Transplant International最新文献

The rate of early pancreas allograft failure remains high due to thrombosis but also to severity of rejection episodes. We investigated if adjunct anti-TNFα therapy was safe and could improve outcomes after pancreas transplantation. We investigated all pancreas transplants performed in our institution between 2010 and 2022. Etanercept, an anti TNFα therapy, was added to our standard immunosuppressive regimen since 2017 after approval from our institutional human ethics committee. Pancreas survival, rejection episodes, as well as infectious complications were analyzed. A total of 236 pancreas transplants were included, among whom 87 received Etanercept for induction. In multivariable analysis, after adjustment on confounding variables, pancreas survival did not differ between groups (HR = 0.92, CI 95% = 0.48; 1.73, p = 0.79). However, patients receiving Etanercept presented a significantly lower occurrence of pancreas rejection in multivariate analysis (HR = 0.36, CI 95% = 0.14; 0.95, p = 0.04). Patients receiving Etanercept did not experienced a higher risk of bacterial, fungal, CMV nor BK virus infections compared to the non-treated group. The use of anti-TNFα after pancreas transplantation was safe and did not increase infectious complications. Despite a similar rate of thrombosis, anti-TNFα significantly reduced pancreatic rejection, thus supporting its use among pancreas transplant recipients.

This study aims to provide objective evidence for the subjectively observed increase in non-utilized donors and to investigate whether they share common risk factors, hypothesizing that the aging of the donor population may be a possible explanation. All referred deceased donors in the Netherlands between 2018 and 2023 were analyzed. A utilized donor was defined as a referred donor that resulted in at least one transplanted organ. A non-utilized donor was defined as a donor from whom no organ was transplanted as a result of the cessation. In total, 2,235 donors were defined as referred; 1,618 donors were utilized and 617 were non-utilized. A significant increase in referred donors aged >66 years was observed, together with an increase of 51% in non-utilized donors. The most frequent reasons for not utilizing a donor were found to be an agonal phase > 2 hours in DCD donors (45%) and an unacceptable medical history at screening (22%). Multivariable logistic regression analysis showed that increasing donor age (age 66-75 years OR 1.81, 95% CI 1.09-3.00), DCD donors (OR 4.37 95% CI 3.24-5.89, p < 0.01), history of hypertension (OR 1.29 95% CI 1.01-1.66, p = 0.04) and/or diabetes (OR 2.48 95% CI 1.75-3.51, p < 0.01) were associated with non-utilization. Non-utilized donors are significantly older, are more often DCD donors and have more co-morbidities, confirming the hypothesis that these donors are the more marginal donors.

Recently, initial clinical experience has been gained with the xenotransplantation of pig organs such as heart and kidney into terminally ill human patients in an effort to overcoming organ shortage. Here, we investigated the use of normothermic machine perfusion (NMP) to advance xenotransplantation research and develop bridging therapies for acute organ failure such as the use of pig livers as a liver dialysis system. We simultaneously analyzed livers and lungs from genetically modified pigs, carrying a knock-out of the GGTA1 gene, which is essential for xenoreactive αGal-KO-epitopes, by applying clinically established normothermic perfusion systems, solutions and human blood. Experiments involved perfusing organs with cell-free solutions as well as human erythrocyte concentrates for up to six hours, analyzing organ quality using invasive and non-invasive methods, and the isolation and analysis of immune cells from the perfusate. The results obtained show stable flow characteristics with physiological perfusion and oxygenation levels of the organs, and a largely intact organ architecture, confirmed by histological sections before and after perfusion. Overall, this study demonstrates the feasibility of normothermic machine perfusion of xenogeneic organs by an interdisciplinary team, thus paving the way for clinical applications of porcine xenografts involving NMP.

Heart transplantation (HT) is the gold standard treatment of end-stage heart failure, but organ shortage remains a challenge. This retrospective cohort study assesses the economic burden and healthcare pathways of patients awaiting HT in a French tertiary center. Direct healthcare resources were collected and valued, and a state sequence analysis was performed. Ninety-two adult patients were included, with 67 (73%) undergoing HT within a median waiting time of 2 months. The mean cost per patient was €21,324.05 with an average of 2.71 hospitalizations. Four clusters were identified. Type 1 patients (n = 43) underwent HT within 1 month, with a mean cost of €5,820.12 per patient. Only 4 (25%) Type 2 patients (n = 16) underwent HT within 30 months, as they were not prioritized for HT, with a mean cost of €22,285.32 per patient. Type 3 patients (n = 20) underwent HT within 10 months, but incurred higher costs (€27,541.11) compared to Type 2 patients over a shorter period. Despite high transplant priority, Type 4 patients (n = 13) died before HT within 3 months, with a mean cost of €61,858.45 and 3 hospitalizations. This work highlights the economic burden of organ shortage. The use of novel heart preservation devices (such as ex-vivo perfusion systems) could help to expand the donor pool and alleviate this burden, but these aspects need to be further investigated.

Kidney transplant outcomes are influenced by donor and recipient age, sex, HLA mismatch, donor type, anti-rejection medication adherence and disease recurrence, but variability in transplant outcomes remains unexplained. We hypothesise that donor and recipient polygenic burden for traits related to kidney function may also influence graft function. We assembled a cohort of 6,060 living and deceased kidney donor-recipient pairs. We calculated polygenic risk scores (PRSs) for kidney function-related traits in both donors and recipients. We investigated the association between these PRSs and recipient eGFR at 1- and 5-year post-transplant as well as graft failure. Donor: hypertension PRS (P < 0.001), eGFR PRS (P < 0.001), and intracranial aneurysm PRS (P = 0.01), along with recipient eGFR PRS (P = 0.001) were associated with eGFR at 1-year post-transplantation. Clinical factors explained 25% of the variation in eGFR at 1-year and 13% at 5-year, with PRSs cumulatively adding 1% in both cases. PRSs were not associated with long-term graft survival. We demonstrate a small, but statistically significant association between donor and recipient PRSs and recipient graft function at 1- and 5-year post-transplant. This effect is, at present, unlikely to have clinical application and further research is required to improve PRS performance.

Xenotransplantation has a rich history, marked by European pioneers who laid the groundwork for many breakthroughs in the field. Pig organ xenotransplantation offers a solution to the global shortage of deceased human donor organs, whilst allowing the modification of the donor graft itself. The field has continued to garner interest, particularly with the recent advent of simpler and faster genetic-engineering technologies. This review highlights the contributions of European researchers to xenotransplantation, spanning pig kidney, heart, liver, and lung transplantation. Research has focused on (i) identifying and deleting key xenoantigens and modifying the source pig by expression of human "protective" proteins and (ii) testing novel immunosuppressive regimens. These contributions have played key roles in advancing xenotransplantation from the laboratory to early clinical experiments. Europeans have also addressed the potential risks of xenozoonotic infections and the regulatory challenges. The research endeavours of groups in Europe are summarized. Several European researchers moved either permanently or temporarily to US institutions, and their insight and innovations are also highlighted. While we aim to recognize the significant contributions of European physicians and scientists in this article, it is not an exhaustive list of all those who have influenced the field.

Kidney donation is a safe procedure for carefully screened donors. The growing shortage of organs and improved survival rates among recipients of living donor transplants have broadened the criteria for acceptable living donors, including older individuals and those with pre-existing health conditions. Consequently, ensuring both the short- and long-term safety of living donors is of paramount importance. The primary objectives are to prevent the need for kidney replacement therapy, major cardiovascular events, or premature death. Lifelong monitoring of living donors is essential to facilitate early treatment for preventable illnesses. To this end, annual follow-up is generally recommended, which should minimally include an assessment of blood pressure, body mass index, kidney function, albuminuria, lifestyle factors, and general wellbeing. However, the management of these risk factors and treatment targets in this population remain inadequately defined. Recommendations for genetic counseling in cases of living-related donation also remain inconsistent. The aim of this mini-review is to address the challenges in evaluating the evidence on the long-term consequences of kidney donation, particularly concerning the risk of developing end-stage kidney disease, cardiovascular mortality, gestational complications, and hypertension. This article aligns with the ESOT call for action to promote living kidney donation and EKITA's mission.

Switching the use of calcineurin inhibitors (CNIs), as basal immunosuppression in liver transplantation (LT) patients, for that of mycophenolate mofetil monotherapy (MMF-MT) is currently considered a good measure in recipients with chronic kidney disease (CKD) and other CNI-related adverse effects. We analyzed a retrospective cohort series of 324 LT patients who underwent long-term follow-up and were switched from CNI immunosuppression to MMF-MT due to CKD and other CNI-related adverse effects (diabetes, hypertension, infection). The median time on MMF-MT was 78 months. The indication for MMF-MT was CKD alone or associated with CNI-related adverse effects in 215 patients, diabetes in 61, hypertension in 42, and recurrent cholangitis in 6. Twenty-four (7.4%) patients developed non-resistant acute rejection post-MMF-MT, and 48 (14.8%) patients experienced MMF-related adverse effects, with MMF-MT withdrawn in only 8 (2.5%) patients. In the comparison between the pre-MMF-MT period and the last outpatient review, using a repeated measures model and taking each patient as its own comparator, we demonstrated a significant increase in GFR and significant decrease in creatinine and ALT values, remaining the other variables (diabetes, hypertension, and hematological and AST) within similar levels. Five-year survival post-MMF-MT conversion was 75.3%. MMF-MT significantly improved renal function, was well tolerated, and had a low rejection rate.