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

Willem G. van Rijt*, Gertrude J. Nieuwenhuijs-Moeke, Harry van Goor, Bente Jespersen, Petra Suichies-Ottens, Rutger J. Ploeg, Henri G. D. Leuvenink

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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.

Original languageEnglish
Article number9
Number of pages8
JournalJournal of translational medicine
Volume11
DOIs
Publication statusPublished - 9-Jan-2013

Keywords

  • ARA290
  • Pyroglutamate helix B-surface peptide
  • Erythropoietin
  • Ischemia/reperfusion injury
  • Kidney transplantation
  • HIGH-DOSE ERYTHROPOIETIN
  • KIDNEY-TRANSPLANTATION
  • GRAFT FUNCTION
  • TISSUE PROTECTION
  • 3D STRUCTURE
  • PEPTIDE
  • INFLAMMATION
  • DARBEPOETIN
  • DEATH
  • BETA

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