Long-term Outcomes With Islet-Alone and Islet-After-Kidney Transplantation for Type 1 Diabetes in the Clinical Islet Transplantation Consortium: The CIT-08 Study.

OBJECTIVE: To determine long-term outcomes for islet-alone and islet-after-kidney transplantation in adults with type 1 diabetes complicated by impaired awareness of hypoglycemia. RESEARCH DESIGN AND METHODS: This was a prospective interventional and observational cohort study of islet-alone (n = 48) and islet-after-kidney (n = 24) transplant recipients followed for up to 8 years after intraportal infusion of one or more purified human pancreatic islet products under standardized immunosuppression. Outcomes included duration of islet graft survival (stimulated C-peptide ≥0.3 ng/mL), on-target glycemic control (HbA1c <7.0%), freedom from severe hypoglycemia, and insulin independence. RESULTS: Of the 48 islet-alone and 24 islet-after-kidney transplantation recipients, 26 and 8 completed long-term follow-up with islet graft function, 15 and 7 withdrew from follow-up with islet graft function, and 7 and 9 experienced islet graft failure, respectively. Actuarial islet graft survival at median and final follow-up was 84% and 56% for islet-alone and 69% and 49% for islet-after-kidney (P = 0.007) with 77% and 49% of islet-alone and 57% and 35% of islet-after-kidney transplantation recipients maintaining posttransplant HbA1c <7.0% (P = 0.0017); freedom from severe hypoglycemia was maintained at >90% in both cohorts. Insulin independence was achieved by 74% of islet-alone and islet-after-kidney transplantation recipients, with more than one-half maintaining insulin independence during long-term follow-up. Kidney function remained stable during long-term follow-up in both cohorts, and rates of sensitization against HLA were low. Severe adverse events occurred at 0.31 per patient-year for islet-alone and 0.43 per patient-year for islet-after-kidney transplantation. CONCLUSIONS: Islet transplantation results in durable islet graft survival permitting achievement of glycemic targets in the absence of severe hypoglycemia for most appropriately indicated recipients having impaired awareness of hypoglycemia, with acceptable safety of added immunosuppression for both islet-alone and islet-after-kidney transplantation.

Defining Outcomes for ß-cell Replacement Therapy in the Treatment of Diabetes: A Consensus Report on the Igls Criteria From the IPITA/EPITA Opinion Leaders Workshop.

ß-cell replacement therapy, available currently as pancreas or islet transplantation, has developed without a clear definition of graft functional and clinical outcomes. The International Pancreas and Islet Transplant Association and European Pancreas and Islet Transplantation Association held a workshop to develop consensus for an International Pancreas and Islet Transplant Association and European Pancreas and Islet Transplant Association Statement on the definition of function and failure of current and future forms of ß-cell replacement therapy. There was consensus that ß-cell replacement therapy could be considered as a treatment for ß-cell failure, regardless of etiology and without requiring undetectable C-peptide, accompanied by glycemic instability with either problematic hypoglycemia or hyperglycemia. Glycemic control should be assessed at a minimum by glycated hemoglobin (HbA1c) and the occurrence of severe hypoglycemia. Optimal ß-cell graft function is defined by near-normal glycemic control (HbA1c ≤6.5% [48 mmol/mol]) without severe hypoglycemia or requirement for insulin or other antihyperglycemic therapy, and with an increase over pretransplant measurement of C-peptide. Good ß-cell graft function requires HbA1c less than 7.0% (53 mmol/mol) without severe hypoglycemia and with a significant (>50%) reduction in insulin requirements and restoration of clinically significant C-peptide production. Marginal ß-cell graft function is defined by failure to achieve HbA1c less than 7.0% (53 mmol/mol), the occurrence of any severe hypoglycemia, or less than 50% reduction in insulin requirements when there is restoration of clinically significant C-peptide production documented by improvement in hypoglycemia awareness/severity, or glycemic variability/lability. A failed ß-cell graft is defined by the absence of any evidence for clinically significant C-peptide production. Optimal and good function are considered successful clinical outcomes.

High risk, high reward: An analysis of outcomes for candidates awaiting hepatic re-transplantation.

 Background. Liver re-transplantation (re-OLT) remains the only feasible option for patients with graft failure following liver transplantation. Sparse resources and a growing waitlist mandate that available grafts are allocated properly. We studied the differences in patient demographics, characteristics, and survival for those listed for re-OLT in a region with prolonged wait times. MATERIAL AND METHODS: We performed a single-center retrospective study, from 2005 to 2013, of adult candidates listed for liver re-OLT at a tertiary care center within United Network for Organ Sharing (UNOS) region 1. RESULTS: Of the 48 patients listed for re-OLT, 1(2%) improved while waiting, 14(29%) died while waiting, and 33(69%) underwent re-OLT. Those re-transplanted represented 11% of the center's adult liver transplant volume during the same time period. Comparing those who died while waiting to those who achieved re-OLT, there was no significant difference in age (median 52 vs. 48 years, p=0.56) or MELD at second listing (median 29 vs. 26, p = 0.90). Waitlisted candidates who failed to achieve re-transplant died on average of 15.5 days (IQR 36 days) days after re-listing. Those re-transplanted achieved 3-year survival of 70% and there was no significant difference in 3-year survival of those re-transplanted within or beyond 90 days of first transplant (70% vs. 69.5%, p = 0.28). CONCLUSIONS: In conclusion, re-OLT is the only viable option for candidates with nonreversible liver graft failure. Inability to achieve re-OLT leads to nearly assured and expeditious death. Despite technical challenges, in experienced hands excellent long term survival following re-OLT can be achieved.

Liver transplantation utilizing a severely fractured graft: every organ counts.

In our current era where shortage of liver grafts is commonplace, utilization of traumatic liver grafts may represent an opportunity to expand the organ donor pool without compromising graft survival. However, data on liver transplantation using a fractured liver allograft is scarce, with only small case series and reports found in the literature. In this report, we describe our experience with utilizing a liver graft with grade IV hepatic fracture for transplantation. At 12 months follow up, the recipient has excellent graft function and has regained an excellent quality of life. We demonstrated that the ability to safely use a fractured liver graft represents an additional avenue for expansion of the deceased donor population, especially in regions with prolonged waitlist times.