Folic acid deficiency modifies the haematopoietic response to recombinant human erythropoietin in maintenance dialysis patients

Abstract

While folic acid deficiency causes macrocytic anaemia in non-renal patients, the relevance of altered folate metabolism in anaemia of end-stage renal disease and its response to rHu-EPO is less clear. Ten haemodialysis patients with macrocytic anaemia due to dietary folic acid deficiency were compared to 10 matched (age, duration of dialysis, degree of anaemia) patients with normocytic normochromic anaemia. Nineteen patients received erythropoietin-alpha intravenously thrice weekly. The study design was a prospective crossover (ABA) comparison of the effects of intravenously administered high doses of folic acid on haemoglobin levels and EPO doses, with 6 months active supplementation (B) and two periods of 6 months duration each without folic acid supplementation (A). The two patient groups did not differ at recruitment. Red blood cell folate levels were normal in patients with normocytic anaemia, but they were subnormal in all patients with macrocytic anaemia. Compared to the first period without folic acid supplementation, patients with macrocytic anaemia had significantly higher haemoglobin levels despite lower EPO doses after 6 months high-dose folic acid, and red cells had become normocytic. The removal of folic acid supplementation resulted in re-occurrence of macrocytosis and in a significantly lower response to rHu-EPO. In contrast, high-dose folic acid supplementation had no effect on response to rHu-EPO in patients with normocytic anaemia. Folic acid deficiency may occur in elderly haemodialysis patients with poor dietary folate intake without regular oral supplementation and may cause hyporesponsiveness to rHu-EPO. Macrocytosis is a simple and cheap indicator for folate deficiency in end-stage renal disease patients on maintenance dialysis.