RECOMBINANT-HUMAN-ERYTHROPOIETIN RESISTANCE IN IRON-REPLETE HEMODIALYSIS-PATIENTS - ROLE OF ALUMINUM TOXICITY

The present study was designed to investigate the impact of aluminum t oxicity on the response to recombinant human erythropoietin (rHuEPO) t herapy in hemodialysis patients, when iron deficiency has been correct ed or excluded. We studied 39 patients on regular hemodialysis (20 mal es and 19 females; mean age 58.8 years), who were under maintenance rH uEPO treatment for at least 6 months, and who had stable hematocrit le vels for more than 3 months. All patients had adequate iron stores and availability with serum ferritin >100 mu g/l and iron saturation >25% . They were classified into two groups: 19 poor responders, who requir ed subcutaneous rHuEPO doses >100 U/kg/week and failed to achieve the target hematocrit level of 30%, and 20 good responders, who needed dos es of less than or equal to 100 U/kg/week to maintain the target level . Serum aluminum levels including basal (Al-basal) and 44 h after desf errioxamine (DFO) infusion (Alpost-DFO), intact parathyroid hormone, a nd inflammatory and hemolytic indices were examined in both groups. Th e results showed that the mean weekly rHuEPO doses were significantly lower and the mean hematocrit levels higher in the good responders tha n in the poor responders. Although the poor responders had markedly hi gher mean Al-basal and Alpost-DFO levels, no differences were observed in the other parameters between the two groups. Furthermore, the poor responders significantly had the greater increment in the serum alumi num levels after DFO infusion (Delta Al=Alpost-DFO - Al-basal) The mea n corpuscular volume had a strong inverse correlation with Delta Al in the poor response group (r = -0.711, p < 0.001). We concluded that th e post-DFO rise of serum aluminum can be used as a means of estimating tissue stores. Subclinical aluminum toxicity may exhibit an inhibitor y effect on erythropoietic response to rHuEPO therapy.