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Renoprotective capacities of non-erythropoietic EPO derivative, ARA290, following renal ischemia/reperfusion injury.

van Rijt WG, Nieuwenhuijs-Moeke GJ, van Goor H, Ottens PJ, Ploeg RJ, Leuvenink HG - J Transl Med (2013)

Bottom Line: Early ARA290 treatment improved renal function.Late- or repetitive treatment did not affect inflammation or acute kidney injury.This study showed the anti-inflammatory effect of ARA290 and suggests early administration in the post-reperfusional phase is most effective.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Surgery, University Medical Center Groningen, Hanzeplein 1, 9713, GZ Groningen, The Netherlands. w.g.van.rijt@umcg.nl.

ABSTRACT

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.

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The effect of ARA290 on markers of renal function. Early ARA290 treatment significantly reduced serum creatinine levels at three days post-reperfusion. Late- and repetitive ARA290 treatment tended to reduce serum creatinine levels to a lesser extent (A, p < 0.05). The treatment effect of ARA290 on serum urea levels showed the same tendency as the effect on serum creatinine levels (B).
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Figure 1: The effect of ARA290 on markers of renal function. Early ARA290 treatment significantly reduced serum creatinine levels at three days post-reperfusion. Late- and repetitive ARA290 treatment tended to reduce serum creatinine levels to a lesser extent (A, p < 0.05). The treatment effect of ARA290 on serum urea levels showed the same tendency as the effect on serum creatinine levels (B).

Mentions: Early ARA290 treatment at one hour post-reperfusion significantly reduced serum creatinine levels at three days post-reperfusion compared to the control group. Late or repetitive treatment did not significantly change serum creatinine levels (Figure 1A). Serum urea levels showed a similar tendency although these differences were not significant (Figure 1B). No differences in serum aspartate transaminase (ASAT) or lactate dehydrogenase (LDH) levels were found.


Renoprotective capacities of non-erythropoietic EPO derivative, ARA290, following renal ischemia/reperfusion injury.

van Rijt WG, Nieuwenhuijs-Moeke GJ, van Goor H, Ottens PJ, Ploeg RJ, Leuvenink HG - J Transl Med (2013)

The effect of ARA290 on markers of renal function. Early ARA290 treatment significantly reduced serum creatinine levels at three days post-reperfusion. Late- and repetitive ARA290 treatment tended to reduce serum creatinine levels to a lesser extent (A, p < 0.05). The treatment effect of ARA290 on serum urea levels showed the same tendency as the effect on serum creatinine levels (B).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3842642&req=5

Figure 1: The effect of ARA290 on markers of renal function. Early ARA290 treatment significantly reduced serum creatinine levels at three days post-reperfusion. Late- and repetitive ARA290 treatment tended to reduce serum creatinine levels to a lesser extent (A, p < 0.05). The treatment effect of ARA290 on serum urea levels showed the same tendency as the effect on serum creatinine levels (B).
Mentions: Early ARA290 treatment at one hour post-reperfusion significantly reduced serum creatinine levels at three days post-reperfusion compared to the control group. Late or repetitive treatment did not significantly change serum creatinine levels (Figure 1A). Serum urea levels showed a similar tendency although these differences were not significant (Figure 1B). No differences in serum aspartate transaminase (ASAT) or lactate dehydrogenase (LDH) levels were found.

Bottom Line: Early ARA290 treatment improved renal function.Late- or repetitive treatment did not affect inflammation or acute kidney injury.This study showed the anti-inflammatory effect of ARA290 and suggests early administration in the post-reperfusional phase is most effective.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Surgery, University Medical Center Groningen, Hanzeplein 1, 9713, GZ Groningen, The Netherlands. w.g.van.rijt@umcg.nl.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus