title: ARA290, a non-erythropoietic EPO derivative, attenuates renal ischemia/reperfusion injury.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. w.g.van.rijt@umcg.nl
authors.forename: Willem G
authors.initials: WG
authors.lastname: van Rijt
authors.forename: Gertrude J
authors.initials: GJ
authors.lastname: Nieuwenhuijs-Moeke
authors.forename: Harry
authors.initials: H
authors.lastname: van Goor
authors.forename: Bente
authors.initials: B
authors.lastname: Jespersen
authors.forename: Petra J
authors.initials: PJ
authors.lastname: Ottens
authors.forename: Rutger J
authors.initials: RJ
authors.lastname: Ploeg
authors.forename: Henri G D
authors.initials: HG
authors.lastname: Leuvenink
mesh_terms: D000818:Animals; D017931:DNA Primers; D005260:Female; D005919:Glomerular Filtration Rate; D007668:Kidney / Q000098:blood supply* / Q000201:enzymology; D016030:Kidney Transplantation; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009842:Oligopeptides / Q000627:therapeutic use*; D060888:Real-Time Polymerase Chain Reaction; D015427:Reperfusion Injury / Q000188:drug therapy*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine
chemical_list: D017931:DNA Primers; D009842:Oligopeptides; C576178:cibinetide; D019001:Nitric Oxide Synthase