Development and implementation of an enhanced recovery after surgery protocol for renal transplantation.

BACKGROUND: Successful implementation of enhanced recovery after surgery (ERAS) in kidney transplantation requires multidisciplinary consultation, education and attention to protocol. This study discusses the process implementation pathway of the ERAS protocol and its outcome. METHODS: A standardized ERAS protocol was designed for the renal transplant recipient and implemented in July 2017. Data collected prospectively of recipients transplanted from July 2017 to December 2018 were compared to prospectively collected data of recipients who were transplanted prior to ERAS implementation from January 2016 to July 2017 from our renal database. The parameters of interest included length of stay, incidence of delayed graft function and readmission rate. RESULTS: There was no difference in the demographics and the incidence of delayed graft function across both groups, although subgroup analysis suggested a significantly lower incidence of delayed graft function with kidneys donated after circulatory death in the cohort that were managed by the ERAS protocol. The median length of stay for patients on the ERAS protocol was 5 days (range 3-16 days). This was 2 days shorter than the median length of stay for patients not on the ERAS protocol (7 days; range 5-14, P < 0.001). This statistically significant difference in length of stay was consistent across all donor subgroups (living donor, donor after cardiac death and donation after brainstem death). Seventy-nine percent of the patients on the ERAS protocol were discharged on post-operative day 4. CONCLUSION: An ERAS protocol for renal transplant patients is feasible. Our data show that successful implementation of ERAS in kidney transplantation is possible and results in significant cost savings due to shorter length of stay.

A Combinatorial Protein Microarray for Probing Materials Interaction with Pancreatic Islet Cell Populations.

Pancreatic islet transplantation has become a recognized therapy for insulin-dependent diabetes mellitus. During isolation from pancreatic tissue, the islet microenvironment is disrupted. The extracellular matrix (ECM) within this space not only provides structural support, but also actively signals to regulate islet survival and function. In addition, the ECM is responsible for growth factor presentation and sequestration. By designing biomaterials that recapture elements of the native islet environment, losses in islet function and number can potentially be reduced. Cell microarrays are a high throughput screening tool able to recreate a multitude of cellular niches on a single chip. Here, we present a screening methodology for identifying components that might promote islet survival. Automated fluorescence microscopy is used to rapidly identify islet derived cell interaction with ECM proteins and immobilized growth factors printed on arrays. MIN6 mouse insulinoma cells, mouse islets and, finally, human islets are progressively screened. We demonstrate the capability of the platform to identify ECM and growth factor protein candidates that support islet viability and function and reveal synergies in cell response.

Gene therapy to improve pancreatic islet transplantation for Type 1 diabetes mellitus.

Pancreatic islet transplantation is a promising treatment option for Type 1 Diabetics, offering improved glycaemic control through restoration of insulin production and freedom from life-threatening hypoglycaemic episodes. Implementation of the Edmonton protocol in 2000, a glucocorticoid-free immunosuppressive regimen has led to improved islet transplantation success. >50% of islets are lost post-transplantation primarily through cytokine-mediated apoptosis, ischemia and hypoxia. Gene therapy presents a novel strategy to modify islets for improved survival post-transplantation. Current islet gene therapy approaches aim to improve islet function, block apoptosis and inhibit rejection. Gene transfer vectors include adenoviral, adeno-associated virus, herpes simplex virus vectors, retroviral vectors (including lentiviral vectors) and non-viral vectors. Adeno-associated virus is currently the best islet gene therapy vector, due to the vectors minimal immunogenicity and high safety profile. In animal models, using viral vectors to deliver genes conferring local immunoregulation, anti-apoptotic genes or angiogenic genes to islets can significantly improve islet survival in the early post-transplant period and influence long term engraftment. With recent improvements in gene delivery and increased understanding of the mechanisms underlying graft failure, gene therapy for islet transplantation has the potential to move closer to the clinic as a treatment for patients with Type 1 Diabetes.

Review of Epstein-Barr virus and post-transplant lymphoproliferative disorder post-solid organ transplantation.

Post-transplant lymphoproliferative disorder (PTLD) following solid organ transplantation is an important form of post-transplant malignancy. PTLD is typically associated with Epstein-Barr virus (EBV) and occurs in the setting of profound immunosuppression resulting in a deficiency of EBV-specific cytotoxic T lymphocytes (CTL). Predisposing factors include EBV mismatch between donor and recipient, use of immunosuppression especially T-cell depletive therapies and genetic predisposition of recipients. The standard approach has been to reduce immunosuppression but is often insufficient to induce tumour regression. Further understanding of the immunobiology of PTLD has resulted in improved monitoring techniques (including EBV viral load determined by polymerase chain reaction) and newer treatment options. Recent work has highlighted a potential role for dendritic cells in both the pathogenesis and treatment of PTLD. Current treatment modalities include adoptive immunotherapy using ex vivo generated autologous EBV-specific CTL or allogeneic CTL, cytokine therapies, antiviral agents, and more recently, rituximab and dendritic-cell based therapies. This review focuses on the developments and progress in the pathogenesis, diagnosis and treatment of PTLD.