The Use of Recombinant Erythropoietin in the Treatment of the Anemia of Chronic Renal Failure a

Anemia was first recognized as a complication of chronic renal failure by Richard Bright in 1836. Alan Erslev was the first to show convincingly that there was an erythropoietic stimulating factor in anemic blood,' and in 1957 Leon Jacobson and colleagues concluded that the kidney was the source of this factor,' now known as erythropoietin (Epo). The purification of human urinary Epo by Miyaki and colleagues in 19773 made it possible for Lin and colleagues in 1985,4 using genetic engineering techniques, to isolate and clone the gene for human Epo. As a result of these advances, we now better understand the pathophysiology of the anemia of chronic renal f a i l ~ r e , ~ . ~ as well as have a means by which to treat it."" This paper briefly reviews the results of therapy with recombinant human Epo (rHuEpo) and, more specifically, the effects of rHuEpo on marrow function as quantitated by ferrokinetic and other measures. Clinical trials using rHuEpo, produced by AMGen (Thousand Oaks, CA), involve anemic hemodialysis patients in the United States, Canada and Europe. In Seattle we have treated 65 patients over the past 2 years and, in all but one case, rHuEpo successfully eliminated the anemia and the need for red cell transfusions and resulted in marked clinical improvement. This experience has been confirmed recently by the results of a multicenter trial in the United States." At a dose of 150 pJkg, given 3 X /wk, the hematocrit typically increases at a rate of 1.8 volume % per week. Therefore, most anemic hemodialysis patients will reach a hematocrit of 35 within 8-12 weeks. Once the hernatocrit goal is attained, the dose of rHuEpo is decreased to 75 wkg, 3 X/wk, and readjusted at 2-4-week intervals, as necessary, to maintain a hematocrit between 33 and 38. Erythropoiesis in patients with chronic renal failure is stimulated by rHuEpo in a dose-dependent fashion. In our patients, erythropoiesis was quantitated by ferrokinetics (the erythron transfemn uptake; ETU[12]) (FIG. l ) , the reticulocyte response (FIG. 2), and by changes in the hematocrit (FIG. 3). Erythropoiesis was evaluated again in our patients after the goal hematocrit was