Erythropoietic response to anemia or erythropoietin injection in uremic rats with or without functioning renal tissue.

T HE ANEMIA of uremia is the result of hemolysis and depression of red cell formation.1 Its aregenerative component has attracted considerable interest after Jacobson et al.2’54 reported the absence of ervthropoietin in the plasma of nephrectomized rats subjected to hypoxia, acute hemorrhage or cobalt administration. The same stimuli applied to rats made anuric by ureteral ligation produced erythropoietin levels comparable to those in stimidated nonuremic controls. Accordingly, the depression of red cell formation was attributed to the lack of erythropoietin and the kidney was proposed as the site of its formation. Other investigators ’4’ have not confirmed the absence of erythropoietin from the plasma of nephrectomized rats exposed to low oxygen tensions. Erslev7 found no significant erythropoietin activity in the serum of either nephrectomized or ureter-ligated rabbits subjected to bleeding. The injection of erythropoietin-containing serum or bleeding did not produce an increase in reticulocytes or erythroblastic bone marrow elements of rabbits made uremic by nephrectomy or by ureteral ligation. These controversial findings indicate a greater complexity in the depression of erythropoiesis in uremia, and its mechanism cannot be fully elucidated by assaying the plasma of uremic animals, a method on which most of the cited evidence is based. The erythropoietic response in the uremic animal itself was, therefore, studied in the present investigation with particular reference to the following questions: (1) is the depression of erythropoiesis attributable to the retention of nitrogenous waste, as measured by the blood urea concentration, or is it related to the absence of functioning renal tissue, and (2) do uremic animals respond to the injection of erythropoietin and, if so, do they also respond equally well to bleeding; i.e. a stimulus that involves the formation of erythropoietin, as vell as a respon-