Islet Oxygen Consumption Rate (OCR) Dose Predicts Insulin Independence in Clinical Islet Autotransplantation

Background: Reliable in vitro islet quality assessment assays that can be performed routinely, prospectively, and are able to predict clinical transplant outcomes are needed. In this paper we present data on the utility of an assay based on cellular oxygen consumption rate (OCR) in predicting clinical islet autotransplant (IAT) insulin independence (II). IAT is an attractive model for evaluating characterization assays regarding their utility in predicting II due to an absence of confounding factors such as immune rejection and immunosuppressant toxicity. Methods: Membrane integrity staining (FDA/PI), OCR normalized to DNA (OCR/DNA), islet equivalent (IE) and OCR (viable IE) normalized to recipient body weight (IE dose and OCR dose), and OCR/DNA normalized to islet size index (ISI) were used to characterize autoislet preparations (n = 35). Correlation between pre-IAT islet product characteristics and II was determined using receiver operating characteristic analysis. Results: Preparations that resulted in II had significantly higher OCR dose and IE dose (p<0.001). These islet characterization methods were highly correlated with II at 6–12 months post-IAT (area-under-the-curve (AUC) = 0.94 for IE dose and 0.96 for OCR dose). FDA/PI (AUC = 0.49) and OCR/DNA (AUC = 0.58) did not correlate with II. OCR/DNA/ISI may have some utility in predicting outcome (AUC = 0.72). Conclusions: Commonly used assays to determine whether a clinical islet preparation is of high quality prior to transplantation are greatly lacking in sensitivity and specificity. While IE dose is highly predictive, it does not take into account islet cell quality. OCR dose, which takes into consideration both islet cell quality and quantity, may enable a more accurate and prospective evaluation of clinical islet preparations

First World Consensus Conference on pancreas transplantation: Part II - recommendations.

Funder: Fondazione Pisa, Pisa, Italy; Id: http://dx.doi.org/10.13039/100007368Funder: Tuscany Region, Italy; Id: http://dx.doi.org/10.13039/501100009888Funder: Pisa University Hospital, Pisa, ItalyFunder: University of Pisa, Pisa, Italy; Id: http://dx.doi.org/10.13039/501100007514The First World Consensus Conference on Pancreas Transplantation provided 49 jury deliberations regarding the impact of pancreas transplantation on the treatment of diabetic patients, and 110 experts' recommendations for the practice of pancreas transplantation. The main message from this consensus conference is that both simultaneous pancreas-kidney transplantation (SPK) and pancreas transplantation alone can improve long-term patient survival, and all types of pancreas transplantation dramatically improve the quality of life of recipients. Pancreas transplantation may also improve the course of chronic complications of diabetes, depending on their severity. Therefore, the advantages of pancreas transplantation appear to clearly surpass potential disadvantages. Pancreas after kidney transplantation increases the risk of mortality only in the early period after transplantation, but is associated with improved life expectancy thereafter. Additionally, preemptive SPK, when compared to SPK performed in patients undergoing dialysis, appears to be associated with improved outcomes. Time on dialysis has negative prognostic implications in SPK recipients. Increased long-term survival, improvement in the course of diabetic complications, and amelioration of quality of life justify preferential allocation of kidney grafts to SPK recipients. Audience discussions and live voting are available online at the following URL address: http://mediaeventi.unipi.it/category/1st-world-consensus-conference-of-pancreas-transplantation/246

2011 Update on Pancreas Transplantation: Comprehensive Trend Analysis of 25,000 Cases Followed Up Over the Course of Twenty-Four Years at the International Pancreas Transplant Registry (IPTR)

AIM: This study aimed to analyze the outcome of pancreas and pancreas-kidney transplantations based on the comprehensive follow-up data reported to the International Pancreas Transplant Registry (IPTR). METHODS: As of December 2010, more than 35,000 pancreas transplantations have been reported to the IPTR: more than 24,000 transplantations in the US and more than 12,000 outside the US. Cases with follow-up information until March 2011 were included in the analysis. RESULTS: Pancreas transplantations in diabetic patients were divided into 3 categories: those performed simultaneously with a kidney (SPK) (75%), those given after a previous kidney transplantation (PAK) (18%), and pancreas transplantation alone (PTA) (7%). The total number of pancreas transplantations steadily increased until 2004 but has since declined. The largest decrease was seen in PAK, which decreased by 50% from 2004 through 2010. Comparatively, the number of SPK decreased by 7% during this time. Era analysis of US transplantations between 1987 and 2010 showed changes in recipient and donor characteristics. Recipient age at transplantation increased significantly as well as transplantations in type 2 diabetes patients. The trend over time was towards tighter donor criteria. There was a concentration on younger donors, preferable trauma victims, with short preservation time. Surgical techniques for the drainage of the pancreatic duct changed over time, too. Now enteric drainage is the predominantly used technique in combination with systemic drainage of the venous effluent of the pancreas graft. Immunosuppressive protocols developed towards antibody induction therapy with tacrolimus and MMF as maintenance therapy. The rate of transplantations with steroid avoidance increased over time in all 3 categories. These changes have led to improved patient and graft survival. Patient survival now reaches over 95% at one year post-transplant and over 83% after 5 years. The best graft survival was found in SPK with 86% pancreas and 93% kidney graft function at one year. PAK pancreas graft function reached 80%, and PTA pancreas graft function reached 78% at one year. In all 3 categories, early technical graft loss rates decreased significantly to 8-9%. Likewise, the 1-year immunological graft loss rate also decreased: in SPK, the immunological 1-year graft loss rate was 1.8%, in PAK 3.7%, and in PTA 6.0%. CONCLUSIONS: Patient survival and graft function improved significantly over the course of 24 years of pancreas transplantation in all 3 categories. With further reduction in surgical complications and improvements in immunosuppressive protocols, pancreas transplantation offers excellent outcomes for patients with labile diabetes

A Decade of Pancreas Transplantation—A Registry Report

Since the first pancreas transplant in 1966, over 67,000 pancreas transplants have been performed worldwide and the number is growing. While the number of transplants in the US has changed only slightly over the past decade, many countries outside the US have shown strong growth in transplant numbers. The worldwide growth in numbers is due to the increasing number of patients with type 2 diabetes mellitus receiving a pancreas transplant. Only during the COVID-19 pandemic in 2020 and 2021 did transplant numbers decline, but they started to recover in 2022. The decline was especially noted for solitary transplants. This development over time was due to excellent patient and graft survival after simultaneous pancreas and kidney transplant (SPK). Patient survival at three years was >90% in SPK as well as in solitary transplants. At 3 years post-transplant, SPK pancreas graft survival was over 86% and SPK kidney graft survival over 90%. In pancreas transplants alone (PTA) and in pancreas after kidney transplants, the 3-year graft function reached 75%. The main reasons for advancement in outcome were reductions in technical failures and immunological graft losses. These improvements were due to better patient and donor selection, standardization of surgical techniques, and superior immunosuppressive protocols

Mycophenolate Mofetil in Pancreas Transplantation

Background: Mycophenolate mofetil (MMF) has been shown to decrease the incidence of acute rejection episodes after kidney transplantation. The use of MMF along with tacrolimus for \u3e or =1 year after pancreas transplantation has not been studied in a large single-center analysis. Methods: Between July 1, 1995 and June 30, 1997, both MMF and tacrolimus were given to 120 pancreas transplant recipients. By category, 61 underwent simultaneous pancreas-kidney transplantation (SPK); 44 underwent pancreas transplantation after previous kidney transplantation (PAK); and 15 underwent pancreas transplantation alone (PTA). By donor source, 86% of the grafts were from a cadaver, and 14% were from a living-related donor. Induction therapy was with MMF, tacrolimus, prednisone, and antithymocyte globulin (n=109) or OKT3 (n=2). Until oral intake was resumed, recipients initially received intravenous azathioprine. Side effects were as follows: gastrointestinal (GI) toxicity in 53% of recipients receiving combined MMF and tacrolimus therapy; bone marrow toxicity in 24% of recipients receiving MMF alone; nephrotoxicity in 18% and neurotoxicity in 11% of recipients receiving tacrolimus alone. We did a matched-pair analysis to compare outcome in MMF versus azathioprine recipients, using the database of the International Pancreas Transplant Registry. Matching criteria included transplantation category, transplantation number, recipient and donor age, duct management, HLA typing, and transplantation year. Results: One-year patient survival rates were 98% for SPK, 98% for PAK, and 100% for PTA (P=NS). For SPK recipients, 1-year pancreas graft survival rates were 86% with MMF versus 79% with azathioprine (P=NS); kidney graft survival rates were 96% with MMF versus 86% with azathioprine (P=NS). The incidence of first rejection episodes at 1 year was significantly lower for MMF recipients (15% with MMF versus 43% with azathioprine) (P = 0.0003). For recipients of solitary pancreas transplants (PTA and PAK), we found no difference in graft survival rates between MMF and azathioprine. The conversion rate from MMF to azathioprine at 1 year was 14% for SPK recipients, 26% for PAK, and 39% for PTA (P \u3c 0.007). The most common reason for conversion was GI toxicity, in particular for nonuremic (PTA) or posturemic (PAK) recipients. The rates of posttransplant infection and lymphoproliferative disease were low for recipients on MMF and tacrolimus. Conclusions: The combination of MMF and tacrolimus after pancreas transplantation is highly effective and safe. For SPK recipients, the incidence of acute reversible rejection episodes was significantly lower with MMF than with azathioprine. The conversion rate from MMF to azathioprine because of GI toxicity was lowest for SPK and highest for PTA recipients

Mycophenolate Mofetil in Pancreas Transplantation

Background: Mycophenolate mofetil (MMF) has been shown to decrease the incidence of acute rejection episodes after kidney transplantation. The use of MMF along with tacrolimus for \u3e or =1 year after pancreas transplantation has not been studied in a large single-center analysis. Methods: Between July 1, 1995 and June 30, 1997, both MMF and tacrolimus were given to 120 pancreas transplant recipients. By category, 61 underwent simultaneous pancreas-kidney transplantation (SPK); 44 underwent pancreas transplantation after previous kidney transplantation (PAK); and 15 underwent pancreas transplantation alone (PTA). By donor source, 86% of the grafts were from a cadaver, and 14% were from a living-related donor. Induction therapy was with MMF, tacrolimus, prednisone, and antithymocyte globulin (n=109) or OKT3 (n=2). Until oral intake was resumed, recipients initially received intravenous azathioprine. Side effects were as follows: gastrointestinal (GI) toxicity in 53% of recipients receiving combined MMF and tacrolimus therapy; bone marrow toxicity in 24% of recipients receiving MMF alone; nephrotoxicity in 18% and neurotoxicity in 11% of recipients receiving tacrolimus alone. We did a matched-pair analysis to compare outcome in MMF versus azathioprine recipients, using the database of the International Pancreas Transplant Registry. Matching criteria included transplantation category, transplantation number, recipient and donor age, duct management, HLA typing, and transplantation year. Results: One-year patient survival rates were 98% for SPK, 98% for PAK, and 100% for PTA (P=NS). For SPK recipients, 1-year pancreas graft survival rates were 86% with MMF versus 79% with azathioprine (P=NS); kidney graft survival rates were 96% with MMF versus 86% with azathioprine (P=NS). The incidence of first rejection episodes at 1 year was significantly lower for MMF recipients (15% with MMF versus 43% with azathioprine) (P = 0.0003). For recipients of solitary pancreas transplants (PTA and PAK), we found no difference in graft survival rates between MMF and azathioprine. The conversion rate from MMF to azathioprine at 1 year was 14% for SPK recipients, 26% for PAK, and 39% for PTA (P \u3c 0.007). The most common reason for conversion was GI toxicity, in particular for nonuremic (PTA) or posturemic (PAK) recipients. The rates of posttransplant infection and lymphoproliferative disease were low for recipients on MMF and tacrolimus. Conclusions: The combination of MMF and tacrolimus after pancreas transplantation is highly effective and safe. For SPK recipients, the incidence of acute reversible rejection episodes was significantly lower with MMF than with azathioprine. The conversion rate from MMF to azathioprine because of GI toxicity was lowest for SPK and highest for PTA recipients