DESFERRIOXAMINE IMPROVES BURST-FORMING UNIT-ERYTHROID (BFU-E) PROLIFERATION IN HEMODIALYSIS-PATIENTS

Background. In chronic renal failure, desferrioxamine (DFO) may improv e erythropoiesis independent from its aluminium (Al) chelating effect. The mechanism of this action is still unknown. Methods. To verify whe ther DFO influences proliferation of erythropoietic precursors, we stu died 10 patients on chronic haemodialysis, free from malignancies or o ther haematological diseases, iron deficiency, bone marrow fibrosis, a nd Al toxicity. Al accumulation was excluded by the DFO test. Peripher al blood samples were drawn for basal burst-forming unit-erythroid (BF U-E) assay. Mononuclear cells were isolated by density gradient centri fugation with Ficoll-Hypaque, and incubated for 15 days with three dif ferent experimental conditions: (a) low-dose recombinant human erythro poietin (rHuEpo) (3 U/ml); (b) high dose rHuEpo, (30 U/ml); (c) both D FO (167 mu g/ml) and rHuEpo (3 U/ml). We determined TIBC, transferrin, ferritin, reticulocytes, hypochromic erythrocytes, soluble transferri n receptor (sTR), haemoglobin (Hb), and haematocrit (Hct) at baseline and then every 14 days. Patients received 5 mg/kg DFO infused during t he last hour of each dialysis session for 6 weeks; six patients remain ed in the study for an additional 6 more weeks. BFU-E assays were set up after 6 and 12 weeks of DFO therapy. Results, At baseline DFO had s mall effect on BFU-E proliferation (33.9+/-25 vs 30.4+/-25.9) and high -dose rHuEpo had a significant effect (45.15+/-27 vs 30.4+/-25.9, P<0. 01). After 6 weeks of DFO therapy a significant increase in BFU-E prol iferation was observed in all culture conditions (78.25+/-32 vs 30.45/-25.9 standard culture, P<0.01; 110.9+/-30 vs 45.15+/-27 high dose rH uEpo, P<0.01; 98.75+/-32 vs 45.15+/-27 DFO culture, P < 0.01). Moreove r, the increase in BFU-E proliferation was significant greater with DF O culture than standard culture (P < 0.01). The same trend was found a t the third BFU-E assay, performed in only six patients, when all cult ure conditions showed a further increase of erythroid precursor prolif eration. However, the DFO culture was not significantly greater than t he standard culture, while the high-dose rHuEpo was significantly grea ter than the DFO culture. Patients in group 1 (n=10), had a significan t increase in reticulocytes (1.5+/-0.6 vs 1.72+/-0.3, P<0.01) and of h ypochromic erythrocytes (PIE) (5.6+/-5.1 vs 14.4+/-12.7, P<0.01), whil e sTR, Epo, Hb, and Hct were only minimally increased. Ferritin decrea sed significantly (448+/-224 vs 196+/-215, P<0.01) and TIBC and transf errin were unchanged. Conclusions. Thus DFO increases erythroid activi ty by BFU-E proliferation and increases reticulocytes in haemodialysis patients. Such an effect may be related to increased iron utilization . DFO may be a useful tool for anaemic patients with good iron stores and without Al overload.