Hyperhomocysteinaemia in end-stage renal failure patients: Effect of low-dose supplementation with folic acid

Cardiovascular disease (CVD) is a leading cause of mortality and morbidity in end-stage renal failure (ESRF) patients. In subjects with normal renal function, homocysteinaemia is an independent risk factor for CVD. We studied biochemical determinants of homocysteine (Hcys) levels in 71 ESRF patients on maintenance haemodialysis (HD) treated with recombinant human erythropoietin and supplemented with B-group vitamins. One third of subjects were supplemented with 300-500 mu g folic acid daily. A reference range for Hcys was determined in 103 apparently healthy adults without renal impairment. Although blood folate and cobalamin levels were generally in the normal range, most (82%) HD subjects had plasma Hcys levels above the reference range. Significant inverse correlations were noted between plasma Hcys and serum folate (r = -0.32, P = 0.009) and red cell folate (r = -0.33, P = 0.004). Homocysteine concentrations were 23% lower in subjects receiving folic acid supplements (33.9 [SD, 13.6] us 44.2 [SD, 26.7] mu mol/L; P = 0.075). No correlations were evident between Hcys and age, time on dialysis, serum cobalamin or measures of vitamin B-6 status (red cell aspartate transaminase or the pyridoxal effect). This study supports the supplementation of HD subjects with folic acid as a measure to reduce plasma Hcys levels and hence possibly atherogenic risk.