Immunosuppression withdrawal in living-donor renal transplant recipients following induction with antithymocyte globulin and rituximab: Results of a prospective clinical trial.

Durable tolerance in kidney transplant recipients remains an important but elusive goal. We hypothesized that adding B cell depletion to T cell depletion would generate an immune milieu postreconstitution dominated by immature transitional B cells, favoring tolerance. The Immune Tolerance Network ITN039ST Research Study of ATG and Rituximab in Renal Transplantation was a prospective multicenter pilot study of live donor kidney transplant recipients who received induction with rabbit antithymocyte globulin and rituximab and initiated immunosuppression (IS) withdrawal (ISW) at 26 weeks. The primary endpoint was freedom from rejection at 52 weeks post-ISW. Six of the 10 subjects successfully completed ISW. Of these 6 subjects, 4 restarted immunosuppressive medications due to acute rejection or recurrent disease, 1 remains IS-free for over 9 years, and 1 was lost to follow-up after being IS-free for 42 weeks. There were no cases of patient or graft loss. CD19+ B cell frequencies returned to predepletion levels by 26 weeks posttransplant; immunoglobulin D+CD27--naïve B cells predominated. In contrast, memory cells dominated the repopulation of the T cell compartment. A regimen of combined B and T cell depletion did not generate the tolerogenic B cell profile observed in preclinical studies and did not lead to durable tolerance in the majority of kidney transplant recipients.

Risk factors and outcomes of persistent post-transplant hypotension among simultaneous pancreas and kidney transplant recipients.

BACKGROUND: The risk factors and outcomes associated with post- transplant hypotension after simultaneous pancreas and kidney (SPK) Transplantation are poorly defined. METHODS: SPK recipients at our center between 2010 and 2021 with functioning pancreas and kidney grafts for >6 months were included. Recipients were then divided into three groups based on active medications for the treatment of hypo-or hypertension at 6-months post-transplant: those with normal blood pressure (NBP) not requiring medication (NBP group), those on antihypertensive medications (HTN group), and those on medications for hypotension (fludrocortisone and/or midodrine) (Hypotensive group). RESULTS: A total of 306 recipients were included in the study: 54 (18%) in the NBP group, 215 (70%) in the HTN group, and 37 (12%) in the Hypotensive group. On multivariate analysis, the use of T-depleting induction (aHR = 9.64, p = .0001, 95% Cl = 3.12-29.75), pre-transplant use of hypotensive medications (aHR = 4.53, p = .0003, 95% Cl = 1.98-10.38), and longer duration of dialysis (aHR = 1.02, p = .01, 95% Cl = 1.00-1.04) were associated with an increased risk of post-transplant hypotension. Post-transplant hypotension was not associated with an increased risk of death-censored kidney or pancreatic allograft failure, or patient death. CONCLUSION: Hypotension was common even 6 months post-SPK transplantation. With appropriate management, hypotension was not associated with detrimental graft or patient outcomes.

The John S. Najarian symposium: The past, present, and future of surgery and transplantation, May 20, 2022, Minneapolis, MN.

Dr John S Najarian (1927-2020), chairman of the Department of Surgery at the University of Minnesota from 1967 to 1993, was a pioneer in surgery, clinical immunology and transplantation. A Covid-delayed Festschrift was held in his honor on May 20, 2022. The speakers reflected on his myriad contributions to surgery, transplantation, and resident/fellow training, as well as current areas of ongoing research to improve clinical outcomes. Of note, Dr Najarian was a founder of the journal Clinical Transplantation.

Helical TomoTherapy Total Lymphoid Irradiation and Hematopoietic Cell Transplantation for Kidney Transplant Tolerance in Rhesus Macaques.

Development of a post-transplant kidney transplant tolerance induction protocol involving a novel total lymphoid irradiation (TLI) conditioning method in a rhesus macaque model is described. We examined the feasibility of acheiving tolerance to MHC 1-haplotype matched kidney transplants by establishing a mixed chimeric state with infusion of donor hematopoietic cells (HC) using TomoTherapy TLI. The chimeric state was hypothesized to permit the elimination of all immunosuppressive (IS) medications while preserving allograft function long-term without development of graft-versus-host-disease (GVHD) or rejection. An experimental group of 11 renal transplant recipients received the tolerance induction protocol and outcomes were compared to a control group (n = 7) that received the same conditioning but without donor HC infusion. Development of mixed chimerism and operational tolerance was accomplished in two recipients in the experimental group. Both recipients were withdrawn from all IS and continued to maintain normal renal allograft function for 4 years without rejection or GVHD. None of the animals in the control group achieved tolerance when IS was eliminated. This novel experimental model demonstrated the feasibility for inducing of long-term operational tolerance when mixed chimerism is achieved using a TLI post-transplant conditioning protocol in 1-haplotype matched non-human primate recipients of combined kidney and HC transplantation.

Post-pancreatic transplant enteric leaks: The role of the salvage operation.

Enteric drainage in pancreas transplantation is complicated by an enteric leak in 5%-8%, frequently necessitating pancreatectomy. Pancreatic salvage outcomes are not well studied. Risk factors for enteric leak were examined and outcomes of attempted graft salvage were compared to immediate pancreatectomy. Pancreas transplants performed between 1995 and 2018 were reviewed. Donor, recipient, and organ variables including demographics, donor type, ischemic time, kidney donor profile index, and pancreas donor risk index were analyzed. Among 1153 patients, 33 experienced enteric leaks (2.9%). Donors of allografts that developed leak were older (37.9y vs. 29.0y, p = .001), had higher KDPI (37% vs. 24%, p < .001), higher pancreas donor risk index (1.83 vs. 1.32, p < .001), and longer cold ischemic time (16.5 vs. 14.8 h, p = .03). Intra-abdominal abscess and higher blood loss decreased the chance of successful salvage. Enteric leak increased 6-month graft loss risk (HR 13.9[CI 8.5-22.9], p < .001). However, 50% (n = 12) of allografts undergoing attempted salvage survived long-term. After 6 months of pancreas graft survival, salvage and non-leak groups had similar 5-year graft survival (82.5% vs. 81.5%) and mortality (90.9% vs. 93.5%). Enteric leaks remain a challenging complication. Pancreatic allograft salvage can be attempted in suitable patients and accomplished in 50% of cases without significantly increased graft failure or mortality risk.

Single center results of simultaneous pancreas-kidney transplantation in patients with type 2 diabetes.

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.

The Fourth International Workshop on Clinical Transplant Tolerance.

The International Workshop on Clinical Transplant Tolerance is a biennial meeting that aims to provide an update on the progress of studies of immunosuppression minimization or withdrawal in solid organ transplantation. The Fourth International Workshop on Clinical Tolerance was held in Pittsburgh, Pennsylvania, September 5-6, 2019. This report is a summary of presentations on the status of clinical trials designed to minimize or withdraw immunosuppressive drugs in kidney, liver, and lung transplantation without subsequent evidence of rejection. All protocols had in common the use of donor or recipient cell therapy combined with organ transplantation. The workshop also included presentations of mechanistic studies designed to improve understanding of the cellular and molecular basis of tolerance and to identify potential predictors/biomarkers of tolerance. Strategies to enhance the safety of hematopoietic cell transplantation and to improve patient selection/risk stratification for clinical trials were also discussed.

Phase 3 trial of human islet-after-kidney transplantation in type 1 diabetes.

Allogeneic islet transplant offers a minimally invasive option for ß cell replacement in the treatment of type 1 diabetes (T1D). The CIT consortium trial of purified human pancreatic islets (PHPI) in patients with T1D after kidney transplant (CIT06), a National Institutes of Health-sponsored phase 3, prospective, open-label, single-arm pivotal trial of PHPI, was conducted in 24 patients with impaired awareness of hypoglycemia while receiving intensive insulin therapy. PHPI were manufactured using standardized processes. PHPI transplantation was effective with 62.5% of patients achieving the primary endpoint of freedom from severe hypoglycemic events and HbA1c  ≤ 6.5% or reduced by ≥ 1 percentage point at 1 year posttransplant. Median HbA1c declined from 8.1% before to 6.0% at 1 year and 6.3% at 2 and 3 years following transplant (P < .001 for all vs baseline), with related improvements in hypoglycemia awareness and glucose variability. The improved metabolic control was associated with better health-related and diabetes-related quality of life. The procedure was safe and kidney allograft function remained stable after 3 years. These results add to evidence establishing allogeneic islet transplant as a safe and effective treatment for patients with T1D and unstable glucose control despite intensive insulin treatment, supporting the indication for PHPI in the post-renal transplant setting.

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

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.

The demise of islet allotransplantation in the United States: A call for an urgent regulatory update.

Islet allotransplantation in the United States (US) is facing an imminent demise. Despite nearly three decades of progress in the field, an archaic regulatory framework has stymied US clinical practice. Current regulations do not reflect the state-of-the-art in clinical or technical practices. In the US, islets are considered biologic drugs and "more than minimally manipulated" human cell and tissue products (HCT/Ps). In contrast, across the world, human islets are appropriately defined as "minimally manipulated tissue" and not regulated as a drug, which has led to islet allotransplantation (allo-ITx) becoming a standard-of-care procedure for selected patients with type 1 diabetes mellitus. This regulatory distinction impedes patient access to islets for transplantation in the US. As a result only 11 patients underwent allo-ITx in the US between 2016 and 2019, and all as investigational procedures in the settings of a clinical trials. Herein, we describe the current regulations pertaining to islet transplantation in the United States. We explore the progress which has been made in the field and demonstrate why the regulatory framework must be updated to both better reflect our current clinical practice and to deal with upcoming challenges. We propose specific updates to current regulations which are required for the renaissance of ethical, safe, effective, and affordable allo-ITx in the United States.

Association of human leukocyte antigen mismatches between donor-recipient and donor-donor in pancreas after kidney transplant recipients.

The effects of HLA mismatching on pancreas outcomes among pancreas after kidney (PAK) recipients are undefined. Outcomes might potentially differ depending on whether there is a mismatch between pancreas donor and recipient (PD-R) or pancreas donor and kidney donor(PD-KD). All primary PAK at our centre were included in this study. Patients were divided into two groups based on the degree of HLA mismatching: low (L-MM) as 0-4 and high (H-MM) as 5-6. We analysed all (N = 73) PAK for PD-R mismatch and the subset of PAK for PD-KD mismatch (N = 71). Comparing PD-R L-MM (n = 39) and H-MM (n = 34) PAKs, we observed no difference in the rate of pancreas graft failure. There was also no difference in the rate of rejection (L-MM 33% vs. H-MM 41%) or the severity of rejection. However, we observed a significantly (P < 0.01) shorter time to acute pancreas rejection in the H-MM group (6.8 ± 8.7 mo) versus the L-MM cohort (29.0 ± 36.2 mo) (P < 0.001). Similar to the PD-R mismatched cohort, we did not observe a detrimental effect of HLA mismatching on graft outcomes in the PD-KD cohort; time to rejection was again shorter in the H-MM subset. In this study, we found no impact of HLA mismatch on either pancreas graft survival or rejection rates, though rejection occurred earlier in high mismatched PAK transplants.

Delayed kidney graft function in simultaneous pancreas-kidney transplant recipients is associated with early pancreas allograft failure.

Delayed graft function (DGF) is a common complication associated with significant untoward effects in kidney-alone transplantation. The incidence and outcomes following kidney delayed graft function (K-DGF) among patients undergoing simultaneous pancreas-kidney (SPK) transplantation are less certain. We analyzed SPK recipients transplanted at our center between January 1994 and December 2017. A total of 632 recipients fulfilled the selection criteria, including 69 (11%) with K-DGF and 563 without. The incidence of K-DGF was significantly higher in recipients of organs from older donors and donation after circulatory death (DCD). The presence of K-DGF was significantly associated with an increased risk of pancreas graft failure during the first 90 days (n = 9, incidence rate [IR] 2.45/100 person-months), but not with late pancreas failure (n = 32, IR 0.84/100 person-months), kidney graft failure, or patient death. Although DCD was associated with K-DGF, it was not associated with either pancreas (hazard ratio [HR] 0.91, 95% CI 0.58-1.44, P = .69) or kidney (HR 1.09, 95% CI 0.66-1.82, P = .74) graft failure after adjustment for potential confounders. We found K-DGF to be a significant risk factor for pancreas graft failure but not kidney graft failure, with the major risk period being early (<90 days) posttransplant, and the major donor risk factor being older donor age.

Third-party vessel allografts in kidney and pancreas transplantation: Utilization, de novo DSAs, and outcomes.

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.

Belatacept-based immunosuppression with simultaneous calcineurin inhibitor avoidance and early corticosteroid withdrawal: A prospective, randomized multicenter trial.

Simultaneous calcineurin inhibitor avoidance (CNIA) and early corticosteroid withdrawal (ESW) have not been achieved primarily due to excessive acute rejection. This trial compared 2 belatacept-based CNIA/ESW regimens with a tacrolimus-based ESW regimen. Kidney transplant recipients were randomized to receive alemtuzumab/belatacept, rabbit anti-thymocyte globulin (rATG)/belatacept, or rATG/tacrolimus. The combinatorial primary endpoint consisted of patient death, renal allograft loss, or a Modification of Diet in Renal Disease-calculated eGFR of <45 mL/min/1.73 m2 at 12 months. Results are reported by treatment group (alemtuzumab/belatacept, rATG/belatacept, and rATG/tacrolimus). Superiority was not observed at 1 year for the primary endpoint (9/107 [8.4%], 15/104 [14.4%], and 14/105 [13.3%], respectively; P = NS) for either belatacept-based regimen. Differences were not observed for secondary endpoints (death, death-censored graft loss, or estimated glomerular filtration rates < 45 mL/min/1.73 m2 ). Differences were observed in biopsy-proved acute cellular rejection (10.3%, 18.3%, and 1.9%, respectively) (P < .001), but not in antibody-mediated rejection, mixed acute rejection, or de novo donor-specific anti-HLA antibodies. Neurologic and electrolyte abnormality adverse events were less frequent under belatacept. Belatacept-based CNIA/ESW regimens did not prove to be superior for the primary or secondary endpoints. Belatacept-treated patients demonstrated an increase in biopsy-proved acute cellular rejection and reduced neurologic and metabolic adverse events. These results demonstrate that simultaneous CNIA/ESW is feasible without excessive acute rejection.

Outcomes of simultaneous pancreas and kidney transplants based on preemptive transplant compared to those who were on dialysis before transplant - a retrospective study.

Among kidney transplant recipients, the duration of pretransplant dialysis is significantly associated with worse post-transplant outcomes. However, data on the outcomes of preemptive simultaneous pancreas and kidney (SPK) are limited. We analyzed primary SPK recipients transplanted between January 2000 and December 2017. Patients were divided into two groups based on pretransplant dialysis history of preemptive versus non-preemptive. Patient and survival of grafts were outcomes of interest. Of the 644 recipients, 174 (27%) were preemptive and 470 (73%) were not. Most of the baseline characteristics were similar between the groups. In the univariable analysis, the non-preemptive transplant was associated with 54% increased risk for kidney death-censored graft failure (DCGF; HR: 1.54; 95% CI: 1.01-2.35; P = 0.05). There was a 29% increased risk after adjustment for confounding factors (HR: 1.29; 95% CI: 0.83-2.02; P = 0.26), although this association was not statistically significant. Similarly, there was a 16% increased risk of pancreas DCGF in univariable analysis and 1% after adjustment, which was also not statistically significant. When outcomes were based on the duration of pretransplant dialysis, the duration was not associated with either patient survival or survival of either graft in K-M analysis. In SPK recipients, with pretransplant dialysis history, there was a tendency toward inferior graft survival, mainly for the kidney more than the pancreas.

Pancreas transplants from small donors: are the outcomes acceptable? A retrospective study.

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.

Alloimmunity in pancreas transplantation.

PURPOSE OF REVIEW: Despite significant improvement in pancreas allograft survival, rejection continues to be a major clinical problem. This review will focus on emerging literature related to the impact of pretransplant and de-novo DSA (dnDSA) in pancreas transplant recipients, and the diagnosis and treatment of T-cell-medicated rejection (TCMR) and antibody-mediated rejection (ABMR) in this complex group of patients. RECENT FINDINGS: Recent data suggest that pretransplant DSA and the emergence of dnDSA in pancreas transplant recipients are both associated with increased risk of ABMR. The pancreas allograft biopsy is essential for the specific diagnosis of TCMR and/or ABMR, distinguish rejection from other causes of graft dysfunction, and to guide-targeted therapy. This distinction is important especially in the setting of solitary pancreas transplants but also in simultaneous pancreas-kidney transplants where solid evidence has now emerged demonstrating discordant biopsy findings. Treatment of rejection in a functioning pancreas can prolong allograft survival. SUMMARY: The accurate and timely diagnosis of active alloimmune destruction in pancreas transplant recipients is paramount to preserving graft function in the long term. This review will discuss new, rapidly evolving information that is valuable for the physician caring for these patients to achieve optimal immunological outcomes.

Isolated pancreas transplantation: Is rank list position related to outcomes of imported grafts?

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.

Enteric conversion after bladder-drained pancreas transplantation is not associated with worse allograft survival.

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.

Outcomes after simultaneous kidney-pancreas versus pancreas after kidney transplantation in the current era.

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.