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2013 - CTS 2013 Congress


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Oral Communications 11

23.5 - Islet oxygen consumption rate predicts clinical islet allo-transplant insulin independence for first transplants

Presenter: Klearchos K, Papas, Tucson, United States
Authors: Jennifer P Kitzmann1,2, Doug O'Gorman1,2, Tatsuya Kin1,2, Angelika C Gruessner1,2, Peter Senior1,2, Sharleen Imes1,2, Rainer W Gruessner1,2, AM James Shapiro1,2, Klearchos K Papas1,2

Islet oxygen consumption rate predicts clinical islet allo-transplant insulin independence for first transplants

Jennifer P Kitzmann1,2, Doug O'Gorman1,2, Tatsuya Kin1,2, Angelika C Gruessner1,2, Peter Senior1,2, Sharleen Imes1,2, Rainer W Gruessner1,2, AM James Shapiro1,2, Klearchos K Papas1,2

1Surgery, University of Arizona, Tucson, AZ, United States; 2Clinical Islet Transplant Program, University of Alberta, Edmonton, AB, Canada

Human islet allo-transplantation (ITx) is in phase III clinical registration trials in the US and standard of care in several other countries. Current clinical islet product release criteria include viability based on cell membrane integrity (>70%), glucose stimulated insulin release (GSIR; >1 stimulation index, SI), and islet equivalent (IE) dose based on counts (IE per kilogram body weight; >5,000). However, only a fraction of patients transplanted with islets that meet or exceed these release criteria become insulin independent. There is a need for more reliable assays that are predictive of clinical transplant outcome (CTO). Measurements of islet oxygen consumption rate (OCR) have been reported as highly predictive of transplant outcome in small and large animal models as well as clinical islet auto-transplantation. In this paper we report on the assessment of clinical islet allograft preparations using OCRtx/kg BW (a measure of transplanted viable IE – the product of total IE transplanted and islet viability measured by OCR/DNA) and current product release assays in a series of 13 first transplant recipients. The predictive capability of each assay was examined using receiver operating characteristic (ROC) curve analysis and the area under the curve (AUC) was determined. Successful graft function was defined as 100% insulin independence within 45 days post-transplant. All transplanted preparations met, or exceeded, current product release criteria. However, only 38% of transplanted recipients were insulin independent within 45 days. The results showed that OCRtx/kg BW was the measure most predictive of CTO (AUC: 1.000; Figure 1a). IE dose was also highly predictive (AUC: 0.975; Figure 1b) while GSIR and membrane integrity stains were not (AUC: 0.825, 0.625 respectively; Figure 1c,d). Interestingly, preparations with higher GSIR were less likely to reverse diabetes. In conclusion, OCRtx/kg BW can predict CTO with high specificity and sensitivity and is a useful tool for evaluating islet preparations prior to clinical ITx.

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