ARA290, a non-erythropoietic EPO derivative, attenuates renal ischemia/reperfusion injury
1 Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
2 Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
3 Department of Anaesthesiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
4 Department of Renal Medicine, Aarhus University Hospital, Skejby, Denmark
5 Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK
Journal of Translational Medicine 2013, 11:9 doi:10.1186/1479-5876-11-9Published: 9 January 2013
In contrast with various pre-clinical studies, recent clinical trials suggest that high dose erythropoietin (EPO) treatment following kidney transplantation does not improve short-term outcome and that it even increases the risk of thrombotic events. ARA290 is a non-erythropoietic EPO derivative and does not increase the risk of cardiovascular events, but potentially has cytoprotective capacities in prevention of renal ischemia/reperfusion injury.
Eight female Dutch Landrace pigs were exposed to unilateral renal ischemia for 45 minutes with simultaneous cannulation of the ureter of the ischemic kidney. ARA290 or saline was administered by an intravenous injection at 0, 2, 4 and 6 hours post-reperfusion. The animals were sacrificed seven days post-reperfusion.
ARA290 increased glomerular filtration rate during the observation period of seven days. Furthermore, ARA290 tended to reduce MCP-1 and IL-6 expression 15 minutes post-reperfusion. Seven days post-reperfusion ARA290 reduced interstitial fibrosis.
The improvement in renal function following renal ischemia/reperfusion and reduced structural damage observed in this study by ARA290 warrants further investigation towards clinical application.