A Systematic Review and Meta-Analysis of Outcomes for Islet Transplantation in Donation after Circulatory Death (DCD) compared with Donation after Brain Death (DBD)

Abstract

Introduction For patients suffering type 1 diabetes, islet transplantation provides long-term insulin independence and restores normoglycaemia, preventing the long-term effects of hyperglycaemia and hypoglycaemic episodes. However, the scarcity of organ donors results in patients remaining on the waitlist for several years prior to receiving a transplant. Donation after Circulatory Death (DCD) donors are increasingly utilised to help stem the increasing organ donor shortage, and DCD lung and kidney transplants have been found to have similar outcomes to donation after brain death (DBD) organs. In this study, the aim was to systematically review islet isolation and recipient outcomes from DCD donors and, where possible, compare these to DBD donors. Materials and Methods Literature was searched following guidelines outlined in the Cochran Handbook for Systematic Reviews of Interventions. The electronic databases MEDLINE and PREMEDLINE via PubMed, EMBASE and The Cochrane Library were searched from inception to July 2017 for studies reporting islet isolation or transplantation outcomes from human DCD donors, with a search script mapped to medical subject headings (MeSH). Studies were included based on reporting of isolation outcomes such as pre- and post-purification islet yield, post-culture yield, purity and viability, and transplantation outcomes such as islet yield transplanted, exogenous insulin requirements, glycated haemoglobin pre- and post-transplant, insulin independence and abrogation of severe hypoglycaemic unawareness. Studies were evaluated for bias using the Newcastle-Ottawa Assessment Scale, and meta-analysed using a random effects model. Results and Discussion 147 studies were identified from the literature search, from which 11 studies met inclusion criteria, were non-overlapping, and scored well in the Newcastle-Ottawa Scale with no observed bias. Five studies included a DBD comparator group and meta-analyses were performed to compare donor characteristics and isolation outcomes. DCD islets proved to be not significantly different with DBD islets in all variables analysed. With the available data we found DCD islets proved comparable in terms of post-purification yield (standard difference in means (SDM), -2.821; 95% confidence interval (95% CI), - 8.385-2.743; P = 0.320), purity (SDM, 0.068; 95% CI, -0.371-0.508; P = 0.762), and viability (SDM, -0.085; 95% CI, -0.606-0.437; P = 0.750), among others. Conclusion Based on the currently available literature, our review found that islet isolations from DCD donors yield outcomes that are comparable to those from DBD donors. The caveat being that careful selection of DCD pancreata may therefore be another potential source for islet isolation and transplantation, helping to alleviate donor shortages and allowing the treatment of those with T1DM and severe hypoglycaemic unawareness.