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Project
Mechanisms and modulation of ischemia-reperfusion injury in decreased donor kidneys.
Delayed graft function is a scarcely studied but major complication of kidney transplantation. Up to 25% of standard brain dead kidney grafts develop delayed graft function and this incidence is likely to increase because of the increased use of "higher-risk" kidneys, i.e. kidneys from expanded criteria donors and kidneys donated after circulatory death. Indeed, delayed graft function can be attributed largely to ischaemia-reperfusion injury of the graft and higher-risk kidney grafts are particularly vulnerable to ischaemia-reperfusion injury with incidences of delayedgraft function between 40% and 80%. Nevertheless, they still provide a better outcome compared to continued dialysis.
Preventing and predicting delayed graft function and quantifying initial graft injury, the focus of this doctoral thesis, is essential to improve results after transplantation of higher-risk kidney grafts and safely increase the overall deceased donor transpant activity.
In a series of clinical and experimental studies, this thesis shows that - until a better preservation method is fully clinically applicable - hypothermic machine perfusion should be the gold standard to preserve higher-risk kidney grafts because it reduces the chance for developing delayed graft function. Furthermore, it shows that machine perfusion characteristics such as renal vascular resistance and perfusate injury markers are independent predictorof delayed graft function, however, they should no longer be used as stand-alone tools to discard kidney grafts. Nevertheless, they can provideadditional information to tailor peri- and postoperative care. And finally, plasma injury markers have the potential to quantify ischaemia-reperfusion injury and might lead to a more accurate and objective definition of short-term graft outcome and could potentially be used to assess the effect of emerging treatment strategies.
Preventing and predicting delayed graft function and quantifying initial graft injury, the focus of this doctoral thesis, is essential to improve results after transplantation of higher-risk kidney grafts and safely increase the overall deceased donor transpant activity.
In a series of clinical and experimental studies, this thesis shows that - until a better preservation method is fully clinically applicable - hypothermic machine perfusion should be the gold standard to preserve higher-risk kidney grafts because it reduces the chance for developing delayed graft function. Furthermore, it shows that machine perfusion characteristics such as renal vascular resistance and perfusate injury markers are independent predictorof delayed graft function, however, they should no longer be used as stand-alone tools to discard kidney grafts. Nevertheless, they can provideadditional information to tailor peri- and postoperative care. And finally, plasma injury markers have the potential to quantify ischaemia-reperfusion injury and might lead to a more accurate and objective definition of short-term graft outcome and could potentially be used to assess the effect of emerging treatment strategies.
Date:1 Oct 2008 → 30 Sep 2012
Keywords:Transplant chirurgy, Deceased donor kidneys
Disciplines:Urology and nephrology, Orthopaedics, Surgery, Nursing, Immunology
Project type:PhD project