American Journal of Transplantation最新文献

{"title":"Multi-Omics Integration Reveals Macrophage Lysosomal Remodeling as a Signature of Reparative Immunity in Human Lung Ischemia-Reperfusion Injury.","authors":"Ming Li, Yixing Li, Hongyi Wang, Tianfei Wang, Zhe Chen, Rongxuan Jiang, Qiang Bai, Jinteng Feng, Guangjian Zhang","doi":"10.1016/j.ajt.2026.08.016","DOIUrl":"https://doi.org/10.1016/j.ajt.2026.08.016","url":null,"abstract":"<p><p>Primary graft dysfunction (PGD) after lung transplantation is driven by ischemia-reperfusion injury (IRI), yet the early myeloid programs bridging inflammatory damage to reparative immunity remain incompletely defined. We integrated proteomic profiling of paired human lung allograft biopsies obtained after cold ischemia and early reperfusion (n = 8 pairs) with a public single-cell RNA-sequencing atlas, followed by functional validation in THP-1-derived macrophages. Reperfusion increased innate immune and extracellular matrix programs while decreasing lysosome- and phagosome-associated proteins. The downregulated signature mapped predominantly to macrophages and monocytes. Myeloid reclustering identified a transitional lipid-associated macrophage (LAM)/phagocytic state characterized by a prominent lysosome-associated transcriptional program. Cathepsin L (CTSL) emerged as a candidate lysosomal effector associated with this reparative state. Cellular origin analysis indicated this dynamic myeloid response involved both donor-resident macrophages and recipient-recruited monocytes. CTSL overexpression enhanced enzymatic activity, partially restored macrophage function, and dampened IRI-associated cytokine responses. These findings support a contributory role for CTSL in macrophage adaptation during early lung allograft reperfusion.</p>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149007626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In policy and in practice: expedited placement and allocation out-of-sequence in liver transplantation.","authors":"Antony Attia, Toshihiro Nakayama, Daniel J Ahn, Tyler York, Chase J Wehrle, Xingxing S Cheng, Vivek Charu, Allison J Kwong, Ben M Stutchfield, Dorry Segev, Sommer Gentry, Marc Melcher, Kazunari Sasaki","doi":"10.1016/j.ajt.2026.09.022","DOIUrl":"10.1016/j.ajt.2026.09.022","url":null,"abstract":"<p><p>The United States liver transplant policy debate has conflated 2 distinct mechanisms: expedited placement (EP, Organ Procurement and Transplantation Network Policy 9.10), a formal route for late turndowns when in-sequence offering risks nonutilization, and allocation out-of-sequence (AOOS), informal organ procurement organization outreach beyond the match-run. Linking Standard Transplant Analysis and Research files to the Potential Transplant Recipient database (March 2021-December 2025), we classified 61 626 match-runs (41 638 transplanted) by pathway: in-sequence <50 offers (n = 32 165), in-sequence ≥50 (n = 3450), AOOS (n = 5486), and EP (n = 537). AOOS rose 132% while EP grew 6% and was absent in 12 of 55 organ procurement organizations. Before acceptance, a median of 10 centers were contacted per AOOS graft vs 6 in-sequence, and AOOS refusals far more often covered entire waitlists (median 28 patients declined per donor vs 2). Most in-sequence acceptances occurred before donor cross-clamp (median 17.0 hours prior), whereas AOOS and EP acceptances occurred after (0.15 and 2.42 hours). AOOS transplants occurred more frequently at centers with higher in-sequence acceptance of hard-to-place organs (Spearman ρ = 0.866), with comparable survival. These patterns are consistent with AOOS occurring after in-sequence placement has stalled, rather than as early bypass of in-sequence candidates; the circumstance for which EP was designed for.</p>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149007597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Declining allocation out of sequence is associated with fewer kidneys recovered and transplanted.","authors":"Shin Lin, Aaron M Delman, Gregory R Martens, Gary F Marklin, Thomas Levanos, Samuel Z Grinberg, Natnael B Doilicho, Jennifer Yu, Yikyung Park, Neeta Vachharajani, Tarek Alhamad, Brendan P Lovasik, Jessica Lindemann, Darren R Cullinan, Adeel S Khan, Majella B Doyle, Jason R Wellen, Clare H Ridley, William C Chapman, Yiing Lin","doi":"10.1016/j.ajt.2026.09.020","DOIUrl":"https://doi.org/10.1016/j.ajt.2026.09.020","url":null,"abstract":"<p><p>Allocation out of sequence (AOOS) increased after Kidney Allocation System 250 (KAS250) and declined during heightened regulatory and public scrutiny beginning in August 2024. In 2025, deceased donor kidney recovery and transplant volume also decreased for the first time after KAS250. Because the donor pool had been shifting toward higher KDRI donors, we asked whether the decline in kidney recovery during this period exceeded that predicted by KDRI, donor type, and seasonality. Using the pre-August 2024 relationship between KDRI, donor type, seasonality, and kidney recovery, a donor-level model estimated expected recovery among the observed post-August 2024 donors. The model predicted 870 more kidney recoveries than were observed. This difference coincided with declining AOOS but could also reflect unmeasured donor characteristics and other changes occurring at the same time. Under alternative post-recovery utilization assumptions, the model-estimated recovery difference corresponded to approximately 360 to 630 potential additional transplants. The highest KDRI kidneys also experienced the greatest declines in recovery and increases in cold ischemic time. These findings document concurrent national trends and support further evaluation of placement pathways for hard-to-place kidneys as the donor pool shifts toward higher KDRI.</p>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149007601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of eculizumab for the prevention of delayed graft function after kidney transplantation in adults: A randomized, double-blind, placebo-controlled trial.","authors":"William H Marks, Anup Patel, Ondrej Viklicky, Denis Glotz, Lloyd E Ratner, Flavio Vincenti, Josep M Cruzado, Sanela Tarabar Galijasevic, Xiaoyu Jiang, Masayo Ogawa, Hermann Haller, Francesc Moreso, Rostand Emmanuel Nguefouet Momo, Richard N Formica, John S Gill, William Irish","doi":"10.1016/j.ajt.2026.09.024","DOIUrl":"https://doi.org/10.1016/j.ajt.2026.09.024","url":null,"abstract":"<p><p>Delayed graft function (DGF), defined as the need for dialysis within the first 7 days post-kidney transplantation, is increasing owing to greater use of expanded criteria donors (ECDs). No approved therapy currently prevents DGF or reduces its severity. Results of a randomized, double-blind, placebo-controlled clinical trial to evaluate eculizumab for the prevention of DGF post-transplantation in adults (aged ≥ 18 years) are presented. In total, 142 patients received eculizumab, and 146 patients received placebo immediately before (eculizumab, 1200 mg, or placebo) and 18-24 hours post-transplantation (eculizumab, 900 mg, or placebo). Eculizumab did not statistically significantly reduce the incidence of DGF in adult deceased donor kidney transplant recipients compared with placebo (n =51/142 [35.9%] vs n=60/144 [41.7%]; treatment difference -5.75% [95% confidence interval -17.03%, 5.52%]). Overall, there were no substantial differences observed in safety results between treatment groups. Post hoc analyses showed patients who received an ECD/cold storage transplant had a -17.8% difference in DGF with eculizumab versus placebo. Although eculizumab did not significantly reduce the incidence of DGF in adult deceased donor kidney transplants, post hoc analyses suggested a treatment benefit in recipients of an ECD kidney managed with cold storage. CLINICAL TRIAL NUMBER: NCT02145182.</p>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149007648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progression to insulin requirement at 1 year after kidney-alone transplantation in insulin-independent type 2 diabetes: Implications for simultaneous pancreas-kidney candidate selection.","authors":"Mohamed Ibraheem, Vugar Isazade, Nan Zhang, Nitin K Katariya, Aditi Kumar, Raymond L Heilman, Sumi S Nair, Girish K Mour, Lavanya Kodali","doi":"10.1016/j.ajt.2026.09.018","DOIUrl":"10.1016/j.ajt.2026.09.018","url":null,"abstract":"<p><p>This single-center retrospective cohort study investigated the incidence and predictors of insulin requirement following kidney transplantation in patients with type 2 diabetes who were insulin-independent at the time of surgery. Eligible patients were aged ≤65 years with a body mass index ≤30 kg/m², matching our center's inclusion criteria for simultaneous pancreas-kidney (SPK) transplantation. We analyzed 132 adult recipients transplanted between 2015 and 2023. One-year posttransplant, 90.9% (120 of 132) progressed to maintenance insulin therapy, including all patients on oral antidiabetic agents at transplant (n = 48). Recipient age, body mass index, and donor characteristics did not significantly predict progression to insulin therapy. This finding is likely attributable to our stringent inclusion criterion. Pretransplant glycated hemoglobin (mean, 6.1%) and C-peptide (mean, 9.4 ng/mL) were also similar between groups. Patients requiring insulin had significantly higher 1-year glycated hemoglobin than those who remained insulin-free. In a comparison group of 449 kidney transplant recipients without diabetes, the incidence of new-onset diabetes was only 8%. These results indicate that pretransplant insulin independence in patients with diabetes is a deceptive marker, likely due to altered insulin clearance in end-stage renal disease. The near-universal progression to insulin requirement suggests the need to reevaluate the current selection criteria for SPK transplantation to include this high-risk population, especially those receiving oral hypoglycemic agents; whether SPK improves outcomes relative to kidney transplantation with intensive medical therapy in this population remains unestablished.</p>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149000937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delayed immune tolerance intentionally achieved years after 2-haplotype matched kidney transplantation.","authors":"Erik L Lum, Nima Nassiri, Caspian Oliai, Ann C Raldow, Elaine F Reed, Jeffrey Veale","doi":"10.1016/j.ajt.2026.09.021","DOIUrl":"10.1016/j.ajt.2026.09.021","url":null,"abstract":"<p><p>In transplant-naïve patients, intentional immune tolerance has been achieved by combining kidney transplantation with donor stem cell infusion within 2 weeks of the kidney transplant operation. Yet, many patients with a preexisting transplant also desire the opportunity to be freed from the burdens of chronic immunosuppression. In this series (n = 6), healthy, stable human leukocyte antigen-matched kidney transplant recipients intentionally underwent nonmyeloablative conditioning and hematopoietic stem cell transplantation from their previous donor to achieve tolerance. All participants achieved engraftment and durable mixed donor chimerism and underwent immunosuppression withdrawal, and none of the patients developed graft-vs-host disease. At the time of publication, 5 patients are immunosuppression free, with 1 patient tolerant for more than 3 years. Of interest, all patients had improved allograft function once removed from immunosuppression. However, 1 patient developed rejection after being off immunosuppression for 15 months, requiring reinitiation of maintenance immunosuppression. Although limited to human leukocyte antigen-matched siblings, we report the first successful series of intentional delayed immune tolerance achieved years after their kidney transplant operation.</p>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149007645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanomedicine in lung transplantation: Emerging solutions for clinical challenges.","authors":"Andreas Maskos, Aravind Krishnan, Matthew M Duda, Edgar Aranda-Michel, Elbert E Heng, Alex Berg, Daniel Alnasir, Jonas Hildinger, Jasper Iske, Sebastian Michel, Mahdi Forouharshad, Mark R Nicolls, Kunal S Parikh, John W MacArthur","doi":"10.1016/j.ajt.2026.09.013","DOIUrl":"10.1016/j.ajt.2026.09.013","url":null,"abstract":"<p><p>Lung transplantation (LT) remains the definitive treatment for select patients with end-stage respiratory failure. Despite refinements in donor selection, organ preservation, and perioperative management, LT is still associated with the shortest median survival among all solid organ transplants. Major clinical bottlenecks include airway complications, ischemia-reperfusion injury, organ rejection and chronic lung allograft dysfunction, and suboptimal donor organ quality. Current management is constrained by delayed diagnosis, anatomical delivery barriers, and the off-target toxicities of conventional systemic drug delivery. Nanomedicine, the medical application of nanoscale materials and devices, offers several distinct opportunities in LT: noninvasive detection and imaging of graft injury, protection of unstable cargo, context-specific controlled drug release, and cell-specific targeting. However, clinical translation is still in its early stages, with only liposomal cyclosporine having advanced to phase 3 clinical trials; most alternative platforms remain preclinical. Here, we categorize the classes of nanomedicines and their specific delivery routes in LT, mapping these technologies onto clinical bottlenecks and critically appraising each platform to frame a path toward clinical translation.</p>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to \"Comment on 'There is nothing equitable about a wasted organ; eliminating out-of-sequence allocation for 30 days decreases utilization of hard-to-place kidneys'\".","authors":"Christopher Curran, Jillian Wojtowicz, James R Rodrigue, Francis Delmonico, Alexandra Glazier","doi":"10.1016/j.ajt.2026.09.016","DOIUrl":"10.1016/j.ajt.2026.09.016","url":null,"abstract":"","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multimodal analysis of vascular remodeling in human obliterative bronchiolitis after lung transplantation.","authors":"Axelle Coppens, Rahel Bodenmann, Janik Riese, Huijuan Wang, Matthias Brunner, Mark Kuehnel, Francois M Carlier, Christopher Werlein, Jan-Christopher Kamp, Lavinia Neubert, Maximilian Ackermann, Birger Tielemans, Therese S Lapperre, Adam Szmul, Joseph Jacob, Daisuke Yamada, Peter D Lee, Theresa Urban, Jonas C Schupp, Jannik Ruwisch, Anne Sieben, Barbara Putman, Geert M Verleden, Wen Wen, Jeroen Mh Hendriks, Danny D Jonigk, Janine Gote-Schniering, Stijn E Verleden","doi":"10.1016/j.ajt.2026.09.004","DOIUrl":"10.1016/j.ajt.2026.09.004","url":null,"abstract":"<p><p>Chronic lung allograft dysfunction (CLAD) is the leading cause of late morbidity and mortality after lung transplantation. Bronchiolitis obliterans syndrome (BOS), a major CLAD phenotype, is characterized by obliterative bronchiolitis (OB). Although microvascular perturbations are described in BOS, their cellular and molecular characteristics remain unclear. Intact human CLAD lungs (n = 3) underwent hierarchical phase-contrast tomography for 3-dimensional vascular mapping. In OB-affected airways vs controls (n = 4 each), endothelial subtypes were characterized by multiplex immunofluorescence imaging, and interactome changes were quantified with CellChat and GeoMx spatial transcriptomics performed on CD31⁺ regions. Hierarchical phase-contrast tomography revealed hypertrophic vessels infiltrating obliterated airways and forming web-like microvascular networks, absent in controls. Immunofluorescent imaging showed increased plasmalemma vesicle-associated protein⁺/Von Willebrand factor A domain containing 1⁺ systemic venous and podoplanin+ lymphatic cells in OB lesions. Cell-cell interaction analysis showed that plasmalemma vesicle-associated protein+/Von Willebrand factor A domain containing 1+ systemic venous cells exhibited increased incoming and outgoing interaction strength, primarily directed toward other endothelial cells and fibroblasts, characterized by inflammatory and fibrotic signaling. Spatial transcriptomics demonstrated upregulation of inflammatory/matrix-remodeling genes and downregulation of homeostatic regulators in BOS endothelial cells. BOS lungs display altered vascular architecture and endothelial composition, with gene expression shifts consistent with proinflammatory and fibrogenic processes in CD31⁺ regions. These findings suggest a potential involvement of vascular remodeling in CLAD pathophysiology.</p>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148954527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Will human-animal chimeras solve the organ shortage problem?","authors":"Fadi G Lakkis","doi":"10.1016/j.ajt.2026.09.019","DOIUrl":"10.1016/j.ajt.2026.09.019","url":null,"abstract":"","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148943962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}