ALUMINUM INTOXICATION IN THE RAT INDUCES PARTIAL RESISTANCE TO THE EFFECT OF RECOMBINANT-HUMAN-ERYTHROPOIETIN

Anaemia is a major complication of chronic renal failure. It is mainly due to a decrease in the production of erythropoietin and at present it can be corrected by recombinant human erythropoietin (rHuEpo). The question has arisen whether aluminium overload, which is frequently observed in uraemic patients, could exert a resistance to the effect of rHuEpo. To answer this question, we submitted two series of rats with two groups in each to an experimental aluminium intoxication. Group II rats received repeated i.p. injections of aluminium, whereas group I (control) rats were given vehicle solution alone. Subsequently, all rats were treated with identical s.c. doses of rHuEpo (100 IU/kg body-weight twice weekly). In the first series, rats were fed ad libitum whereas in the second, rats were pair-fed and received iron supplementation. In the first series, group I rats had an increase of mean haemoglobin in response to rHuEpo: 15.6 ± 0.3 vs 19.8 ± 0.3 g/dl, PÃ0.001. In contrast, group II rats had a decrease: 15.1±0.2 vs 10.1±0.8 g/dl, PÃ 0.001. However, compared to group I rats, group II rats did not gain body-weight and their plasma iron concentration was less. In the second series, mean haemoglobin concentration of group I rats increased from 15.1±0.2 to 18.9±0.3g/dl (PÃ0.001) in response to rHuEpo. In group II rats, mean haemoglobin concentration first decreased due to aluminium intoxication from 15.5±0.1 to 10.6±0.7 g/dl and then increased markedly in response to rHuEpo but did not exceed 16.0±0.7 g/dl, a value significantly less than that reached by group I (PÃ0.003). Body-weight of the latter two groups was similar. Plasma iron concentration was significantly greater in group II than group I rats (26.9±4.1 vs 15.2±2.9Imol/l, P/0.05). In conclusion, aluminium intoxication in non-uraemic rats induced a partial resistance to the haematopoietic action of rHuEpo. © 1990 European Dialysis and Transplant Association-European Renal Association.