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Development of bio-artificial kidney

Research Project

Project/Area Number 16591270
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionJICHI MEDICAL UNIVERSITY

Principal Investigator

FUJIMURA Akio  Jichi Medical University, School of Medicine, Clinical Pharmacology, Professor, 医学部, 教授 (90156901)

Co-Investigator(Kenkyū-buntansha) TSURUOKA Shuichi  Jichi Medical University, School of Medicine, Clinical Pharmacology, Associate Professor, 医学部, 助教授 (50285798)
鈴木 誠  自治医科大学, 医学部, 助教授 (10196868)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2006: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Keywordschronic renal failure / blood purification / organic anion transporter-3 / indoxylsulfate / uremic toxin / arteriosclerosis / 尿素症性物質 / 血管平滑筋 / 有機アニオン輸送体 / ABCA8
Research Abstract

Anionic middle molecule uremic toxins, which can not be removed by conventional hemodialysis, play major role for progress of arteriosclerosis in patients with chronic renal failure. Most of the toxins, such as indoxyl sulfate, is secreted via organic anion transporter-3 (OAT-3) in proximal tubule cells in healthy subjects. To develop a novel hybrid artificial kidney, where the proximal tubular cells over-expressing OAT-3 are cultured on hollow fibers, we performed following experiments.
1) We established cultured proximal tubule cells over-expressing OAT-3. We confirmed higher transport of indoxyl sulfate in the cells and also higher expression of the protein by Western blot and immuno-histochemistry.
2) We succeeded to seed the cells onto hollowfiber modules, which we previously reported.
3) We found higher selective removal of indoxyl sulfate by the system in vitro. The clearance of indoxyl sulfate was 38 ml/min/m2, which was 8-times higher than that with control cells.
4) We also applied this system to dogs with or without renal failure. We found high removal capacity of indoxyl sulfate from circulating blood of renal failure dog with a few adverse reactions.
Thus, we succeeded to develop a novel hybrid artificial kidney with proximal tubular cells over-expressing OAT-3. This system may be useful to remove uremic toxins which can not be removed by conventional hemodialysis.

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report

Research Products

(45 results)

All 2007 2006 2005 2004

All Journal Article (45 results)

  • [Journal Article] TRPV4 as a flow sensor in the flow-dependent K+ secretion from the cortical collecting duct.2007

    • Author(s)
      Taniguchi J, Tsuruoka S, Fujimura A, et al.
    • Journal Title

      Am J Physiol Renal Physiol (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] TRPV4 as a flow sensor in the flow-dependent K+ secretion from the cortical collecting duct.2007

    • Author(s)
      Taniguchi J, Tsuruoka S, Mizuno A, Sato JI, Fujimura A, Suzuki M.
    • Journal Title

      Am J Physiol Renal Physiol (In press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] TRPV4 as a flow sensor in the flow-dependent K+ secretion from the cortical collecting duct.2007

    • Author(s)
      Taniguchi J, Fujimura A(5番目).
    • Journal Title

      Am J Physiol Renal Physiol (In press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Changes of neutrophil function during the inter-dialytic period.2006

    • Author(s)
      Kitoh Y, Tsuruoka S, Fujimura A, et al.
    • Journal Title

      Clin Nephrol 65(1)

      Pages: 75-77

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Indoxyl sulfate stimulates proliferation of rat vascular smooth muscle cells.2006

    • Author(s)
      Yamamoto H, Tsuruoka S, Fujimura A, et al.
    • Journal Title

      Kidney Int 69(10)

      Pages: 1780-1785

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Defect in Parathyroid Hormone-Induced Luminal Calcium Absorption in Connecting Tubules of Klotho Mice.2006

    • Author(s)
      Tsuruoka S, Fujimura A et al.
    • Journal Title

      Nephrol Dial Tranplant 21(10)

      Pages: 2762-2767

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Endothelin and Nitric Oxide Mediate the Adaptation of the Cortical Collecting Duct to Metabolic Acidosis.2006

    • Author(s)
      Tsuruoka S, Fujimura A, et al.
    • Journal Title

      Am J Physiol Renal Physiol 291(4)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A double-compartment cell culture apparatus : its construction and biochemical evaluation for bioartificial liver support system.2006

    • Author(s)
      Takahashi M, Tsuruoka S, et al.
    • Journal Title

      Cell Transplant 15(10)

      Pages: 945-952

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Changes of neutrophil function during the inter-dialytic period.2006

    • Author(s)
      Kitoh Y, Tsuruoka S, Ohmori M, Sugimoto K, Saitoh T, Fujimura A.
    • Journal Title

      Clin Nephrol 65(1)

      Pages: 75-7

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Indoxyl sulfate stimulates proliferation of rat vascular smooth muscle cells.2006

    • Author(s)
      Yamamoto H, Tsuruoka S, Ioka T, Ando H, Ito C, Akimoto T, Fujimura A, Asano Y, Kusano E.
    • Journal Title

      Kidney Int 69(10)

      Pages: 1780-5

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Defect in Parathyroid Hormone-Induced Luminal Calcium Absorption in Connecting Tubules of Klotho Mice.2006

    • Author(s)
      Tsuruoka S, Nishiki K, Ioka T, Ando H, Saito Y, Kurabayashi M, Nagai R, Fujimura A.
    • Journal Title

      Nephrol Dial Tranplant 21(10)

      Pages: 2762-7

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Endothelin and Nitric Oxide Mediate the Adaptation of the Cortical Collecting Duct to Metabolic Acidosis.2006

    • Author(s)
      Tsuruoka S, Watanabe S, Purkerson JM, Fujimura A, Schwartz GJ.
    • Journal Title

      Am J Physiol Renal Physiol 291(4)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A double-compartment cell culture apparatus : its construction and biochemical evaluation for bioartificial liver support system.2006

    • Author(s)
      Takahashi M, Sakurai M, Enosawa S, Endo M, Omasa T, Tsuruoka S, Matsumura T.
    • Journal Title

      Cell Transplant 15(10)

      Pages: 945-52

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Changes of neutrophil function during the inter-dialytic period.2006

    • Author(s)
      Kitoh Y, Fujimura A(6番目).
    • Journal Title

      Clin Nephrol. 65(1)

      Pages: 75-77

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Indoxyl sulfate stimulates proliferation of rat vascular smooth muscle cells.2006

    • Author(s)
      Yamamoto H, Fujimura, A(7番目).
    • Journal Title

      Kidney Int. 69(10)

      Pages: 1780-1785

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Defect in Parathyroid Hormone-Induced Luminal Calcium Absorption in Connecting Tubules of Klotho Mice.2006

    • Author(s)
      Tsuruoka S, Fujimura A(8番目).
    • Journal Title

      Nephrol Dial Tranplant. 21(10)

      Pages: 2762-2767

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Endothelin and Nitric Oxide Mediate the Adaptation of the Cortical Collecting Duct to Metabolic Acidosis.2006

    • Author(s)
      Tsuruoka S, Fujimura A(4番目).
    • Journal Title

      Am J Physiol Renal Physiol. 291(4)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A double-compartment cell culture apparatus : its construction and biochemical evaluation for bioartificial liver support system.2006

    • Author(s)
      Takahashi M, Tsuruoka S(6番目).
    • Journal Title

      Cell Transplantation 15(10)

      Pages: 945-952

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Indoxyl sulfate stimulates proliferation of rat vascular smooth muscle cells.2006

    • Author(s)
      Yamamoto H, Fujimura A et al.(7番目)
    • Journal Title

      Kidney Int (In press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Cyclosporin produces distal Renal Tubular Acidosis by blocking peptidyl cis-trans prolyl isomerase activity of cyclophilin.2005

    • Author(s)
      Watanabe S, Tsuruoka S, et al.
    • Journal Title

      Am J Physiol Renal Physiol 288(1)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Citrate reverses Cyclosporin A-induced metabolic acidosis and bone resorption in rat.2005

    • Author(s)
      Tsuruoka S, Fujimura A. et al.
    • Journal Title

      Am J Nephrol 25(3)

      Pages: 233-239

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The bioreactor with CYP3A4- and glutamine synthetase-introduced H epG2 cells : Treatment of hepatic failure dog with diazepam overdosage.2005

    • Author(s)
      Wang N, Tsuruoka S, Fujimura A, et al.
    • Journal Title

      Artif Org 29(8)

      Pages: 681-684

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effect of trimethoprim-sulfamethoxazole on Na+ and K+ transport in the rabbit cortical collecting duct.2005

    • Author(s)
      Muto S, Tsuruoka S, Fujimura A, et al.
    • Journal Title

      Nephron Physiol 102(3-4)

      Pages: 51-60

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Acute digoxin loading reduces ABCA8 mRNA expression in mouse liver.2005

    • Author(s)
      Wakaumi M, Tsuruoka S et al.
    • Journal Title

      Clin Exp Pharmacol Physiol 32(12)

      Pages: 1034-1041

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cyclosporin produces distal Renal Tubular Acidosis by blocking peptidyl cis-trans prolyl isomerase activity of cyclophilin.2005

    • Author(s)
      Watanabe S, Tsuruoka S, Vijayakumar S, Fischer G, Zhang Y, Fujimura A, Al-Awqati Q, Schwartz GJ.
    • Journal Title

      Am J Physiol Renal Physiol 288(1)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Citrate reverses Cyclosporin A-induced metabolic acidosis and bone resorption in rat.2005

    • Author(s)
      Tsuruoka S, Schwartz GJ, Ioka T, Yamamoto H, Ando H, Fujimura A.
    • Journal Title

      Am J Nephrol 25(3)

      Pages: 233-9

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The bioreactor with CYP3A4- and glutamine synthetase-introduced H epG2 cells : Treatment of hepatic failure dog with diazepam overdosage.2005

    • Author(s)
      Wang N, Tsuruoka S, Yamamoto H, Enosawa S, Omasa T, Sata N, Matsumura T, Nagai H, Fujimura A.
    • Journal Title

      Artif Org 29(8)

      Pages: 681-4

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effect of trimethoprim-sulfamethoxazole on Na+ and K+ transport in the rabbit cortical collecting duct.2005

    • Author(s)
      Muto S, Tsuruoka S, Miyata Y, Fujimura A, Asano Y, Kusano E.
    • Journal Title

      Nephron Physiol 102(3-4)

      Pages: 51-60

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Acute digoxin loading reduces ABCA8 mRNA expression in mouse liver.2005

    • Author(s)
      Wakaumi M, Ishibashi K, Ando H, Kasanuki H, Tsuruoka S.
    • Journal Title

      Clin Exp Pharmacol Physiol 32(12)

      Pages: 1034-41

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Citrate reverses Cyclosporin A-induced metabolic acidosis and bone resorption in rat.2005

    • Author(s)
      Tsuruoka S, Fujimura A et al.(6番目)
    • Journal Title

      Am J Nephrol 25(3)

      Pages: 233-239

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The bioreactor with CYP34A- and glutamine synthetase-introduced HepG2 cells : Treatment of hepatic failure dog with diazepam overdosage2005

    • Author(s)
      Wang N, Fujimura A et al.(9番目)
    • Journal Title

      Artif Org 29

      Pages: 681-684

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Effect of trimethoprim-sulfamethoxazole on Na+ and K+ transport in the rabbit cortical collecting duct.2005

    • Author(s)
      Muto S, Fujimura A et al.(9番目)
    • Journal Title

      Nephron Physiol 102(3-4)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Cyclosporin produces distal Renal Tubular Acidosis by blocking peptidyl cis-trans prolyl isomerase activity of cyclophilin.2005

    • Author(s)
      Watanabe S, Fujimura A et al.(6番目)
    • Journal Title

      Am J Physiol Renal Physiol 288(1)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Cyclosporin produces distal Renal Tubular Acidosis by blocking peptidyl cis-trans prolyl isomerase activity of cyclophilin.2005

    • Author(s)
      Watanabe S, Fujimura A (6番目) et al.
    • Journal Title

      Am J Physiol Renal Physiol 288

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Treatment of digoxin intoxication model by hybrid kidney with hollowfiber module for clinical hemodialysis.2004

    • Author(s)
      Tsuruoka S, Fujimura A. et al.
    • Journal Title

      Nephrol Dial Transplant 19(5)

      Pages: 1339-1340

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Adsorption of oxacalcitriol by polysulfone hemodialyzer in patients with secondary hyperparathyroidism.2004

    • Author(s)
      Tsuruoka S, Fujimura A, et al.
    • Journal Title

      Or J Clin Pharmacol 58(5)

      Pages: 488-495

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] β2-microglobulin adsorption column reduces digoxin trough level during hemodialysis : 3 case reports.2004

    • Author(s)
      Tsuruoka S, Fujimura A, et al.
    • Journal Title

      Ther Drug Monit 26(4)

      Pages: 450-452

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 薬物中毒とハイブリッド型人工臓器。2004

    • Author(s)
      鶴岡秀一
    • Journal Title

      臨床医薬 20(9)

      Pages: 919-924

    • NAID

      10012890883

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 細胞生物学講座 : ハイブリッド型人工腎臓。2004

    • Author(s)
      鶴岡秀一, 他
    • Journal Title

      細胞 36(13)

      Pages: 557-560

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Treatment of digoxin intoxication model by hybrid kidney with hollowfiber module for clinical hemodialysis.2004

    • Author(s)
      Tsuruoka S, Nishiki K, Wakaumi M, Wang N, Yamamoto H, Ando H, Imai M, Fujimura A.
    • Journal Title

      Nephrol Dial Transplant 19(5)

      Pages: 1339-40

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Adsorption of oxacalcitriol by polysulfone hemodialyzer in patients with secondary hyperparathyroidism.2004

    • Author(s)
      Tsuruoka S, Yamamoto H, Wakaumi M, Ando H, Saito T, Fujimura A.
    • Journal Title

      Br J Clin Pharmacol 58(5)

      Pages: 488-95

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] β2-microglobulin adsorption column reduces digoxin trough level during hemodialysis : 3 case reports.2004

    • Author(s)
      Tsuruoka S, Wakaumi M, Yamamoto H, Ando H, Saito A, Fujimura A.
    • Journal Title

      Ther Drug Monit 26(4)

      Pages: 450-2

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Treatment of digoxin intoxication model by hybrid kidney with hollowfiber module for clinical hemodialysis.2004

    • Author(s)
      Tsuruoka S, Fujimura A (8番目) et al.
    • Journal Title

      Nephrol Dial Transplant 19

      Pages: 1339-40

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Adsorption of oxacalcitriol by polysulfone haemodialyzer in patients with secondary hyperparathyroidism.2004

    • Author(s)
      Tsuruoka S, Fujimura A (6番目) et al.
    • Journal Title

      Br J Clin Pharmacol 58

      Pages: 488-495

    • Related Report
      2004 Annual Research Report
  • [Journal Article] β2-microglobulin adsorption column reduces digoxin trough level during hemodialysis : 3 case reports.2004

    • Author(s)
      Tsuruoka S, Fujimura A (7番目) et al.
    • Journal Title

      Ther.Drug Monit 26

      Pages: 450-452

    • Related Report
      2004 Annual Research Report

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Published: 2004-03-31   Modified: 2016-04-21  

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