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 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 microl/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.


CONCLUSIONS
This is the first demonstration of a renal protective effect of EPO on endotoxin-related renal dysfunction.
Mitra
Amit
A
University of Colorado Health Sciences Center, 4200 East 9th Ave. Box C-281, Denver, CO 80262, USA.
Bansal
Shweta
S
Wang
Wei
W
Falk
Sandor
S
Zolty
Einath
E
Schrier
Robert W
RW
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D019446:Endotoxemia / Q000150:complications / Q000188:drug therapy*; D004921:Erythropoietin / Q000627:therapeutic use*; D005919:Glomerular Filtration Rate; D007249:Inflammation; D007668:Kidney / Q000378:metabolism; D007674:Kidney Diseases / Q000150:complications / Q000188:drug therapy*; D008070:Lipopolysaccharides / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D018805:Sepsis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D004921:Erythropoietin; D009569:Nitric Oxide