Solid Organ Assessment and Manipulation for Transplantation from Non Heart Beating Donors

Whilst kidney transplantation is accepted as a cost effective treabnent ofend stage renal failure, the shortage in the kidney donor pool has recently become critical. Historical series ofNHBD renal transplants have been associated with high rates ofallograft failure and dysfunction due to prolonged warm and cold ischaemia. Machine preservation of NHBD kidneys provides a useful tool to test viability pre-transplant and this PhD thesis was directed at improving the existing Newcastle NHBD programme. Newcastle machine preservation is described in which viability criteria is used to reduced primary non function and discard rates. The sequential allograft failures were critically reviewed to develop the new 'IO-point' criteria. Case failures have become a necesSary painful learning experience that allowed improvements in the selection and screening criteria. The long term function ofNHBD renal transplants are presented to illustrate how the function is affected by warm ischaemic injury and delayed graft function. The early dysfunction ofNHBD kidney transplants was found to be temporary and improved with time. Kidney perfusate GST evaluation is an established criteria in the assessment of viability ofNHBD kidneys. In the search for novel biomarkers, perfusate Ala-AP and FABP have been assessed in relation to GST. The novel biomarkers measured a different aspect of allograft injury and comparable results to GST suggest that these could be developed as an adjunct to perfusate GST. The introduction ofstreptokinase pre-flush of the NHBD is illustrated in a porcine and a subsequent human clinical model. The effect on procurement, machine preservation and transplantation has been evaluated. Thrombolytic therapy ofNHB donor facilitated the clearing ofpremorbid intravascular thrombus, thereby improving the preservation and thus the viability of the NHBD kidneys. Allograft dysfunction is a standard feature of ischaemia reperfusion injury. A clinical model ofkidney transplantation is described to illustrate the biochemical and clinical effects of ischaemia reperfusion. An exaggerated response was observed in NHBD kidney transplants that could be attributed to the warm ischaemia insult at time of cardiac arrest.EThOS - Electronic Theses Online ServiceGBUnited Kingdo