{"title":"Donor-specific Mesenchymal Stem Cell Infusion in Human and Non-human Primate Kidney Transplantation.","authors":"Imran J Anwar,Shu Li,Michael Mulvihill,Robin Schmitz,Brian Shaw,Qimeng Gao,Sherri Swan-Nesbit,Lynn A Cheatham,Tam How,Allison Miller,Kyha Williams,Fang-Fang Yin,William Giles,Joanne Kurtzberg,Sindhu Chandran,Nancy Bridges,Lyudmila Lyakh,Cynthia Breeden,Krupa Gandhi,Michelle Sever,Mingqing Song,He Xu,Allan D Kirk","doi":"10.1016/j.ajt.2025.05.008","DOIUrl":"https://doi.org/10.1016/j.ajt.2025.05.008","url":null,"abstract":"We report the results of two independent, concurrently performed studies evaluating the safety and efficacy of donor-derived mesenchymal stromal cell (MSC) infusions in inducing immune-tolerance in nonhuman primate (NHP) and human kidney transplant recipients treated with depletional induction and belatacept/sirolimus maintenance. Fifteen NHPs received rhesus ATG induction and were divided in three groups: control (n=6), pre-transplant thymic irradiation (TI, n=4), and TI with monthly donor-MSC infusion (n=5). Sirolimus was discontinued at day-180, and belatacept at day-365 post-transplantation. In humans, six patients enrolled in ITN062ST underwent transplantation with alemtuzumab induction; four received 12 monthly donor-MSC infusions followed by immunosuppression withdrawal (ISW) if eligible. Donor-MSC infusion was acutely well-tolerated in humans and NHPs. Chimerism was not established, and tolerance was not induced in either study. Two of five NHPs that received MSCs rejected while on belatacept monotherapy with detectable donor-specific antibody (DSA). Two patients did not initiate ISW due to de novo DSA and borderline rejection, and two patients failed ISW due to reversible rejection. In conclusion, donor-MSCs can be given to NHPs or humans repeatedly without acute consequences, but they neither lead to detectable chimerism nor induce tolerance. In a subset of recipients, infused MSCs can be sensitizing. Trial Registration. ClinicalTrials.gov - NCT03504241.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"29 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982455","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}
Tzu-Hao Lee,Kara Wegermann,Ken Sutha,George Cholankeril,Chia-Yu Chu,Nhu Thao Nguyen Galvan,Abbas Rana,John A Goss,Tyler Lambing,Felice Cinque,Giada Sebastiani,Keyur Patel,Susanna Naggie,Cameron R Wolfe
{"title":"Beyond the HOPE Act: Roadmap to Expanding Kidney and Liver Transplants for People with Human Immunodeficiency Virus Utilizing Grafts from Donors with Human Immunodeficiency Virus.","authors":"Tzu-Hao Lee,Kara Wegermann,Ken Sutha,George Cholankeril,Chia-Yu Chu,Nhu Thao Nguyen Galvan,Abbas Rana,John A Goss,Tyler Lambing,Felice Cinque,Giada Sebastiani,Keyur Patel,Susanna Naggie,Cameron R Wolfe","doi":"10.1016/j.ajt.2025.05.013","DOIUrl":"https://doi.org/10.1016/j.ajt.2025.05.013","url":null,"abstract":"People living with HIV (PWH) face limited access to organ transplantation despite higher rates of end-organ disease. The HIV Organ Policy Equity (HOPE) Act, enacted in 2015, allowed transplants from donors with HIV to recipients with HIV (HIV D+/R+) under research protocols. Studies have since demonstrated overall comparable outcomes between HIV D+/R+ and HIV D-/R+ transplants, leading to the removal of the research requirement for HIV D+/R+ kidney and liver transplants in November 2024. However, some remaining medical concerns and systemic barriers still need to be addressed, especially for centers that did not participate in the HOPE Act. This manuscript reviews the history, evidence, and key considerations for HIV D+/R+ kidney and liver transplants. Furthermore, a roadmap for implementation, emphasizing the need for reviewing local regulations, establishing multidisciplinary teams, developing personalized protocols, providing medical and culture training, engaging organ procurement organizations and local PWH community, and continuing data collection and quality improvement, is discussed. The removal of research restrictions offers a critical opportunity to reduce disparities in transplant access for PWH. Transplant providers should embrace this opportunity to expand access while continuing to address the remaining medical and systemic challenges to ensure that more PWH receive life-saving transplants.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"5 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982456","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}
Isaac S Alderete,Alexandria L Soto,Samantha E Halpern,Arya Pontula Bsph,Ewout Muylle,Kentaro Nakata,Kunal J Patel,Jacob Klapper,Matthew G Hartwig
{"title":"The Short End of the Stick: Access to Lung Transplantation for Short-Statured Patients in the Composite Allocation Score Era.","authors":"Isaac S Alderete,Alexandria L Soto,Samantha E Halpern,Arya Pontula Bsph,Ewout Muylle,Kentaro Nakata,Kunal J Patel,Jacob Klapper,Matthew G Hartwig","doi":"10.1016/j.ajt.2025.05.011","DOIUrl":"https://doi.org/10.1016/j.ajt.2025.05.011","url":null,"abstract":"Short-statured lung transplant (LTx) candidates experience longer waitlist times than taller ones. The new Composite Allocation Score (CAS) includes height to enhance allocation equity. We assessed the impact of CAS on waitlist outcomes for different height groups. We queried a national transplant database for LTx candidates listed from 2021 to 2024, categorized into four height groups: ≤162 cm, 162-170 cm, 170-176.5 cm, >176.5 cm. Competing risk and Cox regression models assessed the impact of height on waitlist outcomes, including an interaction term between height and allocation era to assess effect modification. Of the 9,383 candidates identified, those >176.5 cm had an increased likelihood of transplantation (sHR 1.15) compared to the 170-176.5 cm group, while those ≤162 cm had a lower likelihood (sHR 0.70). The overall likelihood of transplantation was higher in the CAS era (sHR 1.17); The interaction term for height ≤162 cm and CAS era was significant (sHR 1.15), suggesting a modest improvement in access for this group under CAS. Further, candidates ≤162 cm experienced a higher hazard of mortality in the CAS era (HR 1.60). These findings suggest that CAS modestly improves access for the shortest candidates, but refinements are needed to address ongoing inequities in this population.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"148 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982511","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}
Edmund Huang,Noriko Ammerman,Ashley Vo,Jean Hou,Sanjeev Kumar,Nicole Badash,Ben Falk,Kathleen Hernando,Matthew Gillespie,Irene Kim,Kathlyn Lim,Reiad Najjar,Alice Peng,Bongha Shin,Justin Steggerda,Tsuyoshi Todo,Todd Brennan,Georgios Voidonikolas,Steven Wisel,Peter S Heeger,Stanley C Jordan
{"title":"Backtable Intra-Arterial Administration of C1 Esterase Inhibitor to Deceased Donor Kidney Allografts Improves Post-Transplant Allograft Function: Results of a Randomized Double-Blind Placebo-Controlled Clinical Trial.","authors":"Edmund Huang,Noriko Ammerman,Ashley Vo,Jean Hou,Sanjeev Kumar,Nicole Badash,Ben Falk,Kathleen Hernando,Matthew Gillespie,Irene Kim,Kathlyn Lim,Reiad Najjar,Alice Peng,Bongha Shin,Justin Steggerda,Tsuyoshi Todo,Todd Brennan,Georgios Voidonikolas,Steven Wisel,Peter S Heeger,Stanley C Jordan","doi":"10.1016/j.ajt.2025.05.003","DOIUrl":"https://doi.org/10.1016/j.ajt.2025.05.003","url":null,"abstract":"Ischemia-reperfusion injury (IRI) commonly causes delayed graft function (DGF) after kidney transplantation and is associated with poorer graft function and lower allograft survival. Activation of the lectin complement pathway is one mediator of IRI. In this randomized double-blind placebo-controlled pilot study, we tested whether pre-implantation intragraft administration of C1 esterase inhibitor (C1INH, a lectin/classical pathway inhibitor) into deceased donor organs improves graft function and/or reduces DGF. Forty patients were randomized 1:1 to receive allografts treated with 500 units C1INH or placebo (normal saline) into the transplant renal artery during back-table preparation. We observed no effect on DGF, but recipients of C1INH-treated allografts showed higher eGFR vs. placebo at 6 months (C1INH median: 55 ml/min/1.73 m2, IQR: 42-63; placebo median: 39 ml/min/1.73 m2, IQR 34-50; p=0.02) and 30 months (C1INH median: 54 ml/min/1.73 m2, IQR: 47-66; placebo median: 43 ml/min/1.73 m2, IQR 38-51; p=0.03) without differences in adverse events. Analysis of post-reperfusion biopsies showed positive intra-arterial C1INH staining and reduced C4d staining in C1INH-treated grafts vs controls. Post-transplant serum MBL and classical pathway activity and bradykinin levels did not differ between study arms. We conclude that this treatment strategy improves allograft function independent of DGF, likely via local intragraft complement inhibition. Clinical trial registration number: NCT04696146.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"19 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932839","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}
Dina Zielinski, Valentin Goutaudier, Marta Sablik, Gillian Divard, Olivier Aubert, Alexis Piedrafita, Fariza Mezine, Jessy Dagobert, Anais Certain, Blaise Robin, Juliette Gueguen, Marion Rabant, Jean-Paul Duong van Huyen, Aurélie Sannier, Christine Randoux-Lebrun, Mehdi Maanaoui, Arnaud Lionet, Jean-Baptiste Gibier, Viviane Gnemmi, Moglie Le Quintrec, Bertrand Chauveau, Agathe Vermorel, Lionel Couzi, Oriol Bestard, Michelle Elias, Kevin Louis, Ivy A. Rosales, R. Neal Smith, Vanderlene L. Kung, Dany Anglicheau, Christophe Legendre, Arnaud Del Bello, Edmund Huang, Benjamin Adam, Nassim Kamar, Robert B. Colvin, Michael Mengel, Carmen Lefaucheur, Alexandre Loupy
{"title":"Molecular diagnosis of kidney allograft rejection based on the Banff Human Organ Transplant (B-HOT) gene panel: a multicenter international study","authors":"Dina Zielinski, Valentin Goutaudier, Marta Sablik, Gillian Divard, Olivier Aubert, Alexis Piedrafita, Fariza Mezine, Jessy Dagobert, Anais Certain, Blaise Robin, Juliette Gueguen, Marion Rabant, Jean-Paul Duong van Huyen, Aurélie Sannier, Christine Randoux-Lebrun, Mehdi Maanaoui, Arnaud Lionet, Jean-Baptiste Gibier, Viviane Gnemmi, Moglie Le Quintrec, Bertrand Chauveau, Agathe Vermorel, Lionel Couzi, Oriol Bestard, Michelle Elias, Kevin Louis, Ivy A. Rosales, R. Neal Smith, Vanderlene L. Kung, Dany Anglicheau, Christophe Legendre, Arnaud Del Bello, Edmund Huang, Benjamin Adam, Nassim Kamar, Robert B. Colvin, Michael Mengel, Carmen Lefaucheur, Alexandre Loupy","doi":"10.1016/j.ajt.2025.04.025","DOIUrl":"https://doi.org/10.1016/j.ajt.2025.04.025","url":null,"abstract":"Transcriptomic analysis of kidney biopsies has demonstrated potential to improve diagnosis of allograft rejection. Here, we developed a molecular assessment of antibody-mediated rejection (AMR) and T-cell-mediated rejection (TCMR) based on the Banff-Human-Organ-Transplant (B-HOT) consensus gene panel. Expression assays of formalin-fixed paraffin-embedded kidney biopsies from well-phenotyped cohorts were used to develop prediction models for AMR and TCMR and an automated report of gene expression-based diagnosis. The study population consisted of 950 kidney allograft biopsies from 10 transplantation centers in Europe and North America. The development cohort included 664 renal allograft biopsies split into a training (n=537) and test set (n=127), and two external validation cohorts (n=286). We performed gene selection using regularized regression and developed several different base models based on B-HOT expression data, which were combined into a single ensemble model for each rejection diagnosis. Model performance was assessed in the test set and the two external validation cohorts, showing good discriminative abilities (respective PR-AUC AMR=0.811, 0.891, 0.832 and TCMR=0.736, 0.810, 0.782). We identified challenging biopsies with histology below diagnostic thresholds for which gene expression-based probability can refine rejection diagnosis. This automated molecular diagnostic system shows potential for improving kidney allograft rejection diagnosis in routine practice and clinical trials.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"27 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143930653","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}
Em Donald,J Batra,Em DeFilippis,J Raikhelkar,D Lotan,Kj Clerkin,G Sayer,N Uriel
{"title":"Comparable Short-Term Survival in HIV-Positive and HIV-Negative Dual Organ Heart Transplant Recipients: A Call for Increased Access to Organ Donation for People Living with HIV.","authors":"Em Donald,J Batra,Em DeFilippis,J Raikhelkar,D Lotan,Kj Clerkin,G Sayer,N Uriel","doi":"10.1016/j.ajt.2025.05.004","DOIUrl":"https://doi.org/10.1016/j.ajt.2025.05.004","url":null,"abstract":"Access to organ transplantation for HIV-positive individuals is expanding, yet the outcomes of HIV-positive patients requiring multiorgan transplant are not well-defined. Adult individuals in the United Network for Organ Sharing (UNOS) registry who were HIV-positive and received HT between 2010 and 2023 were included. The primary outcome was patient survival. During the study period, 175 HIV-positive patients were transplanted. Twenty-six (14.8%) underwent dual organ transplantation (20 heart/kidney, 4 heart/lung, and 2 heart/liver) at 23 centers. Median age at the time of HT was 56 years (IQR 47-60), majority were male (n=18, 69%), and 46% identified as Black (n= 12). Dilated cardiomyopathy was the most common etiology of heart failure (n=13, 50%). All patients received organs from HIV-negative donors. The probability of surviving at least one year was 87.6% (95% CI 81.0- 92.0) for single-organ recipients and 82.9% for dual organ recipients (95% CI 60.0-93.4). There was no difference in overall survival between HIV-positive and HIV-negative matched controls among dual organ recipients (log-rank p-value = 0.8). Over the last decade, only a small number of HIV-positive individuals with end-stage heart failure have undergone dual organ transplantation with encouraging short-term outcomes.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"16 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932493","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}
Camilla W Nonterah,Christina Spivey,Nicole Hayde,Marie Chisholm-Burns,Sixto Giusti,Beau Kelly,Tzu-Hao Lee
{"title":"Diversity, Equity, Inclusion, and Belonging in Organ Transplantation.","authors":"Camilla W Nonterah,Christina Spivey,Nicole Hayde,Marie Chisholm-Burns,Sixto Giusti,Beau Kelly,Tzu-Hao Lee","doi":"10.1016/j.ajt.2025.05.001","DOIUrl":"https://doi.org/10.1016/j.ajt.2025.05.001","url":null,"abstract":"Diversity, equity, inclusion, and belonging (DEIB) have implications for transplant access and outcomes. Inequities in transplantation have been identified over the years for minoritized groups based on race, ethnicity, sex, sexual orientation, gender identity, disability status, and other sociocultural identities. While DEIB initiatives have demonstrated success in improving transplant outcomes for some minoritized groups, many gaps still exist, and additional work is needed. Concerns about these practices have also been brought up, and they may create barriers to achieving DEIB goals. This underscores the importance of transplant organizational commitment to practices that uphold the values of DEIB, as such efforts are effective in reducing transplant inequities and fostering an inclusive community. In this viewpoint, we reviewed existing inequalities in transplant, importance of DEIB, common concerns of DEIB initiatives, and commitment of the American Society of Transplant to DEIB initiatives, including the foundation of Inclusion, Diversity, Equity, and Access to Life (IDEAL) committee. Recommendations for cultivating DEIB practices, as well as tips for managing backlash against DEIB initiatives, were also provided. All professionals within the field of transplantation should carefully consider these recommendations to help promote an inclusive community for patients, providers, and all key stakeholders.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"29 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932489","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":"Alloreactive adaptive Natural Killer cells in renal transplantation: potential contribution to allograft microvascular inflammation.","authors":"Elisenda Alari-Pahissa,Judith Federico-Vega,Michelle Ataya,Anna Buxeda,Víctor Bello-Rico,Javier Gimeno,José Yélamos,Mireia Altadill,Sara Sanz-Ureña,Marta Riera,Carla Burballa,Betty Chamoun,María José Pérez-Sáez,Dolores Redondo-Pachón,Carlos Vilches,Marta Crespo,Miguel López-Botet","doi":"10.1016/j.ajt.2025.04.024","DOIUrl":"https://doi.org/10.1016/j.ajt.2025.04.024","url":null,"abstract":"Inhibitory Killer-cell immunoglobulin-like receptors (iKIR) are randomly expressed by Natural Killer (NK) cell subsets and recognize motifs shared by HLA class-I allotypes. Such interactions prevent NK cell autoreactivity while enhancing their response against cells lacking those HLA-I molecules (missing self), a situation defined in transplantation as iKIR-HLA-I mismatch (iKIR-MM), whose genotypic prediction has been associated with microvascular inflammation (MVI). Herein we compared iKIR-MM in kidney transplant recipients (KTR) with MVI≥2 (n=19) and controls with MVI≤1 (n=36). In parallel to genetic analysis of iKIR-MM, which was more frequent in MVI≥2 patients, putative alloreactive iKIR-MM NK cells were defined by flow cytometry as NKG2A(-) cells bearing self-specific but lacking donor-specific iKIR. Although iKIR-MM NK cells were detected in both groups, their pretransplant numbers were higher in MVI≥2 patients (median=11.02, IQR=0-58.31 vs median=0, IQR=0-9.46), especially in the presence of DSA or C4d and correlated with MVI grade. A subset of MVI≥2 patients showed pretransplant high proportions and numbers of oligoclonal iKIR-MM NK cells, which displayed an NKG2C(+) adaptive phenotype associated with cytomegalovirus infection. This pilot study provides a novel perspective on the contribution of iKIR-MM NK cells to MVI, with potential practical implications.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"143 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926452","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":"The Impact of the Banff v-Lesion on Rejection Classification and Outcomes: Insights from a Multicenter Study.","authors":"Karolien Wellekens,Maarten Coemans,Priyanka Koshy,Thibaut Vaulet,Evert Cleenders,Tim Debyser,Steffi De Pelsmaeker,Valérie Dubois,Marie-Paule Emonds,Dirk Kuypers,Angelica Pagliazzi,Maud Rabeyrin,Aleksandar Senev,Irina Scheffner,Thomas Vanhoutte,Olivier Thaunat,Candice Roufosse,Wilfried Gwinner,Maarten Naesens","doi":"10.1016/j.ajt.2025.04.023","DOIUrl":"https://doi.org/10.1016/j.ajt.2025.04.023","url":null,"abstract":"According to the Banff classification, intimal arteritis (v-lesion) contributes to diagnosing T cell-mediated rejection (TCMR) and antibody-mediated rejection (AMR), and signifies more severe TCMR. This multicenter cohort study (N=5323 kidney transplants, N=16774 post-transplant biopsies) evaluated the impact of v-lesions (N=707 v-positive biopsies in N=534 transplants) on biopsy classification and outcomes. The first v-positive biopsy of each transplant was categorized by additional Banff TCMR/(p)AMR-MVI criteria: 166 (31.1%) isolated v, 87 (16.3%) borderline changes with v, 66 (12.4%) TCMR grade I (TCMR-I) with v, 148 (27.7%) (p)AMR-MVI ((probable) AMR/DSAnegC4dneg MVI) with v, and 67 (12.5%) TCMR-I + (p)AMR-MVI with v. Cases with additional TCMR/(p)AMR-MVI criteria were more often indication biopsies, had lower eGFR, and were more frequently HLA-DSA positive than isolated v. While borderline changes with v had borderline higher 10-year graft failure rates than isolated v, TCMR-I, (p)AMR-MVI, and TCMR-I + (p)AMR-MVI with v were associated with significantly worse outcomes, although variably treated. Matching N=534 v-positive cases to v-negative controls showed no significant impact of v-lesions on outcomes. These findings question the role of isolated v-lesions in rejection diagnosis and emphasize the greater prognostic value of additional TCMR and (p)AMR-MVI criteria. Reconsideration of v-lesions in the Banff classification may be appropriate.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"23 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143921084","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}