Iron metabolism in rhEPO-treated hemodialysis patients.

A number of factors have been shown to limit the response to recombinant human erythropoietin (rhEPO). One major factor appears to be an inadequate iron supply to the bone marrow. Erythropoiesis is dependent upon a continuous supply of iron to the bone marrow. The rate at which iron can be drawn from existing stores may easily limit the rate of delivery for hemoglobin synthesis. This may result in "functional iron deficiency" which is distinct from "absolute iron deficiency" caused by depletion of iron stores. At present there are three main parameters available to clinicians wishing to monitor iron status in their patients: serum ferritin and transferrin saturation (TFS), which are indirect measurements, and the percentage of hypochromic red cells, which directly reflects marrow iron status. Ferritin levels should be measured before starting rhEPO therapy to ensure adequate iron stores (> 200 microg/l), and when patients move from the correction phase to the maintenance phase of therapy (have stores become depleted during the correction phase?). In addition, ferritin levels can give an indication of iron overload following excess parenteral iron administration. The TFS represents a balance between iron supply by the stores and demand by bone marrow. A saturation below 20% probably indicates iron-deficient erythropoiesis. However, this is an indirect measure of marrow iron supply and wide fluctuations have been observed when determined at different time points. The percentage of hypochromic red blood cells is measured by flow cytometry and a hypochromic subpopulation of more than 10% (normal percentage > 2.5%) indicates iron-deficient erythropoiesis. However, not all departments have access to the required equipment. The aim of iron supplementation is to provide sufficient iron for the correction phase and replace iron losses (1,500 - 3,000 mg/year in hemodialysis patients) during the maintenance phase of rhEPO therapy. This amounts to a daily iron need in the range of 5-7 mg, which is well above the normal dietary intake and absorptive capacity of the human intestine. Therefore there is a need for intravenous iron, in particular when the patient ha absolute or functional iron deficiency, is in tolerant of oral iron, or is not complying we with the oral regimen.