RT Journal
A1 Jamison RL, Hartigan P, Kaufman JS, et al
T1 Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease: A randomized controlled trial
JF JAMA
JO JAMA
YR 2007
FD September 12
VO 298
IS 10
SP 1163
OP 1170
DO 10.1001/jama.298.10.1163
UL http://dx.doi.org/10.1001/jama.298.10.1163
AB 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 ≤30 mL/min) (n = 1305) or end-stage renal disease (n = 751) and high homocysteine levels (≥ 15 μmol/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 μmol/L in the vitamin group and 24.2 μmol/L in the placebo group. It was lowered 6.3 μmol/L (25.8%; P < .001) in the vitamin group and 0.4 μmol/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