Hyperhomocysteinemia in children on renal replacement therapy

Hyperhomocysteinemia is an independent risk factor for the development of atherosclerosis in adult patients on dialysis or after kidney transplantation. There are few data on homocysteine (Hey) concentrations in children under these circumstances. The aim of our study was to evaluate plasma Hey levels and their determining factors in children on renal replacement therapy. In 29 children and adolescents on chronic dialysis therapy and in 34 children after renal transplantation (Tx) fasting total plasma Hey, red blood cell (RBC) folate, and serum vitamin B-12 levels were measured. The plasma Hey levels were expressed as number of standard deviations (SD) from mean level in age- and gender-matched controls. In dialysis patients the mean plasma Hey level was elevated (4.4+/-0.8 SDs), without significant difference between patients on hemodialysis or continuous cycling peritoneal dialysis. In the dialysis patients a negative correlation (r=-0.49) between plasma Hey levels and RBC folate concentrations was found. Oral folate supplementation was given to 8 of 21 dialysis patients, resulting in high RBC folate levels (>800 mug/ml) and normalization of the plasma Hey levels (0.4+/-0.5 SDs). In Tx patients the mean plasma Hey level was 5.6+/-1.4 SDs. Multivariate regression analysis revealed that the main factor determining Hey level after kidney Tx was creatinine clearance. Patients with normal kidney function had a mean Hey concentration of 1.69+/-0.86 compared with 10.0+/-2.2 in children with decreased function. Folate and cyclosporine levels had less significant effects on Hey concentrations. Seven patients who were evaluated while on dialysis and after a successful kidney Tx demonstrated a significant reduction in Hey levels. Children and adolescents on dialysis therapy and with impaired renal function after renal Tx have significant hyperhomocysteinemia. Oral folate supplementation normalizes the increased plasma Hey levels and should be added to the medical treatment of all children with impaired renal function.