This thesis has studied several modalities how to increase the organ utilisation rate. The results in this thesis indicate that the acceptance of kidneys with acute kidney injury stage 1 or 2 will... Show moreThis thesis has studied several modalities how to increase the organ utilisation rate. The results in this thesis indicate that the acceptance of kidneys with acute kidney injury stage 1 or 2 will significantly contribute to the donor pool as AKI kidneys have comparable outcomes and should therefore not be discarded. Clinically relevant biomarkers such as cell-free unmethylated-INS DNA, FMN, GSN, IGFBP3 and IGF2R were identified or explored in the first part of this thesis and may, if analysed and/or validated thoroughly, contribute to a better assessment of organ viability supporting the justified decision whether to accept or decline the donor organ.The second part of this thesis describes different aspects of the organ preservation technique of abdominal normothermic regional perfusion (aNRP). This relatively new machine perfusion technique has been shown to be feasible and safe, however, consensus regarding assessment parameters during perfusion, protocols and outcome measurements is still lacking. Despite of an inspiring surgical enthusiasm and keeninterest to accept this modality as a new standard, a randomised clinical trial is still required and entirely ethically justifiable in order to scientifically demonstrate superiority of this method for each individual abdominal organ comparing it to other successful (ex-situ) preservation and perfusion strategies. If aNRP can be shown to obtain better post transplantation outcomes whilst increasing organ utilisation, it may be the least complex and most cost-effective strategy in organ preservation. On the other hand, aNRP will only be used in DCD donors. As such, uncertainty regarding the quality of higher risk organs from DBD donors will still be evaluated ex-situ during cold and/or warm machine perfusion with the potential to repair or even regenerate injured organs and making them ‘transplantable’ again. Show less
This thesis explores methods and strategies to most optimally isolate viable, functional pancreatic islets from donor pancreases. After analyzing the current challenges within the field, the... Show moreThis thesis explores methods and strategies to most optimally isolate viable, functional pancreatic islets from donor pancreases. After analyzing the current challenges within the field, the manuscript examines the applicability of donation after circulatory death pancreases for islet isolation. The results of these isolations are discussed in the next chapter. A novel strategy to judge suitability of all donor pancreases is presented hereafter. The Islet Isolation Outcome Prediction Score is a multifactorial donor risk index in predicting obtained islet equivalents after isolation. After an organ is allocated and accepted, it must be preserved before it arrives at the isolation facility. To optimize this process, the use of hypothermic machine perfusion is explored in a feasibility study. Next, a novel islet isolation technique, the PancReatic Islet Separation Method is presented. This method can vastly improve isolation duration, efficiency, and standardization. Lastly, the results of the thesis are discussed. Show less
