Assessment of the viability of renal cells following an ischaemic insult
Renal transplantation is the best treatment for end-stage renal failure. The relative shortage of organs may be addressed by transplanting kidneys from non heart-beating donors (NHBD). This thesis addresses the results of transplantation from NHBD and how they may be improved, with emphasis on the search for a pre-transplant test of viability. In Chapter 1 the role of NHBD kidney transplantation in addressing the organ shortage is reviewed. Chapter 2 presents the results of the Leicester kidney transplant programme. Kidneys from NHBD show a higher rate of primary non-function than cadaveric donor kidneys but there is no difference in graft survival. A reliable viability test would prevent the transplantation of kidneys severely damaged by ischaemia and so improve results. In Chapter 3 viability testing in renal transplantation is reviewed. Chapter 4 describes experiments resulting in the development and testing of an in vitro model of warm ischaemia. Cultured pig and human tubular epithelial cells were found to be tolerant of anoxia in this model. In Chapter 5 the anaerobic metabolism of these cells is studied. Lactate is produced by glycolysis even in oxygenated conditions. Differences between the metabolism of tubular cells in vivo and in vitro, prevent in vitro modeling of warm ischaemia. In Chapter 6 the utility of detection of apoptosis in pre-transplant biopsies in predicting transplant function is investigated. Apoptosis is seen in the juxta-cortical medulla of NHBD kidneys but not in the cortex. Cadaveric donor kidneys show no apoptosis. The presence of apoptosis does not predict transplant function. In Chapter 7 the utility of histomorphometric analysis of interstitial fibrosis in the assessment of kidney quality is studied. Kidneys from NHBD have more severe interstitial fibrosis than cadaveric kidneys but the difference is small and correlation with transplant function is poor. In Chapter 8 the findings of these experiments are summarized and the future of viability testing in renal transplantation is discussed.