Transplant International最新文献

An overview is provided of the evolution of strategies towards xenotransplantation during the past almost 40 years, focusing on advances in gene-editing of the organ-source pigs, pre-transplant treatment of the recipient, immunosuppressive protocols, and adjunctive therapy. Despite initial challenges, including hyperacute rejection resulting from natural (preformed) antibody binding and complement activation, significant progress has been made through gene editing of the organ-source pigs and refinement of immunosuppressive regimens. Major steps were the identification and deletion of expression of the three known glycan xenoantigens on pig vascular endothelial cells, the transgenic expression of human "protective" proteins, e.g., complement-regulatory, coagulation-regulatory, and anti-inflammatory proteins, and the administration of an immunosuppressive regimen based on blockade of the CD40/CD154 T cell co-stimulation pathway. Efforts to address systemic inflammation followed. The synergy between gene editing and judicious immunomodulation appears to largely prevent graft rejection and is associated with a relatively good safety profile. Though there remains an incidence of severe or persistent proteinuria (nephrotic syndrome) in a minority of cases. This progress offers renewed hope for patients in need of life-saving organ transplants.

The increasing age of patients with end-stage renal disease raises the issue of hostile arterial access for transplantation, with technical difficulties associated with clamping and suturing the iliac artery. Some of these patients - who theoretically represent those who would benefit the most from transplantation in terms of mortality - are contraindicated because of anatomical and medical issues. In this context, a specific endovascular device called EndoPreKiT (Endovascular Preparation for Kidney Transplantation) has been designed, enabling arterial access for transplantation via a mini-invasive procedure. It consists of a woven Dacron supported by self-expanding nitinol rings, ensuring anchorage and allowing arterial clamping. The middle part of the anterior face of the device is stentless, enabling the anastomosis directly onto the Dacron once the calcified artery wall has been removed. After a cadaveric study validating its technical feasibility, such device was successfully implanted in 10 patients considered unfit for transplantation due to severe wall calcification. Two of them have been successfully transplanted with excellent outcomes after 13 and 3 months of follow-up. EndoPreKiT device may be a significant breakthrough in transplant surgery, that could expand the horizon of eligibility to include even the most fragile patients with challenging arterial access.

Kidney transplantation is the treatment of choice for end-stage organ failure. To improve transplantation outcomes, particularly of "marginal" organs from extended criteria donors (ECD), attempts have been made to therapeutically modulate donor or graft pre-transplantation. Anti-thymocyte globulin (ATG) has a history as lymphocyte-depleting, immunosuppressive drug for treating rejection episodes post transplantation. In this study, however, we aimed to comprehensively analyze the effects of ATG donor pre-conditioning in a mouse model of kidney transplantation. ATG pre-treatment of potential donors led to a broad depletion of T- and NK cells in peripheral blood, non-lymphoid (including kidney) and lymphoid organs within 48 h, whereas myeloid cells were spared. ATG was also effectively depleting renal innate lymphoid type 1 and 2 cells. Importantly, transplantation of kidneys from ATG pre-treated donors into fully mismatched recipients showed only mild effects on leukocyte re-composition post transplantation. In line with this, serum creatinine and urea levels were similar in animals receiving kidneys from ATG treated donors or controls, demonstrating that donor treatment had no effect on allograft function in the early post-transplantation phase. In summary, our findings are suggestive of a more cell-type-specific depletion strategy in concert with an experimental model better reflecting aspects of clinical transplantation.

In this unblinded multi-center stepped-wedge randomized controlled trial the effectiveness of the nurse-led ZENN-intervention was tested in promoting self-management skills in comparison to standard care among heart, lung and kidney transplant recipients. This intervention is based on behaviour change theories and was conducted in four sessions over 6 months at the outpatient clinic. The experimental group received standard care, plus the ZENN-intervention, while the control group received only standard care. Both groups completed questionnaires at baseline, at 6 months and 1 year follow-up. At baseline, the experimental group (n = 69) scored significantly lower than the control group (n = 106) on the primary outcome Skills and Technique Acquisition (STA). No significant between-group differences were found on the secondary outcomes self-management, self-regulation, quality of life and medication adherence at T1 and T2. There was a significant increase on the self-management scale STA between T0 and T1 in the experimental group. Therefore, participants included in the experimental group had lower self-management skills at baseline and reported significant improvement after completing the intervention. No significant intervention effect was found in the primary analysis, however, for recipients with reduced self-management skills the intervention may be beneficial.

Clinical trial registration: https://onderzoekmetmensen.nl/en/trial/24150, Netherlands Trial Register NL8469.

Microvascular inflammation (MVI) in kidney transplant biopsies is mainly associated with antibody-mediated rejection (AMR), sparking debate within the Banff Classification of Renal Allograft Pathology regarding its exclusivity. This study reviewed the literature on MVI in T cell-mediated rejection (TCMR) and analyzed MVI in our transplant population. We searched English publications in MEDLINE, Embase, Web of Science, Cochrane, and Google Scholar until June 2024, focusing on glomerulitis (g), peritubular capillaritis (ptc), or MVI in kidney transplant biopsies classified as TCMR. Additionally, we examined g, ptc, and MVI in 69 patients with AMR, TCMR, and no rejection. Our search yielded 541 citations, with 10 studies included, covering 810 TCMR and 156 AMR biopsies. The studies showed g, ptc, and MVI were present in TCMR but were less prevalent and severe than in AMR. In our cohort, AMR had significantly higher g, ptc, and MVI scores compared to aTCMR and ATN, however, aTCMR also displayed MVI. These findings confirm that MVI occurs in aTCMR and should not be exclusively linked to AMR. These findings highlight the need to further explore MVI's significance in TCMR and investigate the inflammatory composition. This could refine the Banff Classification, improving Classification accuracy of kidney transplant pathology assessments.

Highly sensitized (HS) patients in need of kidney transplantation (KTx) typically spend a longer time waiting for compatible kidneys, are unlikely to receive an organ offer, and are at increased risk of antibody-mediated rejection (AMR). Desensitization using imlifidase, which is more rapid and removes total body immunoglobulin G (IgG) to a greater extent than other methods, enables transplantation to occur between HLA-incompatible (HLAi) donor-recipient pairs and allows patients to have greater access to KTx. However, when the project was launched there was limited data and clinical experience with desensitization in general and with imlifidase specifically. Hence, this Delphi methodology was used to reach a consensus from a multi-disciplinary team (MDT) of experts from 15 countries on the management of HS patients undergoing imlifidase HLAi from a deceased donor (DD) KTx. This Delphi consensus provides clinical practice guidance on the use of imlifidase in the end-to-end management of HS patients undergoing an HLAi DD KTx and supports centers in the development of guidelines for the utilization and integration of imlifidase into clinical practice.

Patients with severe alcoholic hepatitis SAH may suffer of undiagnosed psychiatric illnesses, typically depression. Assessment of prevalence and potential impact of psychiatric disturbances on alcohol relapse after LT, were the main objectives of this study. One hundred consecutive patients with SAH from April 2016 to May 2023 were analyzed. All patients were evaluated by an integrated team including psychiatrists, addiction specialists and social workers. Thirty (30%) were listed, of whom 25 underwent early liver transplantation (eLT) after a median time of 36 days from the index episode of SAH with a median model for end stage liver disease (MELD) score of 36, whereas 33 (33%) were excluded, with psycho-social issues being the main cause of exclusion in 18 patients (54.5%). Twenty-four patients (96%) are currently alive after a median follow-up of 32 months from LT. Sixteen transplanted patients had major depression with or without anxiety, with 10 patients (33%) being treated with antidepressants post-LT. Overall, 4 patients (16%) relapsed into alcohol consumption after liver transplantation and 1 died of alcohol related liver disease (4%). From this experience emerged that psychiatric comorbidities are highly prevalent among patients with SAH and that their diagnosis/treatment contributed to mitigate the risk of alcohol relapse.

Here, we retrospectively evaluated the informational yield of 338 post-reperfusion kidney transplant biopsies (including 95 living donations) assessed according to BANFF for the histological characteristics interstitial fibrosis and tubular atrophy (IF/TA), glomerulosclerosis, arteriosclerosis, and acute tubular injury (ATI). Associations with delayed graft function (DGF) and death-censored graft survival were explored through Cox-regression analyses. The maximum follow-up time was 11.4 years, with DGF observed in 108 (32%) cases. After deceased donation there was no association between DGF and histologic parameters. Univariable Cox-regression unveiled an association of IF/TA and glomerulosclerosis with long-term death-censored graft survival (HR per 10% increase: IF/TA 1.63; 95% CI 1.17-2.28; p = 0.003; glomerulosclerosis 1.19; 95% CI 1.01-1.39; p = 0.031). In multivariable Cox regression analyses, adjusted for recognized clinical risk variables like expanded criteria donor-status, donor age, history of diabetes, and HLA-mismatches, only IF/TA maintained association over the total observation period in deceased donations and in the total cohort. Arteriosclerosis and ATI were not associated with clinical outcome after deceased donation. Especially ATI did not affect delayed graft function if only deceased donations were considered. Our data underlines the role of organ quality for transplant outcome prior to acute lesions such as ATI during the transplantation process.

Liver xenotransplantation has emerged as a potential solution to the shortage of deceased human donor organs and is now becoming a reality due to recent developments in genetic engineering and immunosuppressive therapy. Early efforts using non-human primates and genetically modified pigs faced significant challenges such as thrombocytopenia and graft rejection. Understanding the mechanism behind those challenges and using novel genetically engineered pigs enabled researchers to overcome some of the hurdles, but more research is needed. However, new advances might allow pig liver xenotransplantation to potentially serve as a bridge to liver allotransplantation or allow native liver regeneration in the near future.

Lung transplantation is a life-saving therapeutic option for many chronic end-stage pulmonary diseases, but long-term survival may be limited by rejection of the transplanted organ. Since HLA disparity between donor and recipient plays a major role in rejection, we performed a single center, retrospective observational cohort analysis in our lung transplant cohort (n = 128) in which we calculated HLA compatibility scores for B-cell epitopes (HLAMatchmaker, HLA-EMMA), T-cell epitopes (PIRCHE-II) and missing self-induced NK cell activation (KIR Ligand Calculator). Adjusted Cox proportional hazards model was used to investigate the association between mismatched scores and time to development of donor-specific antibodies (DSA) post-transplant, time to first biopsy-proven acute rejection episode, freedom from CLAD, graft survival and overall survival. For time to first DSA, HLA-EMMA DQB1 scores and PIRCHE-II DQB1 scores were significantly associated with more rapidly developing anti-HLA-DQ antibodies. HLA-EMMA DQB1 score was significantly associated with worse survival. KIR ligand Host-versus-Graft (HvG) mismatches was significantly associated with worse graft survival (CLAD or death) and shorter time to first biopsy-proven rejection when 2 mismatches were present. We demonstrated that HLA-DQB1 compatibility scores and KIR ligand HvG 2 mismatches may allow for identification of recipients at risk of poor long-term outcomes after lung transplantation.