Warm perfusion of ischaemically damaged kidneys : ex-vivo function, viability assessment and preservation efficacy

Background: The shortage of kidneys for renal transplantation has prompted renewed interest in non-heart-beating donors (NHBD). While this may increase the number of transplants, it also increases the primary non-function (PNF) rate. This is caused by excessive warm ischaemic injury in some NHBD, and has hindered their more widespread use. A reliable pre-transplant test of organ viability, and a preservation method minimising additional iscahemic damage, would allow the PNF rate to be reduced. The aims of this thesis were to explore the potential of warm ex-vivo perfusion as a preservation method and a means of diagnosing viability pre-transplantation. Methods: Warm ex-vivo perfusion of ischaemically injured porcine kidneys with an oxygenated emulsion of a perflourochemical in tissue culture fluid was used to measure ex-vivo function and preserve kidneys. A cadaveric model was used to assess the relationship of ex-vivo function and warm ischaemic time. An autotransplant model was used to determine the relationship of ex-vivo to post-transplant function, and to compare the efficacy of preservation by warm perfusion with conventional hypothermic techniques of static storage and pulsatile perfusion. Post-transplant outcome measures were survival, renal function and histology. Results: WIT correlated well with ex-vivo function. Ex-vivo function correlated with post-transplant function in terms of survival (and therefore the immediate life supporting function of the kidneys), but not to the extent that it could be used to predict viability better than knowing the WIT alone. The efficacy of warm perfusion was indistinguishable from hypothermic static storage. However hypothermic pulsatile perfusion was slightly superior to both other techniques. Conclusions: Warm perfusion as used in this thesis was broadly equivalent in efficacy to conventional hypothermic organ preservation techniques. Although ex-vivo function correlated with post-transplant function, the correlation was not tight enough to support a diagnostic role for ex-vivo function in viability determination.