Folate metabolism in renal failure.

In most patients with chronic kidney disease, provision of sufficient human recombinant erythropoietin (rHuEPO) and iron replacement therapy will effectively correct renal anaemia. Folate deficiency has been implicated as a contributory factor in renal anaemia and hyporesponsiveness to rHuEPO treatment. As such, the necessity of regular folate supplementation has been debated over the last decade. Although folate loss through dialysis is greater than by urinary excretion, these losses are easily balanced by a normal mixed diet containing 60 g protein/day. Thus, unless patients show significant folate depletion, additional supplementation of folic acid does not appear to have a beneficial effect on erythropoiesis or on responsiveness to rHuEPO therapy. However, a diagnosis of folate deficiency should be considered in patients with chronic renal insufficiency and significant elevation in mean cell volume or hypersegmented polymorphonuclear leucocytes; in patients with malnutrition or a history of alcohol abuse, or in patients hyporesponsive to rHuEPO treatment, especially when accompanied by macrocytosis. Measurements of serum folate are not necessarily indicative of tissue folate stores and red blood cell (RBC) folate measures provide a more accurate picture. Low RBC folate concentrations in these patients indicate the need for folate supplementation. Folate supplementation can also reduce elevated levels of homocysteine in dialysis patients, which may contribute to the high cardiovascular morbidity prevalent in these individuals. High-dose folate therapy (5-15 mg/day) has been shown to reduce plasma homocysteine levels by 25-30% and appears to be well tolerated provided the patient has adequate vitamin B(12) stores. Although long-term benefits of this intervention for cardiovascular protection and patient survival have yet to be established, folic acid is considered a relatively non-toxic and well-tolerated vitamin.