Transplant International最新文献

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.

In transplantation, genetic differences between donor and recipient trigger immune responses that cause graft rejection. Allorecognition, the process by which the immune system discriminates allogeneic grafts, targets major histocompatibility complex (MHC) and minor histocompatibility antigens. Historically, it was believed that allorecognition was solely mediated by the recipient's adaptive immune system recognizing donor-specific alloantigens. However, recent research has shown significant roles for innate immune components, such as lymphoid and myeloid cells, which are sometimes triggered by the mere absence of a self-protein in the graft. This review integrates recent breakthroughs into the current allorecognition paradigm based on the well-established direct and indirect pathways, emphasizing the semi-direct pathway where recipient antigen-presenting cells (APCs) acquire donor MHC molecules, and the inverted direct pathway where donor CD4⁺ T cells within the graft activate recipient B cells to produce donor-specific antibodies (DSAs). The review also explores the role of natural killer (NK) cells in both promoting and inhibiting graft rejection, highlighting their dual role in innate allorecognition. Additionally, it discusses the emerging understanding of myeloid cell-mediated allorecognition and its implications for initiating adaptive immune responses. These insights aim to provide a more comprehensive understanding of allorecognition, potentially leading to improved transplant outcomes.

The pulmonary microbiome has emerged as a significant factor in respiratory health and diseases. Despite the sterile conditions maintained during ex vivo lung perfusion (EVLP), the use of antibiotics in the perfuse liquid can lead to dynamic changes in the lung microbiome. Here, we present the design of a study that aims to investigate the hypothesis that EVLP alters the lung microbiome and induces tissue inflammation. This pilot, prospective, controlled study will be conducted in two Spanish donor centers and will include seven organ donors after brain death or after controlled cardiac death. After standardized retrieval, the left lung will be preserved in cold storage and the right lung will be perfused with EVLP. Samples from bronchoalveolar lavage, perfusion and preservation solutions, and lung biopsies will be collected from both lungs and changes in lung microbiome and inflammatory response will be compared.

As transplant programmes have evolved to allow a wider donor pool, organ acceptance decisions have become increasingly complex and lack transparency and equality. Clinical scoring tools exist but there is limited consensus on their use. From a prospective observation of consecutive deceased-donor kidney offers in a large urban transplant centre, a simple score was developed based on donor age and other risk characteristics, excluding ischemia time and graft histology. The score was validated in subsequent cohorts of consecutive offers in the United Kingdom and Germany. In the development cohort of 389 kidney offers, 110 (28%) were transplanted and 175 (45%) declined. Nine risk factors were incorporated into a score based on age, but adjusted for the number of risk factors present, making an "adjusted donor age," with offers separated into equal quintiles by decade. The score was validated in a UK cohort of 380 subsequent offers, and a German cohort of 431 offers. In both cohorts adjusted donor age discriminated between favourable and poor post-transplant outcomes (C-statistic 0.77 in the United Kingdom, 95% CI 0.65-0.88, and 0.71 in Germany, 95% CI 0.64-0.77). Adjusted donor age is a simple score quantifying deceased donor kidney quality, which is consistent with current practice and predicts post-transplant outcome.

Transplant Renal Artery Stenosis (TRAS) is the leading vascular complication following kidney transplantation (KT), causing premature allograft loss and increased post-KT mortality. While risk factors for TRAS, such as prolonged cold ischemia time and delayed graft function, are well-documented in deceased donor-KT, the risk factors remain less clearly defined in living donor-KT. This matched case-control study, conducted at a leading national transplant center predominantly performing living donor-KT, evaluated risk factors and long-term outcomes of clinical TRAS (cTRAS). cTRAS cases diagnosed from January 2009 to December 2022 were matched with four control kidney transplant recipients (KTRs) in a study powered to assess whether ex-vivo arterial vascular reconstruction of multiple renal arteries (VR-MRA) increases the risk of cTRAS. Among 2,454 KTs, 28 KTRs (1.14%) were diagnosed with cTRAS around 3.62 ± 1.04 months post-KT, with renal allograft dysfunction (92.86%) as the most common presenting feature. Notably, 27 cTRAS cases were successfully treated with endovascular intervention, yielding favorable outcomes over a 6-180 months follow-up period. The study identified ex-vivo VR-MRA as an independent risk factor for cTRAS (P < 0.001). cTRAS cases receiving timely treatment exhibited long-term outcomes in graft and patient survival similar to control KTRs. Early screening and timely intervention for cTRAS post-KT may improve graft and patient outcomes.

[This corrects the article DOI: 10.3389/ti.2024.13029.].

Organs obtained from brain dead donors can have suboptimal outcomes. Activation of the innate immune system and translocation of intestinal bacteria could be causative. Thirty two pigs were assigned to control, brain death (BD), BD + luminal intestinal polyethylene glycol (PEG), and BD + luminal intestinal University of Wisconsin solution (UW) groups. Animals were observed for 360 min after BD before organ retrieval. 2,000 mL luminal intestinal preservation solution was instilled into the duodenum at the start of organ procurement. Repeated measurements of plasma C3a, Terminal Complement Complex (TCC), IL-8, TNF, and lipopolysaccharide binding protein were analysed by immunoassays. C3a was significantly higher in the BD groups compared to controls at 480 min after brain death. TCC was significantly higher in BD and BD + UW, but not BD + PEG, compared to controls at 480 min. TNF was significantly higher in the BD group compared to all other groups at 480 min. LPS binding protein increased following BD in all groups except BD + PEG, which at 480 min was significantly lower compared with all other groups. Brain death induced innate immune system activation was decreased by luminal preservation using PEG during organ procurement, possibly due to reduced bacterial translocation.

Liver transplantation (LT) is a potentially curative experimental treatment for unresectable intrahepatic cholangiocarcinoma (iCC). Pre-transplant downstaging may help defining tumor aggressiveness and drive patient selection. We report the preliminary results of LT for liver-limited unresectable iCC after sequential downstaging with systemic chemotherapy and radioembolization (SYS-TARE). In case of sustained disease stability after SYS-TARE, patients underwent surgical nodal sampling and, if negative, were listed for LT. In this study, 13 patients with unresectable iCC underwent downstaging with SYS-TARE. The median age was 70 years and 77% were female. All had single bulky lesions at diagnosis. After SYS-TARE, 9 (69%) dropped out: 3 due to progressive disease after TARE with no response to second-line, 4 due to extrahepatic disease development and 2 due to positive nodal disease at pre-listing abdominal exploration. The median OS after dropout was 11.5 months. Four (31%) were successfully listed and transplanted. At pathology, viable tumor ranged from 30% to less than 5%. All four patients are alive and disease-free at 73, 40, 12, and 8 months from LT. LT for unresectable iCC after downstaging with SYS-TARE appears to select suitable patients for LT, achieving optimal oncological outcomes in case of response to therapy and no lymphnodal spread.