Delayed Graft Function And Chronic Rejection

Delayed graft function(DGF) occurs in every organ preserved and transplanted. The magnitude and consequences of DGF, however, is different for each organ. In the kidney DGF is characterized as the need for dialysis because of insufficient renal function to regulate the composition of the blood. Most kidney transplant patients with DGF recover near-normal function within a few weeks or so after transplantation. In the liver, delayed graft function (initial poor function) leads to longer ICU stays and can progress to primary nonfunction (PNF), requiring immediate retransplantation. In kidney transplantation there are now very few incidences of primary nonfunction. In heart and lung transplantation, delayed graft function inevitably leads to death because of the immediate need for these two organs to sustain life. However, in transplant of these organs there is often poor functional return immediately after transplantation and various methods of intraoperative assist are required to save the organ.

Delayed graft function as related to preservation has been more comprehensively studied in renal transplantation than in other organs. The incidence of DGF increases with increasing preservation times. The percent of recipients requiring dialysis with kidneys preserved for 0 to 12 hours (n=7264) was 21%, at 13 to 24 hours (n=18682) 24%, at 25 to 36 hours (n=13585) 30%, and greater than 36 hours (n=5246) 35%.72 The incidence of delayed graft function is also a function of the type of cold storage solution;73 there is an approximate 10% reduction of DGF in kidneys preserved in UW versus EuroCollins solution. The method of preservation also affects the rate of DGF: machine perfused kidneys had on average an 18% rate of DGF versus 29% for those cold stored. The incidence of initial poor function (INF) or PNF in liver transplantation is also dependent upon the type of preservation solution used74 and length of preservation.64,65 In general, INF occurs in 10 to 12% of the patients and PNF in 2 to 6% of the recipients.

Although these statistics suggest that DGF is related to preservation injury, it is also clear that DGF and PNF have many other correlates, including donor and recipient health. In fact, the donor and recipient may be greater determinants of the outcome of preservation/reperfusion injury than the conditions of preservation. For instance, kidneys preserved for only 0 to 12 hours showed a significant degree of DGF (21%). From laboratory studies, one would assume that this short period of time should have caused minimal to practically no injury to the kidney. The differences between the clinical and laboratory results could be the status of the donor and recipient; in the laboratory, both are healthy animals. In living-unrelated kidney transplantation, the incidence of DGF is very low since the kidneys are not subjected to lengthy preservation. However, the kidney is also harvested from a relatively healthy individual and this fact, combined with short to no preservation time, may contribute to the lack of DGF.

Chronic rejection as a cause of loss of kidney grafts remains a major problem and there may be a relationship between initial renal injury and chronic injury. Studies from the Minnesota group suggest that both acute and chronic rejection are more prevalent in patients with kidneys that do not regain initial function rapidly.75 This is also supported by information obtained from the kidney transplant registry. The relationship between liver injury due to preservation and long-term complications is not clear. One study suggested greater rejection in livers that showed preservation/reperfusion injury than in those that functioned imme-diately.76 However, other studies did not show this relationship.77

Although the relationship between preservation/reperfusion injury and long-term graft survival may not be entirely clear, due to the many compounding factors involved in the process of transplantation and drug use, there should be little doubt that the most optimal methods of preservation should be advocated. Furthermore, it is also apparent that shorter preservation periods may give a more favorable outcome and since this is one of the few variables that can be controlled in organ transplantation, strong consideration should be given to the use of short preservation periods combined with the most ideal preservation method.

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