NEUTROPHIL IMPAIRMENT ASSOCIATED WITH IRON THERAPY IN HEMODIALYSIS-PATIENTS WITH FUNCTIONAL IRON-DEFICIENCY

Hemodialysis patients treated with recombinant human erythropoietin (r hEPO) need adequate iron supplementation to avoid rhEPO hyporesponsive ness due to iron deficiency, Low serum ferritin reflects absolute iron deficiency, whereas normal or high ferritin values in combination wit h low transferrin saturation (<20%) indicate functional iron deficienc y, In this study, healthy subjects (group I) were compared with intrav enous (i.v.) rhEPO-treated and i.v. iron-saccharate-treated regular he modialysis patients that were subdivided into three groups as follows: patients with serum ferritin >100 and <350 mu g/L (group II), patient s with ferritin <60 mu g/L (group III), and patients with ferritin >65 0 mu g/L but transferrin saturation <20% (group IV). Polymorphonuclear leukocyte (PMNL) parameters (phagocytosis, intracellular killing of b acteria, oxidative metabolism, glucose uptake, intracellular calcium) for each group were compared with those of multitransfused, iron-overl oaded primary hematologic patients (group V) and those of patients suf fering from hereditary hemochromatosis (group VI), Compared with PMNL obtained from healthy subjects (group I), group II hemodialysis patien ts showed mild inhibition of phagocytosis but significant inhibition o f intracellular killing of bacteria. Oxidative burst of PMNL from grou p II patients was also significantly reduced after stimulation in vitr o. These dysfunctions were not affected by absolute iron deficiency (c omparable data in group III patients). However, impairment of PMNL was markedly aggravated in group IV patients. Intracellular calcium conce ntration under basal conditions and after stimulation was not differen t, These data suggest that iron is responsible for the PMNL dysfunctio ns observed in group IV patients, The PMNL defect of group IV patients was comparable to group V and group VI patients with normal renal fun ction, suggesting again a direct inhibitory effect of iron. It is conc luded that hemodialysis patients with high ferritin but low serum iron and low transferrin saturation (''functional iron deficiency'') displ ay a significant impairment of fundamental PMNL functions during i.v. iron and rhEPO therapy. This may result in increased risk of infectiou s complications. Therefore, overtreatment of hemodialysis patients wit h i,v. iron should be avoided.