Role of erythropoietin in the anemia of renal insufficiency in man and in an experimental uremic rabbit model.

ESF deficiency is probably not a major contributing factor in the early stages of the anemia of renal insufficiency. Serum ESF titers are lower in advanced renal failure when compared to that of nonuremic anemic subjects suffering from equivalent anemia. With increasing renal insufficiency a relative ESF deficiency gains increasing importance as a pathogenic factor in reduced erythropoiesis. Kidneys without excretory function may still be erythropoietically effective, since a further increase in the anemia occurs after bilateral nephrectomy. However, a basal erythropoiesis is still maintained by extrarenal ESF production, which is also enhanced by hypoxia. ESF deficiency is compensated after successful renal transplantation. A decreased response of the bone marrow to ESF may be another factor contributing to the hypoproliferative state of erythropoiesis in uremia. As demonstrated in a chronic uremic rabbit model there may be a blockade of further differentiation of the erythroid precursors. The relationship of this blockade in differentiation to the inhibitor of heme synthesis is not clear.