Seminars in Nephrology
Volume 24, Issue 5 , Pages 426-430 , September 2004

Hyperhomocysteinemia and cardiovascular disease in uremia: The newest evidence in epidemiology and mechanisms of action

  • Alessandra F. Perna

      Affiliations

    • First Division of Nephrology, Department of Pediatrics, School of Medicine, Second University of Naples, Naples, Italy
    • Cardiovascular Research Center, School of Medicine, Second University of Naples, Naples, Italy
    • Corresponding Author InformationAddress reprint requests to: Alessandra F. Perna, MD, PhD, Division of Nephrology/Department of Pediatrics, Second University of Naples, Via Pansini 5, Ed. 17, Naples, Italy 80131
    • ,
  • Filomena Acanfora

      Affiliations

    • First Division of Nephrology, Department of Pediatrics, School of Medicine, Second University of Naples, Naples, Italy
    • Cardiovascular Research Center, School of Medicine, Second University of Naples, Naples, Italy
    • ,
  • Ersilia Satta

      Affiliations

    • First Division of Nephrology, Department of Pediatrics, School of Medicine, Second University of Naples, Naples, Italy
    • Cardiovascular Research Center, School of Medicine, Second University of Naples, Naples, Italy
    • ,
  • Cinzia Lombardi

      Affiliations

    • First Division of Nephrology, Department of Pediatrics, School of Medicine, Second University of Naples, Naples, Italy
    • Cardiovascular Research Center, School of Medicine, Second University of Naples, Naples, Italy
    • ,
  • Diego Ingrosso

      Affiliations

    • Cardiovascular Research Center, School of Medicine, Second University of Naples, Naples, Italy
    • Department of Biochemistry and Biophysics F. Cedrangolo, School of Medicine, Second University of Naples, Naples, Italy
    • ,
  • Natale G. De Santo

      Affiliations

    • First Division of Nephrology, Department of Pediatrics, School of Medicine, Second University of Naples, Naples, Italy
    • Cardiovascular Research Center, School of Medicine, Second University of Naples, Naples, Italy

References 

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  8. Perna AF , Castaldo P , Ingrosso D , et al.   Homocysteine, a new cardiovascular risk factor, is also a powerful uremic toxin . J Nephrol . 1999;12:230–240
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  10. Guttormsen AB , Ueland PM , Svarstad E , et al.   Kinetic basis of hyperhomocysteinemia in patients with chronic renal failure . Kidney Int . 1997;52:495–502
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  17. Blom HJ , De Vriese S . Why are homocysteine levels increased in kidney failure? A metabolic approach . J Lab Clin Med . 2002;139:262–268
  18. Brosnan JT . Homocysteine and the kidney . In:  Carmel R ,  Jacobsen D editor. Homocysteine in Health and Disease . Cambridge, UK: Cambridge University Press; 2001;p. 176–182
  19. Foreman JW , Wald H , Blumberg G , et al.   Homocystine uptake in isolated rat renal cortical tubules . Metabolism . 1982;31:613–619
  20. Friedman AN , Bostom AG , Selhub J , et al.   The kidney and homocysteine metabolism . J Am Soc Nephrol . 2001;12:2181–2189
  21. 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
  22. Bostom AG , Selhub J , Jacques PF , et al.   Power shortage (Clinical trials testing the “homocysteine hypothesis” against a background of folic acid-fortified cereal grain flour) . Ann Intern Med . 2001;135:133–137
  23. Clarke R . Large trials of folic acid supplementation for prevention of cardiovascular disease . J Inherit Metab Dis . 2003;26(suppl 1):10; abstr
  24. Mallamaci F , Zoccali C , Tripepi G , et al.  CREED Investigators   Hyperhomocysteinemia predicts cardiovascular outcomes in hemodialysis patients . Kidney Int . 2002;61:609–614
  25. Suliman ME , Qureshi AR , Barany P , et al.   Hyperhomocysteinemia, nutritional status, and cardiovascular disease in hemodialysis patients . Kidney Int . 2000;57:1727–1735
  26. Kalantar-Zadeh K , Block G , Humphreys MH , et al.   Reverse epidemiology of cardiovascular risk factors in maintenance dialysis patients . Kidney Int . 2003;63:793–808
  27. Hossain GS , vanThienen JV , Werstuck G , et al.   TDAG51 is induced by homocysteine, promotes detachment-mediated programmed cell death and contributes to the development of atherosclerosis in hyperhomocysteinemia . J Biol Chem . 2003;278:30317–31327
  28. Ingrosso D , Cimmino A , Perna AF , et al.   Folate treatment and unbalanced methylation and changes of allelic expression induced by hyperhomocysteinaemia in patients with uremia . Lancet . 2003;361:1693–1699
  29. Perna AF , Ingrosso D , Galletti P , et al.   Enzymatic methyl esterification of erythrocyte membrane proteins is impaired in chronic renal failure. Evidence for high levels of the natural inhibitor S-adenosylhomocysteine . J Clin Invest . 1993;91:2497–2503
  30. Perna AF , Ingrosso D , De Santo NG , et al.   Mechanism of erythrocyte accumulation of methylation inhibitor S-adenosylhomocysteine in uremia . Kidney Int . 1995;47:247–253
  31. Perna AF , D’Aniello A , Lowenson JD , et al.   D-aspartate content of erythrocyte membrane proteins is decreased in uremia (Implications for the repair of damaged proteins) . J Am Soc Nephrol . 1997;8:95–104
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  33. JakubowskiH  . Biosynthesis and reactions of homocysteine thiolactone . In:  Carmel R ,  Jacobsen D editor. Homocysteine in Health and Disease . Cambridge, UK: Cambridge University Press; 2001;p. 21–31
  34. 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
  35. Massy ZA . Potential strategies to normalize the levels of homocysteine in chronic renal failure patients . Kidney Int . 2003;63:S134–S136

PII: S0270-9295(04)00103-2

doi: 10.1016/j.semnephrol.2004.06.019

Seminars in Nephrology
Volume 24, Issue 5 , Pages 426-430 , September 2004

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