Intravenous ascorbic acid in hemodialysis patients with functional iron deficiency: a clinical trial

Hemodialysis (HD) patients with functional iron deficiency (FID) often develop resistance to recombinant human erythropoietin (rHuEpo). In these patients, iron therapy may be a hazard, leading to iron overload and consequently to hemosiderosis. Recent studies suggest that intravenous ascorbic acid (IVAA) may circumvent rHuEpo resistance. The aim of our study was to show the effects of IVAA on FID and whether this results in a better correction of anemia in HD patients with stable hemoglobin (Hb) concentration and FID.

Twenty-seven HD patients with serum ferritin >300 microg/l, transferrin saturation (TS) <20% and hemoglobin (Hb) <10 g/dL were selected andrandomly divided into two groups to enter a cross-over trial with IVAA. In group I IV vitamin C 500 mg was administered three times a week for three months and discontinued in the next three months of the study. Vitamin C was not given the first three months in group II (control group, first three months of the study), who then received 500 mg IV three times a week for the next three months.

Hb and TS% significantly increased (baselines vs 3 months, Hb 9.2 +/- 0.2 vs 10.0 +/- 0.3 g/dL, TS% 17.5 +/- 0.6 vs 25.7 +/- 1.7, respectively p < 0.01 and p <0.001) in group I after three months; ferritin fell significantly from 572 +/- 40 to 398 +/- 55 microg/L (p<0.004). Ten patients completed the study: mean Hb and TS% fell significantly (3 months vs final, Hb 9.9 +/- 0.3 vs 8.9 +/- 0.2 g/dL, TS% 25.1 +/- 1.2 vs 19.1 +/- 1.1, respectively p < 0.01 and p <0.001), while mean ferritin did not change. Mean Hb, ferritin and TS% remained unchanged in group II after three months. Hb and TS% mean values rose significantly (3 months vs final, Hb 9.0 +/- 0.2 vs 9.9 +/- 0.2 g/dl, TS% 18.4 +/- 1.0 vs 27.0 +/- 1.0, respectively p < 0.005 and p <0.001), and ferritin markedly decreased from 450 +/- 50 to 206 +/- 24 microg/L (p < 0.001) at the end of the study. The rHuEpo dose was kept unchanged throughout the study. Differences were analyzed after three months. Mean Hb rose (0.8 +/- 0.2 g/dL) in group I but dropped (-0.1 +/- 0.1 g/dL) (p< 0.009) in group II. Ferritin dropped in both groups (group I vs group II, -173 + /-48 vs - 33 +/- 21 microg/L) (p < 0.01) while TS% increased (group I vs group II, 8.2 +/- 1.5 vs 0.4 +/- 0.7) (p < 0.001).

IVAA may partially correct FID and consequently help rHuEpo hyporesponsive anemia.