Transplantation最新文献

Background: Normothermic machine perfusion (NMP) is being explored as a promising method to assess pretransplant viability and potentially enhance the functional performance of deceased-donor kidneys. To realize NMPs full potential, however, understanding ex vivo kidney metabolism and its differences from our clinical in vivo reference frame is essential. Here, a multiomics approach including metabolomics, transcriptomics, and proteomics analyses was used to explore metabolic differences between ex vivo and in vivo kidneys and assess the additional impact of warm ischemia on ex vivo kidney metabolism.

Methods: Paired kidneys from laboratory pigs (n = 30) sustained either minimal or 75 min of warm ischemia. All kidneys underwent 6 h of oxygenated hypothermic machine perfusion followed by 6 h of NMP. Cortical tissue samples were collected in vivo, after cold preservation, and after NMP for metabolomics, transcriptomics, and proteomics analyses.

Results: Metabolomics analysis revealed increased branched-chain amino acid metabolism and decreased uracil- and cytidine-containing pyrimidine metabolism after NMP compared with in vivo. Subsequent analyses demonstrated enhanced glycolysis, decreased gluconeogenesis, impaired tricarboxylic acid cycle activity, and nicotinamide adenine dinucleotide depletion. Multiomics analysis showed associations between metabolic alterations and increased immune response and cell death processes during NMP.

Conclusions: Together, our findings indicate substantial differences between in vivo and ex vivo kidney metabolism and reveal a link between metabolic alterations and potentially detrimental cellular processes.

Background: Utilization rates of potential deceased donors for liver transplantation has declined following the implementation of the acuity circles system in 2020. Since then, ex situ machine perfusion (es-MP) and normothermic regional perfusion (NRP) have been introduced in the United States.

Methods: Liver graft utilization rates were analyzed using the US national registry data from 2022 to 2024. The associations of es-MP and NRP practices with donation after circulatory death (DCD) utilization rates among organ procurement organizations (OPOs) and transplant center volume were evaluated.

Results: DCD donor utilization significantly increased from 21.5% in 2022 to 42.5% in 2024 ( P  < 0.001). Utilization of extended criteria donors (ECDs), including DCD donors aged ≥60 y or with a body mass index ≥40 kg/m 2 , also rose substantially, from 7.1% in 2022 to 33.2% in 2024 ( P  < 0.001). At the transplant center level, a significant correlation was found between the increase in transplant volume and both the es-MP use ( r  = 0.29; P  = 0.01) and ECD utilization ( r  = 0.26; P  = 0.02). At the OPO level, a significant association was observed between the increase in DCD utilization rate and NRP use ( r  = 0.29; P  = 0.03).

Conclusions: DCD liver utilization has significantly increased, with a notable rise in the utilization of ECDs, which may be driven by new technologies such as es-MP and NRP. While es-MP at the center level use may increase transplant volume, NRP use at the OPO level appears to significantly improve DCD liver utilization.

Solid organ transplantation is a life-saving intervention for tens of thousands of patients each year in the United States. A major underlying pathophysiologic process limiting the success of transplantation is inflammation. Since the first transplant >70 y ago, advancements in the fields of surgery and immunosuppression have improved both organ and patient survival. However, inflammation and its damaging effects remain the principal clinical problem limiting enduring organ transplant survival. The discovery of the vagus nerve-mediated inflammatory reflex, an endogenous mechanism attenuating inflammatory processes, has provided novel treatment approaches for patients with autoimmune, neurologic, gastrointestinal, and other immune-mediated disorders. Despite these successes, evaluation of whether the inflammatory reflex can improve graft and patient survival in transplantation has yet to be undertaken. Here, we review the fundamentals of transplant rejection and how the inflammatory reflex may provide potential preemptive therapy in deceased donors before organ recovery, as well as attenuate detrimental inflammatory processes in transplant recipients. With this background, we propose that vagus nerve stimulation could be used to improve organ viability and augment current immunosuppressive medication regimens, thereby improving transplantation outcomes.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a significant indication for liver transplantation (LT) in North America. Yet data on its impact in other countries, such as Spain, remain limited. This study aimed to evaluate the prevalence and trajectory of MASLD-related LT in Spain and compare these findings with broader national data and international data sets.

Methods: Multicenter retrospective cohort study including adults (18 y and older) undergoing LT for MASLD between 2010 and 2023 in 5 large Spanish centers. Additional data were obtained from the Spanish Transplant Registry (Organización Nacional de Trasplantes) and high-prevalence LT centers in the United States (n = 7) and Canada (n = 1).

Results: Among 3448 LTs performed in the 5 Spanish centers, 3.4% (n = 117) were MASLD-related. An increasing trajectory of MASLD-related LT was observed, with predictions suggesting a rise to 5.4%-10.8% of LTs for MASLD by 2028. These trends were consistent with Organización Nacional de Trasplantes data. Compared with North American data, the growth trajectory in Spain showed a less steep increase. Hepatocellular carcinoma rates were higher in the Spanish MASLD-LT recipients, yet metabolic comorbidities were frequent in all populations.

Conclusions: The burden of MASLD-related LT in Spain is growing, yet at a less pronounced rate than in the United States/Canada. Whether this slower increase will persist or decline in the future as newer antiobesity and MASLD-related drugs are increasingly used is still unknown. In the meantime, our results highlight the need for tailored approaches to management and prevention in the Spanish population and underscore the importance of continued monitoring and research into the evolving impact of MASLD on LT in Spain and beyond.

Kidney transplantation outcomes have advanced significantly with modern immunosuppression, yet indefinite graft survival and general-population-comparable patient outcomes remain elusive. At the World Transplant Congress 2025 in San Francisco, immunosuppression emerged as a central theme spanning from bench to bedside, including regulatory processes, innovative trial design, and patient-centered approaches. Key sessions addressed the slowing pace of new drug approvals since the 1990s "golden era" of transplantation and highlighted expedited regulatory pathways, patient advocacy, and the use of surrogate endpoints as accelerators of future drug development. Patient-reported outcomes emphasized the burden of immunosuppression side effects and the need to improve adherence through education, health literacy, and financial support. Optimization of tacrolimus use and refinements of adherence management underscored optimization of currently used immunosuppressive standard regimens, whereas steroid-sparing strategies and induction agent selection were revisited. Belatacept-based regimens demonstrated promise across diverse patient groups, with novel approaches of costimulation blockade (eg, CD154, CD28) advancing toward clinical translation. Biomarkers such as donor-derived cell-free DNA may enable personalized immunosuppression and safe drug minimization. Strategies for desensitization and rejection treatment, including CD38 targeting, show potential for highly sensitized patients or patients with antibody-mediated rejection. Finally, tolerance induction through chimerism, regulatory T cells, and engineered cellular therapies highlighted pathways toward immunosuppression withdrawal. Collectively, these innovations presented at the Congress signal a transition toward safer, more personalized, and durable transplant outcomes.

Background: Measles, mumps, and rubella (MMR) in solid organ transplant (SOT) recipients is rare. We aim to investigate the pretransplant seroprevalence, MMR infection posttransplant, and whether immediate pretransplant MMR vaccination is associated with MMR infection.

Methods: We queried the TriNetX database in December 2024 to assess (1) pretransplant MMR seroprevalence, (2) characteristics and outcomes of posttransplant MMR infections, and (3) outcomes for recipients who received the MMR vaccine within 30 d pretransplant. Only US data were included. MMR infection was identified through International Classification of Diseases (ICD) codes.

Results: Among 313 548 SOT recipients identified in the database (from 2009 to 2024), IgG positivity for MMR was 72%, 80%, and 78% when available (~5% each). Based on ICD codes, posttransplant MMR infections occurred in 107 (0.03%), 124 (0.04%), and 38 (0.01%) recipients, respectively. The 90-d rejection rates were 36%, 27%, and 42%, whereas mortality rates were 7%, 8%, and 5%, respectively, in patients with MMR infection. Among 114 recipients vaccinated within 30 d pretransplant, none developed posttransplant MMR infections.

Conclusions: Overall, posttransplant MMR infections in adult SOT recipients were uncommon in this data set, and no vaccine-associated infections were documented among those who received the MMR vaccine within 30 d pretransplant in real-world practice. The primary limitation of this study is that most MMR infections were identified using ICD codes without confirmation through serological testing or polymerase chain reaction, and we were unable to further characterize the infections because the de-identified database lacked information on the patient's ZIP code and transplant hospital. Our study highlights the need for improvement in MMR serology screening and pretransplant MMR vaccination.