Erythropoietin ameliorates renal dysfunction during endotoxaemia

Background. Sepsis has a high mortality (50-80%) when associated with acute renal failure (ARF). Oxidant injury and proinflammatory cytokines and chemokines have been shown to increase with endotoxaemia-related ARF. Since erythropoietin (EPO) has been demonstrated to possess anti-oxidant and anti-inflammatory properties, EPO may have therapeutic efficacy for treating ARF associated with endotoxaemia. Methods. Wild-type mice were given 2.5 mg/kg of intrapentoneal (i.p.) endotoxin, lipopolysaccharide (LPS), and studied 16 h later. Thirty minutes prior to LPS, the mice were given either EPO or vehicle. Results. During endotoxaemia, EPO was found to significantly attenuate the renal dysfunction, as assessed by glomerular filtration rate (48.1 +/- 12.4 mu l/min vs 136.7 +/- 30.2, P < 0.05). Renal blood flow and mean arterial pressure were not significantly different between the two groups. The renal dysfunction during endotoxaemia was associated with a decrease in renal superoxide dismutase (SOD). The EPO-related renal protection was associated with reversal of the effects of endotoxin on renal SOD. Conclusion. This is the first demonstration of a renal protective effect of EPO on endotoxin-related renal dysfunction.