Resistance to recombinant human erythropoietin due to aluminium overload and its reversal by low dose desferrioxamine therapy.
Seventeen severely anaemic and transfusion-dependent haemodialysis patients with a haemoglobin less than 7 g/dl were treated with recombinant human erythropoietin (r-Hu-EPO). Aluminium toxicity was diagnosed by a positive desferrioxamine (DFO) test and bone biopsy. Seven out of eight patients without aluminium toxicity responded to r-Hu-EPO therapy. Similarly all patients with aluminium toxicity (n = 4) but pre-treated with standard dose of DFO prior to r-Hu-EPO therapy responded but none of the patients with untreated aluminium toxicity (n = 5) responded to r-Hu-EPO therapy. In order to achieve adequate response in these patients, r-Hu-EPO and DFO had to be given in combination. The dose of desferrioxamine used to reverse r-Hu-EPO resistance was less and also used for a short time. We therefore confirm r-Hu-EPO resistance owing to aluminium overload and report its successful and safe reversal with low dose DFO therapy.
Department of Renal Medicine, Royal Liverpool University Hospital, UK.
M
M
Yaqoob
R
R
Ahmad
P
P
McClelland
K A
KA
Shivakumar
D F
DF
Sallomi
I H
IH
Fahal
N B
NB
Roberts
T
T
Helliwell
D000535:Aluminum / Q000506:poisoning*; D000740:Anemia / Q000188:drug therapy* / Q000209:etiology; D003676:Deferoxamine / Q000627:therapeutic use*; D004351:Drug Resistance; D004921:Erythropoietin / Q000172:deficiency / Q000627:therapeutic use*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use; D006435:Renal Dialysis
D011994:Recombinant Proteins; D004921:Erythropoietin; D000535:Aluminum; D003676:Deferoxamine