Importance of iron supply for erythropoietin therapy

BACKGROUND.: rHuEpo and iron therapy corrects renal anaemia. However, dosage,route of administration, and monitoring of iron and rHuEpo therapyin uraemic patients remains controversial. METHODS.: Therefore a 22-month i.v. iron substitution trial, subdividedinto four study periods, was initiated in 64 iron-depleted chronichaemodialysis (HD) patients receiving i.v. rHuEpo therapy. Withinthe first period (6 months) patients were treated with high-doseiron (100mg at the end of HD treatment, mean cumulative i.v.iron saccharate dosage was 2538±810 mg per patient) inorder to replete the iron stores. During the 2nd period (6 months)the available iron pool was maintained with low-dose iron byadministration of 10, 20, or 40 mg iron at each HD, dependingon haemoglobin, serum ferritin and transferrin saturation levels.During the 3rd period (4 months), the iron-replete patientswere randomized to i.v. or s.c. route of rHuEpo administration.During the 4th period (3 months) iron substitution was omittedto exclude severe iron overload. RESULTS.: In the first study period, high-dose iron therapy dramaticallyreduced the weekly rHuEpo requirement by 70% of the initialdose (from 217±179 to 62.6±70.2 U/kg/week). Inthe 2nd period iron storage pools were easily maintained. Serumferritin and transferrin saturation levels remained stable duringthis study period. Randomization for thrice-weekly i.v. or s.c.administration of rHuEpo in the 3rd study period revealed comparableefficacy for both administration routes in iron-replete patients.In well-nourished patients (serum albumin >40 g/1) withouthyperparathyroidism (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 4thstudy period, withdrawal of iron administration led to a rapiddecrease of serum ferritin and transferrin saturation levels,indicating the absence of severe iron overload. CONCLUSIONS.: Long-term thrice-weekly i.v. low-dose iron therapy (10–20mg per HD treatment) proved to be a very effective, economicaland safe treatment schedule for iron-replete HD patients. Intravenousand s.c. rHuEpo therapy was equally efficacious in iron-replete,well-nourished patients. HD patients with increased parathyroidhormone levels require significantly more rHuEpo than HD patientswith parathyroid hormone levels values <100 pg/ml).