Development of hybrid kidney for removal of protein-bound anionic uremic toxins

• Project/Area Number: 19590961
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: University of Tsukuba
• Principal Investigator: TSURUOKA Shuichi University of Tsukuba, 大学院・人間総合科学研究科, 准教授 (50285798)
• Co-Investigator(Kenkyū-buntansha): FUJIMURA Akio 自治医科大学, 医学部, 教授 (90156901)
• Project Period (FY): 2007 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2009: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 慢性腎不全 / バイオ人工臓器 / 尿毒症性物質 / 有機アニオン輸送体

Research Abstract

We developed hybrid kidney with renal cell over-expressed human organic anion transporters. We found that this system can selectively remove protein-bound uremic toxins, such as indoxyl sulfate, in animal model of chronic renal failure. We also found that some protein-bound uremic toxins directly stimulate proliferation of vascular smooth muscle cells in vitro.

Research Products

• [Journal Article] Statins inhibited erythropoietininduced proliferation of rat vascular smooth muscle cells. (2010)
  • Author(s): Kaneda T, Tsuruoka S, Fujimura A.
  • Journal Title: Eur J Pharmacol. 649 Pages: 38-43
  • NAID: 120007137842
  • Peer Reviewed
• [Journal Article] Recovery from acidosis : changes in anion exchanger distribution and expression are major components of reversible adaptation to metabolic acidosis in the cortical collecting duct. (2010)
  • Author(s): Purkerson JM, Tsuruoka S
  • Journal Title: Kidney Int. 78 Pages: 993-1005
  • Peer Reviewed
• [Journal Article] Drug interaction between celecoxib and methotrexate in organic anion transporter 3-transfected renal cells and in rats in vivo. (2010)
  • Author(s): Maeda A, Tsuruoka S
  • Journal Title: Eur J Pharmacol. 640 Pages: 168-171
  • NAID: 120007137989
  • Peer Reviewed
• [Journal Article] Drug interaction between celecoxib and methotrexate in organic anion transporter 3-transfected renal cells and in rats in vivo. (2010)
  • Author(s): Maeda A, Tsuruoka S., et al
  • Journal Title: Eur J Pharmacol Volume: 640 Pages: 168-171
  • NAID: 120007137989
  • Peer Reviewed
• [Journal Article] Recovery from acidosis : changes in anion exchanger distribution and expression are major components of reversible adaptation to metabolic acidosis in the cortical collecting duct. (2010)
  • Author(s): Purkerson JM, Tsuruoka S., et al.
  • Journal Title: Kidney Int. Volume: 78 Pages: 993-1005
  • Peer Reviewed
• [Journal Article] tatins inhibited erythropoietin-induced proliferation of rat vascular smooth muscle cells (2010)
  • Author(s): Kaneda T, Tsuruoka S, et al
  • Journal Title: Eur J Pharmacol Volume: 649 Pages: 38-43
  • Peer Reviewed
• [Journal Article] Hypertension Induced by Erythropoietin Has a Correlation With Truncated Erythropoietin Receptor mRNA in Endothelial Progenitor Cells of Hemodialysis Patients. (2009)
  • Author(s): Ioka T, Tsuruoka S
  • Journal Title: Clin Pharmacol Ther. 86(2) Pages: 154-159
  • Peer Reviewed
• [Journal Article] Basolateral Na(+)/H(+) exchange maintains potassium secretion during diminished sodium transport in the rabbit cortical collecting duct. (2009)
  • Author(s): Muto S, Tsuruoka S
  • Journal Title: Kidney Int. 75(1) Pages: 25-30
  • Peer Reviewed
• [Journal Article] Hypertension Induced by Erythropoietin Has a Correlation With Truncated Erythropoietin Receptor mRNA in Endothelial Progenitor Cells of Hemodialysis Patients (2009)
  • Author(s): Ioka T, Tsuruoka S, Ito C, Iwaguro H, Asahara T, Fujimura F, Kusano E.
  • Journal Title: Clin Pharmacol Ther. 86(2) Pages: 154-9
  • Peer Reviewed
• [Journal Article] Basolateral Na(+)/H(+) exchange maintains potassium secretion during diminished sodium transport in the rabbit cortical collecting duct (2009)
  • Author(s): Muto S, Tsuruoka S, Miyata Y, Fujimura A, Kusano E, Wang W, Seldin D, Giebisch G.
  • Journal Title: Kidney Int. 75 (1) Pages: 25-30
  • Peer Reviewed
• [Journal Article] Basolateral Na(+)/H(+) exchange maintains potassium secretion during diminished sodium transport in the rabbit cortical collecting duct. (2009)
  • Author(s): Muto S, Tsuruoka S., et al
  • Journal Title: Kidney Int. 75 Pages: 25-30
  • Peer Reviewed
• [Journal Article] Hypertension Induced by Erythropoietin Has a Correlation With Truncated Erythropoietin Receptor mRNA in Endothelial Progenitor Cells of Hemodialysis Patients. (2009)
  • Author(s): Ioka T, Tsuruoka S., et al.
  • Journal Title: Clin.Pharmacol.Ther. 86 Pages: 154-159
  • Peer Reviewed
• [Journal Article] Mechanism of Cd-induced inhibition of Na-glucose cotransporter in rabbit proximal tubule cells : Roles of luminal pH and membrane-bound carbonic anhydrase. (2008)
  • Author(s): Tsuruoka S, Swenson ER, Fujimura A, Imai M.
  • Journal Title: Nephron Physiol. 110(2) Pages: 11-20
  • NAID: 120007138513
  • Peer Reviewed
• [Journal Article] Human CYP3A4-introduced HepG2 cells : in vitro screening system of new chemicals for the evaluation of CYP3A4-inhibiting activity. (2008)
  • Author(s): Araki N, Tsuruoka S
  • Journal Title: Xenobiotica. 38 Pages: 1355-1364
  • Peer Reviewed
• [Journal Article] Evaluation of the interaction between nonsteroidal anti-inflammatory drugs and methotrexate using human organic anion transporter 3-transfected cells. (2008)
  • Author(s): Maeda A, Tsuruoka S
  • Journal Title: Eur J Pharmacol. 31;596 Pages: 166-172
  • NAID: 120007138515
  • Peer Reviewed
• [Journal Article] Mechanism of Cd-induced inhibition of Na-glucose cotransporter in rabbit proximal tubule cells : Roles of luminal pH and membrane-bound carbonic anhydrase (2008)
  • Author(s): Tsuruoka S, Swenson ER, Fujimura A, Imai M.
  • Journal Title: Nephron Physiol 110 (2) Pages: 11-20
  • NAID: 120007138513
  • Peer Reviewed
• [Journal Article] Mechanism of Cd-induced inhibition of Na-glucose cotransporter in rabbit proximal tubule cells: Roles of luminal pH and membrane-bound carbonic anhydrase. (2008)
  • Author(s): Tsuruoka S, Swenson ER, Fujimura A, Imai M.
  • Journal Title: Nephron Physiol. 110 (2) Pages: 11-20
  • NAID: 120007138513
  • Peer Reviewed
• [Journal Article] Dosing time-dependent variation of bone resorption by cyclosporin A in rats' femurs. (2007)
  • Author(s): Tsuruoka S, Kaneda T, Maeda A, Ioka T, Fujimura A.
  • Journal Title: Eur J Pharmacol 564 Pages: 226-231
  • Peer Reviewed
• [Journal Article] TRPV4 as a flow sensor in flow-dependent K+ secretion from the cortical collecting duct. (2007)
  • Author(s): Taniguchi J, Tsuruoka S, Mizuno A, Sato J, Fujimura A, Suzuki M.
  • Journal Title: Am J Physiol Renal Physiol 292
  • Peer Reviewed
• [Journal Article] TRPV4 as a flow sensor in flow-dependent K+secretion from the cortical collecting duct. (2007)
  • Author(s): Taniguchi J, Tsuruoka S, ほか4名
  • Journal Title: Am J Physiol Renal Physiol 292
  • Peer Reviewed
• [Journal Article] Clearance of imidapril, an Angiotensin-converting enzyme inhibitor, during hemodialysis in hype (2007)
  • Author(s): Tsuruoka S, 他6名
  • Journal Title: J Clin Pharmacol 47 Pages: 259-263
  • Peer Reviewed
• [Journal Article] Dosing time-dependent variation of bone resorption by cyclosporin A in rats' femurs. (2007)
  • Author(s): Tsuruoka S, 他6名
  • Journal Title: Eur J Pharmacol 564 Pages: 226-231
  • Peer Reviewed
• [Presentation] Drug interaction between celecoxib and methotrexate in organic anion transporter 3-transfected renal cells and in rats. (2010)
  • Author(s): Maeda A, Tsuruoka S
  • Organizer: American Society of Nephrology's 43rd Annual Renal Week
  • Place of Presentation: Denver CO, USA
• [Presentation] Future blood purification system for AKI with hepatic failure . (2010)
  • Author(s): Tsuruoka S, Omasa T, Enosawa S, Yamagata K.
  • Organizer: International Session of The 55th Congress of Japanese Society for Dialysis Therapy
  • Place of Presentation: Kobe, Hyogo
• [Presentation] Future blood purification system for AKI with hepatic failure. (2010)
  • Author(s): Tsuruoka S., et al.
  • Organizer: International Session of The 55th Congress of Japanese Society for Dialysis Therapy
  • Place of Presentation: Kobe, Hyogo
• [Presentation] Dosing Time-Dependent Variation of Bone Resorption by Cyclosporin A in Rats Femurs. (2009)
  • Author(s): Tsuruoka S, Kaneko S, Yamagata K, Fujimura A
  • Organizer: American Society of Nephrology's 42nd Annual Renal Week
  • Place of Presentation: San Diego CA, USA
• [Presentation] Dosing Time-Dependent Variation of Bone Resorption by Cyclosporin A in Rats Femurs (2009)
  • Author(s): Tsuruoka S, Kaneko S, Yamagata K, Fujimura A.
  • Organizer: American Society of Nephrology's 42nd Annual Renal Week
  • Place of Presentation: San Diego CA, USA
• [Presentation] Dosing Time-Dependent Variation of Bone Resorption by Cyclosporin A in Rats Femurs. (2009)
  • Author(s): Tsuruoka S., et al.
  • Organizer: American Society of Nephrology's 42nd Annual Renal Week,
  • Place of Presentation: San Diego CA, USA
• [Presentation] Evaluation of the interaction between nonsteroidal anti-inflammatory drugs and methotrexate using human organic anion transporter 3-transfected cells. (2008)
  • Author(s): Maeda A, Tsuruoka S
  • Organizer: American Society of Nephrology's 41st Annual Renal Week
  • Place of Presentation: Philadelphia, PA, USA
• [Presentation] Statin suppresses erythropoietin (EPO)-induced proliferation of vascular smooth muscle cells in vitro. (2008)
  • Author(s): Kaneda A, Tsuruoka S, Fujimura A
  • Organizer: American Society of Nephrology's 41st Annual Renal Week
  • Place of Presentation: Philadelphia, PA, USA
• [Presentation] Plasticity of Intercalated cells in the Cortical Collecting Duct : Amelioration of Acidosis Restores the Phenotype of beta-intercalated cells. (2008)
  • Author(s): Purkerson JM, Tsuruoka S, Schwartz GJ.
  • Organizer: American Society of Nephrology's 41st Annual Renal Week
  • Place of Presentation: Philadelphia,PA, USA
• [Presentation] スタチンはエリスロポエチンによる培養血管平滑筋細胞増殖を抑制する (2008)
  • Author(s): 金田多絵、鶴岡秀一、藤村昭夫
  • Organizer: 第51回日本腎臓学会学術総会
  • Place of Presentation: 福岡
• [Presentation] Statin suppresses erythropoietin (EPO)-induced proliferation of vascular smooth muscle cells in vitro (2008)
  • Author(s): Kaneda A, Tsuruoka S, Fujimura A.
  • Organizer: American Society of Nephrology's 41st Annual Renal Week
  • Place of Presentation: Philadelphia, PA, USA
• [Presentation] Statin suppresses erythropoietin (EPO)-induced proliferation of vascular smooth muscle cells in vitro. (2008)
  • Author(s): Kaneda A, Tsurupka S, Fujimura A.,
  • Organizer: American Society of Nephrology's 41st Annual Renal Week,
  • Place of Presentation: Philadelphia, PA, USA
• [Presentation] Klothoマウス(K)は接合尿細管(CNT)のPTH依存性Ca再吸収能が消失している。 (2007)
  • Author(s): 鶴岡 秀一, 他6名
  • Organizer: 第49回日本腎臓学会学術総会
  • Place of Presentation: 浜松
  • Year and Date: 2007-05-26
• [Presentation] Mechanism of cadmium(Cd)-induced Na-glucose cotransporter inhibition in isolated perfused rabbit proximal tubule cells : Roles of luminal pH and luminal membrane-bound carbonic anhydrase (CA). (2007)
  • Author(s): Tsuruoka S, Swenson ER, Fujimura A, Imai M.
  • Organizer: American Society of Nephrology's 40th Annual Renal Week
  • Place of Presentation: San Francisco CA, USA
• [Presentation] Erythropoietin-related cGMP production inversely correlated with the ratio of EPO receptor subtype mRNA in circulating endothelial progenitor cells of HD patients and HUVECs. (2007)
  • Author(s): Ioka T., Tsuruoka S.
  • Organizer: American Society of Nephrology's 40th Annual Renal Week
  • Place of Presentation: San Francisco CA, USA