The anaemia of chronic renal failure in sheep: studies in vitro

The presence of inhibitors which accumulate during uraemia has been postulated as a significant factor in the development of anaemia in chronic renal failure (CRF). To determine whether factors in uraemic serum depress erythropoiesis, samples were obtained from sheep prior to and after surgical induction of CRF. The sera were tested in vitro for their effect on erythroid colony growth. The sheep sera were substituted for fetal calf serum (30% concentration) in cultures of serotype-matched or autologous sheep marrow cells at optimal doses of erythropoietin (Ep). Forty-two paired sera from five animals were tested against normal (22) and uraemic marrow (20). In 7/42 random pairs, erythroid colony growth was decreased by 20% in the presence of uraemic serum when compared to a normal sample from the same animal. In the remainder of the cultures, uraemic sera stimulated or supported erythroid colony growth as well as normal sera. When the results were analysed individually, serum from only one of five animals showed minimal (10%) in vitro inhibition of erythroid colony growth. This study, performed in a prospective manner utilizing compatible target cells, disputes the hypothesis that uraemic toxins significantly inhibit in vitro erythropoiesis. These data correlate with the in vivo response to Ep in this sheep model, and suggest Ep would be effective in treating the anaemia of CRF.