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BACKGROUND: Hyperhomocysteinemia is a risk factor for thrombosis, a frequent complication of vascular access (VA) in hemodialysis (HD). The enzyme methylenetetrahydrofolate reductase (MTHFR) is necessary for the remethylation of homocysteine (Hcy) to methionine. It has been postulated that patients homozygous and, to a lesser extent, heterozygous for the C677T thermolabile variant of this enzyme present a reduced catalytic activity, with secondary increases in plasmatic Hcy levels (normal: 10 +/- 5 micromol/L) and an elevated risk of vascular thromboses. METHODS: Sixty-two patients on chronic HD were divided into two groups: group A (n = 23, 37.1%) was normal for the enzyme (CC); group B (n = 39, 62.9%) was heterozygous (CT). Both groups were not different according to age, sex, time on HD, hematocrits (Hct), baseline levels of Hcy, folic acid and vitamin B12. After the 1st HD session patients were started on folic acid 10 mg/day and 500 microg/week of intravenous (i.v.) methylcobalamin. RESULTS: Two years later, thrombotic events were not different between the two groups. Group A = 5 (21.7%) vs. group B = 12 (30.7%), Hcy levels were significantly different between final and baseline measurements (group A 21.5 +/- 5.2 vs. 16.6 +/- 3.9 micromol/L, p = 0.02; group B 22.1 +/- 8.9 vs. 16.1 +/- 3.9 micromol/L, p = 0.008), folic acid (group A 22.1 vs. 346.9 ng/ml, range (r) =166-527, p < 0.001; group B 19.2 vs. 218.5 ng/ml, r = 138-298, p < 0.001) and vitamin B12 (group A 1489 vs. 3192.3 pg/ml, r = 1494-4890, p = 0.01; group B 1086 vs. 1513.8 pg/ml, r = 1092-1934, p = 0.02). CONCLUSIONS: HD patients heterozygous for the C677T variant of the enzyme MTHFR can present a similar risk of thrombotic events in arteriovenous fistulae (AVF) compared to patients normal for the enzyme at a 1-yr follow-up. These results could be explained by an adequate control of Hcy levels after folic acid and methylcobalamin replacement therapy.