Development of artificial kidney for removal of anionic uremic toxins

• Project/Area Number: 23591212
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Nippon Medical School (2012-2015); University of Tsukuba (2011)
• Principal Investigator: TSURUOKA Shuichi 日本医科大学, 医学(系)研究科(研究院), 教授 (50285798)
• Co-Investigator(Kenkyū-buntansha): YAMAGATA Kunihiro 筑波大学, 医療医学系, 教授 (90312850)
• Project Period (FY): 2011-04-28 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 尿毒症性物質 / インドキシル硫酸 / バイオ人工腎臓 / 尿細管輸送

Outline of Final Research Achievements

We found that anionic uremic toxins such as indoxyl sulfate, p-cresyl sulphate, and 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid stimulated proliferation of cultured smooth vascular cells via phosphorylation of proteins related to cell signaling (such as MAP kinase). We also established cultured renal tubular cells with high transport rate of these toxins. We further established the systems of artificial kidney with high capacity to remove these toxins.

Research Products

• [Journal Article] SDF1 induction by acidosis from principal cells regulates intercalated cell subtype distribution. (2015)
  • Author(s): Schwartz GJ, Gao X, Tsuruoka S, Purkerson JM, Peng H, D'Agati V, Picard N, Eladari D, Al-Awqati Q.
  • Journal Title: J Clin Invest. Volume: 125 Issue: 12 Pages: 4365-4374
  • DOI: 10.1172/jci80225
  • Peer Reviewed
• [Journal Article] Clinical benefit of the change of dialysate calcium concentration from 3.0 to 2.75 mEq/L. (2014)
  • Author(s): Otsukua T, Ohno D, Murasawa T, Sakai S, Tsuruoka S.
  • Journal Title: Ther Apher Dial. Volume: 18 Pages: 181-184
  • Peer Reviewed
• [Journal Article] Dialyzability and pharmacokinetics of sitafloxacin following multiple oral dosing in infected hemodialysis patients. (2013)
  • Author(s): Tsuruoka S, Yokota N, Hayasaka T, Saito T, Yamagata K.
  • Journal Title: Ther Apher Dial Volume: 17 Issue: 3 Pages: 319-324
  • DOI: 10.1111/j.1744-9987.2012.01150.x
  • Peer Reviewed
• [Journal Article] 腎臓における尿毒素排泄機構 (2013)
  • Author(s): 鶴岡秀一
  • Journal Title: 日医大医会誌 Volume: 9 Pages: 235-235
• [Journal Article] Inhibition of CYP3A4 by 6',7'-dihydroxybergamottin in human CYP3A4 over-expressed hepG2 cells (2012)
  • Author(s): Araki N, Tsuruoka S, Hasegawa G, Yanagihara H, Omasa T, Enosawa S, Yamazoe Y, Fujimura A.
  • Journal Title: J Pharm Pharmacol. Volume: 64 Pages: 1715-1721
  • Peer Reviewed
• [Presentation] 薬剤性腎障害に対する早期マーカー探索の試み (2014)
  • Author(s): 鶴岡秀一、荒川裕輔、藤村昭夫
  • Organizer: 第４４回日本腎臓学会東部学術大会
  • Place of Presentation: 東京
  • Year and Date: 2014-10-24 – 2014-10-25
  • Invited
• [Presentation] Dialyzability and pharmacokinetics of sitafloxacin following multiple oral dosing in infected hemodialysis patients (2012)
  • Author(s): Tsuruoka S, Yokota N, Hayasaka T, Saito T, Yamagata K.
  • Organizer: 2012 Renal week, American Society of Nephrology 45h Annual meeting.
  • Place of Presentation: San Diego CA, USA,
• [Presentation] Dialyzability and pharmacokinetics of oral levofloxacin in infected hemodialysis patients. (2011)
  • Author(s): Tsuruoka S, Hayasaka T, Yokota N, Saito T, Yamagata K.
  • Organizer: 2011 Renal week, American Society of Nephrology 44th Annual meeting.
  • Place of Presentation: Philadelphia, PA, USA,
• [Presentation] 間質性腎炎
  • Author(s): 鶴岡秀一
  • Organizer: 第43回日本腎臓学会東部学術大会
  • Place of Presentation: 東京
  • Invited
• [Presentation] 維持透析患者におけるシタフロキサシンの透析性および薬物動態
  • Author(s): 鶴岡秀一、横田徳継、早坂常江、斎藤鉄男、山縣邦弘
  • Organizer: 第58回日本透析医学会学術集会・総会
  • Place of Presentation: 福岡