HDCN Article Review/Hyperlink

Shemin D, Lapane KL, Hume Al, Yoburn D, Nadeau M, Bendich A, Selhub J, Rosenberg IH

High dose B vitamin treatment of hyperhomocysteinemia in dialysis patients

Kidney Int (Jan) 49:147-152 1996

Several investigators have demonstrated that moderate hyperhomocysteinemia in the general population is an independent risk factor for premature vascular disease in coronary, cerebrovascular and peripheral vessel beds. Homocysteine levels are markedly elevated in chronic dialysis patients and also appear to confer an increased risk of vascular disease. Patients with normal renal function can usually normalize homocysteine levels with folic acid supplementation in the range of 0.6 to 5 mg per day. In the study by Bostom et al., chronic maintenance dialysis patients were randomly assigned to receive either placebo or supraphysiologic doses of folate (15 mg/day), vitamin B6 (100 mg/day) and vitamin B12 (1 mg/day). All patients received standard supplementation consisting of 1 mg of folic acid, 10 mg of vitamin B6 and 12 ug of vitamin B12.

In the active treatment group, total homocysteine levels decreased from 29.5 umol/liter at baseline to 20.7 umol/liter at four weeks (29.8% decrease from baseline) and 21.9 umol/liter at eight weeks (25.8% decrease from baseline). In addition, there were increases in plasma folate (2077%), pyridoxal 5'-phosphate (the active metabolic form of vitamin B6, 173%) and vitamin B12 (188%) levels that were indicative of adequate compliance with the treatment protocol. Neither homocysteine nor plasma vitamin levels changed significantly in the placebo group during the trial. There was not a significant increase in the incidence of side effects or in serum creatinine or liver transaminase levels in the active treatment group.

Despite the decrease in total homocysteine levels in the active treatment group, only three of twelve patients with a baseline total homocysteine level greater than 20 umol/liter had a decrease in their homocysteine level to within the normal range (less than 15 umol/liter). Further studies are needed to determine the safety and efficacy of doses of folate in excess of 15 mg/day for the normalization of homocysteine elevels in dialysis patients. (Michael V. Rocco, M.D., Bowman Gray School of Medicine)