ARA290, a non-erythropoietic EPO derivative, attenuates renal ischemia/reperfusion injury

Journal of Translational Medicine

Research

Gertrude J Nieuwenhuijs-Moeke¹  Harry van Goor²  Bente Jespersen³  Petra J Ottens⁴  Henri GD Leuvenink⁴  Willem G van Rijt⁵  Rutger J Ploeg⁶ 

[1]Department of Anaesthesiology, 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 Renal Medicine, Aarhus University Hospital, Skejby, Denmark

[4]Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands

[5]Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands

[6]Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands

[7]Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands

[8]Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK

关键词: ARA290;    Pyroglutamate helix B-surface peptide;    Erythropoietin;    Ischemia/reperfusion injury;    Kidney transplantation;   

DOI  :  10.1186/1479-5876-11-9

 received in 2012-11-23, accepted in 2012-12-21,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundIn 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.MethodsEight 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.ResultsARA290 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.ConclusionsThe improvement in renal function following renal ischemia/reperfusion and reduced structural damage observed in this study by ARA290 warrants further investigation towards clinical application.

【 授权许可】

CC BY   
© van Rijt et al.; licensee BioMed Central Ltd. 2013