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Simultaneous pancreas–kidney (SPK) transplantation is the preferred treatment for selected patients with diabetes and end-stage renal failure1, 2. The ongoing imbalance between the supply and demand of suitable donor organs has led to lengthening transplant waiting lists3 and a search for new sources of grafts. These sources include living donors4, paediatric deceased donors5, and older or overweight donation after brain death (DBD) donors6, 7. Pancreas procured from donation after circulatory death (DCD) donors may offer a further alternative. DCD donors are classified as uncontrolled when cardiorespiratory arrest has occurred unexpectedly, and controlled when potential donors, for whom prolongation of treatment is considered futile, undergo planned withdrawal of life-sustaining treatment in a hospital environment, usually intensive care8.
Unlike DBD donor organs, those from controlled DCD donors are subjected to additional warm ischaemia, not only during the time from cardiorespiratory arrest to commencement of cold perfusion, but also from hypotension and/or hypoxia in the period from withdrawal of treatment to cardiorespiratory arrest (the agonal phase). Although more than two-thirds of potential donors die within 4 h (younger age, high oxygen needs and more intensive ventilation requirements are associated with a shorter time to death9), the duration of the agonal phase is unpredictable. Acceptable cardiorespiratory parameters for pancreas donation during this phase have not yet been defined, although the time from withdrawal of treatment to perfusion has generally been less than 30 min10. These uncertainties limit the use of DCD pancreas, with just 32 grafts implanted in the USA in 200811. In addition, potential DCD donors may place a considerable strain on procurement services owing to the difficulty in predicting donor death and the need for prolonged waiting periods to increase organ recovery rates9, 12.
There are relatively few reports on DCD pancreas transplantation13–17, but the results have been encouraging. The largest report is from an United Network of Organ Sharing registry analysis of 47 DCD SPK transplants that showed equivalent graft survival rates at 1, 3 and 5 years for organs from DCD and DBD donors14. Single-centre long-term follow-up has shown no difference in patient and graft survival at 8 years13. However, these findings may reflect more stringent DCD donor selection, as an adjusted survival analysis of the Scientific Registry of Transplant Recipients (SRTR) database has reported an increased, albeit not statistically significant, risk of failure associated with DCD organs10.
The extensive experience of the Cambridge Transplant Unit with kidney transplantation from controlled DCD donors12, 18 led to the use of pancreas from donors with agonal phases that were longer than those reported previously13. Here, the early results of SPK transplantation from DCD donors are reported, comparing these outcomes with those of transplants from DBD donors over the same interval.
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This single-centre study demonstrated comparable short-term outcomes for SPK transplantation from DCD and DBD donors, with no difference in pancreatic allograft survival, endocrine function or graft thrombosis rates. Renal allograft survival and function in the two groups were also similar. DGF rates in DCD kidneys were higher, but the difference was not statistically significant. In addition, there were no significant differences in postoperative length of hospital stay, need for early reoperation, or rates of acute rejection. Analysis of referrals for potential donation showed that the Cambridge Transplant Unit appeared to be similarly selective with both DCD and DBD donors, and just as likely to discard either graft once procured.
These findings mirror those of Fernandez and colleagues13 from the University of Wisconsin. The Wisconsin group reported 37 DCD SPK transplants over 11 years, with a 1-year pancreas survival rate of 83 per cent, compared with 84 per cent in the present series. Importantly, however, the Cambridge results were achieved despite accepting DCD donors with longer times from withdrawal of treatment to perfusion and without prior heparinization of the donor. Fernandez and co-workers13 defined this as the warm ischaemia time, with a mean duration of 17·5 (range 6–48) min; 20 of 37 donors had a warm ischaemia time of 15 min or less in their series. By contrast, in the Cambridge cohort, the time from withdrawal of treatment to cold perfusion ranged from 16 to 110 min. Nonetheless, DBD and DCD outcomes were relatively similar, perhaps emphasizing that brain death also has deleterious effects on the pancreas24–26.
After withdrawal of treatment, DCD donors may show prolonged cardiovascular and respiratory stability before dying relatively rapidly. Using the time from withdrawal to perfusion as a surrogate for warm ischaemic damage may therefore be inadvisable. Recent analyses of kidneys transplanted from DCD donors did not show a statistically significant association between agonal-phase characteristics and long-term graft function12, 27. In contrast, DCD livers appeared more sensitive to ischaemic injury, and a systolic blood pressure of less than 50 mmHg for more than 15 min was associated with poorer graft outcome27. The tolerance of the pancreas to warm ischaemia is likely to be between these extremes, as animal models have shown decreased islet viability after warm ischaemia of more than 30 min28–30. This finding was reinforced in a study of human islets from 12 DCD donors, in which all isolates were biologically functional when the duration of systolic blood pressure below 50 mmHg was less than 25 min26.
Patient numbers in the present study were too small to analyse outcomes on the basis of agonal-phase cardiorespiratory parameters, although more than a quarter of the DCD donors had withdrawal of treatment to cold perfusion times longer than 30 min, with good early graft outcomes. Postwithdrawal cardiorespiratory parameters are therefore likely to be of more use than the extubation to perfusion time13, although further analysis of how agonal-phase cardiorespiratory characteristics affect pancreatic transplant function is essential as experience accrues. Ultimately, decisions on the use of organs from DCD donors must be made individually, taking into account other donor and recipient risk factors10 and graft appearance.
Donor and recipient characteristics were generally similar for DCD and DBD grafts; donors were younger in the DCD group, although this failed to reach statistical significance. Importantly, every effort was made to minimize the cold ischaemia time when using DCD organs. This was achieved by selective omission of the preimplantation cross-match19, or by using peripheral blood to perform the cross-match before withdrawal of treatment in the donor. In addition, planned recipients of both DCD and DBD organs were admitted before the donor went to theatre (DBD) or had treatment withdrawn (DCD). In this study, cold ischaemia times in the DBD group were thus substantially lower than those reported elsewhere14, although this policy did, on several occasions, result in the recipient not receiving a transplant because the organs were unsuitable on inspection or, for DCD donors, asystole did not occur within 4 h after treatment withdrawal.
Although there were no statistically significant differences between DCD and DBD pancreas or kidney graft survival, the number of patients in each group was relatively small and the duration of follow-up short. The survival curves suggest slightly poorer outcomes with DCD donor organs, which may become significant with longer follow-up or larger numbers. Of note, two DCD pancreas grafts failed within the first year owing to rejection; this may have been triggered by inflammation related to the warm ischaemic insult from DCD organ recovery. This appears unlikely, however, because the early clinical course and all biochemical markers of pancreatic inflammation were indistinguishable in the DCD and DBD groups. Notably, HbA1c levels were similar in both groups at 1 year. However, a recent risk-adjusted SRTR database analysis of pancreas transplant outcomes demonstrated a marginally increased risk associated with use of DCD grafts (hazard ratio 1·39), although this was not statistically significant (P = 0·10)10. Even so, transplantation from this donor source is still likely to carry a survival advantage over remaining on the waiting list or receiving a deceased donor kidney alone1, 31.
This single-centre analysis has demonstrated that SPK transplants from controlled DCD donors have acceptable short-term outcomes, which are similar to those of organs from DBD donors. This was achieved despite using donors with a longer agonal phase than usually accepted. This most likely reflects the short cold ischaemia times that were achieved, but further analysis of registry data and collection of postwithdrawal variables are needed to define what constitutes acceptable and unacceptable agonal-phase characteristics for DCD pancreas transplantation. Although there has been a continued rise in DCD donation in the UK over the past 5 years, this has led predominantly to increases in DCD kidney, rather than pancreas, transplantation. The Cambridge Transplant Unit, however, now performs approximately equivalent numbers of DCD and DBD SPK transplants. DCD donors thus represent a significant source of additional pancreas for transplantation and, given the acceptable outcomes achieved, their prudent use is to be encouraged.