Abstract
Renal transplantation is the most effective treatment of end-stage renal disease. The major part of renal transplants is derived from deceased brain dead- or cardiac dead donors. Unfortunately, outcome of deceased donor kidneys is inferior compared to living donor kidneys. In this thesis three strategies are tested in experimental models to improve outcome after deceased donor kidney transplantation.
Earlier experiments showed that α-melanocyte stimulating hormone (α-MSH) is able to protects kidneys against ischemic injury. Recipients of a deceased brain dead donor kidney were therefore treated with α-MSH. Surprisingly, α-MSH impaired recovery of renal function. Thus, α-MSH seems no potential treatment for recipients of a deceased brain dead donor kidney.
The second strategy is normothermic recirculation of deceased cardiac death donor kidneys. The effectiveness of this treatment has already been shown in clinical trials, but the experimental evidence is limited. In this study, we were not able to reproduce the protective effect of normothermic recirculation in an experimental model in the rat.
Erythropoietin (EPO) has a tissue-protective function, besides its regulation of the production of red blood cells. The major disadvantage of protective EPO treatment is an increased risk for cardiovascular adverse events due to stimulation of the production of red blood cells. ARA290 is a protective EPO derivative and does not affect the production of red blood cells. In experimental ischemia/reperfusion models, administration of ARA290 after reperfusion reduced inflammation and improved renal function. ARA290 treatment of recipients of a deceased donor kidney is therefore a promising strategy to improve outcome of renal transplantation.
Earlier experiments showed that α-melanocyte stimulating hormone (α-MSH) is able to protects kidneys against ischemic injury. Recipients of a deceased brain dead donor kidney were therefore treated with α-MSH. Surprisingly, α-MSH impaired recovery of renal function. Thus, α-MSH seems no potential treatment for recipients of a deceased brain dead donor kidney.
The second strategy is normothermic recirculation of deceased cardiac death donor kidneys. The effectiveness of this treatment has already been shown in clinical trials, but the experimental evidence is limited. In this study, we were not able to reproduce the protective effect of normothermic recirculation in an experimental model in the rat.
Erythropoietin (EPO) has a tissue-protective function, besides its regulation of the production of red blood cells. The major disadvantage of protective EPO treatment is an increased risk for cardiovascular adverse events due to stimulation of the production of red blood cells. ARA290 is a protective EPO derivative and does not affect the production of red blood cells. In experimental ischemia/reperfusion models, administration of ARA290 after reperfusion reduced inflammation and improved renal function. ARA290 treatment of recipients of a deceased donor kidney is therefore a promising strategy to improve outcome of renal transplantation.
Translated title of the contribution | Prestatie bevorderende strategieën voor donornieren afkomstig van postmortale donoren |
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Original language | English |
Qualification | Doctor of Philosophy |
Awarding Institution |
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Supervisors/Advisors |
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Award date | 29-Sept-2015 |
Place of Publication | [S.l.] |
Publisher | |
Print ISBNs | 978-90-367-7214-3 |
Electronic ISBNs | 978-90-367-7213-6 |
Publication status | Published - 2014 |