Transplant International最新文献

Antibody-mediated rejection (ABMR) due to non-HLA alloantibodies has gained substantial attention in transplantation research. One candidate for such non-HLA reactivity is the Duffy blood group carrier molecule DARC, which is not only expressed on erythrocytes, but also on kidney microvascular endothelial cells and is postulated as a potential transplantation-relevant alloantigen. However, in vivo observation of anti-Duffy antibodies as trigger of microvascular inflammation (MVI) is lacking. Here we propose a direct relationship between preformed anti-Duffy (anti-Fy^a) antibodies, complement deposition (C4d) in peritubular capillaries (PTC), and MVI. Double immunofluorescence for DARC and C4d in sequential biopsies revealed a striking overlap of DARC expression and C4d staining that was completely restricted to the peritubular capillaries. Remarkably, MVI was confined to PTC with complete absence of glomerulitis and lack of preformed anti-HLA DSA. Retrospective analysis revealed a self-limiting posttransplant flare of a low-level anti-DQ8 DSA after blood transfusions and a high missing-self KIR ligand constellation. Concomitant occurrence of non-HLA and anti-HLA reactivities next to missing-self constellations substantially complicates the assessment of individual contributions for the development and propagation of MVI. Due to the strictly confined distribution of DARC to PTC our report provides in vivo evidence that anti-Fy^a alloantibodies may associate with MVI.

Lungs remain one of the most difficult solid organs for xenotransplantation, owing to its delicate alveolar capillary barrier and intense crosstalk between innate immunity and coagulation system. Multi-gene-engineered donor pig organs combined with co-stimulation pathway blockade based immunosuppressive regimen have extended xenograft survival in preclinical models using non-human primates (NHP) from hours to weeks. Most recently, the first case of lung xenotransplantation into a brain-dead human recipient was reported, confirming technical feasibility without hyperacute rejection while revealing early inflammatory injury and progressive dysfunction. Key barriers include loss of vascular barrier function, dysregulated coagulation and platelet function driven by porcine-human molecular incompatibilities, and antibody-mediated injury. Preclinical data implicate innate immune activation such as natural killer cells and macrophages. Unlike kidney xenotransplantation, which has achieved stable long-term outcomes in NHPs, lungs require attention to immunogenicity against the "fourth antigen" in triple-knockout (TKO) donors that include the positive crossmatch created by the CMAH deletion when TKO organs are tested in NHP. Although consistent multi-month lung xenograft survival has not yet been achieved in preclinical models, the remaining barriers to clinical translation are being defined. This review delineates lung-specific xeno-immune mechanisms and advances aimed at their mitigation, providing insights necessary for future clinical translation.

[This corrects the article DOI: 10.3389/ti.2025.14712.].

Given the increasing number of kidney transplantation in elderly recipients, understanding age-specific risks is essential for optimized post-transplant care. We analyzed 572 kidney transplant recipients from the DZIF Transplant Cohort (2012-2023), stratified by age: <40 (n = 146), 40-60 (n = 279), >60 years (n = 147). Outcomes included infection burden, graft outcomes, and mortality over a median follow-up of 5 years. Multivariable Cox models with inverse probability weighting, adjusted for clinical confounders, was applied. In older recipients, the unadjusted 5-year rates of graft failure, mortality, and infections were significantly higher-both overall and for specific types, including pneumonia, urinary tract infections, invasive opportunistic infections, and multidrug-resistant infections. After adjustment, age remained only independently associated with mortality (HR = 6.21, p = 0.02), but not with overall infection burden or graft loss. Older patients exhibited a shift in pathogen prevalence, particularly for Pseudomonas aeruginosa and more severe herpesvirus infections, as well as higher infection-related morbidity, which contributed to graft failure. The first post-transplant year was critical, with infection burden strongly predicting graft failure (HR 1.16, p < 0.01). Age alone generally does not predict adverse transplant outcomes. Post-transplant care in elderly recipients should focus on early infection control with pathogen-targeted surveillance.

Artificial intelligence (AI) is rapidly transforming healthcare, and the field of kidney transplantation (KT) is no exception. While much of the AI-related work has focused on deceased donor KT, there is a growing body of research applying AI tools to living kidney donation (LKD). This review explores AI's current and potential roles in LKD, focusing on predictive and social applications of AI in LKD. Additionally, we discuss the challenges and limitations of implementing AI in clinical settings and highlight emerging research trends. This review consolidates existing research and provides a foundation for both transplant professionals and data scientists seeking to integrate AI responsibly into living donor programs.

This study compares outcomes between Simultaneous Pancreas-Kidney Transplantation (SPKT) and Deceased Donor Kidney Transplantation (DDKT) in recipients with diabetes, assessing survival benefits against surgical and immunological risks. We analyzed Scientific Registry of Transplant Recipients data (2014-2023) to assess patient and kidney graft survival. Overlap propensity score weighting was applied to adjust for group differences. Kaplan-Meier and Cox proportional hazards models were used to estimate survival outcomes in unadjusted, covariate-adjusted, and weighted analyses. Among 22,545 recipients with diabetes (25% SPKT), those receiving SPKT were younger (41 vs. 52 years), predominantly non-Hispanic white, had type 1 diabetes, lower BMI, shorter dialysis duration, and higher preemptive transplant rates (all p < 0.001). Overlap-weighted (ow) analyses showed no significant differences in 5- and 10-year patient (SPKT: 86%, 71%; DDKT: 87%, 74%) and kidney graft survival (SPKT: 80%, 66%; DDKT: 83%, 62%). SPKT recipients with graft survival at 1 year experienced higher 1-year treated acute rejection (owOR: 2.80, 95% CI: 1.75-4.49) and hospital readmissions (owOR: 2.05, 95% CI: 1.62-2.60). However, among recipients with type 1 diabetes and BMI <30, SPKT was associated with lower mortality compared to DDKT. After adjustment for selection bias, SPKT did not improve long-term survival compared to DDKT and was associated with greater early morbidity.

The true comparative effectiveness of simultaneous pancreas-kidney transplantation (SPKT) versus kidney transplantation alone (KTA) in patients with diabetes and end-stage renal disease remains incompletely defined. Using the TriNetX Global Collaborative Network (2010-2024), we identified 3,679 SPKT and 27,062 KTA recipients aged 18-59 years. In unmatched comparisons, SPKT recipients showed lower mortality, fewer cardiovascular events, and improved kidney graft survival relative to KTA recipients, but also higher early rejection, infection, and readmission rates. After 1:1 propensity score matching, the cohorts were well balanced across all measured covariates, and long-term estimates for survival (HR 1.00, 95% CI 0.90-1.10), kidney graft failure (HR 0.99, 95% CI 0.94-1.04), and cardiovascular events (HR 0.99, 95% CI 0.94-1.05) no longer differed over 10 years. In contrast, SPKT recipients maintained significantly lower HbA1c levels throughout follow-up (mean 6.2% vs. 6.6% at 5 years; p < 0.001), reflecting sustained physiologic glycaemic control and a high probability of insulin independence. Sensitivity analyses restricted to type 1 diabetes and non-obese recipients yielded consistent results. After accounting for measured differences between recipients, we did not detect a long-term survival advantage of SPKT over KTA, whereas durable metabolic benefits persisted. Because key donor and immunologic characteristics were not available, a modest intrinsic survival benefit cannot be excluded. These findings highlight the major role of patient selection and support individualised use of SPKT for metabolic indications and quality-of-life improvement rather than survival gain alone.