Desferrioxamine improves burst-forming unit-erythroid (BFU-E) proliferation in haemodialysis patients

In chronic renal failure, desferrioxamine (DFO) may improve erythropoiesis independent from its aluminium (Al) chelating effect. The mechanism of this action is still unknown.

To verify whether DFO influences proliferation of erythropoietic precursors, we studied 10 patients on chronic haemodialysis, free from malignancies or other haematological diseases, iron deficiency, bone marrow fibrosis, and Al toxicity. Al accumulation was excluded by the DFO test. Peripheral blood samples were drawn for basal burst-forming unit erythroid (BFU E) assay. Mononuclear cells were isolated by density gradient centrifugation with Ficoll Hypaque, and incubated for 15 days with three different experimental conditions: (a) low-dose recombinant human erythropoietin (rHuEpo) (3 U/ml); (b) high dose rHuEpo, (30 U/ml); (c) both DFO (167 microg/ml) and rHuEpo (3 U/ml). We determined TIBC, transferrin, ferritin, reticulocytes, hypochromic erythrocytes, soluble transferrin receptor (sTR), haemoglobin (Hb), and haematocrit (Hct) at baseline and then every 14 days. Patients received 5 mg/kg DFO infused during the last hour of each dialysis session for 6 weeks; six patients remained in the study for an additional 6 more weeks. BFU E assays were set up after 6 and 12 weeks of DFO therapy.

At baseline DFO had small 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 proliferation 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 rHuEpo, P<0.01; 98.75+/-32 vs 45.15+/-27 DFO culture, P<0.01). Moreover, the increase in BFU E proliferation was significant greater with DFO culture than standard culture (P<0.01). The same trend was found at the third BFU E assay, performed in only six patients, when all culture conditions showed a further increase of erythroid precursor proliferation. However, the DFO culture was not significantly greater than the standard culture, while the high-dose rHuEpo was significantly greater than the DFO culture. Patients in group I (n=10), had a significant increase in reticulocytes (1.5+/-0.6 vs 1.72+/-0.3, P<0.01) and of hypochromic erythrocytes (HE) (5.6+/-5.1 vs 14.4+/-12.7, P<0.01), while sTR, Epo, Hb, and Hct were only minimally increased. Ferritin decreased significantly (448+/-224 vs 196+/-215, P<0.01) and TIBC and transferrin were unchanged.

Thus DFO increases erythroid activity 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.