Nephrology Dialysis Transplantation, Vol 13, Issue 5 1194-1199, Copyright © 1998 by Oxford University Press
F Aucella, M Vigilante, P Scalzulli, P Musto, A Crisetti, S Modoni, M Carotenuto and C Stallone
Background: In chronic renal failure, desferrioxamine
(DFO) may improve erythropoiesis independent from its aluminium (Al)
chelating effect. The mechanism of this action is still unknown.
Methods: 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 &mgr;g/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.
Results: 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
vs45.15±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 1 (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. Conclusions: 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. Key
words: desferrioxamine; erythroid progenitors; erythropoiesis;
haemodialysis
ORIGINAL ARTICLES
Desferrioxamine improves burst-forming unit-erythroid (BFU-E) proliferation in haemodialysis patients
Departments of Nephrology and Dialysis, Haematology, and Nuclear Medicine, Casa Sollieo della Sofferenza Hospital, IRCS, I-71013 San Giovanni Rotondo, (FG), Italy; Corresponding author
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