Frontiers in transplantation最新文献

{"title":"The risk of kidney transplant graft loss in sensitized vs. unsensitized patients is modified by prior transplant status.","authors":"A Nicholson, K Tennankore, A J Vinson","doi":"10.3389/frtra.2026.1712618","DOIUrl":"10.3389/frtra.2026.1712618","url":null,"abstract":"<p><strong>Background: </strong>A prior kidney transplant (KT) has been associated with an increased risk of graft loss following repeat transplantation. This study examined the risk of adverse posttransplant outcomes between patients with and without a prior transplant, depending on sensitization status.</p><p><strong>Methods: </strong>We used propensity score matching to examine the combined exposure of sensitization status [panel-reactive antibody (PRA) 0%, >0%-80%, and >80%] and first/repeat KT as a nested variable in adults across the US [2000-2017; Scientific Registry of Transplant Recipients (SRTR)]. We then used multivariable Cox and logistic regression models to examine the association between the nested variable and death-censored graft loss (DCGL), all-cause graft loss (ACGL), and delayed graft function (DGF). Effect modification between PRA status (20%) and prior KT status was assessed for each outcome.</p><p><strong>Results: </strong>Among 38,660 matched patients, DCGL (adjusted Hazard Ratio (aHR) 1.56, 95% CI 1.47-1.66), ACGL (aHR 1.42, 95% CI 1.35-1.49), and DGF (adjusted Odds Ratio (aOR) 1.89, 95% CI 1.75-2.03) risk was highest with a prior KT and PRA >80% (vs. unsensitized transplant-naïve patients). The risk associated with increased PRA was greater in those with a prior transplant. Prior KT modified the association between increased PRA and DCGL, ACGL, and DGF (<i>p</i>-value < 0.001).</p><p><strong>Conclusion: </strong>Prior KT status modified the association between PRA and adverse outcomes. Sensitized patients (PRA >80%) with a prior KT faced higher risks of DCGL, ACGL, and DGF compared with sensitized patients without a prior KT.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"5 ","pages":"1712618"},"PeriodicalIF":0.0,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12950723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147349984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impaired graft survival in kidney transplants from expanded criteria donors with HLA-DR mismatch.","authors":"Uwe Scheuermann, Philipp Rhode, Claudia Lehmann, Jan Kowald, Sophie Seiffer, Fabian Haak, Daniel Seehofer, Sebastian Murad Rabe, Hans-Michael Tautenhahn","doi":"10.3389/frtra.2026.1733351","DOIUrl":"10.3389/frtra.2026.1733351","url":null,"abstract":"<p><p>Human leukocyte antigen (HLA)-DR mismatches are known to increase the risk of graft rejection following kidney transplantation (KT). Especially in KT using grafts of lower quality from expanded criteria donors (ECD), the immune response plays a critical role. Therefore, the aim of this study was to investigate the impact of HLA-DR mismatches on both short- and long-term outcomes in primary ECD KT. 537 KT recipients were stratified into four groups based on their HLA-DR mismatch status [absent (-) or present (+)] and donor type [standard criteria donor (SCD) or ECD]: (1) SCD-DR-(<i>N</i> = 126), (2) SCD-DR+ (<i>N</i> = 167), (3) ECD-DR- (<i>N</i> = 60) and (4) ECD-DR+ (<i>N</i> = 184). Clinicopathological characteristics, transplant outcomes and survival were evaluated across the groups. Rejection-free graft survival was significantly decreased in recipients of ECD-DR + KT (<i>P</i> = 0.005). In comparison with ECD-DR- KTs, ECD-DR + KTs were associated with a significantly reduced graft survival (15.1 vs. 10.7 years; <i>P</i> = 0.034). After adjusting for relevant cofactors using multivariate Cox regression analysis, HLA-DR mismatch remained an independent predictor of graft rejection and graft survival in ECD kidney grafts. These results suggest that HLA-DR compatibility should be considered in allocation protocols for this donor category to improve long-term outcomes.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"5 ","pages":"1733351"},"PeriodicalIF":0.0,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12936035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147328980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"24-hour <i>ex vivo</i> perfusion of vascularized composite allografts in a large animal total limb model.","authors":"Çağdaş Duru, Alina Stoian, Felor Biniazan, Florian Le Billan, Golnaz Karoubi, Shaf Keshavjee, Siba Haykal","doi":"10.3389/frtra.2026.1718484","DOIUrl":"10.3389/frtra.2026.1718484","url":null,"abstract":"<p><strong>Background: </strong>Static cold storage (SCS) at 4 °C remains the standard for preserving vascularized composite allotransplants (VCA) but limits viability to approximately 6 h. <i>Ex-vivo</i> perfusion offers a promising alternative. This study presents a 24-h sub-normothermic perfusion protocol in a swine hindlimb model using autologous red blood cells (RBCs).</p><p><strong>Methods: </strong>Limbs perfused for 24 h were compared with cold-stored limbs. The perfusate contained LPD, 2.5 g/dlBSA, heparin, methylprednisolone, dextrose, insulin, L-alanyl L-glutamine, sodium bicarbonate, and washed RBCs (hematocrit 10%-15%). Perfusion was maintained at 60-65 mmHg and 28 °C-32 °C. Perfusate was monitored hourly. Biopsies (thigh and distal foot) were collected every 6 h for histology and ATP. Limbs were weighed at baseline and endpoint.</p><p><strong>Results: </strong>Perfusion preserved stable ATP in proximal muscle (0.416-0.367 nmol/μl) and distal muscle (0.315-0.267 nmol/μl). In contrast, SCS showed significant ATP depletion in proximal muscle (0.502-0.15 nmol/μl, <i>p</i> = 0.0086) and distal muscle (0.335-0.078 nmol/μl, <i>p</i> = 0.0216). Injury scores corroborated these findings. In proximal muscle, scores remained stable with perfusion (3.03-3.26) but increased with SCS (2.4 increasing to 3.73, <i>p</i> = 0.0079). In the distal muscle, scores rose in both groups (perfusion: 2.90 increasing to 4.63; SCS: 2.56 increasing to 4.0), with significance only in the control group (<i>p</i> = 0.0291). Limb weight was unchanged (-0.53% perfusion vs. -0.62% SCS).</p><p><strong>Conclusion: </strong>Twenty-four-hour swine hindlimb perfusion preserved ATP, morphology, and function. Perfusion prevented ATP depletion and mitigated muscle damage compared with SCS, supporting its potential to extend VCA preservation. Transplant studies are warranted.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"5 ","pages":"1718484"},"PeriodicalIF":0.0,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12935989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147329052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovative approaches targeting innate immune cells to promote organ transplant tolerance.","authors":"Chiyoshi Toyama, Angus W Thomson","doi":"10.3389/frtra.2026.1776806","DOIUrl":"10.3389/frtra.2026.1776806","url":null,"abstract":"<p><p>Achieving long-term allograft survival while minimizing systemic immunosuppression (IS) remains a critical unmet need in transplantation. While adaptive immunity has traditionally been the primary focus of IS therapy, innate immune cells-that include neutrophils, monocytes, macrophages, dendritic cells, myeloid-derived suppressor cells, innate lymphoid cells (ILCs), natural killer (NK) cells, and gamma delta (γδ) T cells act as key upstream orchestrators of allograft rejection and tolerance. Recent advances in single-cell RNA sequencing and spatial transcriptomics have unveiled the profound heterogeneity of these cell populations, identifying distinct regulatory subsets and novel inhibitory checkpoints. These high-resolution insights provide the scientific rationale for developing innovative precision therapies that can selectively modulate innate immune reactivity without compromising global immunity. Here, we review innovative strategies to target/amplify these mechanisms, including targeting the myeloid inhibitory checkpoints (e.g., leukocyte immunoglobulin-like receptor B; sialic acid-binding immunoglobulin-like lectin-E) to induce tolerogenic phenotypes. We further discuss the modulation of metabolic reprogramming to prevent \"trained immunity\" using mammalian target of rapamycin inhibitor (mTORi)-loaded nanoparticles, and the use of CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 gene editing to silence T cell costimulatory signals. We evaluate the adoptive transfer of regulatory myeloid cells, -specifically donor-derived regulatory macrophages and regulatory dendritic cells, and innate lymphoid cells in transplant recipients. Furthermore, the potential of targeting specific NK cell and ILC subsets associated with graft regulation is addressed. Collectively, these emerging approaches aim to reprogram the allograft microenvironment, offering a promising paradigm shift towards establishing transplant tolerance.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"5 ","pages":"1776806"},"PeriodicalIF":0.0,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12926429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147286891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine perfusion for liver transplantation: opportunities and challenges for the next generation of transplant surgeons.","authors":"Cody L Mullens, Kumaran Shanmugarajah, Glenn K Wakam","doi":"10.3389/frtra.2026.1736191","DOIUrl":"10.3389/frtra.2026.1736191","url":null,"abstract":"<p><p>Machine perfusion is reshaping liver transplantation by turning preservation from passive storage into an active, physiologic intervention. This review synthesizes randomized and real-world evidence on hypothermic oxygenated and normothermic approaches and translates these data into practical guidance for training programs. Across studies, hypothermic oxygenated perfusion reduces ischemic biliary injury, especially in donation after circulatory death, while normothermic perfusion lowers early biochemical injury, decreases early allograft dysfunction, and increases organ utilization through ex situ viability testing. Contemporary cohorts show that \"back-to-base\" workflows can lessen early complications without increasing ninety-day costs, and that extended preservation, often paired with donor-care unit models, shifts many cases into planned daytime surgery. These operational gains matter for education: daytime cases enable rested faculty, deliberate practice, and graded autonomy. Perfusion broadens the case mix, and the pump itself introduces teachable competencies in setup, troubleshooting, and data-driven accept or decline decisions. Challenges include potential erosion of donor procurement experience, uneven access, and a still-evolving science of viability. We propose a competency-based curriculum spanning setup and safety, physiology, assessment and decision-making, and systems leadership, and outline research priorities as an area of inquiry for future transplantation surgeon-scientists in their training. Aligning training with this platform will improve care and strengthen the transplant workforce.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"5 ","pages":"1736191"},"PeriodicalIF":0.0,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12926501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147286937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Does sex matter? Longitudinal course and predictors of knowledge about immunosuppressant medication in patients after kidney transplantation: a KTx360° substudy.","authors":"Mariel Nöhre, Deborah Meier, Julia Talamo, Uwe Tegtbur, Lars Pape, Mario Schiffer, Martina de Zwaan","doi":"10.3389/frtra.2026.1697923","DOIUrl":"10.3389/frtra.2026.1697923","url":null,"abstract":"<p><strong>Background: </strong>To ensure long term graft and patient survival after kidney transplantation, the correct intake of the immunosuppressive medication is mandatory. To correctly administer the medication, specific knowledge is required. While the significance of adherence has been recognized by many, the potential adverse effects of insufficient knowledge levels-often associated with poor health literacy-have been overlooked for a long time; therefore, little is known about sex-specific differences and other predictors of knowledge in this patient group.</p><p><strong>Methods: </strong>We analyzed the longitudinal course of the self-developed and previously successfully applied knowledge test in kidney transplant recipients participating in the KTx360° trial over a period of up to three years. The patients participated in a multidisciplinary aftercare program that included case management, psychosocial assessments and interventions, as well as exercise assessments and interventions, supported by telemedicine. We aimed to identify potential baseline predictors of knowledge trajectories, with a specific focus on sex-specific differences.</p><p><strong>Results: </strong>The analysis sample, which consisted of participants with at least one valid measurement on the knowledge test, included 783 adult patients (41.6% women) with a mean age of 52.3 years (SD 13.6). Knowledge levels improved significantly over the period of the KTx360° trial. Especially younger male participants and men not living in a partnership showed an increase in knowledge levels.</p><p><strong>Conclusions: </strong>Over the period of the KTx360° trial we observed an increase in knowledge, mainly in patients with below-average baseline knowledge levels. While some improvements might be due to the catch-up effect, other changes suggest a different response to the same stimulus. In sex-specific analyses, we found higher knowledge levels in female participants at the start, but sex did not impact the progression of knowledge levels. Since there was no control group, it is not possible to determine the program's effect on knowledge levels.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"5 ","pages":"1697923"},"PeriodicalIF":0.0,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12916695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147274167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case Report: Bezoar in allograft duodenum-rare cause of bowel obstruction 13 years post-pancreas transplant.","authors":"Marlena Urvater, Cora Ianiro, David S Bruce, Tuesday Jensen, Erik B Finger, Justin Barr","doi":"10.3389/frtra.2026.1706203","DOIUrl":"10.3389/frtra.2026.1706203","url":null,"abstract":"<p><p>Small bowel obstruction (SBO) following pancreatic transplantation is a recognized complication, most often caused by adhesive disease and hernias. To our knowledge, a pancreatic allograft duodenal bezoar has not been previously described as a cause of obstruction. A 69-year-old female presented to the emergency department (ED) with severe abdominal pain and computed tomography (CT) findings concerning for a SBO. Given imaging characteristics concerning for a mass and her complete obstruction, we performed an immediate exploratory laparotomy. Intraoperatively, a large, solidified bezoar within the pancreatic allograft duodenum and a smaller bezoar causing a SBO in the efferent jejunal limb were removed. This case reveals a previously undescribed cause of life-threatening obstruction within a pancreaticoduodenal allograft and highlights the importance of considering rare entities in pancreas transplant patients to preserve graft function and prevent further complications.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"5 ","pages":"1706203"},"PeriodicalIF":0.0,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12907407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146215431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sir Roy Calne: a renaissance man of modern medicine.","authors":"Angeles Baquerizo, Neville Jamieson, Peter Friend","doi":"10.3389/frtra.2025.1765992","DOIUrl":"https://doi.org/10.3389/frtra.2025.1765992","url":null,"abstract":"<p><p>It is a challenging task to encapsulate the prolific life and accomplishments of Sir Roy Calne, a unique individual and pioneer who transformed the impossible into clinical reality, forging a new era of organ transplantation. In the annals of medical history, few figures embody the intersection of science and humanity as did Sir Roy Calne. A pioneering transplant surgeon, scientist, accomplished artist, visionary leader, and devoted family man, Calne's multifaceted legacy continues to influence both medical science and the arts, demonstrating how these two fields can intersect to advance human understanding and compassion. Sir Roy Calne died peacefully in Cambridge on January 6, 2024, leaving behind a legacy that continues to define the field of transplantation.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"4 ","pages":"1765992"},"PeriodicalIF":0.0,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12886468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146169015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pediatric-adult split liver transplantation: an ethical imperative and systems-based roadmap for global expansion.","authors":"Tran Cong Duy Long, Huynh Tran Bao Chau, Dat Tien Le, Thi Tran Nguyen Minh, Bui Cong Minh, Anh Le Thien Diep, Hoang Bao Tran Van, Truc Thi Thu Huynh, Nguyen Tien Huy","doi":"10.3389/frtra.2025.1709770","DOIUrl":"10.3389/frtra.2025.1709770","url":null,"abstract":"<p><p>This paradox emphasizes the urgent need to re-engineer transplant systems around pediatric-adult split liver transplantation (SLT). Despite being as effective as whole-liver transplants, SLT remains underutilized due to logistical and policy barriers. We believe that expanding SLT is not only clinically acceptable but a just and effective moral necessity. We propose a five-point action plan, including centralized splitting hubs, NMP-enabled transport, and global pilot programs, to transform SLT from an exception into standard practice.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"4 ","pages":"1709770"},"PeriodicalIF":0.0,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12876239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146145639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnosis of rejection following heart transplantation: diving into the future.","authors":"Shaline Rao, Syed Zain Ali, Arushi Singh, Mittal Rana, Mohamed Moussa, Kinza Ahmed, Stephanie Golob, Lauren Cusumano, Alana Harrington, Andrew Wang, Sanjay Chandrasekhar, Amit Alam","doi":"10.3389/frtra.2025.1693821","DOIUrl":"10.3389/frtra.2025.1693821","url":null,"abstract":"<p><p>Since the standardization of the grading system for pathologic diagnosis of antibody-mediated and acute cellular rejection, endomyocardial biopsy has remained the gold-standard. However, biopsies are invasive, costly, and limited by sampling error. As such, adjuvant non-invasive methods including cardiac biomarkers, imaging including cardiac magnetic resonance and echocardiography, and donor-specific antibodies and non-HLA antibodies have been traditionally used. However, all these techniques are limited by either sensitivity or specificity. More recently, there has been a shift to other contemporary non-biopsy surrogate markers for rejection surveillance including donor-derived cell free DNA, gene expression profiling, and messenger RNA and micro-RNA in tissue. Herein we review the methods currently utilized to diagnose rejection and their limitations. We find that while there have been significant advancements in technology and non-invasive techniques, no current method alone adequately diagnoses rejection (Central Image). Thus, future studies are warranted to investigate new strategies involving a multi-modal approach that incorporates non-invasive diagnostic methods and personalized medicine to monitor postoperative progression in heart transplant patients.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"4 ","pages":"1693821"},"PeriodicalIF":0.0,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12872891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146145406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}