title: Homocysteine-lowering and cardiovascular disease outcomes in kidney transplant recipients: primary results from the Folic Acid for Vascular Outcome Reduction in Transplantation trial.
abstract: BACKGROUND
  Kidney transplant recipients, like other patients with chronic kidney disease, experience excess risk of cardiovascular disease and elevated total homocysteine concentrations. Observational studies of patients with chronic kidney disease suggest increased homocysteine is a risk factor for cardiovascular disease. The impact of lowering total homocysteine levels in kidney transplant recipients is unknown.
  
  
  RESULTS
  In a double-blind controlled trial, we randomized 4110 stable kidney transplant recipients to a multivitamin that included either a high dose (n=2056) or low dose (n=2054) of folic acid, vitamin B6, and vitamin B12 to determine whether decreasing total homocysteine concentrations reduced the rate of the primary composite arteriosclerotic cardiovascular disease outcome (myocardial infarction, stroke, cardiovascular disease death, resuscitated sudden death, coronary artery or renal artery revascularization, lower-extremity arterial disease, carotid endarterectomy or angioplasty, or abdominal aortic aneurysm repair). Mean follow-up was 4.0 years. Treatment with the high-dose multivitamin reduced homocysteine but did not reduce the rates of the primary outcome (n=547 total events; hazards ratio [95 confidence interval]=0.99 [0.84 to 1.17]), secondary outcomes of all-cause mortality (n=431 deaths; 1.04 [0.86 to 1.26]), or dialysis-dependent kidney failure (n=343 events; 1.15 [0.93 to 1.43]) compared to the low-dose multivitamin.
  
  
  CONCLUSIONS
  Treatment with a high-dose folic acid, B6, and B12 multivitamin in kidney transplant recipients did not reduce a composite cardiovascular disease outcome, all-cause mortality, or dialysis-dependent kidney failure despite significant reduction in homocysteine level.
authors.affiliation: Rhode Island Hospital, 110 Lockwood Street, Providence, RI 02903, USA. abostom@lifespan.org
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Bostom
authors.forename: Myra A
authors.initials: MA
authors.lastname: Carpenter
authors.forename: John W
authors.initials: JW
authors.lastname: Kusek
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Levey
authors.forename: Lawrence
authors.initials: L
authors.lastname: Hunsicker
authors.forename: Marc A
authors.initials: MA
authors.lastname: Pfeffer
authors.forename: Jacob
authors.initials: J
authors.lastname: Selhub
authors.forename: Paul F
authors.initials: PF
authors.lastname: Jacques
authors.forename: Edward
authors.initials: E
authors.lastname: Cole
authors.forename: Lisa
authors.initials: L
authors.lastname: Gravens-Mueller
authors.forename: Andrew A
authors.initials: AA
authors.lastname: House
authors.forename: Clifton
authors.initials: C
authors.lastname: Kew
authors.forename: Joyce L
authors.initials: JL
authors.lastname: McKenney
authors.forename: Alvaro
authors.initials: A
authors.lastname: Pacheco-Silva
authors.forename: Todd
authors.initials: T
authors.lastname: Pesavento
authors.forename: John
authors.initials: J
authors.lastname: Pirsch
authors.forename: Stephen
authors.initials: S
authors.lastname: Smith
authors.forename: Scott
authors.initials: S
authors.lastname: Solomon
authors.forename: Matthew
authors.initials: M
authors.lastname: Weir
mesh_terms: D000328:Adult; D000368:Aged; D001161:Arteriosclerosis / Q000401:mortality / Q000517:prevention & control; D002318:Cardiovascular Diseases / Q000401:mortality / Q000517:prevention & control*; D016757:Death, Sudden, Cardiac / Q000453:epidemiology / Q000517:prevention & control; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D005500:Follow-Up Studies; D006801:Humans; D020138:Hyperhomocysteinemia / Q000188:drug therapy* / Q000401:mortality; D053208:Kaplan-Meier Estimate; D007676:Kidney Failure, Chronic / Q000401:mortality / Q000601:surgery; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000401:mortality / Q000517:prevention & control; D012307:Risk Factors; D040242:Risk Reduction Behavior; D020521:Stroke / Q000401:mortality / Q000517:prevention & control; D014803:Vitamin B Complex / Q000008:administration & dosage*
chemical_list: D014803:Vitamin B Complex; D005492:Folic Acid