Effetto sinergico di desferoxamina (DFO) ed eritropoietina sulla proliferazione dei precursori eritroidi nell'uremia cronica

Desferoxamine has been suggested to improve erythopoiesis in end-stage renal failure also independently by its aluminium - chelating effect. We yet proved the effect of DFO on erythroid precursor proliferation. In order to verify whether there may be a synergic action of DFO and r-HuEpo, we enrolled 11 patients treated by hemodialysis, free from other chronic or hematological diseases. All had a negative DFO test, very low serum Al levels, below 20 mcg/l, ferritin > 100 ng% and iPTH <200 pg/l. Samples were drawn for a basal erythroid precursors (Burst Forming Unit-Erythroid, BFU-E) evaluation: after isolation by Ficoll - Hypaque a 14-day incubation was carried out with: A) r- HuEpo 3u/ml: B) r-HuEpo 30 u/l and C) r-HuEpo 30 u/ml + DFO 167 mcg/ml. Patients then received DFO 5 mg/kg infused during the last hour of each dialysis session for 12 weeks. New BFU-E evaluations were set up after 2, 6 and 12 weeks of treatment. At the same points we also evaluated hemoglobin, ferritin transferrin, retycolocites, hypochronic erythrocites, soluble transferrin receptor and serum erythroprotein. As expected, high-dose r- HuEpo showed a higher proliferation versus low-dose r-HuEpo during all the phases of the study; interestingly, culture C yet basally showed an increased proliferation respect to cultures B: the same feature was found after 2, 6 and 12 weeks. Moreover, all studied cultures showed an increased proliferation after DFO therapy. Hemoglobin levels showed a slightly increase, such as reticolocites and sTR, while ferritin decreased. Thus, DFO increases eryhtroid precursors proliferation in chronic renal failure patients and shows a synergic effect with r-HuEpo: further investigation is needed, to ascertain whether such an effect may have clinical application.