ANEMIA OF CHRONIC-RENAL-FAILURE - CHARACTERIZATION IN THE MOUSE AND CORRECTION WITH HUMAN RECOMBINANT ERYTHROPOIETIN

Anemia is a cardinal feature of chronic renal failure (CRF) which cont ributes significantly to the clinical syndrome of chronic uremia. We h ave conducted a detailed examination of the hematological changes in C RF in the inbred mouse strain C57BL/6J. As in the human situation, CRF mice presented major hematological changes affecting primarily the er ythroid cell series. Despite the presence of abundant iron stores in t he bone marrow, the CRF mice developed a hypoproliferative anemia of a severity commensurate with the degree of renal impairment. The levels of circulating erythropoietin (EPO) in CRF mice were not significantl y different from those in normal control littermates and were therefor e inappropriately low for the degree of anemia. In contrast acutely bl ed control mice with normal renal function showed a significant invers e correlation between the serum EPO level and hemoglobin concentration , indicating an appropriate response to anemia. The chronic administra tion of recombinant human EPO raised the hemoglobin concentration of C RF mice, a therapeutic effect which was independent of the initial deg ree of anemia. These observations suggest that this animal model has w ide applicability for the study of anemia secondary to CRF.