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Insulin therapy in pancreas donors as a predictor of subsequent transplant outcome

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Presented at

BTS 2017

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Abstract

Introduction: Brain stem death results in high levels of systemic catecholamines and inflammation affecting all donor organs. These changes, and the routine use of high-dose corticosteroids in intensive care units (ICU), contribute to hyperglycaemia which is managed with insulin in about half of all donors. We hypothesised that donor insulin use (DIU) may be a surrogate of irreversible pancreatic beta-cell death. We aimed to assess relationships of DIU to pancreas transplant outcome and function. Methods: National data from the UK Transplant registry (2004-2016) was reviewed retrospectively to determine donor variables associated with DIU and its relationship with graft survival. Early non-technical graft failure (transplant pancreatitis) was assessed from histology reports using our regional data (2010-2015). In a sub-group, we determined relationships between DIU and early c-peptide secretion. Results: In 1943 pancreas transplant donors nationally, 1005 (52%) required insulin. Insulin-treated donors were older (p=0.016, T-test), female (p<0.0001, Chi2), DBDs (p<0.0001, Chi2), hypotensive (p=0.004, Chi2) and more likely to die from meningitis (p=0.0001, Chi2). Donors not treated with insulin were more likely to die from hypoxic brain damage (p=0.005, Chi2) or trauma (p=0.002, Chi2), and were more likely to have suffered cardiac arrest (p=0.015, Chi2). Using a Cox-regression analysis, there was no difference in graft survival (median follow-up: 3 years) by DIU: donor variable-adjusted HR (95%CI), insulin vs. no insulin: 0.93 (0.76-1.14), p=0.684; donor and recipient variable-adjusted HR 1.0, (0.77-1.29), p= 0.978. Early pancreas graft loss due to non-technical failure was more commonly associated with DIU (proportion failing: with vs. without insulin: 6/72 (8.3%) vs 1/96 (1%), p=0.02, Chi2). In a sub-group (n=46), pancreas graft function (c-peptide levels) 72-hours post-transplant was lower in donors requiring insulin (insulin vs. no insulin donors: 4.3 vs. 7.5 ng/mL, p<0.001, T-test). Discussion: DIU could be a useful clinical predictor of early pancreas graft outcome and function. Further understanding of the physiological processes causing hyperglycaemia in donors could improve donor selection and lead to better outcomes.

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© Copyright 2020 Morressier GmbH.
All rights reserved.