Studies on the mechanism of the anemia of renal insufficiency.

1. The present studies have demonstrated that the titers of erythropoietin may be elevated to varying degrees in patients with anemia associated with end-stage renal disease. However, the increase in erythropoietin titers was apparently not sufficient to meet the increase in demand for new red blood cells created by their shortened life span and the inhibitors of heme synthesis and/or erythroid colony forming cells (CFU-E). 2. Inhibitors of heme synthesis were demonstrated in the plasma of some but not all patients with anemia associated with renal disease and in rabbits 72 hrs following bilateral nephrectomy. 3. CFU-E were both increased and decreased in the bone marrows of the chronic anemic uremic rabbits, when compared with that of sham operated controls, 14 and 21 days after 5/6th nephrectomy and depended on the rate of regeneration of the renal erythropoietic and excretory functions. CFU-E in marrows of 5/6th nephrectomy rabbits were decreased after 35 days. 4. An inhibitor of CFU-E was increased in the sera from chronic anemic uremic rabbits, when compared with that of the sham-operated controls, 35 days after 5/6th nephrectomy. 5. It is possible that in the anemia of uremia in addition to inadequate production of erythropoietin there is a defect in the differentiation of the CFU-E into the heme synthesizing erythroid series due to the presence of a specific inhibitor of CFU-E and/or heme synthesis.