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2002 Fiscal Year Final Research Report Summary

Toward better dialysis compatibility: Advances in the biochemistry and pathophysiology of the peritoneal membranes

Research Project

Project/Area Number 13307031
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionTokai University

Principal Investigator

MIYATA Toshio  Tokai University, Medical Research Institute, Associate professor, 総合医学研究所, 助教授 (10222332)

Co-Investigator(Kenkyū-buntansha) KUROKAWA Kiyoshi  Tokai University , Medical Research Institute, Professor', 総合医学研究所, 教授 (30167390)
Project Period (FY) 2001 – 2002
Keywordsreactive carbonvl compound / advanced glycation end product / carbonyl stress / irreversible protein modification / glyoxalase / carbonyl trap bead / peritoneal dialysis
Research Abstract

Peritoneal solute transport progressively increases with time on PD, enhances the dissipation of the osmotic gradient, and eventually reduces ultrafiltration capacity. Functionally, the changes of the failing peritoneal membrane are best described as an increased functional area of exchange for small solutes between blood and dialysate. Histologically, these events are associated with vascular proliferation and structural changes of pre-existing vessels. Gathered evidence, including informations on the composition of peritoneal cavity fluids and its dependence on the uremic environment, have cast a new light on the molecular mechanisms of decline in peritoneal membrane function. Chronic uremia per se modifies the peritoneal membrane and increases the functional area of exchange for small solutes. Biochemical alterations in the peritoneum inherent to uremia might be, at least in part, accounted for by severe reactive carbonyl compounds overload originating both from uremic circulation and PD fluid ("peritoneal carbonyl, stress"). The molecular events associated with long-term PD are similar but more severe than those present in chronic uremia without PD, including modifications of nitric oxide synthase (NOS) and angiogenic growth factors expression, and advanced glycation and lipoxidation of the peritoneal proteins. Furthermore, the progresses made in the dissection of the molecular events leading to peritoneal membrane failure open new avenues to develop a safe, more biocompatible peritoneal dialysis technologies, i.e., the glyoxalase detoxification system and RCO trapping bead.

  • Research Products

    (72 results)

All Other

All Publications (72 results)

  • [Publications] Takeda A, et al.: "Neuronal and glial advanced glycation end poduct [N^ε-(carboxymethyl)lysine] in Alzheimer's disease brains"Acta Neuropathol. 101. 27-35 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hou FF, et al.: "β2-Microglobulin modified with advanced glycation end products delays monocyte apoptosis and induces differenciation into macrophage-like cells"Kidney Int. 59. 990-1002 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyata T, et al.: "Reactive carbonyl compound-related uremic toxicity (carbonyl stress)"Kidney Int. 59[Suppl 78]. 25-31 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ueda Y, et al.: "Does removal of glucose lower the carbonyl stress of glucose containing peritoneal dialysis? : effect of dwell time on icodextrin and amino acid PD fluids"Kidney Int. 58. 2518-2524 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamada K, et al.: "Clusterin is up-regulated in glomerular mesangial cells in complement-mediated injury"Kidney Int. 59. 137-146 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyata T, et al.: "Reactive carbonyl compounds as uremic toxins"Contrib Nephrol. 133. 71-80 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyata T, et al.: "Advanced glycation and lipoxidation end products : reactive carbonyl compounds-related uraemic toxicity"Nephrol Dial Transplant. 16[Suppl 4]. 8-11 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nangaku M, et al.: "Cloning of rodent megsin revealed its up-regulation on mesangioproliferative nephritis"Kidney Int. 60. 641-652 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shao J, et al.: "Protective role of nitric oxide in a model of thrombotic microangiopathy in rats"J Am Soc Nephrol. 12. 2088-2097 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Inagi R, et al.: "Specific tissue distribution of megsin, a novel serpin, in the glomerulus and its up-regulation in IgA nephropathy"Biochem Biophys Res Commun. 286. 1098-1106 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Suzuki D, et al.: "Carbonyl Stress, Type-2 diabetic nephropathy in Japan from bench to bedside"Contributions to Nephrology. 13. 36-45 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Combet S, et al.: "Chronic uremia induces permeability changes, increased nitric oxide synthase expression, and structural modifications in the peritoneum"J Am Soc Nephrol. 12. 2146-2157 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akhand AA, et al.: "Glyoxal and methylglyoxal induce aggergation and inactivation of ERK in human endothelial cells"Free Radic Biol Med. 15. 1228-1235 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyata T, et al.: "Glyoxalase I deficiency is associated with an unusual level of advanced glycation end products in a hemodialysis patient"Kidney Int. 60. 2351-2359 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Wada T, et al.: "Cloning and characterization of a novel subunit of protein serine/threonine phosphatase 4 from mesangial cells"J Am Soc Nephrol. 12. 2601-2608 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Chen J, et al.: "Delayed branching of endothelial capillary cords in glycated collagens is mediated by the early induction of PAI-1"Am J Physiol. 281. 71-80 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Morimoto K, et al.: "Cytoprotective role of heme oxygenase (HO)-1 in human kidney with various renal diseases"Kidney Int. 60. 1858-1866 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Zoccali C, et al.: "Pentosidine, carotid atherosclerosis and alterations in left ventricular geometry in hemodialysis patients"J Nephrol. 14. 293-298 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Asano M, et al.: "Renal proximal tubular metabolism of protein-linked pentoisidine, an advanced glycation end product"Nephron. 91. 688-694 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Inagi R, et al.: "Efficient detoxification of carbonyl stress by the gloxalase system in peritoneal dialysis"Kidney Int. 62. 679-687 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyata T, et al.: "Angiotensine II receptor antagonist and angiotensine converting enzyme (ACE) inhibitor scavenge oxidative radicals and lower the formation of advanced glycation end products"J Am Soc Nephrol. 13. 2478-2487 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyata T, et al.: "Towards better dialysis compatibility : Advances in the biochemistry and pathophysiology of the peritoneal membranes"Kidney Int. 61. 375-386 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Dei R, et al.: "Lipid peroxidation and advanced glycation endproducts in the brain in normal aging and in alzheimer's disease"Acta Neuropathol. 104. 113-122 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Panuccio V, et al.: "Low parathyroid hormone and pentosidine in hemodialysis patients"Am J Kid Dis. 40. 810-815 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kurokawa K, et al.: "Perspectives of chronic renal failure"Nephrology. 7. 145-150 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ishibashi Y, et al.: "Glucose dialysate induces mitochondrial DNA damage in peritoneal mesothelial cells"Perit Dial Int. 22. 11-21 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kurokawa K, et al.: "Current issues and future perspectives of chronic renal failure"J Am Soc Nephrol. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyata T, et al.: ""Carbonyl Stress" and long-term uremic complications"Advanced in Nephrology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kurokawa K, et al.: "Future perspectives of chronic renal failure"Am J Kidney Dis. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyata T, et al.: "Progressive mesangial expansion and hypercellularity in transgenic mice of mesangial cell-predominant serpin, megsin"J Clin Invest. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyata T, et al.: "Inhibition of AGE formation : angiotensine converting enzyme inhibitor/angiotensin type 2 receptor blocker"Arch Biochem Biophy. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyata T, et al.: "Advanced glycation end products in chronic renal failure"Advances in Renal Replacement Therapy. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyata T, et al.: "Massry and Glassock's Text Book of Nephrology"Alterations in nonenzymatic biochemistry of carbohydrates and lipids in uremia. 1275-1278 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyata T, et al.: "Nutritional Management of Renal Disease"Carbonyl stress in uremia. 1275-1278 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyata T.: "Bulletin et Memoires de l'Academie royale de Medecine de Belgique"Alterations of non-enzymatic biochemistry in uremia, diabetes, and atherosclerosis (《carbonyl stress》). PALAIS DES ACADEMIES 1000 BRUXELLES. 189-198 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nangaku M, et al.: "Forum Issue of ARS"Relevance of oxidative and carbonyl stress in uremia (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takeda A et al: "Neuronal and glial advanced glycation end poduct [Nε-(carboxymethyl) lysine] in Alzheimer's disease brains"Acta Neuropathol. 101. 27-35 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hou FF et. al: "b2-Microglobulin modified with advanced glycation end products delays monocyte apoptosis and induces differenciation into macrophage-like cells"Kidney Int. 59. 990-1002 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyata T et. al: "Carbonyl stress in Uremia: Alterations in nonenzymatic biochemistry of carbohydrates and lipids in uremia"Massry and Glassock's Text Book of Nephrology. 68. 1275-1278 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyata T et. al: "Reactive carbonyl compounds related uremic toxicity (carbonyl stress)"Kidney Int. 59[Suppl 78]. 25-31 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ueda Y et al: "Effect of dwell time on carbonyl stress using icodextrin and amino acid peritoneal dialysis fluids"Kidney Int. 58. 2518-2524 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamada K et al: "Clusterin is up-regulated in glomerular mesangial cells in complement-mediated injury"Kidney Int. 59. 137-146 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyata T et. al: "Reactive carbonyl compounds as uremic toxins"Contrib Nephrol. 133. 71-80 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyata T et. al: "Advanced glycation and lipoxidation end products: reactive carbonyl compounds-related uraemic toxicity"Nephrol Dial Transplant. 16[Suppl 4]. 8-11 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nangaku M et. al: "Cloning of rodent megsin revealed its up-regulation in mesangioproliferative nephritis"Kidney Int. 60. 641-652 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shao J et. al: "Protective role of nitric oxide in a amodel of thrombotic microangiopathy in rats"J Am Soc Nephrol. 12. 2088-2097 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Inagi R et. al: "Specific tissue distribution of megsin, a novel serpin, in the glomerulus and its up-regulation in IgA nephropathy"Biochem Biophys Res Commun. 286. 1098-1106 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suzuki D et. al: "Carbonyl Stress, Type-2 diabetic nephropathy in Japan from bench to bedside"Contributions to Nephrology. 134. 36-45 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Combet S et. al: "Chronic uremia induces permeability changes, increased nitric oxide synthase expression, and structural modifications in the peritoneum"J Am Soc Nephrol. 12. 2146-2157 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akliand AA et. al: "Glyoxal and methylglyoxal induce aggergation and inactivation of ERK in human endothelial cells"Free Radic Biol Med. 15. 1228-1235 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyata T et. al: "Glyoxalase I deficiency is associated with an unusual level of advanced glycation end products in a hemodialysis patient"Kidney Int. 60. 2351-2359 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Wada T et. al: "Cloning and characterization of a novel subunit of protein serine/threonine phosphatase 4 from mesangial cells"J Am Soc Nephrol. 12. 2601-2608 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Chen J et. al: "Delayed branching of endothelial capillary-like cords in glycated collagen is mediated by early induction of PAI-1"Am J Physiol. 281. 71-80 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Morimoto K et. al: "Cytoprotective role of heme oxygenase (HO)-1 in human kidney with various renal diseases"Kidney Int. 60. 1858-1866 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Zoccali C et. al: "Pentosidine, carotid atherosclerosis and alterations in left ventricular geometry in hemodialysis patients"J Nephrol. 14. 293-298 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyata T et. al: "Towards better dialysis compatibility: Advances in the biochemistry and pathophysiology of the peritoneal membranes"Kidney Int. 61. 375-386 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Asano M et. al: "Renal proximal tubular metabolism of protein-linked pentoisidine, an advanced glycation end product"Nephron. 91. 688-694 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Inagi R et. al: "Efficient detoxification of carbonyl stress by the gloxalase system in peritoneal dialysis"Kidney Int. 62. 679-687 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Dei R et. al: "Lipid peroxidation and advanced glycation endproducts in the brain in normal aging and in alzheimer's disease"Acta Neuropathol. 104. 113-122 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyata T et. al: "Carbonyl stress in uremia"Nutritional Managementof Renal Disease (2nd Edition). 1275-1278 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kurokawa K et. al: "Perspectives of chronic renal failure"Nephrology. 7. S145-S150 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishibashi Y et. al: "Glucose dialysate induces mitochondrial DNA damage in peritoneal mesothelial cells"Prit Dial Int. 22. 11-21 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Panuccio V et. al: "Low parathyroid hormone and pentosidine in hemodialysis patients"Am J Kid Dis. 40. 810-815 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyata T et al.: "Angiotensine II receptor antagonist and angiotensine converting enzyme(ACE) inhibitor scavenge oxidative radicals and lower the formation of advanced glycation end products"J Am Soc Nephrol. 13. 2478-2487 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyata T et. al: "Alterations of non-enzymatic biochemistry in uremia, diabetes, and atherosclerosis (《carbonyl stress》)"Bulletin et Memoires de l'Academie royale de Medecine de Belgique. 157. 189-198 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kurokawa K et. al: "Current issues and future perspectives of chronic renal failure"J Am Soc Nephrol. in press.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyata T et. al: ""Carbonyl Stress" and long-term uremic complications"Advanced in Nephrology. in press.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kurokawa K et. al: "Future perspectives of chronic renal failure"Am J Kidney Dis. in press.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyata T et. al: "Progressive mesangial expansion and hypercellulanty in transgenic mice of mesangial cell-predominant serpin, megsin"J Clin Invest. in press.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nangaku M et. al: "Relevance of oxidative and carbonyl stress in uremia"Forum Issue of ARS. in press.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyata T et. al: "Inhibition of AGE formation: angiotensine converting enzyme inhibitor/angiotensin type 2 receptor blocker"Arch Biochem Biophy. in press.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyata T et. al: "Advanced glycation end products in chronic renal failure"Advances in Renal Replacement Therapy. in press.

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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