Renoprotective capacities of non-erythropoietic EPO derivative, ARA290, following renal ischemia/reperfusion injury.
BACKGROUND
ARA290 is a non-erythropoietic EPO derivative which only binds to the cytoprotective receptor complex (EPOR2-βcR2) consisting of two EPO-receptors (EPOR) and two β common receptors (βcR). ARA290 is renoprotective in renal ischemia/reperfusion (I/R). In a renal I/R model we focussed on timing of post-reperfusional administration of ARA290. Furthermore, we investigated the anti-inflammatory properties of ARA290.


METHODS
Twenty-six male Lewis/HanHsd rats were exposed to unilateral ischemia for 30 minutes, with subsequent removal of the contralateral kidney. Post-reperfusion, ARA290 was administered early (one hour), late (four hours) or repetitive (one and four hours). Saline was used as vehicle treatment. Rats were sacrificed after three days.


RESULTS
Early ARA290 treatment improved renal function. Late- or repetitive treatment tended to improve clinical markers. Furthermore, early ARA290 treatment reduced renal inflammation and acute kidney injury at three days post-reperfusion. Late- or repetitive treatment did not affect inflammation or acute kidney injury.


CONCLUSIONS
ARA290 attenuated renal ischemia/reperfusion injury. This study showed the anti-inflammatory effect of ARA290 and suggests early administration in the post-reperfusional phase is most effective. ARA290 is a candidate drug for protection against ischemic injury following renal transplantation.
Department of Surgery, University Medical Center Groningen, Hanzeplein 1, 9713, GZ Groningen, The Netherlands. w.g.van.rijt@umcg.nl.
Willem G
WG
van Rijt
Gertrude J
GJ
Nieuwenhuijs-Moeke
Harry
H
van Goor
Petra J
PJ
Ottens
Rutger J
RJ
Ploeg
Henri G D
HG
Leuvenink
D058186:Acute Kidney Injury / Q000517:prevention & control; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D007249:Inflammation / Q000175:diagnosis; D007668:Kidney / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000503:physiopathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D009842:Oligopeptides; C576178:cibinetide