IRON-METABOLISM INDEXES FOR EARLY PREDICTION OF THE RESPONSE AND RESISTANCE TO ERYTHROPOIETIN THERAPY IN MAINTENANCE HEMODIALYSIS-PATIENTS

A prospective study with 65 maintenance hemodialysis (MHD) patients on recombinant human erythropoietin (rHuEPO) therapy was conducted to as sess the effect of iron balance on responsiveness. An attempt to defin e the predictors of erythropoietin (EPO) response and identify the spe cific causes of EPO resistance was undertaken in the present study. Th e treatment protocol consisted of two stages, the first was rHuEPO the rapy for 6 months and the second was iron supplementation plus rHuEPO therapy in patients without response to EPO for the next 6 months. Acc ording to the hemoglobin (Hb) changes (increment exceeded 30% of basel ine or did not exceed 15% of baseline for 3 consecutive months) and wh ether or not there was an achievement of target Hb level (> 10.5 g/dl) , all patients (n = 65) were divided into EPO-responsive (n = 20) and EPO-resistant (n = 45) groups. The EPO-resistant patients were then fu rther stratified into iron-responsive (n = 29) and iron-irresponsive ( n = 16) groups. Iron metabolism and red cell indices were analyzed pri or to and following rHuEPO therapy and iron supplementation. We found the following: (1) only serum ferritin (SF) was a reliable discriminat or between the EPO-responsive (SF >300 mu g/l) and EPO-resistant (SF < 300 mu g/l) groups; (2) similarly, transferrin saturation (TFS) 25% wa s quoted as the best cut-off value between the iron-responsive (TFS <2 5%) and iron-irresponsive (TFS >25%) groups; (3) EPO-resistant patient s with TFS <25% regained proper EPO response (Hb before and 6 months a fter therapy: 7.8 +/- 0.9 vs. 10.6 +/- 0.8 g/dl, p < 0.01) and the mea n TFS increased significantly (initial TFS and peak level after therap y: 18.9 +/- 4.7 vs. 34.5 +/- 10.8%, p < 0.01) following iron therapy; (4) the cumulative incidence of TFS <25% elevated to 44.5% 6 months fo llowing initial rHuEPO therapy, and (5) there was a strong inverse rel ationship between initial TFS and the changes of Hb following iron the rapy in EPO-resistant patients (r = -0.75, p < 0.0001). By means of ea rly detection and correction of functional iron deficiency, the goal o f increment of therapeutic efficacy and prevention from unnecessarily high doses of rHuEPO can be achieved. In summary, SF >300 mu g/l equat es adequate or increased body iron stores and seems to exclude iron de ficiency in MI-ID patients. On the contrary, SF less than or equal to 300 mu g/l appears to be an insufficient diagnostic threshold for iron deficiency. Once resistance occurs during the rHuEPO therapy, in our opinion only patients with TFS <25% need iron supplementation. However , in patients with TFS >25% and resistance to EPO, further investigati ons are necessary before increasing the dose of rHuEPO to explore othe r possible conditions, such as aluminum overload, severe hyperparathyr oidism, occult blood loss or hemolysis, and episodes of infection or i nflammatory processes.