Transplant International最新文献

The machine perfusion (MP) of transplantable grafts has emerged as an upcoming field in Cardiothoracic (CT) transplantation during the last decade. This technology carries the potential to assess, preserve, and even recondition thoracic grafts before transplantation, so it is a possible game-changer in the field. This technology field has reached a critical turning point, with a growing number of publications coming predominantly from a few leading institutions, but still need solid scientific evidence. Due to the increasing need to expand the donor pool, especially in Europe, where the donor age is steeply increased, a consensus has been established to address the growing need and knowledge of machine perfusion in cardiothoracic transplantation, targeting the unmet scientific need in this growing field but also, priorities for development, and regional differences in utilization rates and organizational issues. To address MP in CT, the European Society of Organ Transplantation (ESOT) convened a dedicated Working group comprised of experts in CT to review literature about MP to develop guidelines that were subsequently discussed and voted on during the Consensus Conference that took place in person in Prague during the TLJ 3.0 in November 2022. The findings and recommendations of the Cardiothoracic Working Group on MP are presented in this article.

There have been significant advances in short-term outcomes in renal transplantation. However, longer-term graft survival has improved only minimally. After the first post-transplant year, it has been estimated that chronic allograft damage is responsible for 5% of graft loss per year. Transplant glomerulopathy (TG), a unique morphologic lesion, is reported to accompany progressive chronic allograft dysfunction in many cases. While not constituting a specific etiologic diagnosis, TG is primarily considered as a histologic manifestation of ongoing allo-immune damage from donor-specific anti-HLA alloantibodies (DSA). In this review article, we re-evaluate the existing literature on TG, with particular emphasis on the role of non-HLA-antibodies and complement-mediated injury, cell-mediated immune mechanisms, and early podocyte stress in the pathogenesis of Transplant Glomerulopathy.

Acute cellular rejection (ACR) frequently occurs following lung transplantation (LuTx) and represents a risk factor for the development of chronic lung allograft dysfunction (CLAD) as well as long-term survival. The histopathological diagnosis of ACR carries a burden of interobserver variability. The widespread utilization and cost-effectiveness of immunohistochemistry (IHC) was proven beneficial in diagnosing rejection in human kidney transplantations and LuTx rat models. However, its potential for ACR detection in patients remains unexplored. We analyzed surface markers (CD3, CD4, CD8, CD20, CD68, CD47, PD-1, PD-L1, and CD31/PECAM-1) on lung tissue cryobiopsy samples collected within 6 months post-LuTx from 60 LuTx recipients, 48 of whom were diagnosed with ACR. Additionally, serum samples from 51 patients were analyzed using a multiplex bead-based Luminex assay. The cytokines and markers included PD-L1, IL2, TNFα, IFNγ, and Granzyme B. We observed a significant increase in PD-L1 tissue expression within the rejection group, suggesting a concerted effort to suppress immune responses, especially those mediated by T-cells. Furthermore, we noted significant differences in PECAM-1 levels between ACR/non-ACR. Additionally, peripheral blood C-reactive-protein levels tended to be higher in the ACR group, while Luminex serum analyses did not reveal any significant differences between groups. In conclusion, our findings suggest the potential value of PECAM-1 and PD-L1 markers in diagnosing ACR.

SARS-CoV-2 infection represents a new challenge for solid organ transplantation (SOT) with evolving recommendations. A cross-sectional survey was performed (February-June 2024) to describe practices among Member States of the Council of Europe (COE) on the use of organs from deceased donors with resolved or active SARS-CoV-2 infection. Overall, 32 out of 47 Member States with a transplant program participated in the study. Four (12.5%) countries did not use organs from deceased donors either with resolved or with active SARS-CoV-2 infection and 8 (25%) countries accepted organs only from deceased donors with resolved SARS-CoV-2 infection. Donor evaluation for SARS-CoV-2 included universal screening with standard PCR testing on respiratory specimens generally (61.4%) performed within 24 h prior to organ recovery. Further microbiological, immunological and radiological investigations varied. Most waitlisted patients receiving organs from a deceased donor with active (94.5%) or resolved (61.5%) SARS-CoV-2 infection were preferred to have natural, vaccine-induced or hybrid SARS-CoV-2 immunity. Most countries did not require recipients to undergo specific anti-SARS-CoV-2 treatment as pre-exposure (0%), post-exposure prophylaxis (15.4%) or modification of immunosuppression regimen (24%). This study highlights similarities and heterogeneities in the management of SARS-CoV-2 positive donors between COE countries, and a potential to safely expand donors' pool.

Normothermic ex-situ heart perfusion (ESHP) enables assessment of hearts donated after circulatory death (DCD) prior to transplantation. However, sensitive parameters of cardiac function of DCD hearts on ESHP are needed. This study proposes a novel approach using electrophysiological (EP) parameters derived from electrical mapping as biomarkers of post-ischemic cardiac performance. Porcine slaughterhouse hearts (PSH) were divided in two groups based on the type of warm ischemia (Group 1: 10 ± 1 min with animal depilation vs. Group 2: ≤5 min without depilation). Electrical mapping of the right (RV) and left ventricle (LV) was performed on ESHP. Potential voltages, slopes and conduction velocities were computed from unipolar electrograms and compared between groups. Voltages were lower in Group 1 compared to Group 2 (RV: 3.6 vs. 15.3 mV, p = 0.057; LV: 10.8 vs. 23.6 mV, p = 0.029). In addition, the percentage of low-voltage potentials was higher and potential slopes were flatter in Group 1. Voltages and slopes strongly correlated with the visual contractile performance of PSH, but showed weaker correlation with lactate profiles. In conclusion, unipolar potential voltages and potential slopes were decreased in hearts with severe warm ischemia. As such, EP parameters could aid transplantation teams in decision-making on transplantability of DCD hearts.

Thoraco-abdominal normothermic regional perfusion (TA-NRP), utilizing Extra Corporeal Membrane Oxygenation (ECMO) devices, has emerged as an effective strategy for heart recovery in donors declared dead by circulatory criteria (DCDD). After death declaration, TA-NRP restores heart activity by reperfusing the arrested heart with oxygenated blood at normothermia. Mechanical ventilation resumption in the donor enables weaning from ECMO and restores systemic circulation and oxygenation using the donor's heart and lungs. However, if pre-existing conditions prevent the donor's lungs from oxygenating blood post-cardiac activity restoration, weaning from veno-arterial ECMO may lead to systemic hypoxia, jeopardizing the restored cardiac function. Anticipating this scenario may guide planning a split ECMO circuit to facilitate earlier and more effective recovery of donor heart function post-ECMO weaning. This manuscript describes three cases of DCDD donors with hypoxic respiratory failure undergoing TA-NRP for heart recovery. By establishing a bridge in the arterial portion of the circuit, clamped out after weaning from veno-arterial ECMO, donor heart function was assessed exclusively with veno-venous ECMO support, leading to successful heart transplantation.

Post-transplantation diabetes mellitus (PTDM) and prediabetes are associated with increased cardiovascular morbidity and mortality in kidney transplant recipients (KTR), when diagnosed by an oral glucose tolerance test (oGTT). Hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) display low concordance with the oGTT in the early phase posttransplant. For this prospective cross-sectional pilot study, 41 KTR from years one to five after transplantation without known preexisting PTDM (defined by HbA1c ≥ 6.5% (NGSP) or 48 mmol/mol (IFCC) at last visit or glucose-lowering therapy) were recruited at the Charité Transplant Outpatient Clinic. For each study participant HbA1c, FPG and an oGTT were followed by CGM. 38 of the 41 patients recruited had sufficient CGM-recordings (≥10 days). PTDM and impaired glucose tolerance (IGT), as defined by the gold standard oral glucose tolerance test (oGTT)-derived 2-h plasma glucose (2hPG), were diagnosed in one (3%) and twelve (32%) patients, respectively. HbA1c exhibited good test characteristics regarding IGT (ROC-AUC: 0.87); sensitivity/specificity of HbA1c-threshold 5.7% (NGSP) or 39 mmol/mol (IFCC) were 1.0/0.64, respectively. Best performing CGM-readouts mean sensor glucose and percent of time >140 mg/dL (%TAR (140 mg/dL)) displayed acceptable diagnostic performance (ROC-AUC: 0.78 for both). Thus, HbA1c can aid in timely diagnosis of IGT in the stable phase after kidney transplantation.

Burnout is increasingly relevant among healthcare professionals. The aim of this study is to describe the prevalence of burnout and other parameters of professional satisfaction among different specialists dedicated to Liver Transplantation (LT) in transplant teams. A working group from the Spanish Society of LT designed a survey with 39 questions evaluating the prevalence of parameters related to professional satisfaction, including burnout. It was distributed among 496 specialists dedicated to liver transplantation in Spanish transplant teams. Responders included surgeons (49%), hepatologists (27%), anesthesiologists (16%), intensivists (4%), and other specialties (4%). Among responders, 78% reported some degree of burnout. Moreover, 46% of responders did not see themselves working in transplantation in 5 years. The rates of burnout and dissatisfaction among anesthesiologists and surgeons were higher than other specialists. The highest levels of dissatisfaction were in economic remuneration and work-life balance. Being younger than 60 years old and non-head of department showed to be risk factors of burnout. In conclusion, the prevalence of burnout among LT physicians in Spain was notably high. Among the various specialties, anesthesiologists and surgeons exhibited the highest dissatisfaction rates. The results of this work may be of interest to healthcare management and planning.

Normothermic machine perfusion (NMP) is a clinical strategy to reduce renal ischemia-reperfusion injury (IRI). Optimal NMP should restore metabolism and minimize IRI induced inflammatory responses. Microdialysis was used to evaluate renal metabolism. This study aimed to assess the effect of complement inhibition on NMP induced inflammatory responses. Twenty-two pig kidneys underwent 18 h of static cold storage (SCS) followed by 4 h of NMP using a closed-circuit system. Kidneys were randomized to receive a C5-inhibitor or placebo during SCS and NMP. Perfusion resulted in rapidly stabilized renal flow, low renal resistance, and urine production. During SCS, tissue microdialysate levels of glucose and pyruvate decreased significantly, whereas glycerol increased (p < 0.001). In the first hour of NMP, glucose and pyruvate increased while glycerol decreased (p < 0.001). After 4 h, all metabolites had returned to baseline. Inflammatory markers C3a, soluble C5b-9, TNF, IL-6, IL-1β, IL-8, and IL-10 increased significantly during NMP in perfusate and kidney tissue. C5-inhibition significantly decreased perfusate and urine soluble C5b-9 (p < 0.001; p = 0.002, respectively), and tissue IL-1β (p = 0.049), but did not alter other inflammatory markers. Microdialysis can accurately monitor the effect of NMP on renal metabolism. Closed-circuit NMP induces inflammation, which appeared partly complement-mediated. Targeting additional immune inhibitors should be the next step.

Angiotensin II type-1 receptor antibody (AT1R-Ab) has been mooted as a potential effector of both acute and chronic antibody mediated rejection (AMR). A growing body of literature on the topic is now coming under scrutiny in the context of the evolving Banff AMR diagnostic classification system and refinement of recommendations for histocompatibility testing by the Sensitization in Transplantation Assessment of Risk (STAR) workgroup. This mini-review discusses the latest understanding of pathophysiological mechanisms, clinical evidence for the pathogenicity of AT1R-Ab, and methods of laboratory testing.