Erythropoietin enhances recovery from cisplatin-induced acute renal failure

Acute renal failure (ARF) is associated with erythropoietin (EPO) deficiency anemia. The present study was designed to determine whether the course of ARF can be altered by preventing EPO deficiency and the associated anemia. Sprague-Dawley rats were injected with a single dose of cisplatin (CP), 7 mg/kg intraperitoneally, and randomized into recombinant EPO-treated (EPO), placebo-treated (control), recombinant EPO-treated pair-fed (EPO-PF), and EPO-treated anemic (EPO-anemic) groups. They were then treated with daily injections of recombinant EPO, 100 U/kg, or placebo for 9 days. Animals in the EPO-anemic group received daily phlebotomies gauged to maintain hematocrits equal to those in the control group. Rats in the EPO-PF group were pair fed with the controls. The control and EPO-anemic groups showed a fall, whereas the EPO and EPO-PF groups showed a rise in hematocrit on day 9. Although blood volume on day 9 was significantly greater in the EPO group than in either the EPO-anemic group or the control group, it was comparable in the latter groups. An equally severe reduction in creatinine clearance (C_Cr) was found in all groups on day 4. However, measurements of C_Cr and inulin clearance on day 9 revealed a significantly greater functional recovery in the EPO, EPO-PF, and EPO-anemic groups than in the controls. The enhanced functional recovery with EPO administration was accompanied by an increased tubular regeneration and [³H]thymidine incorporation in the cortical tissue. No significant difference was found in either cortical tissue iron content or arterial blood pressure in the study groups. Thus EPO enhances recovery of CP-induced ARF. This seems to be due to a direct action of EPO at the cellular level rather than its effects on nutrition, erythrocyte mass, blood volume, blood pressure, or renal tissue iron content.