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LIMITING WARM ISCHEMIA TIME IMPROVES ISLET CELL GRAFTS FROM DONOR PANCREASES AFTER CONTROLLED CIRCULATORY DEATH

Introduction: Islet transplant programs are highly dependent on quality donor pancreases that lead to beta cell isolates containing a sufficiently large number of functional beta cells. Donors after controlled circulatory death (DCD III) are a valuable source for expanding the organ donor pool but they are considered at higher risk for graft dysfunction due to an initial period of warm ischemia. The present study examines whether DCD III impairs pancreatic islet isolation and investigates whether procurement and preservation limits can define a subgroup of DCD III organs equivalent to organs removed after brain death (DBD). Materials and Methods: Pancreases retrieved by procurement teams affiliated to the Eurotransplant network and shipped to our Beta Cell Bank are retrospectively analysed for donor and procurement characteristics as well as quality control data of islet cell isolates (in particular beta cell yield and clinical transplantation utility). Organs from 141 DCD III and 609 DBD were included for comparative analysis. Results and Discussion: In our cohort, beta cell yield per DCD III-organ was significantly lower than that per DBD-organ (58 x 10 beta cells versus 84 x 10 beta cells; p < 0.001), leading to a lower clinical utility rate (34% versus 42%) which can at least partially be attributed to an initial period of warm ischaemia. In the DCD III subgroup, both these outcome parameters are negatively correlated to the duration of acirculatory warm ischemia time (WIT), defined as the time elapsed from circulatory arrest to initiation of organ preservation (r = -0.197, p = 0.010), rather than to the duration of the agonal phase. When acirculatory WIT was limited to ten minutes (68/141), transplantation utility was similar to that in the DBD group (being 44%). When also restricting pancreatectomy time (≤ 70min) and cold ischaemia time (≤ 9h), two parameters known to influence organ quality, DCD III organs (43/141) also yield the same amount of beta cells as DBD organs (75 x 10 beta cells; p = 0.413). Conclusion: Selecting DCD III organs for clinical islet cell graft preparation on their acirculatory WIT, pancreatectomy time and CIT, helps to avoid wasting efforts and resources on excluded organs and leads to isolates that meet similar quality control data as those prepared from DBD.