One of the main causes of early graft dysfunction in kidney transplantation is ischaemia reperfusion (I/R) injury. This unavoidable event occurs immediately when oxygenated blood is re-introduced into the transplanted kidney. Its severity is influenced by many predetermined factors. However, the condition under which an organ is preserved has a significant bearing on the outcome. Traditionally, organs are preserved using hypothermic temperatures, to reduce metabolism and the requirement for oxygen. Although practical and simple, hypothermic conditions are not entirely favourable and over time the depletion of energy substrates causes substantial cellular injury. This is thought to be a particular problem in kidneys from marginal donors, which are often exposed to a period of warm ischaemia (WI) prior to retrieval. The aim of this thesis was to determine the effects of varying degrees of the combined insults of warm and cold ischaemic injury and to develop a technique of normothermic perfusion (NP) to reduce ischaemic injury. The effects were assessed using ex-vivo and in-vivo porcine kidney models before translation of NP into clinical practice for marginal donor kidneys. This research demonstrated that prolonging the hypothermic preservation period after a minimal and a substantial degree of WI injury increased the severity of acute I/R injury and graft dysfunction. A short period of NP after hypothermic preservation was able to resuscitate the kidney, replenish ATP and reverse some of the detrimental effects of cold ischaemic injury. When translated into an autotransplant model, NP was found to be a safe and feasible method of preservation. NP was then adapted for use in clinical practice for kidneys from marginal donors. This first in man clinical series of 15 cases has demonstrated the safety and feasibility of NP for marginal kidneys. Although, the high rate of initial graft function is notable, further comparative studies are required to assess the effects on delayed graft function.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:555470 |
| Date | January 2012 |
| Creators | Hosgood, Sarah Anne |
| Contributors | Nicholson, Michael |
| Publisher | University of Leicester |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/2381/10924 |
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