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People with type 1 diabetes and kidney failure have an increased risk for major adverse cardiovascular events (MACE). Simultaneous pancreas and kidney transplantation (SPKT) improves survival, but the long-term risk for MACE is uncertain. RESEARCH DESIGN AND METHODS We assessed the frequency and risk factors for MACE (defined as fatal cardiovascular disease and nonfatal myocardial infarction or stroke) and related nonfatal MACE to allograft failure in SPKT recipients with type 1 diabetes who underwent transplantation between 2001 and 2015 in the U.K. In a subgroup, we related a pretransplant cardiovascular risk score to MACE. RESULTS During 5 years of follow-up, 133 of 1,699 SPKT recipients (7.8%) experienced a MACE. In covariate-adjusted models, age (hazard ratio 1.04 per year [95% CI 1.01-1.07]), prior myocardial infarction (2.6 [1.3-5.0]), stroke (2.3 [1.2-4.7]), amputation (2.0 [1.02-3.7]), donor history of hypertension (1.8 [1.05-3.2]), and waiting time (1.02 per month [1.0-1.04]) were significant predictors. Nonfatal MACE predicted subsequent allograft failure (renal 1.6 [1.06-2.6]; pancreas 1.7 [1.09-2.6]). In the subgroup, the pretransplant cardiovascular risk score predicted MACE (1.04 per 1% increment [1.02-1.06]). CONCLUSIONS We report a high rate of MACE in SPKT recipients. There are a number of variables that predict MACE, while nonfatal MACE increase the risk of subsequent allograft failure. It may be beneficial that organs from hypertensive donors are matched to recipients with lower cardiovascular risk. Pretransplant cardiovascular risk scoring may help to identify patients who would benefit from risk factor optimization or alternative transplant therapies and warrants validation nationally. Type 1 diabetes affects ;400,000 people in the U.K. (1). Type 1 diabetes significantly reduces life expectancy predominantly because of cardiovascular disease (CVD) complications (2,3). The addition of chronic kidney disease further increases CVD risk (4). We have shown that simultaneous pancreas and kidney transplantation (SPKT)

Aims/hypothesis Approximately 50% of organ donors develop hyperglycaemia in intensive care, which is managed with insulin therapy. We aimed to determine the relationships between donor insulin use (DIU) and graft failure in pancreas transplantation. Methods UK Transplant Registry organ donor data were linked with national data from the UK solid pancreas transplant programme. All pancreas transplants performed between 2004 and 2016 with complete follow-up data were included. Logistic regression models determined associations between DIU and causes of graft failure within 3 months. Area under the receiver operating characteristic curve (aROC) and net reclassification improvement (NRI) assessed the added value of DIU as a predictor of graft failure. Results In 2168 pancreas transplant recipients, 1112 (51%) donors were insulin-treated. DIU was associated with a higher risk of graft loss from isolated islet failure: OR (95% CI), 1.79 (1.05, 3.07), p = 0.03, and this relationship was duration/dose dependent. DIU was also associated with a higher risk of graft loss from anastomotic leak (2.72 [1.07, 6.92], p = 0.04) and a lower risk of graft loss from thrombosis (0.62 [0.39, 0.96], p = 0.03), although duration/dose-dependent relationships were only identified in pancreas transplant alone/pancreas after kidney transplant recipients with grafts failing due to thrombosis (0.86 [0.74, 0.99], p = 0.03). The relationships between donor insulin characteristics and isolated islet failure remained significant after adjusting for potential confounders: DIU 1.75 (1.02, 2.99), p = 0.04; duration 1.08 (1.01, 1.16), p = 0.03. In multivariable analyses, donor insulin characteristics remained significant predictors of lower risk of graft thrombosis in pancreas transplant alone/pancreas after kidney transplant recipients: DIU, 0.34 (0.13, 0.90), p = 0.03; insulin duration/dose, 0.02 (0.001, 0.85), p = 0.04. When data on insulin were added to models predicting isolated islet failure, a significant improvement in discrimination and risk reclassification was observed in all models: no DIU aROC 0.56; DIU aROC 0.57, p = 0.86; NRI 0.28, p < 0.00001; insulin duration aROC 0.60, p = 0.47; NRI 0.35, p < 0.00001. Conclusions/interpretation DIU predicts graft survival in pancreas transplant recipients. This assessment could help improve donor selection and thereby improve patient and graft outcomes. Graphical abstract