Análisis crítico de un artículo: ¿Sirve reducir los niveles de homocisteinemia en los pacientes con insuficiencia renal avanzada?

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 Participant: 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 15 micromol/L). Intervention: Participants received a daily capsule containing 40 mg off olic 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 allow 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. 436placebo 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: clinical trials.gov Identifier: NCT00032435.