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Title: 8 day kidney preservation
Author: Cohen, Geoffrey Leonard
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 1982
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The aims of this research were to investigate the factors that limit in vitro storage of kidneys, establish how long kidneys could be preserved when storage conditions were made optimum, and determine whether measurements of the release of - the lysosomal enzyme N-Acetyl glucosaminidase, by kidneys during storage, could be used to predict the function of the kidneys after reimplantation. Methods are needed for storing human kidneys, after removal from cadaver donors, to allow sufficient time for transport of the kidneys, tissue typing of the donors, ' and pre-operative preparation of the recipients. At present, reliable 24 hour storage would provide adequate time for these -procedures to be performed. In future, as tissue typing techniques become more refined, and as more potential recipients develop antibodies as a result of previous failed transplants, it is likely that fewer kidneys will be able to be matched with recipients in the locality of the donor. , It will then be necessary to store kidneys reliably for longer periods if the best possible tissue. match is to be obtained. More reliable long term storage techniques would also allow mixed lymphocyte cultures (MLC) to be performed between donor and- recipient white cells; this may provide better evidence of the likelihood of graft rejection than serological determined incompatibility of HLA tissue types. At present the MLC test takes between 5 and 7 days. The techniques for storing a human kidney that are currently in use involve cold flushing the kidney with electrolyte solution, and then storage either in ice, or on a machine in which cooled oxygenated fluid is pumped continuously through the kidney's vascular system (hypothermic perfusion storage). The best results that have been published for ice storage of non warm injured human kidneys are, those of Squifflet (101) who reported 15 of 22 kidneys functioning immediately after storage for between 40 and ý 50 hours; the best results for hypothermic perfusion storage of -human kidneys are those of McCabe (78), who had 18 of 19 kidneys functioning immediately after storage for between 17 and 50 hours. These results are exceptional, and many -human kidneys - that are transplanted fail to function immediately after reimplantation, despite removing the kidneys from heart beating donors, and using storage times of less than 24 hours. Little is known about the nature of the injuries that limit long term kidney storage. It is well known that any period of warm injury prior to storage is harmful, but the progressive deterioration in the viability of non warm injured kidneys remains unexplained. If, the nature of these storage injuries could be determined, then not only could attempts be made to minimise the injury, but measurements made during storage might be used to predict the viability and function of kidneys after reimplantation. - One consequence of cellular injury is thought to be that the lysosomes rupture and release their contents. The lysosomal enzyme N-Acetyl glucosaminidase (NAG) is known to be present in high concentrations In kidney tubular cells, is stable after long periods, of storage, and can be easily assayed. Measurement of the release of this lysosomal enzyme, by non warm-injured kidneys during storage,, may therefore be of value in predicting the function of the kidneys after reimplantation. Experimentally, the dog kidney behaves, in a similar way to the human kidney when subjected to the same -storage, conditions. Use of an animal kidney auto-transplant model allows , the effects of the storage injury to be assessed without the additional complications of the immediate and delayed rejection phenomena that occur in human kidney transplantation. For the present study, uninjured dog kidneys were removed under controlled conditions and stored on a hypothermic perfusion apparatus, using a perfusate based on human albumin (Plasma Protein Fraction - PPF). After a period of storage, the kidneys were reimplanted as autografts, and at these operations contralateral nephrectomies were performed. During storage, the physical and chemical changes that occurred in the perfusate were measured, and serial estimations were made of the release by the kidneys of the lysosomal enzyme N-Acetyl glucosaminidase (NAG). After reimplantation, function of the kidneys was assessed by the clinical condition of the dogs, and by serial estimations of the dogs' serum creatinines. Post mortems were performed on all the dogs that died. Light, electron and immunofluorescent microscopy were performed on kidney biopsy specimens removed during perfusions, after reimplantation, and at post mortem.
Supervisor: Not available Sponsor: Not available
Qualification Name: Ch.M Qualification Level: Doctoral
EThOS ID:  DOI: Not available