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Given the increasing frequency of simultaneous pancreas-kidney transplants performed in recipients with Type II diabetes and CKD, we sought to evaluate possible differences in the rates of allograft rejection, infection, and surgical complications in 298 Type I (T1D) versus 47 Type II (T2D) diabetic recipients of simultaneous pancreas-kidney transplants between 2006-2017. There were no significant differences in patient or graft survival. The risk of biopsy-proven rejection of both grafts was not significantly different between T2D and T1D recipients (HR pancreas = 1.04, p = 0.93; HR kidney = 0.96; p = 0.93). Rejection-free survival in both grafts were also not different between the two diabetes types (p pancreas = 0.57; p kidney = 0.41). T2D had a significantly lower incidence of de novo DSA at 1 year (21% vs. 39%, p = 0.02). There was no difference in T2D vs. T1D recipients regarding readmissions (HR = 0.77, p = 0.25), infections (HR = 0.77, p = 0.18), major surgical complications (HR = 0.89, p = 0.79) and thrombosis (HR = 0.92, p = 0.90). In conclusion, rejection, infections, and surgical complications after simultaneous pancreas-kidney transplant are not statistically significantly different in T2D compared to T1D recipients., Competing Interests: The authors of this manuscript have conflicts of interest to disclose as described by the Transplant International. JO is co-founder of, has equity interest in and serves as Chair of the Scientific Advisory Board of Regenerative Medical Solutions, Inc. He receives clinical trial support from Veloxis Pharmaceuticals, CareDx Transplant Management, Inc., Natera, Inc. and Vertex Pharmaceuticals, Inc. DK reports serving as a scientific advisor for, or member of, eGenesis, and receiving research funding from Medeor Pharma and the National Institutes of Health. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Martinez, Pham, Wang, Stalter, Welch, Leverson, Marka, Al-Qaoud, Mandelbrot, Parajuli, Sollinger, Kaufman, Redfield and Odorico.)

The 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., (© 2021 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

Studies have found similar outcomes of Simultaneous Pancreas-Kidney transplantation (SPKT) in patients with Type 2 (T2D) and Type 1 diabetes (T1D). However, there are scarce data evaluating the association of recipient factors such as age, BMI, or pretransplant insulin requirements with outcomes, thus the criteria for the optimal recipient selection remains unclear. In this study, 284 T1D and 39 T2D patients, who underwent SPKT between 2006 and 2017 with 1 year of follow-up at minimum, were assessed for potential relationship of pretransplant BMI and insulin requirements with posttransplant diabetes and pancreatic graft failure. Kaplan-Meier analysis showed similar rates of freedom from posttransplant diabetes (94.7% T2D vs. 92.3% T1D at 1 yr, and 88.1% T2D vs. 81.1% T1D at 5 yrs) and graft survival (89.7% T2D vs. 90.4% T1D at 1 yr, and 89.7% T2D vs. 81.2% T1D at 5 yrs). There was no significant association between BMI or pretransplant insulin requirements with posttransplant diabetes occurrence in either T1D (p = .10, .43, respectively) or T2D (p = .12, .63) patients in the cohort; or with graft failure (T1D: p = .40, .09; T2D: p = .71, .28). These observations suggest a less restricted approach to selective use of SPKT in patients with T2D., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Third-party vascular allografts (VAs) are an invaluable resource in kidney and pancreas transplantation when vascular reconstruction is needed and additional vessels from the organ donor are not available. We report the largest single-center experience to date on VA use, at a high-volume U.S. transplant center. Over a 7-year period, VAs were used for vascular reconstruction of 65 kidneys and 5 pancreases, in 69 recipients. The renal vein required reconstruction more often with right kidney transplantation (72.5% vs 27.5%, P < .001), and the renal artery required reconstruction more often with left kidney transplantation (67.6% vs 32.4%, P = .003). Eleven patients (15.9%) developed anti-VA de novo HLA donor-specific antibodies (dnDSAs) at a median time after transplantation of 19.0 months. Higher number of HLA mismatches between the VA donor and the recipient, and development of anti-organ allograft dnDSAs were significant predictors of anti-VA dnDSA development. Those with anti-VA dnDSAs had a higher rate of organ allograft rejection (45.4% vs 13.8%, P = .03) compared to those without, but there was no significant difference in incidence of vascular complications or graft outcomes. VAs can help circumvent challenging surgical situations. Anti-VA dnDSAs do not adversely affect organ allograft outcomes; however, they can contribute to HLA sensitization in the recipients., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Despite good organ quality, pancreata from extremely small pediatric donors (<30 kg) are generally avoided by many centers because of concerns of reduced islet cell mass and early technical failure. Therefore, we sought to compare the outcomes of small pancreas grafts (<30 kg) to those from higher weight donors from transplants performed between 1994 and 2015 (n = 1183). A total of 33 pancreata were from donors' ≤30 kg (3%), with a mean weight of 23.8 kg and mean age of 7.8 years. Patient survival was similar at 1, 5, and 10 years between recipients of ≤30 and >30 kg donors (≤30 kg: 96.8%, 86.8%, and 78.1% vs. >30 kg: 96.8%, 89.5%, and 79.1%, P = 0.5). Pancreas graft survival at 1, 5, and 10 years was also similar, ≤30 kg: 93.9%, 73.2%, and 61.0% vs. >30 kg: 87%, 73.3%, and 58.3% (P = 0.7). This graft survival pattern was also seen when comparing pancreata from ≤20 kg donors to those from >20 to 30 kg. Cause of graft loss, and metabolic and physiologic outcomes did not differ between the groups. After assessing the impact of donor weight as a continuous variable and calculating recipient-to-donor weight ratio (RDWR), we observed no effect of donor weight on patient and graft outcomes., (© 2020 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

Background: The first simultaneous pancreas and kidney (SPK) transplant was performed in 1966. Early procedures were associated with significant morbidity and mortality and were performed in very low numbers in select patients., Methods: This study includes all recipients of an SPK at the University of Wisconsin-Madison between 1986 and 1993, who were actively followed and had a functional pancreas allograft for >25 years as of October 31, 2018., Results: A total of 291 SPK were performed during the study period; of these, 39 patients still had a functional graft at last follow up and 9 (18.8%) pancreas grafts were lost due to patient death or graft failure after >25 years. At last follow up, all 39 patients with functional pancreas graft had at least one comorbidity, such as hypertension, hyperlipidemia, or coronary artery disease. Twenty-seven required enteric conversion; 11 patients experienced renal allograft failure (10 underwent a repeat kidney transplant); and 6 required amputation of part of the lower extremity. In the Cox regression analysis, bladder drained pancreas was associated with lower probability of prolonged pancreas graft survival (hazard ratio: 0.52; confidence interval: 0.32-0.85; P = 0.01)., Conclusions: With careful and detailed follow-up and attention to complications, some recipients of pancreas grafts have outstanding outcomes. As the number of pancreas recipients with prolonged graft survival may be rising, healthcare providers should be aware of the management of complications associated with this unique group of patients.

Simultaneous pancreas and kidney (SPK) and pancreas after kidney (PAK) transplant are both potential options for diabetic ESRD patients. Historically, PAK pancreas graft outcomes were felt to be inferior to SPK pancreas graft outcomes. Little is known about outcomes in the modern era of transplantation. We analyzed our SPK and PAK recipients transplanted between 01/2000 and 12/2016. There were a total of 635 pancreas and kidney transplant recipients during the study period, 611 SPK and 24 PAK. Twelve of the PAK patients received a living donor kidney. There were no significant differences between the two groups in kidney or pancreas graft rejection at 1 year. Similarly, 1-year graft survival for both organs was not different. At last follow-up, uncensored and death-censored graft survival was not statistically different for kidney or pancreas grafts. In addition, in Cox regression analysis SPK and PAK were associated with similar graft survival. Although the majority of pancreas transplants are in the form of SPK, PAK is an acceptable alternative. Simultaneous pancreas and kidney avoids donor risks associated with live donation, so may be preferable in regions with short wait times, but PAK with a living donor kidney may be the best alternative in regions with long SPK wait times., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Transplant centers may decline an import pancreas offer based on demographics and laboratory test results, without information on actual gland quality. The relationship between position on the match run, indicative of the number of centers that chose not to use a pancreas, and patient and death-censored graft survival, is not known. We studied all 199 isolated pancreas grafts transplanted at the University of Wisconsin since July 2000 and compared overall patient and death-censored graft survival based on import vs local status. Of the 199 isolated pancreas transplants, 184 (92.5%) were imported from another donor service area with a median match rank of 49 (interquartile range 14-129). Median cold ischemia time was longer for imported pancreata (16.6 vs 13.4 hours, P = .02). In multivariate Cox modeling, there was no association with position on the rank list and patient (P = .44) or death-censored graft survival (P = .99). There was an overall rate of 6.5% of graft failure within 30 days; however, there was no association with position on the rank list and graft failure at 30 days (P = .33). Although the logistics may be challenging, sound judgment to accept offers independent of prior centers' decisions can result in quality utilization of imported pancreata., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)

In the early experience of pancreas transplantation, bladder drainage was favored, but it often caused urologic, metabolic, and infectious complications that necessitated conversion to enteric drainage. Long-term graft survival after enteric conversion and the impact of time interval from transplantation to enteric conversion on graft survival is poorly understood. We studied all bladder-drained first-time pancreas transplantations performed at the University of Wisconsin from 1985 to 2000. Time to conversion was estimated with the Kaplan-Meier technique, whereas risk factors associated with conversion were estimated via a time-varying Cox proportional hazards model. Of 386 bladder-drained pancreata, 162 (41.9%) eventually required enteric conversion, 29 (17.9%) within the first year. Median time to conversion varied by indication: 0.68 years for surgical, 3.1 years for urologic, and 2.7 years for metabolic disorders. In a time-varying Cox model adjusting for donor and recipient factors, enteric conversion did not affect the risk of pancreas graft loss (hazard ratio [HR] 0.86, P = .26). Kidney survival was not associated with enteric conversion. When necessary due to symptoms or complications, enteric conversion of bladder-drained pancreata is safe and does not affect overall graft survival. This relationship appears to be true no matter when the conversion is performed., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Development of de novo donor-specific antibodies (dnDSA) has detrimental effects on graft survival in several types of solid organ transplants. However, limited information exists about the effect of dnDSA on pancreas transplant graft survival., Methods: We report our experience with pancreas recipients transplanted between January 01, 2005, and August 31, 2017., Results: We identified 541 pancreas transplant recipients, of which 121 developed dnDSA and 420 did not. Thirty-two percent developed dnDSA against HLA class I antigens, 56% developed against class II antigens, and 12% developed against both. Fifty-two percent of the patients in the dnDSA+ and 24% in the dnDSA- group underwent pancreas biopsy, mainly due to a rise in pancreatic enzymes. Rejection was found in 42% of the dnDSA+ group, and 20% of the dnDSA- group(P < 0.001). There were 36% uncensored graft failures in the dnDSA+ group and 17% uncensored failures in the dnDSA- group (P < 0.001). A similar trend was seen in death-censored graft failure between the groups. In univariate Cox regression analyses, male sex, older age, and recipients of simultaneous pancreas and kidney transplant were found to be protective for death-censored graft failure; multiple transplants, dnDSA, requirement for pancreas biopsy and presence of pancreas rejection were associated with increased risk of graft failure. In multivariate analysis, only older age and dnDSA were significantly associated with death-censored graft failure., Conclusions: Our findings suggest that dnDSA in pancreas transplant recipients are associated with increased rates of rejection and graft failure. Timely detection of dnDSA through regular screening and early treatment of pancreas rejection may ultimately improve graft outcomes.

Purpose of Review: Pancreas transplantation in type 2 diabetes mellitus (T2DM) candidates remains disproportionately lower than in type 1 diabetes mellitus (T1DM); however, outcomes in carefully selected patients mirrors that of T1DM. Despite the 2014 United Network for Organ Sharing (UNOS) eligibility criteria for simultaneous pancreas/kidney transplant (SPK) transplantation in T2DM patients, an expected increase in the number of transplants was not observed., Recent Findings: In an updated International Pancreas and Transplant Registry (IPTR) analysis, 1514 primary deceased donor pancreas transplants were performed in T2DM recipients [1995-2015, SPK 88%, pancreas after kidney (PAK) 9%, pancreas transplant alone (PTA) 3%]. In contrast to the declining number of SPK transplants for T1DM, the number of primary SPK transplants in T2DM patients is increasing over time in the USA. Improvement over time was noted for T2DM SPK patient and graft survival, and the rate of technical failures decreased, paralleling similar overall trends for pancreas transplants in general. Long-term follow-up data of pancreas outcomes in C-peptide positive vs. negative demonstrate noninferior outcomes. BMI does not appear to impact outcomes in carefully selected T2DM candidates., Summary: The current UNOS regulations that currently limit access of T2DM to pancreas transplantation based on strict BMI criteria and C-peptide levels need to be liberated.

Literature on the behavior of cystic lesions in pancreas transplants is scarce, and hence a better understanding is warranted. Data on recipients and their respective donors that underwent simultaneous kidney and pancreas, pancreas transplant alone, and pancreas after kidney between 1994 and 2015 were reviewed (n = 1185). Cystic lesions of the transplant pancreas developed in 22 patients (1.8%): 12 pseudocysts, 2 cysts/remnants, 4 intraductal papillary mucinous neoplasms (IPMN), 2 adenocarcinomas, 1 low-grade intraepithelial pancreatic neoplasia, and 1 case of polycystic kidney disease. The median size was 3.6 cm (1.6-5.5 cm), and occurred at a median time of 65.5 months (2-183 months) posttransplant. The median age of the graft at time of diagnosis was 42 years (25.7-54.5), with 17 of 22 grafts (77%) functioning at time of diagnosis. Triggers for investigation were elevations in pancreatic enzymes, re-admissions for abdominal pain, and incidentalomas. High-resolution imaging and diagnostic biopsy/aspiration with ancillary tests were the main diagnostic tests. Most pseudocysts were managed by percutaneous drainage, and although no firm inference can be made from such a small series, we have observed that the behavior and management of IPMN and adenocarcinoma in the pancreas graft appears congruent to that of the native pancreas., (© 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.)

It is commonly assumed that in simultaneous pancreas and kidney (SPK) recipients, rejection of the two organs is concordant. As a result, concurrent biopsies of both organs are rarely performed and there are limited histological data on how often rejection is in fact discordant. We reviewed all SPK recipients transplanted at the University of Wisconsin between January 01, 2001, and December 31, 2016, that underwent biopsy of both organs. We included all patients whose biopsies were within 30 days. If patients were treated for rejection between biopsies, they were excluded if the biopsies were more than 4 days apart. Ninety-one simultaneous biopsies were performed within 30 days of each other, and 40 met our inclusion criteria. A total of 25 (62.5%) patients had concordance of biopsy findings: 11 had rejection of both organs, and 14 had no rejection of either organ. The other 15 (37.5%) were discordant for rejection, with 10 having pancreas-only rejection and five kidney-only rejection. It was striking to find that four of the 11 patients with concordance for rejection (36%) had different types (AMR, ACR, or mixed) of rejection in the two organs. This large series of simultaneous pancreas and kidney biopsies demonstrates the continued utility of performing biopsies of both organs., (© 2017 Steunstichting ESOT.)

Background: Hemoglobin A1C (HbA1c) levels are often obtained in potential pancreas graft donors to assess the overall long-term functional glycemic control or the possibility of unrecognized diabetes. Although routinely measured, the impact of donor HbA1c levels on pancreas graft outcomes has not been reported. Here, we researched the relationship between donor HbA1c levels and postoperative pancreas graft survival., Methods: Data from 266 pancreas transplant patients including 182 simultaneous kidney-pancreas and 84 pancreas alone transplants were reviewed for the study. The patients were separated into groups according to their HbA1c levels (5 groups: HbA1c < 5.0, 5.0-5.4, 5.5-5.9, ≥6.0 % and not available, or 2 groups: HbA1c <5.7, ≥5.7%). Overall, death-censored and technically successful pancreas graft survival and rejection rates of each group were compared. In the case of technically successful graft survival, graft losses due to technical problems in the first 60 days were excluded., Results: All groups were similar with regard to donor variables including age, sex, ABO blood type, ethnicity, donor type and recipient variables including recipient age, sex, induction agents and maintenance treatment. Mean follow-up time was 4.2 ± 1.97 years. The overall graft survivals and death censored graft survivals among groups were not statistically different from one other (P > 0.05). Additionally, excluding early technical losses in 18 patients did not reveal any differences in graft survivals. Patient survival and biopsy-proven acute rejections were statistically similar among HbA1c strata., Conclusions: This univariate retrospective analysis of a single center/organ procurement organization use of HbA1c shows that donor HbA1c levels between 3.5 and 6.2 in otherwise transplantable pancreata are not associated with different short-term outcomes.

Pancreas transplant outcomes have progressively improved. Despite this, some centers have continued to employ historical age limits for pancreas transplant candidates. We sought to determine the importance of chronological age in determining patient and graft survival rates after pancreas transplantation. A single-center, retrospective study of adult, deceased donor simultaneous pancreas and kidney (SPK) and solitary pancreas transplants (SP, including pancreas transplant alone and pancreas after kidney transplants) in recipients ≥ 55 years (55 + ), occurring between July 1, 1999, and June 30, 2012, was performed. Seven-hundred and forty patients underwent pancreas transplantation, of which 28 patients were 55 + . Patient survival was comparable for younger and older pancreas transplant recipients. Both non-death-censored and death-censored pancreatic graft survival rates were similar in younger and in older patients. Patients aged 45-54 and those aged 55 +  had more frequent cardiovascular events than younger pancreas transplant recipients. There was no difference in renal graft survival for SPK patients when compared with diabetic kidney transplant alone recipients aged 55 years and older. Older pancreas transplant recipients had acceptable long-term patient and graft survival rates, although complications may occur. Chronological age alone should not exclude a patient for pancreas transplant candidacy., (© 2016 Steunstichting ESOT.)

Background: Imported pancreata accumulate cold ischemia time (CIT), limiting utilization and worsening outcomes. Flow cytometric crossmatching (FXM) is a standard method to assess recipient and donor compatibility, but can prolong CIT. Single-antigen bead assays allow for detection of recipient donor-specific HLA antibodies, enabling prediction of compatibility through a "virtual crossmatch" (VXM). This study investigates the utility and outcomes of VXM after transplantation of imported pancreata., Methods: We retrospectively compared outcomes of 153 patients undergoing pancreas transplantation at our institution over a 3.5-year period., Results: Three patient groups were analyzed based on geographic source of the pancreas graft and the type of prospective crossmatch performed: (1) imported VXM-only, n = 39; (2) imported VXM + FXM, n = 12; and (3) local VXM + FXM, n = 102. There were no episodes of hyperacute rejection and 1 episode of early antibody-mediated rejection (<90 days) in the imported VXM group. Death-censored graft survival, patient survival, and rejection rates were comparable among the recipient groups. For pancreata imported from United Network of Organ Sharing regions 3 and 4, proceeding to surgery without an FXM reduced CIT by 5.1 hours (P < 0.001). The time from organ arrival at the hospital to operation start was significantly shorter in the VXM-only group compared with the VXM + FXM group (P < 0.001)., Conclusions: Virtual crossmatch helps minimize CIT without increasing rejection or adversely affecting graft survival, making it a viable method to increase pancreas graft utilization across distant organ sharing regions.

The field of pancreas transplantation has evolved from an experimental procedure in the 1980s to become a routine transplant in the modern era. With short- and long-term outcomes continuing to improve and the significant mortality, quality-of-life, and end-organ disease benefits, pancreas transplantation should be offered to more patients. In this article, we review current indications, patient selection, surgical considerations, complications, and outcomes in the modern era of pancreas transplantation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose of Review: Important trends are being observed in pancreas transplantation in the USA. We will describe recent trends in simultaneous pancreas kidney (SPK) transplantation related to immunosuppression, treatment of rejection, and transplantation for patients of advanced age and C-peptide positive diabetes., Recent Findings: Rates of pancreas transplantation have declined, despite improved pancreatic graft outcomes. Regarding immunosuppression, trends in SPK transplantation include T-cell depletion induction therapy, waning mammalian target of rapamycin inhibitor use and steroid use in greater than 50% of pancreas transplant recipients with few patients undergoing late steroid weaning. Rejection of the pancreas may be discordant with the kidney after SPK and there is a greater appreciation of antibody-mediated rejection of the pancreas allograft. De-novo donor-specific antibody without graft dysfunction remains an active area of study, and the treatment for this condition is unclear. SPKs are being performed with greater frequency in type 2 diabetes mellitus patients and in patients of advanced age, with exemplary results., Summary: The current state of the art in SPK transplantation is yielding superb and improving results.