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AST-120 Improves Microvascular Endothelial Dysfunction in End-Stage Renal Disease Patients Receiving Hemodialysis

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Purpose: Endothelial dysfunction (ED) is a pivotal phenomenon in the development of cardiovascular disease (CVD) in patients receiving hemodialysis (HD). Indoxyl sulfate (IS) is a known uremic toxin that induces ED in patients with chronic kidney disease. The aim of this study was to investigate whether AST-120, an absorbent of IS, improves microvascular or macrovascular ED in HD patients. Materials and Methods: We conducted a prospective, case-controlled trial. Fourteen patients each were enrolled in respective AST-120 and control groups. The subjects in the AST-120 group were treated with AST-120 (6 g/day) for 6 months. Microvascular function was assessed by laser Doppler flowmetry using iontophoresis of acetylcholine (Ach) and sodium nitroprusside (SNP) at baseline and again at 3 and 6 months. Carotid arterial intima-media thickness (cIMT) and flow-mediated vasodilation were measuredat baseline and 6 months. The Wilcoxon rank test was used to compare values before and after AST-120 treatment. Results: Ach-induced iontophoresis (endothelium-dependent response) was dramatically ameliorated at 3 months and 6 months in the AST-120 group. SNP-induced response showed delayed improvement only at 6 months in the AST-120 group. The IS level was decreased at 3 months in the AST-120 group, but remained stable thereafter. cIMT was significantly reduced after AST-120 treatment. No significant complications in patients taking AST-120 were reported. Conclusion: AST-120 ameliorated microvascular ED and cIMT in HD patients. A randomized study including a larger population will be required to establish a definitive role of AST-120 as a preventive medication for CVD in HD patients.

Abstract

Purpose: Endothelial dysfunction (ED) is a pivotal phenomenon in the development of cardiovascular disease (CVD) in patients receiving hemodialysis (HD). Indoxyl sulfate (IS) is a known uremic toxin that induces ED in patients with chronic kidney disease. The aim of this study was to investigate whether AST-120, an absorbent of IS, improves microvascular or macrovascular ED in HD patients. Materials and Methods: We conducted a prospective, case-controlled trial. Fourteen patients each were enrolled in respective AST-120 and control groups. The subjects in the AST-120 group were treated with AST-120 (6 g/day) for 6 months. Microvascular function was assessed by laser Doppler flowmetry using iontophoresis of acetylcholine (Ach) and sodium nitroprusside (SNP) at baseline and again at 3 and 6 months. Carotid arterial intima-media thickness (cIMT) and flow-mediated vasodilation were measuredat baseline and 6 months. The Wilcoxon rank test was used to compare values before and after AST-120 treatment. Results: Ach-induced iontophoresis (endothelium-dependent response) was dramatically ameliorated at 3 months and 6 months in the AST-120 group. SNP-induced response showed delayed improvement only at 6 months in the AST-120 group. The IS level was decreased at 3 months in the AST-120 group, but remained stable thereafter. cIMT was significantly reduced after AST-120 treatment. No significant complications in patients taking AST-120 were reported. Conclusion: AST-120 ameliorated microvascular ED and cIMT in HD patients. A randomized study including a larger population will be required to establish a definitive role of AST-120 as a preventive medication for CVD in HD patients.

참고문헌 (41)

  1. Parfrey PS, "The clinical epidemiology of cardiac disease in chronic renal failure", J Am Soc Nephrol, 10, pp.1606~1615 (1999)
  2. Zimmermann J, "Inflammation enhances cardiovascular risk and mortality in hemodialysis patients", Kidney Int, 55, pp.648~658 (1999)
  3. Hogas SM, "Methods and potential biomarkers for the evaluation of endothelial dysfunction in chronic kidney disease: a critical approach", J Am Soc Hypertens, 4, pp.116~127 (2010)
  4. Kolluru GK, "Endothelial dysfunction and diabetes: effects on angiogenesis, vascular remodeling, and wound healing", Int J Vasc Med, 2012, pp.918267~ (2012)
  5. Corrado E, "Endothelial dysfunction and carotid lesions are strong predictors of clinical events in patients with early stages of atherosclerosis: a 24-month follow-up study", Coron Artery Dis, 19, pp.139~144 (2008)
  6. Kruger A, "Laser Doppler flowmetry detection of endothelial dysfunction in end-stage renal disease patients: correlation with cardiovascular risk", Kidney Int, 70, pp.157~164 (2006)
  7. Elherik K, "Circadian variation in vascular tone and endothelial cell function in normal males", Clin Sci (Lond), 102, pp.547~552 (2002)
  8. Brodsky SV, "Prevention and reversal of premature endothelial cell senescence and vasculopathy in obesity-induced diabetes by ebselen", Circ Res, 94, pp.377~384 (2004)
  9. Aoyama I, "An oral adsorbent ameliorates renal overload of indoxyl sulfate and progression of renal failure in diabetic rats", Am J Kidney Dis, 37(1 Suppl 2), pp.S7~S12 (2001)
  10. Dou L, "The uremic solutes p-cresol and indoxyl sulfate inhibit endothelial proliferation and wound repair", Kidney Int, 65, pp.442~451 (2004)
  11. Barreto FC, "Serum indoxyl sulfate is associated with vascular disease and mortality in chronic kidney disease patients", Clin J Am Soc Nephrol, 4, pp.1551~1558 (2009)
  12. Yu M, "Indoxyl sulfate-induced endothelial dysfunction in patients with chronic kidney disease via an induction of oxidative stress", Clin J Am Soc Nephrol, 6, pp.30~39 (2011)
  13. Celermajer DS, "Impaired endothelial function occurs in the systemic arteries of children with homozygous homocystinuria but not in their heterozygous parents", J Am Coll Cardiol, 22, pp.854~858 (1993)
  14. Cupisti A, "Responses of the skin microcirculation to acetylcholine in patients with essential hypertension and in normotensive patients with chronic renal failure", Nephron, 85, pp.114~119 (2000)
  15. Niwayama J, "Development of a new method for monitoring blood purification: the blood flow analysis of the head and foot by laser Doppler blood flowmeter during hemodialysis", Hemodial Int, 9, pp.56~62 (2005)
  16. Nilsson GE, "Evaluation of a laser Doppler flowmeter for measurement of tissue blood flow", IEEE Trans Biomed Eng, 27, pp.597~604 (1980)
  17. Tenland T, "Spatial and temporal variations in human skin blood flow", Int J Microcirc Clin Exp, 2, pp.81~90 (1983)
  18. Morris SJ, "Responses of the skin microcirculation to acetylcholine and sodium nitroprusside in patients with NIDDM", Diabetologia, 38, pp.1337~1344 (1995)
  19. Davis KR, "Microvascular vasodilator response to acetylcholine is increased in women with pre-eclampsia", BJOG, 108, pp.610~614 (2001)
  20. Schabauer AM, "Cutaneous laser Doppler flowmetry:applications and findings", Mayo Clin Proc, 69, pp.564~574 (1994)
  21. Silverman DG, "Peripheral assessment of phenylephrine-induced vasoconstriction by laser Doppler flowmetry and its potential relevance to homeostatic mechanisms", Circulation, 90, pp.23~26 (1994)
  22. Yanase T, "Evaluation of a new carotid intima-media thickness measurement by B-mode ultrasonography using an innovative measurement software, intimascope", Am J Hypertens, 19, pp.1206~1212 (2006)
  23. Owada A, "Effects of oral adsorbent AST-120 on the progression of chronic renal failure: a randomized controlled study", Kidney Int Suppl, 63, pp.S188~S190 (1997)
  24. Aoyama I, "Preventive effects of an oral sorbent on nephropathy in rats", Miner Electrolyte Metab, 25, pp.365~372 (1999)
  25. Namikoshi T, "Oral adsorbent AST-120 ameliorates endothelial dysfunction independent of renal function in rats with subtotal nephrectomy", Hypertens Res, 32, pp.194~200 (2009)
  26. Yamamoto S, "Oral activated charcoal adsorbent (AST-120) ameliorates extent and instability of atherosclerosis accelerated by kidney disease in apolipoprotein E-deficient mice", Nephrol Dial Transplant, 26, pp.2491~2497 (2011)
  27. Lee CT, "Effects of AST-120 on blood concentrations of protein-bound uremic toxins and biomarkers of cardiovascular risk in chronic dialysis patients", Blood Purif, 37, pp.76~83 (2014)
  28. Cracowski JL, "Methodological issues in the assessment of skin microvascular endothelial function in humans", Trends Pharmacol Sci, 27, pp.503~508 (2006)
  29. Kaneto H, "Role of reac-tive oxygen species in the progression of type 2 diabetes and atherosclerosis", Mediators Inflamm, 2010, pp.453892~ (2010)
  30. Witting PK, "Hydrogen peroxide promotes endothelial dysfunction by stimulating multiple sources of superoxide anion radical production and decreasing nitric oxide bioavailability", Cell Physiol Biochem, 20, pp.255~268 (2007)
  31. Ozkor MA, "Endothelium-derived hyperpolarizing factor and vascular function", Cardiol Res Pract, 2011, pp.156146~ (2011)
  32. Urakami-Harasawa L, "Importance of endothelium-derived hyperpolarizing factor in human arteries", J Clin Invest, 100, pp.2793~2799 (1997)
  33. Coats P, "Endothelium-derived hyperpolarizing factor: identification and mechanisms of action in human subcutaneous resistance arteries", Circulation, 103, pp.1702~1708 (2001)
  34. Scotland RS, "Investigation of vascular responses in endothelial nitric oxide synthase", cyclooxygenase-1 double-knockout mice: key role for endothelium-derived hyperpolarizing factor in the regulation of blood pressure in vivo, 2005, pp.111, 796~803
  35. Holowatz LA, "Mechanisms of acetylcholine-mediated vasodilatation in young and aged human skin", J Physiol, 563(Pt 3), pp.965~973 (2005)
  36. Durand S, "Prostaglandins participate in the late phase of the vascular response to acetylcholine iontophoresis in humans", J Physiol, 561(Pt 3), pp.811~819 (2004)
  37. Nakamura T, "Oral ADSORBENT AST-120 decreases carotid intima-media thickness and arterial stiffness in patients with chronic renal failure", Kidney Blood Press Res, 27, pp.121~126 (2004)
  38. Morris SJ, "Skin blood flow responses to the iontophoresis of acetylcholine and sodium nitroprusside in man: possible mechanisms", J Physiol, 496(Pt 2), pp.531~542 (1996)
  39. Farkas K, "Non-invasive assessment of microvascular endothelial function by laser Doppler flowmetry in patients with essential hypertension", Atherosclerosis, 173, pp.97~102 (2004)
  40. Brown H, "Transient hyperaemic response to assess vascular reactivity of skin: effect of locally iontophoresed acetylcholine, bradykinin, epinephrine and phenylephrine", Br J Anaesth, 90, pp.446~451 (2003)
  41. Fredriksson I, "Measurement depth and volume in laser Doppler flowmetry", Microvasc Res, 78, pp.4~13 (2009)

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