Recombinant erythropoietin rapidly treats anemia in ischemic acute renal failure

Background. The anemia associated with acute renal failure (ARF) is current ly treated with blood transfusions, while the anemia of chronic renal failu re is treated with recombinant erythropoietin (EPO). We hypothesized that E PO treatment during ARF could rapidly improve hemoglobin levels and be a us eful therapeutic approach. In addition, as tubular epithelial cells have EP O receptors that can mediate proliferation, enhanced recovery of renal func tion may occur with EPO use. Methods. An established rat model of ischemic ARF was studied, using either moderate or severe ischemia. EPO was administered in a dose of 500 or 3000 U/kg starting at time of ischemia. Hematocrit (Hct), serum creatinine, ret iculocyte count, and mortality rate were measured. Results. EPO treatment led to a rapid and significant increase in Hct at 48 and 72 hours after moderate ischemic renal reperfusion injury (IRI) in EPO (500 U/kg)-treated rats compared with control (saline treated) rats (mean +/- SE; 45.6 +/- 0.3% vs. 42.0 +/- 1.0%, P < 0.01) and (46.6 +/- 0.3 vs. 41 .0 +/- 1.0, P < 0.01, N = 3 per group). In severe renal IRI, EPO treatment also led to significantly increased Hct at 48 (40.0 +/- 4.4% vs. 36.8 +/- 0 .3%, P < 0.01, N = 3 per group) and 72 hours (43.5 +/- 1.5% vs. 34.7 +/- 2. 3%, P < 0.01, N = 3 per group). Higher dose (3000 U/kg) EPO led to a more p ronounced Hct increase after severe IRI at 48 hours compared with the 500 U /kg dose (43.5 +/- 0.3 vs. 40.3 +/- 0.3, P < 0.01, N = 3 per group). EPO tr eatment during moderate or severe renal IRI did not change the course of th e renal dysfunction. EPO treatment (N = 19) had a significant protective ef fect on mortality during severe IRI. In addition, loss of body weight durin g ARF was not affected by EPO therapy. Conclusions. Recombinant EPO can rapidly increase Hct and improve mortality during ARF. Human studies are warranted to evaluate the clinical applicabi lity of this important finding.