| Title | Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease: a randomized controlled trial. | | Author(s) | Jamison RL, Hartigan P, Kaufman JS, Goldfarb DS, Warren SR, Guarino PD, Gaziano JM, Veterans Affairs Site Investigators | | Institution | Veterans Affairs Palo Alto Health Care Systems and Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, California 94304, USA. rjamison@stanford.edu | | Source | JAMA 2007 Sep 12; 298(10):1163-70. | | MeSH | Aged
Cause of Death
Double-Blind Method
Female
Folic Acid
Homocysteine
Humans
Kaplan-Meiers Estimate
Kidney Failure, Chronic
Male
Middle Aged
Proportional Hazards Models
Pyridoxine
Renal Insufficiency, Chronic
Vascular Diseases
Vitamin B 12
Vitamin B Complex
| | Abstract | CONTEXT: High plasma homocysteine levels are a risk factor for mortality and vascular disease in observational studies of patients with chronic kidney disease. Folic acid and B vitamins decrease homocysteine levels in this population but whether they lower mortality is unknown.
OBJECTIVE: To determine whether high doses of folic acid and B vitamins administered daily reduce mortality in patients with chronic kidney disease.
DESIGN, SETTING, AND PARTICIPANTS: Double-blind randomized controlled trial (2001-2006) in 36 US Department of Veterans Affairs medical centers. Median follow-up was 3.2 years for 2056 participants aged 21 years or older with advanced chronic kidney disease (estimated creatinine clearance < or =30 mL/min) (n = 1305) or end-stage renal disease (n = 751) and high homocysteine levels (> or = 15 micromol/L).
INTERVENTION: Participants received a daily capsule containing 40 mg of folic acid, 100 mg of pyridoxine hydrochloride (vitamin B6), and 2 mg of cyanocobalamin (vitamin B12) or a placebo.
MAIN OUTCOME MEASURES: The primary outcome was all-cause mortality. Secondary outcomes included myocardial infarction (MI), stroke, amputation of all or part of a lower extremity, a composite of these 3 plus all-cause mortality, time to initiation of dialysis, and time to thrombosis of arteriovenous access in hemodialysis patients.
RESULTS: Mean baseline homocysteine level was 24.0 micromol/L in the vitamin group and 24.2 micromol/L in the placebo group. It was lowered 6.3 micromol/L (25.8%; P < .001) in the vitamin group and 0.4 micromol/L (1.7%; P = .14) in the placebo group at 3 months, but there was no significant effect on mortality (448 vitamin group deaths vs 436 placebo group deaths) (hazard ratio [HR], 1.04; 95% CI, 0.91-1.18). No significant effects were demonstrated for secondary outcomes or adverse events: there were 129 MIs in the vitamin group vs 150 for placebo (HR, 0.86; 95% CI, 0.67-1.08), 37 strokes in the vitamin group vs 41 for placebo (HR, 0.90; 95% CI, 0.58-1.40), and 60 amputations in the vitamin group vs 53 for placebo (HR, 1.14; 95% CI, 0.79-1.64). In addition, the composite of MI, stroke, and amputations plus mortality (P = .85), time to dialysis (P = .38), and time to thrombosis in hemodialysis patients (P = .97) did not differ between the vitamin and placebo groups.
CONCLUSION: Treatment with high doses of folic acid and B vitamins did not improve survival or reduce the incidence of vascular disease in patients with advanced chronic kidney disease or end-stage renal disease. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00032435. | | Language | eng | | Pub Type(s) | Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, U.S. Gov't, Non-P.H.S.
| | PubMed ID | 17848650 |
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