Results Of Pancreas Transplantation Research Articles

Influence of Recipient Education on the Outcome of Simultaneous Pancreas and Kidney Transplantation

Influence of Recipient Education on the Outcome of Simultaneous Pancreas and Kidney Transplantation

325.6: Impact of pre-transplant HbA1c levels on pancreas transplant outcomes.

325.6: Impact of pre-transplant HbA1c levels on pancreas transplant outcomes.

325.3: A comparative analysis of pancreas transplant outcomes in type 1 and type 2 diabetes recipients at a single center.

325.3: A comparative analysis of pancreas transplant outcomes in type 1 and type 2 diabetes recipients at a single center.

Donor Blood Tests do Not Predict Pancreas Graft Survival After Simultaneous Pancreas Kidney Transplantation; a National Cohort Study.

Simultaneous pancreas-kidney (SPK) transplantation improves quality of life and limits progression of diabetic complications. There is reluctance to accept pancreata from donors with abnormal blood tests, due to concern of inferior outcomes. We investigated whether donor amylase and liver blood tests (markers of visceral ischaemic injury) predict pancreas graft outcome using the UK Transplant Registry (2016-2021). 857 SPK recipients were included (619 following brainstem death, 238 following circulatory death). Peak donor amylase ranged from 8 to 3300U/L (median = 70), and this had no impact on pancreas graft survival when adjusting for multiple confounders (aHR = 0.944, 95% CI = 0.754-1.81). Peak alanine transaminases also did not influence pancreas graft survival in multivariable models (aHR = 0.967, 95% CI = 0.848-1.102). Restricted cubic splines were used to assess associations between donor blood tests and pancreas graft survival without assuming linear relationships; these confirmed neither amylase, nor transaminases, significantly impact pancreas transplant outcome. This is the largest, most statistically robust study evaluating donor blood tests and transplant outcome. Provided other factors are acceptable, pancreata from donors with mild or moderately raised amylase and transaminases can be accepted with confidence. The use of pancreas grafts from such donors is therefore a safe, immediate, and simple approach to expand the donor pool to reach increasing demands.

Pancreas Transplantation Outcome Predictions-PTOP: A Risk Prediction Tool for Pancreas and Pancreas-Kidney Transplants Based on a European Cohort.

For patients with complicated type 1 diabetes having, for example, hypoglycemia unawareness and end-stage renal disease because of diabetic nephropathy, combined pancreas and kidney transplantation (PKT) is the therapy of choice. However, the shortage of available grafts and complex impact of risk factors call for individualized, impartial predictions of PKT and pancreas transplantation (PT) outcomes to support physicians in graft acceptance decisions. Based on a large European cohort with 3060 PKT and PT performed between 2006 and 2021, the 3 primary patient outcomes time to patient mortality, pancreas graft loss, and kidney graft loss were visualized using Kaplan-Meier survival curves. Multivariable Cox proportional hazards models were developed for 5- and 10-y prediction of outcomes based on 26 risk factors. Risk factors associated with increased mortality included previous kidney transplants, rescue allocations, longer waiting times, and simultaneous transplants of other organs. Increased pancreas graft loss was positively associated with higher recipient body mass index and donor age and negatively associated with simultaneous transplants of kidneys and other organs. Donor age was also associated with increased kidney graft losses. The multivariable Cox models reported median C-index values were 63% for patient mortality, 62% for pancreas loss, and 55% for kidney loss. This study provides an online risk tool at https://riskcalc.org/ptop for individual 5- and 10-y post-PKT and PT patient outcomes based on parameters available at the time of graft offer to support critical organ acceptance decisions and encourage external validation in independent populations.

Elevated liver enzymes at the time of deceased donor organ donation do not affect recipient or pancreas allograft survival following pancreas transplantation

BackgroundThere is a lack of data on the impact of donor liver function tests (LFTs) on pancreas transplantation outcomes. Understanding their contribution could expand the donor pool. MethodsUsing the UNOS database, data from January 2010–2022 was retrospectively analyzed. Multivariable cox regressions were performed to evaluate the association between LFTs (AST, ALT and total bilirubin levels), graft failure and mortality up to three years post-transplant. Results9138 pancreas transplants were completed. Multivariate analysis showed no association between donor AST values > 500 U/L and increased rates of graft failure (p = 0.826) or mortality (p = 0.836). Similar findings were noted for donor ALT values > 500 U/L (p = 0.522 and p = 0.997, respectively). There was no correlation with graft failure (p = 0.322) or mortality (p = 0.423) for total bilirubin levels >3 mg/dL. ConclusionLFTs in the deceased pancreas donor did not increase risk of graft failure or mortality following pancreas transplantation. Elevated LFTs should not serve as absolute contraindications to transplant.

Pancreas Transplantation for the Treatment of Pancreatic Exocrine Disorders

Pancreas transplantation is mostly performed to cure diabetes mellitus. However, patients with chronic pancreatitis, cystic fibrosis, benign pancreatic tumors or patients with other exocrine disorders of the pancreas can also be candidates for a pancreas transplant in combination with a kidney, liver or lung or for a pancreas transplant alone. With improvement in surgical techniques and immunosuppressive therapy, pancreas transplant outcomes have improved significantly over the past decade. Mounting evidence supports pancreas transplantation for the treatment of exocrine disorders as an important therapeutic option to restore both endocrine and exocrine function of the pancreas. Patient and graft survival rates are similar to those for pancreas transplants in diabetic patients. A successful pancreas transplant is also more cost efficient and puts less burden on health care spending. However, the risk of immunosuppression and surgery should be carefully evaluated and discussed with the patient. In this review article, we discuss pancreas transplantation for pancreatic exocrine disorders: indications, other treatment options, and outcomes.

O172: Donor blood tests and pancreas outcome in simultaneous pancreas kidney transplantation, a national cohort study

Abstract Introduction Simultaneous pancreas-kidney (SPK) transplantation improves quality of life in people with diabetes and end-stage renal disease, and limits the progression of diabetes related complications. Many surgeons are reluctant to accept the pancreas of a donor with raised amylase, due to concern of potentially inferior outcomes. We aim to ascertain whether donor amylase and liver blood tests (a marker of visceral ischaemic injury) predict pancreas transplant outcome. Methods This retrospective cohort study used the NHS registry on adult SPK transplantation (2016-2021). Adjusted regressions models assessed the effect of donor amylase and liver blood tests on pancreas transplant outcome. Results 857 SPK recipients were included (619 following brainstem death, 238 following circulatory death). Peak donor amylase ranged from 8-3300U/L (median=70). Donor peak amylase had no significant impact on pancreas graft survival when adjusting for multiple confounders (aHR=0.944, 95% CI=0.754-1.81). Median peak alanine transaminase and aspartate transaminase was 67U/L and 72U/L (range 8-5930 and 0-7910U/L). Neither of these influenced pancreas graft survival in multivariable models (aHR=0.967, 95% CI=0.848-1.102 and aHR=0.908, 95% CI=0.771-1.070, respectively). Restricted cubic splines were used to assess the relationship between donor blood tests and pancreas graft survival without assuming linear relationships; these confirmed neither amylase, nor transaminases, significantly impact on pancreas transplant outcome. Conclusions Donor amylase and transaminases do not predict transplant outcomes. Therefore, raised donor amylase or transaminases should not be considered a barrier to organ utilisation. The use of pancreas grafts from donors with hyperamylasaemia is a safe, immediate, and simple approach to expand the donor pool.

O236: The Impact of HLA Matching on Pancreas and Simultaneous Pancreas-Kidney (SPK) Transplantation Outcomes

Abstract Background This study evaluates the controversial impact of human leukocyte antigen (HLA) matching on pancreas graft survival and acute rejection. Methods Utilizing a large-scale multi-center database (UNOS/OPTN), we identified 8,005 pancreas and 7,850 simultaneous pancreas-kidney (SPK) transplant patients. Patients were classified into HLA matched (0-3 mismatches) and mismatched (4-6 mismatches) groups. Subsequently, utilizing multivariate Cox analysis, we evaluated risk-adjusted outcomes, represented through Kaplan-Meier survival curves. We also examined differences in graft survival and acute rejection based on transplant type (SPK or pancreas alone) within the same HLA mismatch group. Findings There were no significant differences in pancreas graft survival or acute rejection observed between HLA matched and mismatched groups for both pancreas and SPK transplant recipients (P > 0.05). However, among HLA mismatched patients, pancreas patients exhibited a 629-day lower pancreas graft survival than SPK patients (3774 vs. 4403 days, P < 0.001) and had a higher likelihood of experiencing acute rejection post-transplant (P < 0.001). Similarly, within the HLA matched groups, pancreas patients showed lower graft survival compared to SPK patients (3774 vs. 4403 days, P < 0.001); however, their acute rejection rates did not significantly differ (P > 0.05). Interpretation Although HLA matching was not associated with improved pancreas graft survival or a reduction in acute rejection, the results suggest a potential protective effect of the kidney in SPK transplants against the consequences of HLA mismatching. This underscores the clinical significance of considering the kidney component in donor-recipient matching for pancreas transplantation.

Medical and Surgical Management of the Failed Pancreas Transplant.

Despite the continued improvements in pancreas transplant outcomes in recent decades, a subset of recipients experience graft failure and can experience substantial morbidity and mortality. Here, we summarize what is known about the failed pancreas allograft and what factors are important for consideration of retransplantation. The current definition of pancreas allograft failure and its challenges for the transplant community are explored. The impacts of a failed pancreas allograft are presented, including patient survival and resultant morbidities. The signs, symptoms, and medical and surgical management of a failed pancreas allograft are described, whereas the options and consequences of immunosuppression withdrawal are reviewed. Medical and surgical factors necessary for successful retransplant candidacy are detailed with emphasis on how well-selected patients may achieve excellent retransplant outcomes. To achieve substantial medical mitigation and even pancreas retransplantation, patients with a failed pancreas allograft warrant special attention to their residual renal, cardiovascular, and pulmonary function. Future studies of the failed pancreas allograft will require improved reporting of graft failure from transplant centers and continued investigation from experienced centers.

313.7: Impact of C1q-fixing donor-specific antibodies on pancreas transplant outcomes

313.7: Impact of C1q-fixing donor-specific antibodies on pancreas transplant outcomes

313.8: Mean fluorescence intensity evolution is a more sensitive predictor than simple positivity of posttransplant donor-specific antibodies in pancreas transplantation outcomes

313.8: Mean fluorescence intensity evolution is a more sensitive predictor than simple positivity of posttransplant donor-specific antibodies in pancreas transplantation outcomes

Association of Procurement Time With Pancreas Transplant Outcomes in Brain-Dead Donors.

A brain-death-induced cytokine storm damages organs in an organ donor. However, a longer time period between declaration of brain death and organ procurement (procurement interval) is associated with improved outcomes in kidney, liver, heart, and lung transplantation. The aim of this study was to find the optimal procurement interval for pancreas transplantation. Association of procurement interval with pancreas graft outcomes was analyzed using multivariable models adjusted for variables possibly affecting procurement interval and outcomes. Altogether 10,119 pancreas transplantations were included from the Scientific Registry of Transplant Recipients. The median follow-up was 3.2 (IQR 1.01-6.50) years. During the first year, 832 (9.0%) grafts were lost, including 555 (6.0%) within the first 30days. Longer procurement interval was associated with increased death-censored graft survival in a multivariable model (HR 0.944 95% CI 0.917-0.972, per 10-h increase, p < 0.001). A decreasing hazard of graft loss was observed also with 1-year, but not with 30-day graft survival. During 1-year follow-up, 953 (12.1%) patients had an acute rejection, and longer procurement interval was also associated with less acute rejections (OR 0.937 95% CI 0.900-0.976, per 10-h increase, p = 0.002) in the multivariable model. In conclusion, longer procurement interval is associated with improved long-term outcomes in pancreas transplantation.

Pretransplant C-peptide Levels and Pancreas Transplant Outcomes: Risk and Reward.

We read with interest the report by Parajuli et al1, chronicling the University of Wisconsin experience in simultaneous pancreas-kidney transplantation (SPKT) according to the pretransplant fasting serum C-peptide levels. The authors demonstrated that higher pretransplant C-peptide levels predicted the risk of a composite outcome (combination of pancreas graft failure according to the United Network for Organ Sharing definition and pancreas graft dysfunction defined as initiation of any antidiabetic agent) posttransplant in patients with a type 2 diabetes phenotype.1,2 Recipients were categorized into 3 groups based on pretransplant fasting serum C-peptide levels: low (≤2 ng/mL, n = 14), medium (>2–8 ng/mL, n = 47), and high (>8 ng/mL, n = 15). The uncensored composite outcome of pancreas graft failure or dysfunction occurred in 0% in the low, 23% in the medium, and 33% of patients in the high C-peptide groups, respectively, suggesting that higher levels of pretransplant C-peptide are associated with inferior posttransplant outcomes. These findings confirm our recent report based on a case-controlled, single-center, retrospective study of 46 SPKT patients with pretransplant fasting serum C-peptide levels ≥2.0 ng/mL compared with 46 control patients (C-peptide level <0.5 ng/mL) matched for recipient age, gender, race, and transplant date.3 In our study, we likewise reported inferior mid-term outcomes in the group with higher pretransplant C-peptide levels. In our overall SPKT experience, we have 205 patients with a minimum of 5-y follow-up. Using the above C-peptide categories as per the Wisconsin study, we identified 166 patients in the low, 32 patients in the medium, and 7 patients in the high C-peptide groups. Five-y actual (uncensored) patient and graft survival rates were as follows: patient (91% low versus 93.8% medium versus 85.7% high) and kidney (80.7% versus 71.9% versus 71.4%), respectively. Using the composite end point of pancreas graft failure or dysfunction, pancreas outcomes were 25.3% low versus 34.4% medium versus 71.4% high C-peptide (P = 0.10). Similar to the Wisconsin study, we are limited by the small sample size in the high pretransplant C-peptide group but the findings indicate a trend toward a greater need for supplemental antidiabetic therapy in patients with higher pretransplant C-peptide levels. Unfortunately, what is missing from these studies is a better characterization of patients with partial pancreas allograft function (dysfunction) who continue to be free from wide glycemic excursions and do not experience hypoglycemia (despite the need for antidiabetic therapy) because of preserved counterregulatory function of the pancreas allograft.4 In our experience, we identified posttransplant weight gain, insulin resistance, and rejection as potential mitigating factors to explain these inferior outcomes. Consequently, we recommend greater emphasis on weight management strategies, behavioral modification, nutritional counseling, structured physical training programs, timely adjustments in (and use of less diabetogenic) immunosuppression, more intense long-term monitoring by the transplant center, and increased use of novel antidiabetic agents such as Glucagon-like peptide 1 receptor agonists and Sodium-glucose cotransporter-2 inhibitors when indicated in this unique population. We congratulate the authors on this excellent study and agree that these findings should not be an impetus to limit access to pancreas transplantation but rather help guide clinical decision-making and optimize posttransplant management.

Outcomes of Pancreas Transplantation for Lower-Ranked Candidates

To perform more pancreas transplantation (PTx), our center sometimes performs pancreas transplantation for candidates ranked sixth place or lower. In this study, we analyzed the outcomes of PTx performed in our center to compare the outcomes of higher- and lower-ranked candidates. Seventy-two cases in which PTx was performed at our center were divided into 2 groups according to the candidate's rank. Cases in which PTx was performed for candidates up to fifth place were classified into the higher rank candidate group (HRC group; n=48), whereas PTx for candidates who were ranked sixth place or lower were classified into the lower rank candidate group (LRC group; n=24). The outcomes of PTx were retrospectively compared. Although the LRC group included a greater number of older donors (age ≥60 years), a greater number of donors with deteriorated renal function, and a greater number of HLA mismatches, the 1- and 5-year patient survival rates in the HRC group were 91.6% and 91.6%, respectively, compared with 95.8% and 87.0%, respectively, in the LRC group (P=.755). In terms of both pancreas and kidney graft survival, there were no significant differences between the 2 groups. Additionally, there were no significant differences between the 2 groups regarding the glucagon stimulation test and 75 g OGTT results, insulin independence rate, HbA1c, or serum creatinine level after transplantation. In Japan, where there is a severe donor shortage, the performance of transplantation for lower-ranked candidates would increase the number of opportunities for patients to receive PTx.

Outcomes of pancreas transplantation in patients with underlying inflammatory bowel disease: a retrospective case series.

This was a retrospective case series of patients between January 1996 and July 2021, with all patients being followed up until December 2021. All consecutive patients with end-stage DM who underwent pancreas transplantation (alone, simultaneous with kidney transplantation or after kidney transplantation) and had pre-existing IBD were included in the study. A Comparison of 1-, 5-, 10-year survival was done with pancreas transplant recipients without underlying IBD using Kaplan-Meir curves. Of the total 630 pancreas transplants performed between 1996 and 2021, eight patients had IBD, mostly Crohn's disease. Following pancreas transplantation, two of the eight patients had duodenal leaks, with one a requiring graft pancreatectomy. The 5-year graft survival rate for the cohort was 75% compared to 81.6% for the overall cohort of patients undergoing pancreas transplantation (P=0.48) with a median graft survival of 48.4 months compared to 68.1 months in the latter (P=0.56). The findings of the series provide a snapshot of the outcome of pancreas transplantation in the background of IBD, suggesting a graft and overall patient survival rates comparable with pancreas transplantation in patients without underlying IBD, with further validation of the findings required in a larger cohort of patients in the future.

Donor noradrenaline use is associated with better allograft survival in recipients of pancreas transplantation.

Outcomes following pancreas transplantation are suboptimal and better donor selection is required to improve this. Vasoactive drugs (VaD) are commonly used to correct the abnormal haemodynamics of organ donors in intensive care units. VaDs can differentially affect insulin secretion positively (dobutamine) or negatively (noradrenaline). The hypothesis was that some VaDs might induce beta-cell stress or rest and therefore impact pancreas transplant outcomes. The aim of the study was to assess relationships between VaD use and pancreas transplant graft survival. Data from the UK Transplant Registry on all pancreas transplants performed between 2004 and 2016 with complete follow-up data were included. Univariable- and multivariable-adjusted Cox regression analyses determined risks of graft failure associated with VaD use. In 2,183 pancreas transplants, VaDs were used in the following numbers of donors: dobutamine 76 (3.5%), dopamine 84 (3.8%), adrenaline 161 (7.4%), noradrenaline 1,589 (72.8%) and vasopressin 1,219 (55.8%). In multivariable models, adjusted for covariates and the co-administration of other VaDs, noradrenaline use (vs non-use) was a strong predictor of better graft survival (hazard ratio [95% confidence interval] 0.77 [0.64-0.94], p = 0.01). Noradrenaline use was associated with better graft survival in models adjusted for donor and recipient variables - this may be related to inhibition of pancreatic insulin secretion initiating pancreatic beta-cell 'rest'. Further research is required to replicate these findings and establish whether relationships are causal. Identification of alternative methods of inducing beta-cell rest could be valuable in improving graft outcomes.

Normothermic Regional Perfusion Can Improve Both Utilization and Outcomes in DCD Liver, Kidney, and Pancreas Transplantation.

Using the US national registry data between 2020 and 2021, donation after circulatory death (DCD) donors were separated into 2 groups: DCD with TA-NRP and without TA-NRP. There were 5234 DCD donors; among them 34 donors were with TA-NRP. After 1:4 propensity score matching, the utilization rates were compared between DCD with and without TA-NRP. Although the utilization rates of kidney and pancreas were comparable (P = 0.71 and P = 0.06, 94.1% versus 95.6% and 8.8% versus 2.2%, respectively), that of liver in DCD with TA-NRP was significantly higher (P < 0.001; 70.6% versus 39.0%). Among 24 liver transplantations, 62 kidney transplantations, and 3 pancreas transplantations from DCD with TA-NRP, there were 2 liver grafts and 1 kidney graft that failed within 1 y after transplantation. TA-NRP in the United States significantly increased the utilization rate of abdominal organs from DCD donors with comparable outcomes after transplantation. Increasing use of NRP may expand the donor pool without compromising transplant outcomes.

Patient and graft survival in pancreas transplant recipients: The EFISPAN study

Introduction and objectivesGraft outcomes in pancreas transplantation have improved in recent decades, but data are mainly derived from registries or prospective single-centre studies. This large epidemiological study was undertaken to investigate the impact of clinical and demographic factors on graft and patient survival in pancreas transplant recipients in Spain, and to provide robust, country-wide, practice-based data to complement registry findings. Patients and methodsWe conducted a retrospective, longitudinal, epidemiological study to assess risk factors impacting patient and graft survival in pancreas transplant recipients in eight centres in Spain. All patients transplanted between 1 January 2008 and 31 December 2012 were included; data were collected until 31 December 2015. The Kaplan–Meier method was used for all time-to-event analyses, including patient survival, graft survival, acute rejection, and BPAR. For graft survival analysis, in cases of death with functioning graft, patients were censored without any event on the date of death. For acute rejection and BPAR, patients were censored without any event on the date of death or graft loss. Univariable and multivariable analyses (Cox proportional hazards model) were conducted to assess the association between baseline clinical and demographic characteristics and patient/graft survival. ResultsData were included for 241 (80.1%) simultaneous pancreas-kidney transplants, 56 (18.6%) pancreas-after-kidney transplants and 4 (1.3%) pancreas transplants alone. Mean±standard deviation time from diagnosis until transplantation was 26.1±7.5 years. Nineteen patients died, mainly due to infections (n=10); the remaining 282 patients (93.7%) survived from transplantation until the end of the study. Among 55 patients (18.3%) with pancreas graft loss, the main reasons were vascular thrombosis (n=19), chronic rejection (n=10), acute rejection (n=6) and death with a functioning graft (n=5). The overall rate of vascular-related death was 1.3% at 5 years post transplant. Univariable analysis showed that patient age and weight, donor age, previous kidney transplantation, previous cardiovascular events and need for insulin more than 48h post transplantation were significantly associated with pancreas graft survival. Of these, in multivariable analyses pancreas graft survival was inferior in patients who had received a previous kidney transplant prior to pancreas transplantation (log-rank test, p=0.0002). Glucose metabolism, renal function and cardiovascular risk factors were generally stable following transplantation. ConclusionsThe results of this multicentre study highlight the excellent patient and graft outcomes following pancreas transplantation, with a notably low incidence of cardiovascular events.

Post-Simultaneous Kidney and Pancreas Transplant Outcomes in Type 2 Diabetics Compared to Type 1 Diabetics

Post-Simultaneous Kidney and Pancreas Transplant Outcomes in Type 2 Diabetics Compared to Type 1 Diabetics