Simultaneous Pancreas And Kidney Research Articles

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

The risk factors and outcomes associated with post- transplant hypotension after simultaneous pancreas and kidney (SPK) Transplantation are poorly defined. 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). 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. Hypotension was common even 6 months post-SPK transplantation. With appropriate management, hypotension was not associated with detrimental graft or patient outcomes.

Pancreas Transplantation Alone for Brittle Diabetes Mellitus

Only about 8% of all pancreas transplants for insulin-dependent diabetes mellitus are performed in the Pancreas Transplant Alone (PTA) category. PTAs are primarily performed in diabetic, non-uremic patients with unstable glucose control, hypoglycemia unawareness, and an increased risk of diabetes-related mortality, and who have failed all of the more traditional approaches to glycemic control. Tremendous, yet not widely noticed, progress in PTA outcome has been made over the past two decades. PTA is a very safe procedure with 1-and 5-year patient survival rates of 98.3% and 90.5% according to International Pancreas Transplant Registry (IPTR) data. Since the introduction of tacrolimus and mycophenolate mofetil maintenance therapy in the 1990s and the use of depleting antibody induction therapy, PTA graft survival rates at 1-and 5-years posttransplant are 87.2% and 65.0%. To avoid the need for a future kidney after pancreas (KAP) transplant due to impaired pretransplant native kidney function and the posttransplant use of calcineurin inhibitors, the estimated Glomerular Filtration Rate (eGFR) of PTA candidates should be well within the normal range and preferably > 80 mL/min/1.73m². PTAs with stable, long-term function have been shown to have a positive impact on secondary complications of diabetes mellitus. Considering the significantly improved outcome results, PTA should become the pancreas transplant option of choice before the manifestation of devastating secondary complications (kidney failure, cardio-cerebrovascular events, and blindness) that require simultaneous pancreas and kidney (SPK) transplants in qualified candidates, but with higher morbidity and mortality risks. It is important for diabetologists, endocrinologists, and other health professionals involved in the care of diabetic patients to learn about these positive PTA outcome results. Despite improvements in intensive insulin therapy, insulin-delivering devices, bioartificial pancreas, and islet transplantation, a successful PTA is the only treatment option for patients with brittle diabetes that consistently restores normal glucose homeostasis long-term without exposing recipients to the risks of severe hypoglycemia and prevents, halts, or reverses the development or progression of secondary diabetes complications.

Amelioration of Diabetes and Neuropathy After Pancreas Transplantation: Measurable Differences in Vibration Perception Thresholds Impact Outcomes.

Amelioration of Diabetes and Neuropathy After Pancreas Transplantation: Measurable Differences in Vibration Perception Thresholds Impact Outcomes.

Pancreas transplantation from donors after cardiac death – The US experience

IntroductionSince the beginning of pancreas transplantation, the rate of donation after cardiac (or circulatory) death (DCD) accounts for only 3% of all transplants in the US. This is the result of perceived higher complication rates and overall worse outcome with DCD donors. Such misconceptions and an increased demand for deceased donor (DD) organs warrant a systematic review of the use of DCD compared with donation after brain death (DBD) pancreata to objectively assess DCD outcome after pancreas transplantation in the US. MethodsAll 22,160 DD pancreas transplants performed in diabetic patients between 1/1/2001 and 12/31/2020 were included in this analysis. To assess changes in outcomes, patient and graft survival was computed using the Kaplan-Meier method in 5-year intervals. Comprehensive univariate and multivariable comparisons of posttransplant complications and patient and pancreas and kidney graft survival between DCD and DBD pancreas transplants were performed to assess the donor impact. ResultsIn the US over the past 20 years most DCD donors were used for simultaneous pancreas and kidney (SPK) transplants and less often for solitary pancreas transplants. DCD transplants never accounted for more than 4% per year of all pancreas transplants. A comparison of the pancreas donor risk index (pDRI) between DCD and DBD pancreata showed that the only distinguishing factor was DCD donation. SPK patient, pancreas, and kidney graft survival for DCD donors did not change significantly over time. One- and 3 -year DCD patient survival reached 96% and 93%, pancreas graft survival 90% and 84%, and kidney graft survival 96% and 91%, respectively. For the last decade, no differences in patient and graft survival between DCD and DBD donors were detected (P > 0.67). The relative risk for the use of a DCD donor was not increased (P > 0.6). Influential risk factors were older donor and recipient age as well as longer preservation times. Larger transplant center accepted DCD donors more frequently and showed better outcome. While the rate of early pancreas complications was the same for DCD vs. DBD transplants, delayed kidney graft function was significantly higher in DCD kidneys secondary to more long-distance shipping across the country. The multivariable analysis showed a 4-times higher rate in delayed graft function. Longer cold preservation time and older donor age further increased the risk of graft failure. The use of machine perfusion of the kidney graft reduced the relative risk of delayed graft function by 50%. SummaryThe use of DCD donor organs in pancreas transplantation is not associated with higher failure or complication rates in the US. A pancreas offer from a DCD donor should not be the sole reason to decline the organ for transplantation. Careful selection of specific donor and recipient factors, as well as advanced preservation techniques are essential for good outcome.

Early Experience Using Donor-derived Cell-free DNA for Surveillance of Rejection Following Simultaneous Pancreas and Kidney Transplantation.

Background.Allograft biopsy is the gold standard for diagnosing graft rejection following simultaneous pancreas and kidney (SPK) transplant. Intraperitoneal biopsies are technically challenging and can be burdensome to patients and the healthcare system. Donor-derived cell-free DNA (dd-cfDNA) is well-studied in kidney transplant recipients; however, it has not yet been studied in the SPK population.Methods.We hypothesized that dd-cfDNA could be utilized for rejection surveillance following SPK transplant. We prospectively collected dd-cfDNA in 46 SPK patients at a single institution.Results.There were 10 rejection events, 5 of which were confirmed with biopsy. The other 5 were treated based on dd-cfDNA and clinical data alone with favorable outcomes. Among all patients who did not have rejection, 97% had dd-cfDNA <0.5%. Dd-cfDNA may also help differentiate rejection from graft injury (ie, pancreatitis) with median values in rejection 2.25%, injury 0.36%, and quiescence 0.18% (P = 0.0006).Conclusions.Similar to kidneys, dd-cfDNA shows promise for rejection surveillance in SPK transplant recipients.

Letermovir treatment for CMV infection in kidney and pancreas transplantation: A valuable option for complicated cases.

Cytomegalovirus (CMV) infection remains a major challenge in solid organ transplantation. Ganciclovir has changed the prognosis, but with the expense of possible viral resistance. New antiviral drugs, such as letermovir, have not been studied sufficiently in kidney and pancreas transplant recipients. We reviewed abdominal organ transplants recipients with CMV infection from the national transplant registry and identified patients treated with letermovir from electronic medical records. We report on letermovir treatment in one kidney and three simultaneous pancreas and kidney (SPK) transplant patients with refractory or ganciclovir-resistant CMV infection (UL54/ UL97 mutation). In SPK patients, persistent leukopenia undermined immunosuppressive and antiviral treatment, favoring life-threatening bacterial infections or ganciclovir resistance. All patients achieved viral clearance after letermovir monotherapy of 1.5-6 months. Letermovir was well tolerated and leukopenia resolved. Adjustments of calcineurin inhibitor doses were challenging. One acute rejection occurred because of under immunosuppression. After the end of treatment, recurrent low-grade CMV-DNAemia was common requiring reinitiating antiviral therapy to achieve viral clearance. To conclude, letermovir was a well-tolerated valuable option for the treatment of refractory or resistant CMV infection in kidney and pancreas transplantation.

P.137: Multi-centre UK Analysis After SPK in Recipients With Type 2 Diabetes Mellitus

Background: From 1994 - 2019 only 4% of simultaneous pancreas and kidney (SPK) transplants in the United Kingdom (UK) have been performed for recipients with Type 2 diabetes mellitus. The aim of this study was to compare outcomes after SPK transplantation for recipients with either Type 1 (T1DM) or Type 2 (T2DM) diabetes. Methods: Retrospective data on all UK SPK Transplants from 1994 - 2019 were obtained from the NHSBT UK Transplant Registry, n=2,236. Current SPK selection criteria for Type 2 diabetes mellitus specifically requires insulin treatment and recipient BMI less than 30kg/m2 at the time of listing. Cases where the aetiology of diabetes was missing or had been classified as ‘other’ rather than specifically Type 1 or Type 2 diabetes were excluded, as were recipients who had received a re-transplant, resulting in a final cohort of n=2,154. Graft and patient survival analyses were conducted using Kaplan-Meier plots and Cox regression models. Complications were compared using chi-squared analyses. Results: The majority of SPK transplants were performed in recipients with T1DM (95.6%, n=2,060), and 3.4% (n=94) were performed in recipients with T2DM. Recipients with T2DM were statistically significantly more likely to be older (p<0.0001), male (p<0.0001), with a higher body mass index (BMI) (p=0.0191) and not requiring dialysis (p<0.0001). Univariate analysis showed no statistically significant difference in graft (GS) or patient (PS) survival between recipients with T1DM or T2DM at 1 year (GS T1DM-88.9%, T2DM-85.1% p=0.120; PS T1DM-96.9% T2DM-96.8%, p=0.886) or 3 years (GS T1DM-85.2% T2DM-83.0%, p=0.316; PS T1DM-96.9%, T2DM-96.8% p=0.237). Multi-variate analysis also failed to reveal a statistically significant difference between graft (p=0.564, HR 1.221, 95%CI 0.619, 2.406) or patient (p=0.556, HR 1.280, 95%CI 0.563, 2.911) survival between these two cohorts. Common complications after pancreas transplant such as myocardial infarction, cerebrovascular accident, infection and rejection were analysed and again no statistically significant differences were seen between recipients regardless of type of diabetes.Conclusions: This is one of the largest national studies evaluating outcomes after SPK transplants comparing recipients with T1DM or T2DM. Carefully selected recipients with Type 2 diabetes were not shown to have any statistically significant difference in graft or patient survival and had comparable rates of complications.

306.6: Importing Pancreata for Transplantation: An 18-year Single Center Experience

Introduction: Pancreatic Transplant (PTX) is a safe surgical procedure offered to diabetic patients with or without chronic kidney disease. With the new allocation system in the US, more pancreas offers are coming from beyond one’s donor service area (DSA), and region. Whether transplanting grafts from beyond one’s DSA or region is a safe practice is unknown. In this study, we analyzed our experience with importing pancreata according to DSA and UNOS region source and distance from the donor hospital to the transplant center, resembling the newest changes mandated by UNOS allocation policies. Methods: We analyzed primary PTXs performed between January 2000 and December 2018. Recipients of simultaneous pancreas and kidney (SPK), primary solitary pancreas (PAN) including pancreas after kidney (PAK) and pancreas transplant alone (PTA) transplants were analyzed. Two separate analyses were performed: i) based on graft origin (local, regional and national) and ii) based on nautical mile (NM) distances form the (< 250 NM, 250 and 750 NM and > 750 NM) which were retrospectively determined. Primary outcome was DC-graft survival (DC-GS), overall and stratified by transplant type and geographical source. DC-GS survival was analyzed using Kaplan-Meier analyses. All grafts were enterically drained with systemic venous drainage. Results: There were 884 PTXs; 676 underwent SPK and 208 PAN. Of these, 152 underwent PTA and 56 PAK. Donor PDRI and recipient baseline characteristics were similar between groups. Evaluating all PTX together, we observed no statistical differences in the DC-GS based on local, regional or national organ source; nor did we see a difference based on NM distance. Analyzing by graft origin (local vs regional vs national): the 5-year DC-GS rates for SPK were similar at 83% vs 83% vs 85% (p=0.50) and the 5-year DC-GS rates for PAN were 82% vs 64% vs 75% (p=0.17). The 5-year DC-GS rates were also similar across locales for both PTA (83% vs 60% vs 77%; p=0.14) and PAK (78% vs 73% vs 69%; p=0.55). Based on the NM distance from donor to transplant hospital (<250NM, 250-750NM and >750NM): the 5-year DC-GS rates for SPK were similar across distances at 83% vs 84% vs 89% (p=0.69). The 5-year DC-GS rates for PAN were not different from one another at 73% vs 72% vs 78% (p=0.96). The 5-year DC-GS rates across distances for PTA (71% vs 73% vs 81%; p=0.79) and PAK (76% vs 70% vs 67%; p=0.65) were not statistically different from one another. Conclusions: With greater sharing mandated by new UNOS allocation policies, we aim to demonstrate the utility of importing selected pancreata from non-local regions and DSAs and from > 250NM from the transplant center. This experience emphasizes the possibility of importing pancreatic grafts to increase organ utilization, increase center transplant rates and reduce waiting times for patients.

Outcomes of pregnancy in simultaneous pancreas and kidney transplant recipients: A single-center retrospective study.

Simultaneous pancreas and kidney (SPK) transplantation, in uremic women with insulin-dependent diabetes, increases the chance of a successful pregnancy and minimizes the risk to infants. The aim of this study was to document pregnancy and explore the challenges in this cohort of women. Retrospective analysis of women who underwent pancreas transplantation between January 1, 1998 and 8 January, 2019 was conducted. Seventeen pregnancies were identified in 13 women. Mean transplant-to-pregnancy interval was 4.6 years (range, 1.1-10.2years). Eleven pregnancies resulted in live birth (65%), and six (35%) ended in miscarriage/fetal loss at a median gestational age of 8.5weeks. Mean gestational age at delivery was 34.9weeks (SD ±3weeks). Preeclampsia and C-section rates were 77% and 67%, respectively. Adverse fetal and graft outcomes were observed in 100% of unplanned pregnancies, compared to 10% of planned pregnancies (P<.001). One kidney allograft was lost during pregnancy; one pancreas and two kidney allografts were lost within 3years of pregnancy. This is a high-risk group for grafts and offspring. Pre-pregnancy planning is vital. A multidisciplinary approach by obstetric and transplant teams is important pre-pregnancy, antenatally, and peripartum. This is the largest published series of pregnancies in SPK recipients from a single center.

Pancreas transplantation.

To define recent changes and future directions in the practice of pancreas transplantation (PT). Two major events have occurred in the past 18 months: COVID-19 pandemic, and the first world consensus conference on PT. Several innovative studies were published after the consensus conference. During COVID-19 pandemic PT activity decreased. COVID-19 in transplant recipients increases mortality rates, but data from kidney transplantation show that mortality might be higher in waitlisted patients.The world consensus conference provided 49 jury deliberations on the impact of PT on management of diabetic patients and 110 practice recommendations.Recent evidence demonstrates that PT alone is safe and effective, that results of simultaneous pancreas and kidney (SPK) remain excellent despite older recipient age and higher prevalence of type 2 diabetes, that use of hepatitis C virus (HCV)-positive donors into HCV-negative recipients is associated with good outcomes, and that use of sirolimus as primary immunosuppressant and costimulation blockade does not improve results of SPK. COVID-19 pandemic and the first world consensus conference on PT were major events. Although COVID-19 pandemic should not reduce PT activity in the future, a major positive impact on both volume and outcomes of PT is awaited from the proceedings of the world consensus conference.

Simultaneous Pancreas and Kidney Composite Graft Transplant

Purpose: Limited vascular access could be encountered in an obese or re-transplant patient. We described modifications that facilitated an en bloc simultaneous pancreas and kidney (SPK) composite graft transplant in an obese type 2 diabetic patient with renal failure under hemodialysis. Methods: At the back-table, the superior mesenteric artery and splenic artery of the pancreas graft were reconstructed with a long "Y" iliac artery graft. The smaller left renal artery is anastomosed end-to-side to the larger and longer common limb of the arterial Y graft and the shorter portal vein is anastomosed end-to-side to the longer graft left renal vein. Thus, this en bloc composite graft allowed to facilitate “real” SPK transplant using single common graft artery and vein for anastomosis to one recipient arterial and venous site. The en bloc pancreas and kidney composite graft was implanted by suturing the graft left renal vein to IVC and graft common iliac artery the recipient distal aorta. Exocrine drainage was provided by anastomosis of the graft duodenum to a roux-en-y jejunum limb in an side-to-side fashion. Immunosuppressants included basiliximab, tacrolimus, mycophenolate mofetil, and methylprednisolone. Results: The operative time was 7 hours with cold ischemic time of 6 hours and 25 min. and warm ischemic time of 47 min. The patient was discharged on postoperative day 20, with a serum creatinine level of 1.4 ng/ml and a blood glucose level of 121 mg/dL. Conclusion: En bloc pancreas and kidney composite graft might be an option for patients with limited vascular access.

One more time, emphasizing the advantage of simultaneous pancreas and kidney transplantation for patients with type 1 diabetes and end-stage renal disease.

Simultaneous pancreas and kidney (SPK) transplantation is considered the best treatment option for patients with diabetes and end-stage renal disease (ESRD). SPK recipients with a functioning pancreas graft have significantly better kidney graft survival and patient survival compared to those who received a kidney-only transplant or those with a failed pancreas graft. In addition, SPK recipients with isolated pancreas graft failure who undergo pancreas retransplant still have better kidney graft survival.

Impact of Sarcopenia on Simultaneous Pancreas and Kidney Transplantation Outcomes: A Retrospective Observational Cohort Study.

Sarcopenia has been identified as a predictive variable for surgical outcomes. We hypothesized that sarcopenia could be a key measure to identify frail patients and potentially predict poorer outcomes among recipients of simultaneous pancreas and kidney (SPK) transplants. We estimated sarcopenia by measuring psoas muscle mass index (PMI). PMI was assessed on perioperative computed tomography (CT) scans of SPK recipients. Of the 141 patients identified between 2010 and 2018, 107 had a CT scan available and were included in the study. The median follow-up was 4 years (range, 0.5-9.1 y). Twenty-three patients had a low PMI, and 84 patients had a normal PMI. Patient characteristics were similar between the 2 groups except for body mass index, which was significantly lower in low PMI group (P < 0.001). Patient and kidney graft survival were not statistically different between groups (P = 0.851 and P = 0.357, respectively). A multivariate Cox regression analysis showed that patients with a low PMI were 6 times more likely to lose their pancreas allograft (hazard ratios, 5.4; 95% confidence intervals, 1.4-20.8; P = 0.015). Three out of 6 patients lost their pancreas graft due to rejection in the low PMI group, compared with 1 out of 9 patients in the normal PMI group. Among low PMI patients who had a follow-up CT scan, 62.5% (5/8) of those with a functional pancreas graft either improved or resolved sarcopenia, whereas 75.0% (3/4) of those who lost their pancreas graft continued to lose muscle mass. Sarcopenia could represent one of the predictors of pancreas graft failure and should be evaluated and potentially optimized in SPK recipients.

Small Bowel Perforation as the Initial Manifestation of Post-Transplant Lymphoproliferative Disorder in a Kidney and Pancreas Transplant Recipient: A Case Report

Post-transplant lymphoproliferative disorder (PTLD) comprises a broad spectrum of diseases and is a rare but serious complication of solid organ transplantation. We report the case of a 45-year-old simultaneous pancreas and kidney (SPK) transplant recipient with diffuse, early-onset PTLD, manifesting as jejunal perforation at 6 months after transplantation. The patient underwent urgent small bowel resection of the affected portion of jejunum. The surgical pathology report was significant for diffuse large B-cell lymphoma. Subsequently, the patient underwent a full workup, including upper and lower endoscopy and whole-body positron emission tomography that revealed involvement of the axial skeleton and multiple abdominal organs with sparing of the grafts. He was treated with rituximab and intrathecal methotrexate for central nervous system prophylaxis. The patient experienced complete resolution of disease by positron emission tomography 8 months after initial presentation. We found no previous report in the literature of intestinal perforation as the initial presentation of PTLD in SPK transplant recipients.

Anticoagulation in simultaneous pancreas kidney transplantation - On what basis?

BACKGROUNDDespite technical refinements, early pancreas graft loss due to thrombosis continues to occur. Conventional coagulation tests (CCT) do not detect hypercoagulability and hence the hypercoagulable state due to diabetes is left untreated. Thromboelastogram (TEG) is an in-vitro diagnostic test which is used in liver transplantation, and in various intensive care settings to guide anticoagulation. TEG is better than CCT because it is dynamic and provides a global hemostatic profile including fibrinolysis.AIMTo compare the outcomes between TEG and CCT (prothrombin time, activated partial thromboplastin time and international normalized ratio) directed anticoagulation in simultaneous pancreas and kidney (SPK) transplant recipients.METHODSA single center retrospective analysis comparing the outcomes between TEG and CCT-directed anticoagulation in SPK recipients, who were matched for donor age and graft type (donors after brainstem death and donors after circulatory death). Anticoagulation consisted of intravenous (IV) heparin titrated up to a maximum of 500 IU/h based on CCT in conjunction with various clinical parameters or directed by TEG results. Graft loss due to thrombosis, anticoagulation related bleeding, radiological incidence of partial thrombi in the pancreas graft, thrombus resolution rate after anticoagulation dose escalation, length of the hospital stays and, 1-year pancreas and kidney graft survival between the two groups were compared.RESULTSSeventeen patients who received TEG-directed anticoagulation were compared against 51 contemporaneous SPK recipients (ratio of 1: 3) who were anticoagulated based on CCT. No graft losses occurred in the TEG group, whereas 11 grafts (7 pancreases and 4 kidneys) were lost due to thrombosis in the CCT group (P = 0.06, Fisher’s exact test). The overall incidence of anticoagulation related bleeding (hematoma/ gastrointestinal bleeding/ hematuria/ nose bleeding/ re-exploration for bleeding/ post-operative blood transfusion) was 17.65% in the TEG group and 45.10% in the CCT group (P = 0.05, Fisher’s exact test). The incidence of radiologically confirmed partial thrombus in pancreas allograft was 41.18% in the TEG and 25.50% in the CCT group (P = 0.23, Fisher’s exact test). All recipients with partial thrombi detected in computed tomography (CT) scan had an anticoagulation dose escalation. The thrombus resolution rates in subsequent scan were 85.71% and 63.64% in the TEG group vs the CCT group (P = 0.59, Fisher’s exact test). The TEG group had reduced blood product usage {10 packed red blood cell (PRBC) and 2 fresh frozen plasma (FFP)} compared to the CCT group (71 PRBC/ 10 FFP/ 2 cryoprecipitate and 2 platelets). The proportion of patients requiring transfusion in the TEG group was 17.65% vs 39.25% in the CCT group (P = 0.14, Fisher’s exact test). The median length of hospital stay was 18 days in the TEG group vs 31 days in the CCT group (P = 0.03, Mann Whitney test). The 1-year pancreas graft survival was 100% in the TEG group vs 82.35% in the CCT group (P = 0.07, log rank test) and, the 1-year kidney graft survival was 100% in the TEG group vs 92.15% in the CCT group (P = 0.23, log tank test).CONCLUSIONTEG is a promising tool in guiding judicious use of anticoagulation with concomitant prevention of graft loss due to thrombosis, and reduces the length of hospital stay.

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.

More Than 25 Years of Pancreas Graft Survival After Simultaneous Pancreas and Kidney Transplantation: Experience From the World's Largest Series of Long-term Survivors.

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. 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. 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). 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.

Polyomavirus and cytomegalovirus infections are risk factors for grafts loss in simultaneous pancreas and kidney transplant.

Published literature on predictors of polyomavirus (BKV) and cytomegalovirus (CMV) infections in simultaneous pancreas and kidney (SPK) transplant and their impact on allograft outcomes remain sparse. We hypothesize that BKV and CMV viremia infections decrease allograft survival in SPK. Identifying modifiable predictors of BKV and CMV may help tailor immunosuppression and improve allograft survival. All SPK recipients at our institution between January 2000 and April 2016 were included (n=757). Thirty-nine recipients had BKV only and 25 had CMV only, and infection occurred at median follow-up times of 217 and 163days, respectively. Event density sampling was used to match recipients with BKV or CMV to up to 10 recipients without infection by age, sex, and HLA mismatch status, and these were followed for a median of 4.3years after infection. Older age (HR 1.49 for each decade; 95% CI: 0.95, 2.35; P=.083) and tacrolimus use (HR 20.6; 95% CI: 2.37, 179.53; P=.006) were associated with increased incidence of BKV, but not CMV, infection. Both BKV and CMV infections were associated with increased risk of allograft failure for both pancreas (BKV [HR 2.17; 95% CI 1.47, 3.208; P=.000], CMV [HR 1.7; 95% CI 1.077, 2.687; P=.023]) and kidney (BKV [HR 2.65; 95% CI 1.765, 3.984; P=.000], CMV [HR 2.07; 95% CI 1.295, 3.308; P=.002]). Older age at time of transplant and tacrolimus may help predict BKV infection in SPK recipients.

Geographic Disparities in Access to Simultaneous Pancreas and Kidney Transplant in the Pre- and Post-Pancreas Allocation System Eras.

The 2014 pancreas allocation system (PAS) intended to decrease geographic variability in listing practices for simultaneous pancreas and kidney (SPK) transplant and define eligibility criteria for those with type 2 diabetes mellitus (T2DM). Our primary aims were to evaluate geographic disparities in access to SPK and assess T2DM SPK listings in the pre- and post-PAS eras. Adult listings for SPK and kidney transplant (pre-PAS, January 2010 to October 29, 2014; post-PAS, October 30, 2014, to June 2, 2017) were identified in the Scientific Registry of Transplant Recipients. Multivariable logistic regression models tested associations of geography and/or diabetes mellitus type on the likelihood of SPK versus kidney transplant listing pre- and post-PAS. Competing risk models tested the likelihood of SPK transplantation within 2 years of listing for SPK. Among 41 205 listings (27 393 pre-PAS; 24 439 T2DM), univariate analysis showed reduced percentages for SPK post-PAS (22.1%-20.8%; P = 0.003). After adjusting for patient and center characteristics, geographic disparities declined slightly but persisted post-PAS (era by region interaction P < 0.001). The era by type of diabetes mellitus interaction effect was statistically significant (P = 0.039), reflecting that the proportions of SPK listings for T2DM increased in the post-PAS era (3.4%-3.9%; univariate P = 0.038), while those for type 1 diabetes mellitus remained statistically stable (47.9%-48.4%; univariate P = 0.571). Among people listed for SPK, geographic disparities in the cumulative incidence of transplantation within 2 years declined and the overall likelihood of transplantation increased in the post-PAS era (both P < 0.001). Geographic disparities in access to SPK declined slightly but persisted post-PAS. With new allocation change proposals and elimination of listing criteria for T2DM, further monitoring is warranted.

Tacrolimus- versus sirolimus-based immunosuppression after simultaneous pancreas and kidney transplantation: 5-year results of a randomized trial.

Tacrolimus, the cornerstone immunosuppression after simultaneous pancreas and -kidney (SPK) transplantation, may exert nephrotoxic and diabetogenic effects. We therefore prospectively compared in an open-label, randomized, monocentric, 5-year follow-up study, a tacrolimus- and a sirolimus-based immunosuppressive regimen. Randomization using the block method allowing a blind allocation was done at the time of surgery. All patients received anti-thymocyte globulin and maintenance therapy with tacrolimus, mycophenolate mofetil, and steroids. At month 3, tacrolimus was continued or replaced by sirolimus. The primary endpoint was kidney and pancreas graft survival at 1 and 5years. Fifty patients were included in the final analysis in each group. At 1 year, differences for kidney and pancreas graft survival between sirolimus and tacrolimus were 0% (90% confidence interval -4.61% to 4.61%) and 6% (90% confidence interval -6.32% to 18.32%), respectively. There was no difference in renal and pancreas graft survival at 5years. Thirty-four patients (68%) in the sirolimus group vs three (6%) in the tacrolimus group needed definitive withdrawal of the study drug. Despite noninferiority of sirolimus compared to tacrolimus for kidney and pancreas graft survival, the high rate of sirolimus discontinuation does not favor its use as cornerstone therapy after SPK transplantation (NCT00693446).