Hyperhomocysteinemia in hemodialysis patients: Effects of 12-month supplementation with hydrosoluble vitamins

Background. High-efficiency hemodialysis may induce a deficiency in hydroso luble vitamins. Supplementation with B-complex vitamins has been shown to l ower serum homocysteine concentrations in several groups, but relatively fe w studies have concerned hemodialysis patients. Our objectives were to dete rmine the status in B-complex vitamins in a large cohort of unsupplemented hemodialysis patients and to assess the effects of supplementation with hyd rosoluble vitamins on serum homocysteine over one year. Methods. Serum total homocysteine (tHcy), vitamin B-12, folate, pyridoxal-5 '-phosphate (P-5'-P; the active moiety of vitamin B-6), as well as red bloo d cell folate concentrations, were measured in 168 chronic dialysis patient s on three times weekly high-efficiency hemodialysis and not supplemented w ith hydrosoluble vitamins. Their methylenetetrahydrofolate reductase C677T (MTHFR) genotypes were also determined (homozygotes TT, heterozygotes CT, w ithout mutation CC). All involved patients were then supplemented with hydr osoluble vitamins (once daily by mouth, DiaVite(R); R&D Laboratories, Minne apolis, MN, USA), and half of them were randomized to receive in addition 1 0 mg intravenously of folic acid posthemodialysis (30 mg intravenously per week). Serum tHcy was monitored after 6 and 12 months of supplementation in the 140 and 128 patients available for follow-up. Results. At baseline, serum and red blood cell folate concentrations were w ithin normal limits in all patients except for two with borderline serum fo late (mean values of 21 +/- 8 and 1195 +/- 454 nmol/L), whereas serum vitam in B-12 and P-5'-P were below normal in 11 and 65 patients, respectively (m ean values of 327 +/- 215 pmol/L and 19 +/- 16 nmol/L for the 168 patients) . Initial tHcy levels were increased in all patients (mean 33.3 +/- 16.6 fo r a normal below 11.8 +/- 1.5 mu mol/L); tHcy significantly decreased to 23 .5 +/- 7.6 mu mol/L after six months (P < 0.0001 vs. baseline) and to 21.7 +/- 6.1 mu mol/L after 12 months (P < 0.0001 vs. baseline) for the entire g roup, but was normalized in only four patients at 12 months. After six mont hs, the mean reduction in tHcy was slightly but significantly greater for p atients receiving intravenous folic acid (12.2 +/- 18.5 mu mol/L) compared with patients not receiving it (8.3 +/- 9.8 mu mol/L, P < 0.05). However, a t 12 months, no difference between both subgroups persisted. When consideri ng the different genotypes, tHcy at baseline tended to be higher for TT tha n CT and CC (39.8 +/- 30.9 vs. 31.4 +/- 10.5 vs. 31.6 +/- 11.8 mu mol/L) an d decreased to respective values of 21.1 +/- 6.9 versus 21.4 +/- 6.1 versus 22.2 +/- 5.9 mu mol/L at 12 months. The impact of the addition of folic ac id to DiaVite(R) appeared particularly significant in TT patients at six mo nths. Conclusions. (1) Hyperhomocysteinemia was present in 100% of our hemodialys is patients. (2) Nearly 40% of our unsupplemented hemodialysis patients wer e deficient in vitamin B-6. (3) Supplementation with DiaVite(R) has resulte d in significant tHcy reductions for all three genotypes. (4) The impact of the proposed supplementation protocol was found after six months and was m aintained, but did not increase further after 12 months of the same regimen . (5) The addition of intravenous folic acid has been associated with a mor e pronounced decrease in tHcy in TT patients.