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NDT Advance Access published online on April 16, 2007
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfm216
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© The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Erythropoietin ameliorates renal dysfunction during endotoxaemia

Amit Mitra, Shweta Bansal, Wei Wang, Sandor Falk, Einath Zolty and Robert W. Schrier

University of Colorado Health Sciences Center, Denver, Colorado

Correspondence and offprint requests to: Robert W. Schrier, MD, Professor of Medicine, Department of Medicine, University of Colorado Health Sciences Center, 4200 East 9th Ave. Box C-281, Denver, CO 80262, USA. Email: robert.schrier{at}uchsc.edu



  Abstract

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 intraperitoneal (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 µl/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.

Keywords: acute renal failure; lipopolysaccharide; sepsis; super oxide dismutase

Received for publication: 25. 8.06
Accepted in revised form: 19. 3.07


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