The Anaemia of Chronic Renal Insufficiency

Correction of Anaemia with Recombinant Human Erythropoietin

“…Several factors may contribute to the pathogenesis of uraemic anaemia [1][2][3][4] but the bulk of the evidence indicates that uraemic anaemia is mainly caused by an insufficient production of erythropoietin from the diseased kidneys [5], Human erythropoietin is a 166 amino acid polypep tide, heavily glycosylated, with a molecular weight of 34,000 daltons [6], The gene coding for human erythro poietin has been recently isolated [7], characterized [8] and cloned in cultured mammalian cells [9], The material secreted by these cells into the culture medium was found to be indistinguishable from native human erythropoie tin. It has been purified, tested in animals and found to be non-toxic and to stimulate the erythropoietin in a typical, dose-dependent manner [10].…”

Erythropoietic Function in Uremic Rabbits

“…From 5 to 15% of the red cells were reticulated but due to the low red cell count after bleeding the absolute number of reticulocytes was changed only insignifi cantly from the pre-operative base line values. In the normal rabbit nucleated red cells mature into adult non-rcticulatcd red cells in less than 48 hours but it is possible that this maturation time is somewhat prolonged in uremic animals (13). However, radioactive iron was found to be incorporated into red cells both 20 and 48 hours after nephrectomy (tables I and II) and it appears im probable that a severe enough maturation arrest existed to explain the presence of reticulocytes in the circulating blood up to 9 days after nephrectomy.…”

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

“…Although inadequate erythropoietin (Ep) production is a major cause of anaemia in chronic renal failure (CRF) (Fisher, 1980;Cotes, 1982), uraemic toxins or inhibitors of erythropoiesis present in serum are also said to play a significant role in the development of the anaemia. Both in vivo (Fisher et al, 1968;Scigalla et al, 1980) and in vitro (Markson & Rennie, 1956;Fisher et al, 1974;Moriyama et al, 1975;Wallner et al, 1975Wallner et al, , 1976Wallner et al, , 1977Wallner et al, , 1978Wallner& Vautrin, 1978Urabeetal, 1976;Ohno&Fisher, 1977;Ohnoetal, 1978;Freedmanet al, 198 3 ) studies of uraemic sera have supported the concept that uraemic toxins accumulate in serum to suppress erythropoiesis, and that dialysis may remove these factors (Radtke et al, 1979(Radtke et al, , 1981Gutman & Huang, 1980: Wallner & Vautrin, 1981. Only a single study has been unable to demonstrate significant inhibition of erythropoiesis in vitro (Zucker et al, 1976).…”