Background: In observational studies, hyperhomocysteinemia has been found to be a risk factor for total mortality and cardiovascular events in patients with end-stage renal disease. These patients have grossly elevated homocysteine levels that can be lowered by supplementation with folic acid and vitamin B(12). We conducted a randomized clinical trial with B vitamins to reduce homocysteine levels and therefore cardiovascular events and total mortality.

Methods and results: This randomized, double-blind multicenter study was conducted in 33 dialysis centers in north and east Germany between July 2002 and July 2008. We randomly assigned 650 patients with end-stage renal disease who were undergoing hemodialysis to 2 postdialysis treatments: 5 mg folic acid, 50 microg vitamin B(12), and 20 mg vitamin B(6) (active treatment) or 0.2 mg folic acid, 4 microg vitamin B(12), and 1.0 mg vitamin B(6) (placebo) given 3 times per week for an average of 2 years. The primary outcome was total mortality; the secondary outcome was fatal and nonfatal cardiovascular events. The primary outcome occurred in 102 patients (31%) receiving the active treatment and in 92 (28%) receiving placebo (hazard ratio, 1.13; 95% confidence interval, 0.85 to 1.50; P=0.51). The secondary outcome occurred in 83 patients (25%) receiving the active treatment and in 98 (30%) receiving placebo (hazard ratio, 0.80; 95% confidence interval, 0.60 to 1.07; P=0.13).

Conclusions: Increased intake of folic acid, vitamin B(12), and vitamin B(6) did not reduce total mortality and had no significant effect on the risk of cardiovascular events in patients with end-stage renal disease. Clinical Trial Registration- URL: www.anzctr.org.au. Unique identifier: ACTRN12609000911291. URL: www.cochrane-renal.org. Unique identifier: CRG010600027.