Nephrol Dial Transplant (2001) 16: 102-110
© 2001 European Renal Association-European Dialysis and Transplant Association
Effects of methionine loading on plasma and erythrocyte sulphur amino acids and sulph-hydryls before and after co-factor supplementation in haemodialysis patients
1 Divisions of Baxter Novum and Renal Medicine, Department of Clinical Science, Huddinge University Hospital 2 Sophiahemmet Dialysis Unit, Karolinska Institutet, Stockholm, Sweden
Background. Hyperhomocysteinaemia, which is potentially atherogenic, is common in chronic haemodialysis (HD) patients but the reason for this is not yet known. The methionine (Met) loading test (MLT) is used to test the capacity of homocysteine (Hcy) disposal by the trans-sulphuration pathway and thus may provide information on the metabolism of sulphur amino acids. The availability of vitamin B6 and folic acid, as co-factors for Hcy metabolism may affect the response to MLT. In the present study, we compared the effect of Met loading on plasma and erythrocyte (RBC) sulphur amino acids and sulph-hydryls before and after co-factor supplementation in healthy subjects and HD patients.
Methods. In 10 HD patients and 10 healthy subjects the effect of Met loading, 0.1 g/kg BW, on plasma and RBC methionine metabolites was studied over 7 h, before and after 4 weeks supplementation with high daily doses of vitamin B6 (200 mg) and folic acid (15 mg).
Results. MLT before vitamin supplementation in HD patients, compared to the healthy subjects, caused significantly greater increases in plasma Hcy levels (43±12 vs 15±5 µmol/l), cysteinesulphinic acid (CSA) (1.34 vs 0.36 µmol/l) and 
-glutamylcysteine (0.98±0.83 vs –01±0.42 µmol/l) and no decline in plasma cysteine (Cys) (0.5±33.9 vs -31±26 µmol/l), but no significant differences in plasma taurine, cysteinylglycine, and glutathione concentrations. In RBCs there was a small increase in Hcy levels and a more marked increase in Tau levels, with no difference between the healthy subjects and HD patients. Vitamin supplementation in pharmacological doses failed to correct the abnormal responses to MLT in the HD patients.
Conclusions. Oral methionine loading in HD patients leads to higher accumulation of Hcy and other Met metabolites in plasma and RBCs than in healthy subjects, indicating impaired metabolism of sulphur amino acids via the trans-sulphuration pathway. Supplementation with high doses of vitamin B6 and folic acid does not correct this impairment, suggesting that it most probably is not due to lack of these co-factors.
Keywords: erythrocyte; folic acid; haemodialysis; homocysteine; methionine loading test; sulphur amino acids; vitamin B6
Professor Jonas Bergström, Division of Baxter Novum and Renal Medicine, K-56, Huddinge University Hospital, Karolinska Institutet, S-14186 Stockholm, Sweden.
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