Clinical islet isolation and transplantation outcomes with deceased cardiac death donors are similar to neurological determination of death donors

Abstract

SummaryIn islet transplantation, deceased cardiac death (DCD) donation has been identified as a potential extended source. There are currently no studies comparing outcomes between these categories, and our goal was to compare islet isolation success rates and transplantation outcomes between DCD and neurological determination of death (NDD) donors. Islet isolations from 15 DCD and 418 NDD were performed in our centre between September 2008 and September 2014. Donor variables, islet yields, metabolic function of isolated isled and insulin requirements at 1-month post-transplant were compared. Compared to NDD, pancreata from DCD were more often procured locally and donors required less vasopressive support (P < 0.001 and P = 0.023, respectively), but the other variables were similar between groups. Pre-and postpurification islet yields were similar between NDD and DCD (576 vs. 608 9 10 3 islet equivalent, P = 0.628 and 386 vs. 379, P = 0.881, respectively). The metabolic function was similar between NDD and DCD, as well as the mean decrease in insulin requirement at 1-month post-transplantation (NDD: 64.82%; DCD: 60.17% reduction, P = 0.517). These results support the broader use of DCD pancreata for islet isolation. A much larger DCD islet experience will be required to truly determine noninferiority of both short-and long-term outcomes.

A novel redox-active metalloporphyrin reduces reactive oxygen species and inflammatory markers but does not improve marginal mass engraftment in a murine donation after circulatory death islet transplantation model

“…Moreover, examination of insulin requirement one month post-transplant in recipients of islets from NDD or DCD pancreata revealed no significant difference between groups. 5 WI significantly impaired islet yield in our murine model, but DCD islets exhibited similar in vivo islet function to standard control islet recipients, as evidenced by the restoration of euglycemia and IPGTT responses at 60 d post-transplant. Though MnP administration did not enhance islet function, the findings in the present study demonstrate that MnP supplementation is safe and non-toxic to islets.…”

“…4 Despite numerous advances in clinical islet transplantation, most recipients require more than one intraportal islet infusion to establish and maintain periods of insulin independence. 5 Cadaveric donor pancreata are currently the sole, scarce source of islets. As such, to meet clinical demand, transplant centers routinely process extended criteria donor organs to expand the donor pool.…”

“…Recently, donation after circulatory death (DCD) donors have been identified as a potential source of extended donors. 5 In whole pancreas transplantation, DCD and neurological determination of death (NDD) organ recipients have demonstrated similar rates of patient survival and graft function. 6 Alternatively, DCD donation is associated with poor graft function in liver transplantation.…”

Does Islet Size Really Influence Graft Function After Clinical Islet Transplantation?

“…The latter is a positive output, directly measuring graft function whereas changes in insulin requirement are indirect and may not be necessarily linearly responsive to graft size. This less objective parameter however, has been used as the indicator of islet graft function in previous studies on islet transplant recipients [25,41].…”

Organ donor pancreases for the study of human islet cell histology and pathophysiology: a precious and valuable resource

“…Furthermore, it must be taken into account that little information, if any, is available on the histology of the human pancreas should the gland come from donors after cardiac death (i.e. with permanent cessation of circulatory and respiratory functions) [39,40]. In Europe [41] and in the USA [42] there are around 10,000 deceased organ donors per year and only 10-20% of the available pancreases are used for clinical transplantation.…”