Importance of iron supply for erythropoietin therapy

Abstract

rHuEpo and iron therapy corrects renal anaemia. However, dosage, route of administration, and monitoring of iron and rHuEpo therapy in uraemic patients remains controversial. Therefore a 22-month i.v. iron substitution trial, subdivided into four study periods, was initiated in 64 iron-depleted chronic haemodialysis (HD) patients receiving i.v. rHuEpo therapy. Within the first period (6 months) patients were treated with high-dose iron (100 mg at the end of HD treatment, mean cumulative i.v. iron saccharate dosage was 2538 +/- 810 mg per patient) in order to replete the iron stores. During the 2nd period (6 months) the available iron pool was maintained with low-dose iron by administration of 10, 20, or 40 mg iron at each HD, depending on haemoglobin, serum ferritin and transferrin saturation levels. During the 3rd period (4 months), the iron-replete patients were randomized to i.v. or s.c. route of rHuEpo administration. During the 4th period (3 months) iron substitution was omitted to exclude severe iron overload. In the first study period, high-dose iron therapy dramatically reduced the weekly rHuEpo requirement by 70% of the initial dose (from 217 +/- 179 to 62.6 +/- 70.2 U/kg/week). In the 2nd period iron storage pools were easily maintained. Serum ferritin and transferrin saturation levels remained stable during this study period. Randomization for thrice-weekly i.v. or s.c. administration of rHuEpo in the 3rd study period revealed comparable efficacy for both administration routes in iron-replete patients. In well-nourished patients (serum albumin > 40 g/l) without hyperparathyroidism (parathyroid hormone levels < 100 pg/ml), 50-60 U/kg/week rHuEpo were required in contrast to > 100 U/kg/week in patients with hyperparathyroidism. In the 4th study period, withdrawal of iron administration led to a rapid decrease of serum ferritin and transferrin saturation levels, indicating the absence of severe iron overload. Long-term thrice-weekly i.v. low-dose iron therapy (10-20 mg per HD treatment) proved to be a very effective, economical and safe treatment schedule for iron-replete HD patients. Intravenous and s.c. rHuEpo therapy was equally efficacious in iron-replete, well-nourished patients. HD patients with increased parathyroid hormone levels require significantly more rHuEpo than HD patients with parathyroid hormone levels values < 100 pg/ml).