿部倫明,小柴生造,西岡浩一郎,川口和彦,山崎里美,寺中康行
    • Industrial Property Rights Holder
      阿部倫明,小柴生造,西岡浩一郎,川口和彦,山崎里美,寺中康行
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 尿細管機能維持又は改善剤2018

    • Inventor(s)
      伊藤貞嘉,阿部,小柴,西岡,川口,山崎,寺中康行
    • Industrial Property Rights Holder
      伊藤貞嘉,阿部,小柴,西岡,川口,山崎,寺中康行
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] アルカリ性化剤による血液浄化2017

    • Inventor(s)
      阿部倫明,小柴生造,西岡浩一郎,川口和彦,山崎里美,寺中康行
    • Industrial Property Rights Holder
      阿部倫明,小柴生造,西岡浩一郎,川口和彦,山崎里美,寺中康行
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Related Report
      2017 Research-status Report
  • [Patent(Industrial Property Rights)] 経口アルカリ性化剤による尿毒症物質の薬物的血液浄化作用の実現化2017

    • Inventor(s)
      阿部倫明,小柴生造,西岡浩一郎,川口和彦,山崎里美,寺中康行
    • Industrial Property Rights Holder
      阿部倫明,小柴生造,西岡浩一郎,川口和彦,山崎里美,寺中康行
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-075610
    • Filing Date
      2017-04-05
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2021-02-19  

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