Adipose Tissue Can Have a Protective Effect on Outcome After Simultaneous Pancreas-Kidney Transplantation in Non-Obese Recipients.

BACKGROUND Obesity is suggested to impair the outcome after simultaneous pancreas-kidney transplantation, which affects survival, but the quantity and distribution of adipose tissue is not yet considered in obesity assessment. We aimed to evaluate the impact of body composition on outcome after simultaneous pancreas-kidney transplantation. MATERIAL AND METHODS We retrospectively analyzed data from 40 patients who underwent simultaneous pancreas-kidney transplantation due to type 1 diabetes mellitus with consecutive end-stage renal disease. Uni- and multivariate analyses, including donor's characteristics, were performed. RESULTS Only 6 (15%) recipients were obese. The incidence of postoperative complications was correlated with lower body fat proportion (p=0.03). This correlation remained significant in the multivariate analysis (p=0.015). Nevertheless, obesity was significantly associated with worse overall survival (p<0.001). Visceral tissue proportion was correlated with a higher level of glycated hemoglobin in long-term follow-up (p=0.003). CONCLUSIONS Fat quantity and distribution should be included in the assessment of obesity. A protective effect of adipose tissue was detected on outcome after simultaneous pancreas-kidney transplantation in normosthenic recipients, but obesity still appears to have a negative effect on outcome after transplantation. Visceral fat distribution can promote de novo diabetes mellitus.

Subclinical Pancreas Rejection on Protocol Biopsy Within the First Year of Simultaneous Pancreas Kidney Transplant.

This single-center retrospective study investigated subclinical rejection prevalence and significance in simultaneous pancreas and kidney transplant (SPKT) recipients. We analyzed 352 SPKT recipients from July 2003 to April 2022. Our protocol included pancreas allograft surveillance biopsies at 1, 4, and 12months post-transplant. After excluding 153 patients unable to undergo pancreas biopsy, our study cohort comprised 199 recipients. Among the 199 patients with protocol pancreas biopsies, 107 had multiple protocol pancreas biopsies in the first year, totaling 323. Subclinical rejection was identified in 132 episodes (41%). Of these, 72% were Grade 1, 20% were indeterminate, and 8% were Banff Grade 2 or higher. All episodes of subclinical rejection were treated. Rates of pancreas graft loss (10% vs. 7%) and clinical rejection (21% vs. 20%) at 3 years were similar between those with and without subclinical rejection. Subclinical rejection Banff Grade 2 or more was associated with poor pancreas graft survival HR of 5.5 (95% CI: 1.24-24.37, p = 0.025). Of 236 simultaneous protocol kidney and pancreas biopsies, 102 (43%) showed pancreas subclinical rejection, while only 17% had concurrent kidney subclinical rejection. Our findings suggest limited predictive value of pancreatic enzymes and euglycemia in detecting pancreas rejection. Furthermore, poor concordance existed between pancreas and kidney subclinical rejection.

Small Donors, Big Impact: Optimizing Organ Utilization in Simultaneous Pancreas and Kidney Transplantation From Extra Small Pediatric Donors.

INTRODUCTION: Simultaneous pancreas-kidney transplantation (SPK) is the preferred treatment for individuals with type-1 diabetes and end-stage renal disease. However, a limited supply of "Ideal Pancreas Donors" contributed to a growing disparity between available organs and recipients. Even though SPK outcomes from pediatric donors match those from adult donors, unclear guidelines on minimum age and weight criteria for extra small pediatric pancreas donors lead to hesitancy among several transplant centers to utilize these grafts due to concerns about inadequate islet mass, technical challenges, and increased risk of allograft thrombosis. METHODS: This report details the successful outcomes of SPK transplantations performed at the study center between December 2021 and January 2024, using four extra small pediatric brain-dead donors (ESPDs). Each donor was aged ≤5 years and weighed <20 kg. RESULTS: All SPK recipients achieved immediate posttransplant euglycemia without requiring insulin. None of the recipients experienced graft pancreatitis, graft thrombosis, allograft rejection, or required re-exploration. During a 5-27-month follow-up period, all ESPD recipients maintained optimal graft function, as evidenced by normal glucose tolerance tests and HbA1c (4.9%-5.2%), with 100% graft and patient survival. CONCLUSION: This report examines the usage of ESPDs in SPK transplantation, highlighting their potential to expand the donor pool and reduce wait times in areas with scarce deceased organ donations, thereby increasing the number of available organs for transplantation with acceptable outcomes. Revising donor selection guidelines to reflect the diverse risk-benefit profiles of waitlisted individuals is crucial to addressing geographical disparities and reducing organ discard rates.

Management of Failing Kidney and Pancreas Transplantations.

Survival rates for allografts have improved over the last 2 decades, yet failing allografts remains a challenge in the field of transplant. The risks of mortality and morbidity associated with failed allografts are compounded by infectious complications and metabolic abnormalities, emphasizing the need for a standardized approach to management. Management of failing allografts lacks consensus, highlighting the need for unified protocols to guide treatment protocols and minimize risks with postdialysis initiation. The decision to wean off immunosuppression depends on various factors, including living donor availability and infectious risks, necessitating improved coordination of care and a standard guideline. Treatment of failed pancreas focuses on glycemic control, with insulin as the mainstay, while considering surgical interventions such as graft pancreatectomy in advanced symptomatic cases. Navigating the complexities of failed allograft management demands a multidisciplinary approach and standardized stepwise protocol. Addressing the gaps in management plans for failing allografts and employing a systematic approach to transplant decisions will enhance patient outcomes and facilitate informed decision-making.

Salvage Endovascular Thrombectomy for Splenic Vein Thrombosis After Pancreas Transplantation: A Single-Center Experience and Systematic Literature Review.

OBJECTIVES: Technical graft loss, usually thrombotic in nature, accounts for most of the pancreas grafts that are removed early after transplant. Although arterial and venous thrombosis can occur, the vein is predominantly affected, with estimated overall rate of thrombosis of 6% to 33%. In late diagnosis, the graft will need to be removed because thrombectomy will not restore its functionality. However, in early diagnosis, a salvage procedure should be attempted. MATERIALS AND METHODS: We conducted a retrospective, descriptive analysis of a prospective database of patients who underwent pancreas transplant from April 2008 to June 2020 at a single center. We evaluated post-transplant clinical glucose levels, imaging, treatment, and outcomes. We also performed a systematic review of publications for endovascular treatment of vascular graft thrombosis in pancreas transplant. RESULTS: In 67 pancreas transplants analyzed, 13 (19%) were diagnosed with venous thrombus. In 7 of 13 patients (54%), systemic anticoagulation was prescribed because of a non-occlusive thromboses, resulting in complete resolution for all 7 patients. Six patients (46%) required endovascular thrombectomy because of the presence of complete occlusive thrombosis; 4 of these patients (67%) needed a second procedure because of recurrence of the thrombosis. One of the 6 patients (17%) required a surgical approach, resulting in successful removal of the recurrent clot. Twelve of the 13 grafts (92%) were rescued. Graft survival at 1 year was 84%; graft survival at 3, 5, and 10 years remained at 70%. CONCLUSIONS: Pancreas vein thrombosis represents a frequent surgical complication and remains as a challenging problem. In our experience, early diagnoses and an endovascular approach combined with aggressive medical treatment and follow-up can be used for successful treatment and reduce graft loss.

Liver and pancreas transplantation in adult donor and recipients with situs inversus totalis: a case series and review of the literature.

BACKGROUND: Situs inversus totalis is a rare congenital anomaly characterized by a mirror-image orientation of abdominal, and in some cases, thoracic organs. Here, we report our situs inversus totalis transplantation experience and further review liver transplantations in adult recipients and donors with situs inversus totalis. CASE PRESENTATION: We describe three cases with situs inversus totalis. The first case was liver transplantation in a recipient (a 61-year-old Iranian man) with situs inversus totalis, the second was a liver transplantation from a donor (a 52-year-old Iranian woman) with situs inversus totalis, and finally, for the first time, a simultaneous pancreas and kidney transplantation in a recipient (a 26-year-old Iranian man) with situs inversus totalis. In patient one, hepatectomy could be performed according to the standard method and on the basis of preoperative studies. Hepatic vein and arterial anastomosis were performed as in every other patient without situs inversus totalis. To prevent biliary complications, a Roux-en-Y hepaticojejunostomy was performed. In patient two, implantation time, suprahepatic vein, portal vein, arterial, and biliary reconstruction could be done as in any other case without situs inversus totalis. Plication of the right-sided diaphragm and fixation of the falciform ligament was done for our patient. In patient three, systemic drainage was preferred to portal flow for establishing the outflow drainage of the pancreas compared with otherwise normal patients. CONCLUSION: Although situs inversus totalis is a rare condition, our reported techniques are suitable, considering advantages such as easier accessibility, more acceptable placement of the implanted organs regarding vascular variations, and the appropriate location of the allograft in the proximity of other organs.

Introduction of the donor centre virtual crossmatch in Eurotransplant.

On 24 January 2023, Eurotransplant has introduced the virtual crossmatch for kidney and pancreas allocation as a better alternative for the physical Complement Dependent Cytotoxicity (CDC) crossmatches at the donor centre, which were associated with a longer cold ischaemia time and false positive reactions. For the time being, the physical CDC crossmatch at the recipient centre will remain in place as the final histocompatibility check. While Eurotransplant is certainly not the first organ allocation organisation to introduce virtual crossmatching, several novel aspects have been introduced, such as calculation of the virtual panel reactive antibody (vPRA) on 11 loci at the second-field level in addition to the serological broad and split level, electronic HLA typing data transmission using Histoimmunogenetics Markup Language (HML) file format, and the actual virtual crossmatch based on ambiguous, second-field HLA typing of the donor on all 11 loci. This short communication will focus on these novel aspects of the virtual crossmatch in Eurotransplant.

Accessibility of Percutaneous Biopsy in Retrocolic-Placed Pancreatic Grafts With a Duodeno-Duodenostomy.

Duodeno-duodenostomy (DD) has been proposed as a more physiological alternative to conventional duodeno-jejunostomy (DJ) for pancreas transplantation. Accessibility of percutaneous biopsies in these grafts has not yet been assessed. We conducted a retrospective study including all pancreatic percutaneous graft biopsies requested between November 2009 and July 2021. Whenever possible, biopsies were performed under ultrasound (US) guidance or computed tomography (CT) guidance when the US approach failed. Patients were classified into two groups according to surgical technique (DJ and DD). Accessibility, success for histological diagnosis and complications were compared. Biopsy was performed in 93/136 (68.4%) patients in the DJ group and 116/132 (87.9%) of the DD group (p = 0.0001). The graft was not accessible for biopsy mainly due to intestinal loop interposition (n = 29 DJ, n = 10 DD). Adequate sample for histological diagnosis was obtained in 86/93 (92.5%) of the DJ group and 102/116 (87.9%) of the DD group (p = 0.2777). One minor complication was noted in the DD group. The retrocolic position of the DD pancreatic graft does not limit access to percutaneous biopsy. This is a safe technique with a high histological diagnostic success rate.

Posttransplant Lymphoproliferative Disease Following Pancreas Transplantation: A 40 Year Single-Center Experience.

BACKGROUND: Chronic immunosuppression following pancreas transplantation carries significant risk, including posttransplant lymphoproliferative disease (PTLD). We sought to define the incidence, risk factors, and long-term outcomes of PTLD following pancreas transplantation at a single center. METHODS: All adult pancreas transplants between February 1, 1983 and December 31, 2023 at the University of Minnesota were reviewed, including pancreas transplant alone (PTA), simultaneous pancreas-kidney transplants (SPK), and pancreas after kidney transplants (PAK). RESULTS: Among 2353 transplants, 110 cases of PTLD were identified, with an overall incidence of 4.8%. 17.3% were diagnosed within 1 year of transplant, 32.7% were diagnosed within 5 years, and 74 (67.3%) were diagnosed after 5 years. The overall 30-year incidence of PTLD did not differ by transplant type-7.4% for PTA, 14.2% for SPK, and 19.4% for PAK (p = 0.3). In multivariable analyses, older age and Epstein-Barr virus seronegativity were risk factors for PTLD, and PTLD was a risk factor for patient death. PTLD-specific mortality was 32.7%, although recipients with PTLD had similar median posttransplant survival compared to those without PTLD (14.9 year vs. 15.6 year, p = 0.9). CONCLUSIONS: PTLD following pancreas transplantation is associated with significant mortality. Although the incidence of PTLD has decreased over time, a high index of suspicion for PTLD following PTx should remain in EBV-negative recipients.

Measuring the Impact of Postsimultaneous Pancreas-Kidney Transplantation Complications: Comparing the Comprehensive Complication Index and Clavien-Dindo Classification.

INTRODUCTION: The Clavien-Dindo classification (CDC) is commonly used for assessing postoperative complications; however, it may not be comprehensive. A comprehensive complication index (CCI) was introduced to address this limitation. This study aimed to compare the effectiveness of the CCI and CDC in evaluating the complications after simultaneous pancreas-kidney (SPK) transplantation. METHODS: Data were collected from patients who underwent SPK transplantation at our center between February 2018 and February 2021. Complications encountered during hospitalization were assessed using both the CDC and CCI. Linear regression analyses were performed to identify the factors related to postoperative length of stay (PLOS). RESULTS: Overall, 125 patients were included, with an average age of 46.87 years. Type 2 diabetes was present in 79% of the recipients. Among them, 117 patients experienced postoperative complications of CDC grades I (2.4%), II (57.6%), IIIa (8.0%), IIIb (9.6%), IVa (14.4%), IVb (0.8%), and V (0.8%) postoperative complications. The median CCI for the entire cohort was 37.2. Spearman's correlation analysis revealed significant associations between the CDC and PLOS and the CCI and PLOS. Notably, CCI exhibited a stronger correlation with PLOS (CCI: ρ = 0.698 vs. CDC: ρ = 0.524; p = 0.024). CONCLUSION: The CCI demonstrated a stronger correlation with PLOS than CDC. Our finding suggests that the CCI may be a useful tool for comprehensively assessing complications following SPK transplantation.

An unmet need: Pancreatic beta cell replacement.

Diabetes mellitus (DM) is a growing public health concern in South Africa (SA) and poses a substantial economic burden on healthcare globally. A century has passed since the discovery of insulin, and despite advances in diabetes management, exogenous insulin remains a primary treatment for type 1 DM, posing challenges of hyperglycaemia and hypoglycaemia. Pancreas transplantation should be considered a treatment for insulin-deficient DM, offering sustained euglycaemia and preventing complications associated with the disease. However, there has been a global decrease in the number of transplants performed. In SA, only a few pancreas transplants have been performed, primarily because of surgical risks and the need for immunosuppression. Islet transplantation is an alternative but faces limitations due to donor scarcity and immunosuppression requirements. This review explores recent progress in pancreas and islet transplants for DM, with the aim of providing insights into expanding treatment options for people with insulin-deficient DM.

Comparison Between Black Non-Hispanic and White Non-Hispanic Simultaneous Pancreas-Kidney Transplant Candidates and Recipients.

INTRODUCTION: This study examined simultaneous pancreas-kidney transplant (SPKt) in Black and White patients to identify disparities in transplantation, days on the waitlist, and reasons for SPKt waitlist removal. METHODS: Using the United Network for Organ Sharing Standard Transplant Analysis and Research file, patients between January 1, 2009, and May 31, 2021, were included. Three cohorts (overall, SPKt recipients only, and those not transplanted) were selected using propensity score matching. Conditional logistic regression was used for categorical outcomes. Days on the waitlist were compared using negative binomial regression. RESULTS: Black patients had increased odds of receiving a  SPKt (OR, 1.25 [95% CI, 1.11-1.40], p < 0.001). White patients had increased odds of receiving a kidney-only transplant (OR 0.48 [95% CI, 0.38-0.61], p < 0.001), and specifically increased odds of receiving a living donor kidney (OR 0.34 [0.25-0.45], p < 0.001). CONCLUSION: This study found that Black patients are more likely to receive a SPKt. Results suggest that there are opportunities for additional inquiry related to patient removal from the waitlist, particularly considering White patients received or accepted more kidney-only transplants and were more likely to receive a living donor kidney-only transplant.

The Impact of Kidney/Pancreas Transplantation on Peripheral Arterial Disease.

INTRODUCTION: It is unclear whether kidney/pancreas (KP) transplantation will prevent the progression of peripheral arterial disease (PAD) in patients with insulin dependent diabetes (IDDM) and end-stage renal disease. We sought to determine the pre- and posttransplant prevalence of symptomatic PAD and changes in carotid artery intima-media thickness (IMT) in KP recipients. METHODS: In this single center study, outcomes were compared between KP recipients with and without a history of PAD. A subset of recipients underwent pre- and posttransplant IMT measurements. RESULTS: Among the study group (N = 107), 18 (17%) recipients admitted to a pretransplant history of symptomatic PAD, comprised 11 foot infections and 7 amputations (5 minor and 2 major). Baseline characteristics of age, gender, race, years of diabetes, dialysis history, smoking history, years of hypertension, and history of coronary artery disease (CAD) were equivalent between PAD and non-PAD cohorts. At a median follow-up of 60 months (IQR: 28, 110), 16 (15%) KP recipients had suffered a PAD event. In multivariate analysis, a pretransplant history of PAD (hazard ratio [HR] 9.66, p < 0.001) and CAD (HR 3.33, p = 0.04) were independent predictors of posttransplant PAD events. Among a subset of 20 recipients (3 with PAD), mean IMT measurements pretransplant and at a median of 24 (range 18-24) months posttransplant, showed no evidence of disease progression. CONCLUSION: Based on IMT measurements and clinical results, KP transplantation stabilized PAD in most patients, but did not alter outcomes of symptomatic PAD recipients. A pretransplant history of PAD and CAD was an independent predictor of posttransplant PAD events.

The Pancreas After Kidney Transplant is a Competitive Option, Comparable to the Simultaneous Pancreas and Kidney Transplant.

BACKGROUND: Simultaneous pancreas and kidney transplant (SPK) is the most common type of pancreas transplant performed worldwide. In contrast, there are a few drawbacks to pancreas after kidney transplant (PAK), such as the requirement for an additional operation, the immunologic risk, etc. SPK is the best option, but because of a lack of deceased donors and a lengthy waiting period, it is not always possible to use it. METHODS: From 2015 to 2022, we performed 23 SPKs and 21 PAKs at the Pusan National University Yangsan Hospital in Korea. We compared the findings of PAK and SPK conducted within the same time period. RESULTS: The waiting time for pancreatic graft was significantly shorter in the PAK than SPK group (345 days vs 1350 days, P ≤ .001). Throughout the monitoring period, just 1 pancreatic graft was lost in patients who underwent PAK, and the 7-year graft survival was 95%, with no statistically significant difference compared to SPK (90.3%, P = .600). Moreover, the graft survival of SPK or PAK was superior to that of pancreatic transplant alone (63.7%, P = .016). Only 1 pancreatic graft loss was a case of mortality with a functioning graft. No additional kidney transplant loss was observed in PAK recipients. There was no variation in creatinine levels between the pretransplant and posttransplant periods. There were 2 incidents of pancreatic graft and kidney graft rejection, respectively, but the grafts entirely recovered following rejection treatment. CONCLUSION: According to our experiences, PAK could be another best choice for individuals with diabetic end-stage renal disease, especially in cases where deceased donors were severely deficient but living donor kidney transplants were actively performed in countries like Korea.

Pancreas transplantation: review.

Pancreas transplant (PTx) is the only treatment that establishes normal glucose levels for patients diagnosed with diabetes types 1 and 2. The paper aims to review and analyze graft survival, patient survival, and the impact on diabetic complications. We describe that the graft survival was 82-98% at 1 year, 90% at 5 years, and 75-54% at 10 years for simultaneous pancreas-kidney recipient; 71% pancreas after kidney (PAK), and 62% PTx alone at 1 year. Patient survival: At 1 year for recipients was 96.9% simultaneous pancreas-kidney transplantation (SPK); for PAK transplantation recipients, 96.3%; and for PTx alone recipients, 98.3%. In general, the pancreas transplantation improves and reverses diabetic complications. Finally, the pancreatic transplant is a morbid procedure and emerges as a significant alternative in diabetes management, directly competing with conventional insulin therapies. Results so far suggest that the most effective transplant model is the SPK. While more patients could benefit from this procedure, surgical complications and the need for immunosuppression pose significant challenges.

El trasplante de páncreas es el único tratamiento que estabiliza los niveles normales de glucosa en los pacientes diagnosticados con diabetes tipo 1 o tipo 2. En esta revisión se analizan la supervivencia del injerto, la supervivencia del paciente y el impacto en las complicaciones diabéticas. Se describe la supervivencia del injerto: 82-98% al año para los receptores de trasplante simultáneo de páncreas y riñón, 71% para trasplante páncreas después de riñón y 62% para trasplante de páncreas solitario al año. Supervivencia de los pacientes a 1 año: 96.9% para los receptores de trasplante simultáneo de páncreas y riñón, 96.3% para los receptores de trasplante de páncreas después de riñón y 98.3% para los receptores de páncreas solitario. En general, el trasplante de páncreas mejora y revierte las complicaciones diabéticas. Finalmente, el trasplante de páncreas, un procedimiento mórbido, surge como una alternativa significativa en el manejo de la diabetes, compitiendo directamente con las terapias convencionales de insulina. Hasta ahora, los resultados indican que el modelo de trasplante más efectivo es el simultáneo de páncreas y riñón. Aunque más pacientes podrían beneficiarse de este procedimiento, las complicaciones quirúrgicas y la necesidad de inmunosupresión plantean desafíos significativos.

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 3300 U/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.

Ten Years of Quality Monitoring of Abdominal Organ Procurement in the Netherlands and Its Impact on Transplant Outcome.

In this study, 10 years of procurement quality monitoring data were analyzed to identify potential risk factors associated with procurement-related injury and their association with long-term graft survival. All deceased kidney, liver, and pancreas donors from 2012 to 2022 and their corresponding recipients in the Netherlands were retrospectively included. The incidence of procurement-related injuries and potential risk factors were analyzed. Of all abdominal organs procured, 23% exhibited procurement-related injuries, with a discard rate of 4.0%. In kidneys and livers, 23% of the grafts had procurement-related injury, with 2.5% and 4% of organs with procurement-related injury being discarded, respectively. In pancreas procurement, this was 27%, with a discard rate of 24%. Male donor gender and donor BMI >25 were significant risk factors for procurement-related injury in all three abdominal organs, whereas aberrant vascularization was significant only for the kidney and liver. In the multivariable Cox regression analyses, procurement-related injury was not a significant predictor for graft failure (kidney; HR 0.99, 95% CI 0.75-1.33, p = 0.99, liver; HR 0.92, 95% CI 0.66-1.28, p = 0.61, pancreas: HR 1.16; 95% CI 0.16-8.68, p = 0.88). The findings of this study suggest that transplant surgeons exhibited good decision-making skills in determining the acceptability and repairability of procurement-related injuries.

The role of donor hypertension and angiotensin II in the occurrence of early pancreas allograft thrombosis.

Background: About 10-20% of pancreas allografts are still lost in the early postoperative period despite the identification of numerous detrimental risk factors that correlate with graft thrombosis. Methods: We conducted a multicenter study including 899 pancreas transplant recipients between 2000 and 2018. Early pancreas failure due to complete thrombosis, long-term pancreas, kidney and patient survivals were analyzed and adjusted to donor, recipient and perioperative variables using a multivariate cause-specific Cox model stratified to transplant centers. Results: Pancreas from donors with history of hypertension (6.7%), as well as with high body mass index (BMI), were independently associated with an increased risk of pancreas failure within the first 30 post-operative days (respectively, HR= 2.57, 95% CI from 1.35 to 4.89 and HR= 1.11, 95% CI from 1.04 to 1.19). Interaction term between hypertension and BMI was negative. Donor hypertension also impacted long-term pancreas survival (HR= 1.88, 95% CI from 1.13 to 3.12). However, when pancreas survival was calculated after the postoperative day 30, donor hypertension was no longer a significant risk factor (HR= 1.22, 95% CI from 0.47 to 3.15). A lower pancreas survival was observed in patients receiving a pancreas from a hypertensive donor without RAAS (Renin Angiotensin Aldosterone System) blockers compared to others (50% vs 14%, p < 0.001). Pancreas survival was similar among non-hypertensive donors and hypertensive ones under RAAS blockers. Conclusion: Donor hypertension was a significant and independent risk factor of pancreas failure. The well-known pathogenic role of renin-angiotensin-aldosterone system seems to be involved in the genesis of this immediate graft failure.

Interruption of anti-thymocyte globuline treatment in solid organ transplantation is effectively monitored through a low total lymphocyte count.

Introduction: Anti-Thymocyte Globulin (ATG) is a cornerstone in immune suppression for solid organ transplantation. The treatment is a delicate balance between complications arising from over-immunosuppression such as infections and cancer versus rejection stemming from under-immunosuppression. CD3+ T-lymphocyte measurements are frequently employed for treatment monitoring. However, this analysis is costly and not always accessible. The aim of this study was to investigate whether the total count of lymphocytes could replace CD3+ T-lymphocyte measurements based on data from our transplantation center combined with a review of the literature. The hypothesis was that the total lymphocyte count could serve as a diagnostic surrogate marker for CD3+ T-lymphocytes. Methods: A retrospective cohort study was conducted, including patients who underwent kidney and/or a pancreas transplantation and received ATG as induction therapy or for rejection treatment. The inclusion criterium was that the total lymphocyte count and CD3+ T-lymphocyte measurements were measured simultaneously on the same day. Additionally, PubMed and Embase were searched up to 18/10/2023 for published studies on solid organ transplantation, ATG, T-lymphocytes, lymphocyte count, and monitoring. In the retrospective cohort study, a total of 91 patients transplanted between 2016 and 2023, with 487 samples, were included. Results: Total lymphocyte counts below 0.3 x 109/L had a high sensitivity (86%) as a surrogate marker of CD3+ T-lymphocytes below 0.05 x 109/L, but the specificity was low (52%) for total lymphocyte counts above 0.3 x 109/L as a surrogate marker for CD3+ T-lymphocytes above 0.05 x 109/L. A review of the literature identified seven studies comparing total lymphocyte counts and CD3+ T-lymphocytes in ATG monitoring. These studies supported the use of a low total lymphocyte count as a surrogate marker for CD3+ T-lymphocytes and an indicator to omit ATG treatment. However, there was no consensus regarding high total lymphocyte counts as an indicator for continued treatment. Discussion: Results supports that the total lymphocyte count can be used to omit ATG treatment when below 0.3 x 109/L whereas the CD3+ T-lymphocyte analysis should be reserved for higher total lymphocyte counts to avoid ATG overtreatment.

Safety and Efficacy of Mycophenolate Mofetil Associated With Tacrolimus for Kidney-pancreas and Kidney Transplantation: A Systematic Review and Meta-Analysis of Randomized Studies.

INTRODUCTION: This study evaluated the efficacy and safety of mycophenolate mofetil (MMF) associated with tacrolimus (TAC) in patients undergoing kidney-pancreas and kidney transplants, in comparison with cyclosporine (CyA), azathioprine (AZA), everolimus (EVL), sirolimus (SRL), manitimus (MAN), mizoribine (MZR), and enteric-coated mycophenolate sodium (ECMPS) in combination or monotherapy. METHODS: A systematic review and meta-analysis of randomized clinical trials was performed. The outcomes comprised acute rejection, graft loss, and adverse events. RESULTS: Thirty studies were included. The main adverse events related to the TAC+MMF scheme were infection (36%; 95%CI: 26%-46%), including cytomegalovirus (CMV) (14%; 95%CI: 8%-20%); anemia (20%; 95%CI: 2%-37%); leukopenia (18%; 95%CI: 3%-33%); nausea (20%; 95%CI: 1%-39%); and diarrhea (26%; 95%CI:13%-40%). TAC+MMF was compared to the schemes AZA+TAC, CyA+AZA, CyA+MMF, CyA+SRL, ECMPS, EVL, MAN+TAC, MMF+SRL, MZR, TAC+AZA, TAC+EVR, TAC+MZR, TAC +SRL and TAC. TAC+MMF was associated with a lower risk of rejection than MMF monotherapy (RD: -0.24; 95%CI -0.46; -0.02). Comparing TAC+MMF with the other regimens, no significant difference was found for graft loss. TAC+MMF was associated with a higher risk of infections than MZR (RD: 0.174; 95%CI: 0.25; 0.323) and TAC monotherapy (RD: 0.07; 95%CI 0.003; 0.138). CONCLUSION: Gastrointestinal and hematological adverse events and infections are the most common with TAC+MMF for kidney-pancreas and kidney. TAC+MMF effectively prevents acute cellular rejection, and alternatives with AZA, CyA, SRL, ECMPS, EVL, MAN, and MSR have similar efficacy and safety profiles. TAC monotherapy and MZR may be associated with a lower risk of infections.