American Journal of Kidney Diseases
Volume 51, Issue 4 , Pages 549-553 , April 2008

Approaching the End of the Homocysteine Hype?

  • Gere Sunder-Plassmann, MD

      Affiliations

    • Medical University Vienna, Vienna, Austria
    • Corresponding Author InformationAddress correspondence to Gere Sunder-Plassman, MD, Department of Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, Austria.
    • ,
  • Wolfgang C. Winkelmayer, MD, ScD

      Affiliations

    • Harvard Medical School, Boston, Massachusetts
    • ,
  • Manuela Födinger, MD

      Affiliations

    • Medical University Vienna, Vienna, Austria

References 

  1. Refsum H, Smith AD, Ueland PM, et al. Facts and recommendations about total homocysteine determinations: An expert opinion. Clin Chem. 2004;50:3–32
  2. The Homocysteine Studies Collaboration. Homocysteine and risk of ischemic heart disease and stroke (A meta-analysis). JAMA. 2002;288:2015–2022
  3. Winkelmayer WC, Kramar R, Curhan GC, et al. Fasting plasma total homocysteine levels and mortality and allograft loss in kidney transplant recipients: A prospective study. J Am Soc Nephrol. 2005;16:255–260
  4. Zoccali C, Mallamaci F, Tripepi G. It is important to lower homocysteine in dialysis patients. Semin Dial. 2007;20:530–533
  5. Menon V, Sarnak MJ, Greene T, et al. Relationship between homocysteine and mortality in chronic kidney disease. Circulation. 2006;113:1572–1577
  6. Loscalzo J. The oxidant stress of hyperhomocyst(e)inemia. J Clin Invest. 1996;98:5–7
  7. Jamison RL, Hartigan P, Kaufman JS, et al. Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease: A randomized controlled trial. JAMA. 2007;298:1163–1170
  8. Jamison RL, Hartigan P, Gaziano JM, et al. Design and statistical issues in the homocysteinemia in kidney and end stage renal disease (HOST) study. Clin Trials. 2004;1:451–460
  9. Bostom AG, Shemin D, Lapane KL, et al. High dose B-vitamin treatment of hyperhomocysteinemia in dialysis patients. Kidney Int. 1996;49:147–152
  10. Sunder-Plassmann G, Födinger M, Buchmayer H, et al. Effect of high dose folic acid therapy on hyperhomocysteinemia in hemodialysis patients: Results of the Vienna Multicenter Study. J Am Soc Nephrol. 2000;11:1106–1116
  11. Wrone EM, Hornberger JM, Zehnder JL, McCann LM, Coplon NS, Fortmann SP. Randomized trial of folic acid for prevention of cardiovascular events in end-stage renal disease. J Am Soc Nephrol. 2004;15:420–426
  12. Zoungas S, McGrath BP, Branley P, et al. Cardiovascular morbidity and mortality in the Atherosclerosis and Folic Acid Supplementation Trial (ASFAST) in Chronic Renal Failure: A multicenter, randomized, controlled trial. J Am Coll Cardiol. 2006;47:1108–1116
  13. Mann JF, Sheridan P, McQueen MJ, et al. Homocysteine lowering with folic acid and B vitamins in people with chronic kidney disease: Results of the renal HOPE-2 Study. Nephrol Dial Transplant. 2008;23:645–653
  14. Bostom AG, Carpenter MA, Kusek JW, et al. Rationale and design of the Folic Acid for Vascular Outcome Reduction In Transplantation (FAVORIT) trial. Am Heart J. 2006;152:e441–e448
  15. The VITATOPS (Vitamins to Prevent Stroke) Trial: Rationale and design of an international, large, simple, randomised trial of homocysteine-lowering multivitamin therapy in patients with recent transient ischaemic attack or stroke. Cerebrovasc Dis. 2002;13:120–126
  16. Bowman L, Armitage J, Bulbulia R, Parish S, Collins R. Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH): Characteristics of a randomized trial among 12064 myocardial infarction survivors. Am Heart J. 2007;154:815–823
  17. Schnyder G, Roffi M, Pin R, et al. Decreased rate of coronary restenosis after lowering of plasma homocysteine levels. N Engl J Med. 2001;345:1593–1600
  18. Schnyder G, Roffi M, Flammer Y, Pin R, Hess OM. Effect of homocysteine-lowering therapy with folic acid, vitamin B12, and vitamin B6 on clinical outcome after percutaneous coronary intervention: The Swiss Heart Study: A randomized controlled trial. JAMA. 2002;288:973–979
  19. Durga J, van Boxtel MP, Schouten EG, et al. Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: A randomised, double blind, controlled trial. Lancet. 2007;369:208–216
  20. Liem A, Reynierse-Buitenwerf GH, Zwinderman AH, Jukema JW, van Veldhuisen DJ. Secondary prevention with folic acid: Effects on clinical outcomes. J Am Coll Cardiol. 2003;41:2105–2113
  21. Toole JF, Malinow MR, Chambless LE, et al. Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: The Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. JAMA. 2004;291:565–575
  22. McMahon JA, Green TJ, Skeaff CM, Knight RG, Mann JI, Williams SM. A controlled trial of homocysteine lowering and cognitive performance. N Engl J Med. 2006;354:2764–2772
  23. Lonn E, Yusuf S, Arnold MJ, et al. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med. 2006;354:1567–1577
  24. Ray JG, Kearon C, Yi Q, Sheridan P, Lonn E. Homocysteine-lowering therapy and risk for venous thromboembolism: A randomized trial. Ann Intern Med. 2007;146:761–767
  25. den Heijer M, Willems HP, Blom HJ, et al. Homocysteine lowering by B vitamins and the secondary prevention of deep vein thrombosis and pulmonary embolism: A randomized, placebo-controlled, double-blind trial. Blood. 2007;109:139–144
  26. Lange H, Suryapranata H, De Luca G, et al. Folate therapy and in-stent restenosis after coronary stenting. N Engl J Med. 2004;350:2673–2681
  27. Bonaa KH, Njolstad I, Ueland PM, et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med. 2006;354:1578–1588
  28. Dhar M, Bellevue R, Carmel R. Pernicious anemia with neuropsychiatric dysfunction in a patient with sickle cell anemia treated with folate supplementation. N Engl J Med. 2003;348:2204–2207
  29. Klahr S, Levey AS, Beck GJ, et al. The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease (Modification of Diet in Renal Disease Study Group). N Engl J Med. 1994;330:877–884
  30. Besarab A, Bolton WK, Browne JK, et al. The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. N Engl J Med. 1998;339:584–590
  31. Eknoyan G, Beck GJ, Cheung AK, et al. Effect of dialysis dose and membrane flux in maintenance hemodialysis. N Engl J Med. 2002;347:2010–2019
  32. Holdaas H, Fellstrom B, Jardine AG, et al. Effect of fluvastatin on cardiac outcomes in renal transplant recipients: A multicentre, randomised, placebo-controlled trial. Lancet. 2003;361:2024–2031
  33. Wanner C, Krane V, März W, et al. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med. 2005;353:238–248
  34. Singh AK, Szczech L, Tang KL, et al. Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med. 2006;355:2085–2098
  35. Suki WN, Zabaneh R, Cangiano JL, et al. Effects of sevelamer and calcium-based phosphate binders on mortality in hemodialysis patients. Kidney Int. 2007;72:1130–1137

PII: S0272-6386(08)00044-9

doi: 10.1053/j.ajkd.2008.01.007

American Journal of Kidney Diseases
Volume 51, Issue 4 , Pages 549-553 , April 2008

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