Abstract
Background and Aims
Hepcidin is a key regulatory peptide in iron homeostasis, inhibiting iron absorption by binding to ferroportin. Inflammatory mediated increase in hepcidin levels and reduced clearance in hemodialysis (HD) patients lead to functional iron deficiency ( FID) and Erythropoiesis-stimulating agent (ESA) resistance. Ascorbic acid (Vitamin C) may be used as adjuvant therapy in FID anemia through its anti-inflammatory and anti-oxidant nature, but there was limited studies investigating the direct relation between vitamin C and hepcidin level in HD patients. We Aimed to test the reducing therapeutic effect of oral vitamin C supplement on hepcidin level among hemodialysis patients with functional iron deficiency anaemia.
Method
This study is an open label randomized controlled clinical trial that was conducted in hemodialysis units of Ain Shams University hospitals, 48 prevalent HD patients with mean age of 46.48 ± 15.57 years were included ,Group 1 (study group) :31 patients [13(41.9%) males & 18(58.1%) females] who received the conventional treatment of erythropoietin stimulating agents together with oral supplementation of vitamin C 500 mg every other day dose for 3 months. Group 2 (control group): included 17 patients [8(47.1%) males and 9 (52.9%) females] who received only the conventional therapy of erythropoietin stimulating agents according to their Hb levels. The patients enrolled in the study were patients on regular conventional HD for more than 6 months with functional iron deficiency anemia, defined as: hemoglobin level <11 gm/dl, ferritin level >200 ng/ml and TSAT >20 %. Patients with history of non-renal causes of anemia including malignancy, end-stage liver disease, or chronic hypoxia, patients with evidence of active or occult bleeding, patients who received blood transfusion within the last 4 months, history of recent hospitalization or infection requiring antibiotics within the last 4 weeks and patients with evidenced iron deficiency anemia were all excluded from the study .Laboratory parameters including serum hepcidin level, highly sensitive CRP (hsCRP) titer, CBC, kidney function tests and iron indices were measured at baseline and after 3 months .
Results
Oral vitamin C supplementation in Group 1(study group) resulted in statistically significant reduction in Hepcidin levels in the study group [mean 2506.45± 1320.53 pg/ml to 1748.39 ±1432.28 pg/ml ](P=0.03), and highly significant reduction in hsCRP level [mean 8603.23 ±2547.77 ng/ml to 5611.29 ±2829.27 ng/ml](P=0.001) after 3months of treatment. On comparing the two groups regarding changes in Hepcidin levels during follow up, illustrates that vitamin C together with time resulted in significant reduction of hepcidin levels in the study group (P<0.05) by repeated measure ANOVA test (Figure 1). Comparison between the two groups regarding change in hsCRP levels during follow up showed there was a highly significant change in the mean hsCRP over time, and the mean hsCRP differed significantly between the two groups (Figure 2). A significant reduction in serum iron and ferritin levels was observed in study group after treatment vitamin C but the change of the mean of S. ferritin level didn’t differ significantly in comparison to control group . Decreased EPO requirements and elevation of hemoglobin level were observed in the study group but without a statistical significance compared to the control group, this might be attributed to the short period of vit C supplementation. There was a highly significant correlation between serum hepcidin and hsCRP (r=0.46, P<0.01) .
Conclusion : Oral Vitamin C may be promising therapy in decreasing serum hepcidin and hsCRP in prevalent hemodialysis patients with functional iron deficiency anemia.
Lowering the Erythropoietin Requirement for Dialysis Patients with Functional Iron Deficiency Using Ascorbic Acid (Vitamin C)