Delayed administration of darbepoetin or erythropoietin protects against ischemic acute renal injury and failure

Administration of human recombinant erythropoietin (EPO) at time of acute ischemic renal injury (IRI) inhibits apoptosis, enhances tubular epithelial regeneration, and promotes renal functional recovery. The present study aimed to determine whether darbepoetin-alfa (DPO) exhibits comparable renoprotection to that afforded by EPO, whether pro or antiapoptotic Bcl-2 proteins are involved, and whether delayed administration of EPO or DPO 6 h following IRI ameliorates renal dysfunction. The model of IRI involved bilateral renal artery occlusion for 45 min in rats (N=4 per group), followed by reperfusion for 1–7 days. Controls were sham-operated. Rats were treated at time of ischemia or sham operation (T0), or post-treated (6 h after the onset of reperfusion, T6) with EPO (5000 IU/kg), DPO (25 μg/kg), or appropriate vehicle by intraperitoneal injection. Renal function, structure, and immunohistochemistry for Bcl-2, Bcl-XL, and Bax were analyzed. DPO or EPO at T0 significantly abrogated renal dysfunction in IRI animals (serum creatinine for IRI 0.17±0.05 mmol/l vs DPO-IRI 0.08±0.03 mmol/l vs EPO-IRI 0.04±0.01 mmol/l, P=0.01). Delayed administration of DPO or EPO (T6) also significantly abrogated subsequent renal dysfunction (serum creatinine for IRI 0.17±0.05 mmol/l vs DPO-IRI 0.06±0.01 mmol/l vs EPO-IRI 0.03±0.03 mmol/l, P=0.01). There was also significantly decreased tissue injury (apoptosis, P