Effect of high-dose folic acid on hemodialysis patients with poor erythropoietin response

Erythropoietin (EPO) can improve the anemia of renal failure and may increase the demand for folic acid. The role of folic acid supplementation in dialysis patients with anemia remains controversial. We investigated whether high-dose folic acid (HDFA) can improve EPO response and macrocytic anemia (MCV ≥100 fl) in hemodialysis (HD) patients with severe anemia. Seventeen HD patients with renal anemia and poor EPO response (i.e., hematocrit ≤26% with subcutaneous EPO of 4,000 units per week) were randomized into two groups; one received 5 mg folic acid orally thrice weekly (FA5 group), and the other received 20 mg folic acid orally thrice weekly (FA20 group). Hemoglobin, hematocrit, MCV, transferrin saturation and ferritin levels, folate levels of plasma and RBC, and plasma vitamin B12 levels were measured and followed up. In the FA20 group, HDFA supplementation significantly increased the plasma and RBC folate levels, but failed to reduce the EPO dosage or increase the hematocrit value. Seven patients (5 in the FA20 group and 2 in the FA5 group) presenting with macrocytic anemia were further analyzed. Their high MCV values did not improve following HDFA supplementation. There were no differences in clinical parameters, folate levels of plasma and RBC, and plasma vitamin B12 levels between patients with and without macrocytic anemia. We conclude, therefore, that HDFA supplementation in HD patients does not improve the EPO response, nor does it improve the MCV values in patients with macrocytic anemia.