Transplant International最新文献

Solid organ transplantation (SOT) faces significant challenges in managing allograft rejection, with current immunosuppressive therapies often associated with substantial adverse effects. Extracorporeal photopheresis (ECP) has emerged as a promising adjunctive treatment for rejection prevention and management in heart and lung transplants, with growing evidence supporting its use in kidney and liver transplants. Despite this, the availability of ECP and its place in standard treatment pathway is widely variable across Europe. This narrative review, supported by a European survey of 51 transplant clinicians, highlights the current usage of ECP in SOT. Findings reveal that ECP is primarily used for recurrent rejection in heart and lung transplants, with limited application currently in kidney and liver transplants. ECP has shown some efficacy in managing acute and chronic rejection, and stabilizing graft function. Barriers including lack of standardized protocols, availability of ECP, lack of high-quality clinical trial data and lack of a defined mechanism of action hinder its broader adoption. Future directions include the development of standardized protocols, multicenter registries, and further controlled clinical trials to define the role of ECP. Increased awareness, cost-effectiveness studies, mechanistic studies and equitable access are essential to integrate ECP into routine SOT management.

Techniques such as retroperitoneal graft placement have further enhanced the ability to replicate the physiology of the "native" pancreas. In our center, from January 2000, duodenojejunostomy (DJ) was the standard technique for exocrine drainage (n = 337). Herein, we report a series of 188 pancreas transplantations performed between May 2016 to July 2025, using a fully retrocolic graft position, systemic venous drainage and enteric drainage via duodenoduodenostomy. The primary endpoint was the assessment of intestinal events and their impact on graft and patient survival. A total of 14 patients (7.4%) experienced complications, including paralytic ileus (n = 2), intestinal obstruction (n = 4), duodenal dehiscence following pancreas transplantectomy (n = 1), anastomotic dehiscence (n = 5), and anastomotic bleeding (n = 2). Of these, 11 cases required relaparotomy for adhesiolysis (n = 2), internal hernia repair (n = 1), Hartmann's procedure (n = 1), transplantectomy (n = 2), primary leak closure (n = 3), and hemostasis with duodenal re-anastomosis (n = 2). After a median follow-up of 42.8 months [IQR 21.8-71.1], graft survival at 1 and 5 years was 87% and 83.4%, respectively (P = 0.688 vs. DJ group), while patient survival was 100% and 98.2% (P = 0.031 vs. DJ group). Duodenoduodenostomy proved to be a feasible and effective technique, offering competitive outcomes in terms of graft and patient survival.

The development of de novo donor-specific anti-HLA antibodies (dnDSA) after lung transplantation (LuTX) has been increasingly linked to the onset of antibody-mediated rejection (AMR), chronic lung allograft dysfunction (CLAD), and impaired long-term outcomes. However, the therapeutic impact of intravenous immunoglobulin (IVIG) therapy in patients with dnDSA remains unclear. We conducted a retrospective single-center study of LuTX recipients (2015-2019) who developed dnDSA post-transplantation and received IVIG-based therapy. Patients were classified as responders or non-responders based on post-treatment antibody clearance. Clinical, immunological and functional outcomes were compared. Among 47 patients with dnDSA and IVIG-based therapy, 23 (48.9%) achieved complete antibody elimination. Preemptive treatment, defined as initiation of IVIG therapy before onset of clinical symptoms, was found to be an independent predictor of antibody clearance (odds ratio 29.5; p = 0.013). Responders showed significantly lower baseline MFI. While differences in CLAD-free survival favored responders, they did not reach statistical significance. Preemptive IVIG therapy in asymptomatic dnDSA-positive LuTX recipients may enhance antibody clearance and reduce CLAD risk. These findings support early intervention strategies and underscore the need for prospective trials to define optimal therapeutic thresholds and timing.

Low tacrolimus trough concentration-to-dose ratio (CDR) is recognized as an indicator of high tacrolimus metabolism. However, its impact on long-term transplant outcomes and potential for clinical intervention remains unclear. In the largest study to date, we analyzed the impact of a low CDR at post-transplant year 1 on graft loss and patient mortality in 21,865 kidney transplants. We also performed a longitudinal analysis of CDR dynamics and conducted a genetic correlation in a subset of 1,257 patients. Low CDR at year 1 was significantly associated with increased hazards of graft failure (HR up to 2.80) and infection-related mortality (HR = 1.63), even in patients with therapeutic trough levels and good graft function. In the longitudinal analysis, normalizing initially low CDR by year 2 significantly improves graft survival. Low CDR was identified in a substantial proportion of the cohort (25.2%). Black, female, and younger recipients (<50 years) had higher odds of having a low CDR. The CYP3A5*1A genotype was also strongly associated with low CDR (approximately 8-fold higher odds). Patients with a low tacrolimus CDR represent a large high-risk population. The normalization of tacrolimus CDR through co-medication with diltiazem and reductions in steroid dosing may improve graft survival. Our findings support personalized tacrolimus management based on metabolic profiling and genetic testing.

Grade 3 primary graft dysfunction at 72 h (PGD3-T72) is a severe complication following lung transplantation. We aimed to develop an intraoperative machine-learning tool to predict PGD3-T72. We retrospectively analyzed perioperative data from 477 patients who underwent double-lung transplantation at a single center between 2012 and 2019. Data were structured into nine chronological steps, and supervised machine-learning models (XGBoost and logistic regression) were trained to predict PGD3-T72, with hyperparameters optimized via grid search and cross-validation. PGD3-T72 occurred in 83 patients (17.3%). XGBoost outperformed logistic regression, achieving peak performance at second graft implantation with an AUROC of 0.84 IQR: 0.065, p < 0.001, with a sensitivity of 0.81 and a specificity of 0.68. The top predictors included extracorporeal membrane oxygenation (ECMO) use, blood lactate levels, PaO2/FiO2 ratio, and total lung capacity mismatch. Subgroup analyses confirmed robustness across ECMO and non-ECMO cohorts. PGD3-T72 can be reliably predicted intraoperatively, offering potential for early intervention.

Controlled donation after the circulatory determination of death (cDCDD) is currently one of the most promising ways to increase organ availability. In France, a national cDCDD protocol requiring abdominal normothermic regional perfusion (A-NRP) has been in place since 2015. The recent consideration of heart procurement from cDCDD donors has reignited clinical and ethical debates within the critical care community. This position paper, endorsed by the two French intensive care societies, provides a critical care perspective on this evolving practice. Two key challenges are identified. First, heart procurement may require the withdrawal of life-sustaining measures (WLSM) to occur in or near the operating room, in contrast with French current practice where WLSM mostly takes place in the ICU. Intensivists strongly advocate maintaining ICU-based WLSM whenever possible, and ensuring continuity of care and end-of-life support when relocation is unavoidable. Second, the use of NRP raises concerns about the permanence of death and compliance with the dead donor rule. These concerns can be addressed through targeted biomedical research and a robust ethical framework affirming that death is declared prior to NRP and that no return to life is possible thereafter. Transparent engagement with these challenges is essential to sustain trust in the cDCDD pathway.

Improved biomarkers are needed to enhance prognostication in kidney transplantation. We evaluated urinary Epidermal Growth Factor (uEGF) as a predictor of long-term allograft loss. We conducted a prospective, single-center cohort study of 290 adult kidney transplant recipients with uEGF measured 3 months post-transplant. The primary outcome was allograft loss, defined as return to dialysis or pre-emptive re-transplantation. Multivariable cause-specific Cox models assessed the independent association between uEGF and allograft loss. Model performance was compared to the iBox prediction model using 7-year time-dependent AUC and Akaike Information Criterion (AIC), with internal validation via bootstrap resampling. Temporal validation was performed in an independent cohort of 203 patients. uEGF correlated with markers of chronic injury, including eGFR, donor age, and interstitial fibrosis. After a median 8.8-year follow-up, lower uEGF was independently associated with allograft loss (adjusted HR 0.19; 95% CI, 0.11-0.32). Adding uEGF to the iBox improved discrimination (AUC 0.72 vs. 0.63) and reduced AIC (383 vs. 394). While results were robust to internal validation, temporal validation did not show an independent association of uEGF with allograft loss. These findings suggest uEGF may provide independent prognostic value, but further studies in larger and more diverse cohorts are needed to confirm its clinical utility.