Hyperhomocysteinemia is related to residual glomerular filtration and folate, but not to methylenetetrahydrofolate-reductase and methionine synthase polymorphisms, in supplemented end-stage renal disease patients undergoing hemodialysis

Glomerular filtration is one of the major determinants of plasma total homo cysteine (tHcy). To evaluate the respective roles of residual glomerular fi ltration (by measuring a specific protein marker, cystatin C), genetic poly morphisms and nutritional status in tHcy blood levels in end-stage renal di sease patients (ESRD) under hemodialysis and supplemented with folate, we m easured tHcy, folate, vitamin B-12 (B-12), creatinine, cystatin C, albumin and C-reactive protein and determined the polymorphism of methylenetetrahyd rofolate reductase (MTHFR) (C677T and A1289C) and of methionine synthase (M S) (A2756G) in 114 ESRD patients before hemodialysis and 76 control subject s. All patients received a folate supplementation of 700 mug/day. Hyperhomo cysteinemia was observed in all patients and exceeded the upper normal limi t by 2-fold in 52.4% of the patients. Serum folate was significantly increa sed and the B-12 level was not different from controls. Folate, Cystatin C and creatinine were significantly correlated to tHcy, while no correlation was found between tHcy, albumin and C-reactive protein. No difference in ge notype frequency between ESRD patients and controls was found for MTHFR A12 89C and MS A2756G. The MTHFR 677TT genotype was less frequent and was assoc iated with a significantly higher tHcy level in patients. Folate and residu al glomerular filtration estimated by cystatin C and creatinine levels were two independent determinants of tHcy in ESRD patients. These data suggest that hyperhomocysteinemia is a consequence as well as a complicating factor of renal failure.