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Kidney transplantation is the treatment of choice for most patients with End-Stage-Renal-Failure (ESRF). Transplantation offers improved quality of life as well as reducing the mortality rate of patients with ESRF when compared with being on dialysis. As the prevalence of chronic kidney disease, and therefore ESRF, is increasing, there is a growing demand for transplants. This means that transplant clinicians have to expand the kidney donor pool by utilising kidneys from older donors with potentially multiple co-morbidities. The on-going challenges in donation and transplantation now are to be able to accept and transplant these higher risk donor organs, without compromising outcomes. My doctoral research has evaluated the effects that each stage of the donation process has on the organs to evaluate whether we can still get good outcomes from these organs. I have used data from the National Transplant Registry to explore whether the duration of Brain Death, thought to be a period of pro-inflammation, affects the outcomes of transplantation, and this has shown that there is no detrimental effect when durations of brain death are longer. This raises the possibility that this time can be used to observe, investigate and potentially deliver therapeutic interventions to improve organ quality. I also used data from the National Transplant Registry to evaluate the effect that acute kidney injury (AKI) has on outcomes following kidney transplantation. This showed that although there is a statistical difference in outcomes between kidneys with and without and AKI (1-year graft survival 91% versus 93%), this is unlikely to be of clinical significance and therefore kidneys with an AKI should be considered for transplantation and could further expand the donor pool. I used an animal model for Donation after Circulatory Death to investigate whether the current preservation solutions used for retrievals are effective at cooling the organs and washing them out. I looked at histology as well as specific cellular markers to look for signs of injury to see whether any solution is inferior to the others (as has previously been suggested). This study found that the preservation solution used in the UK for retrievals is not inferior to the other solutions, and could perhaps even cool the kidneys more effectively. Finally I did a systematic review of studies that have evaluated whether donor biopsies correlate with clinical outcomes, and therefore can be used to aid clinicians in their organ utilisation decision-making. The review found that there is no consensus as to whether biopsy findings predict outcomes. Based on the findings in this thesis, future work should concentrate on identifying markers of injury or repair in kidneys from donors with different durations of brain death or with AKI. Interventions that could be used in donors during brain death and retrieval techniques are also studies that could be carried out. |
