2026-04-13T15:06:50Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/126042025-10-24T08:54:27Zcom_2072_378070com_2072_378040com_2072_378071col_2072_378092col_2072_378097

Evaluation of non-invasive biomarkers of kidney allograft rejection in a prospective multicenter unselected cohort study (EU-TRAIN) Danger, Richard Catar, Rusan Racapé, Maud Philippe, Aurélie Elias, Michelle Crespo, Elena Goutaudier, Valentin Moreso, Francesc Bestard, Oriol Marcadors bioquímics Ronyons - Trasplantació - Complicacions Rebuig (Biologia) Antígens HLA CHEMICALS AND DRUGS::Biological Factors::Biomarkers CHEMICALS AND DRUGS::Biological Factors::Antigens::Antigens, Surface::Histocompatibility Antigens::HLA Antigens PHENOMENA AND PROCESSES::Immune System Phenomena::Transplantation Immunology::Host vs Graft Reaction::Graft Rejection ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Surgical Procedures, Operative::Transplantation::Organ Transplantation::Surgical Procedures, Operative::Kidney Transplantation Other subheadings::Other subheadings::Other subheadings::/adverse effects COMPUESTOS QUÍMICOS Y DROGAS::factores biológicos::biomarcadores COMPUESTOS QUÍMICOS Y DROGAS::factores biológicos::antígenos::antígenos de superficie::antígenos de histocompatibilidad::antígenos HLA FENÓMENOS Y PROCESOS::fenómenos del sistema inmunitario::inmunología del trasplante::reacción huésped contra injerto::rechazo del injerto TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::intervenciones quirúrgicas::trasplante::trasplante de órganos::intervenciones quirúrgicas::trasplante de riñón Otros calificadores::Otros calificadores::Otros calificadores::/efectos adversos Biomarkers; Kidney transplantation; Rejection Biomarcadors; Trasplantament renal; Rebuig Biomarcadores; Trasplante renal; Rechazo Non-invasive biomarkers are promising tools for improving kidney allograft rejection monitoring, but their clinical adoption requires more evidence in specifically designed studies. To address this unmet need, we designed the EU-TRAIN study, a large prospective multicentric unselected cohort funded by the European Commission. Here, we included consecutive adult patients who received a kidney allograft in nine European transplant centers between November 2018 and June 2020. We prospectively assessed gene expression levels of 19 blood messenger RNAs, four antibodies targeting non-human leukocyte antigen (HLA) endothelial antigens, together with circulating anti-HLA donor-specific antibodies (DSA). The primary outcome was allograft rejection (antibody-mediated, T cell-mediated, or mixed) in the first year post-transplantation. Overall, 412 patients were included, with 812 biopsies paired with a blood sample. CD4 gene expression was significantly associated with rejection, while circulating anti-HLA DSA had a significant association with allograft rejection and a strong association with antibody-mediated rejection. All other tested biomarkers, including AKR1C3, CD3E, CD40, CD8A, CD9, CTLA4, ENTPD1, FOXP3, GZMB, ID3, IL7R, MS4A1, MZB1, POU2AF1, POU2F1, TCL1A, TLR4, and TRIB1, as well as antibodies against angiotensin II type 1 receptor, endothelin 1 type A receptor, C3a and C5a receptors, did not show significant associations with allograft rejection. The blood messenger RNAs and non-HLA antibodies did not show an additional value beyond standard of care monitoring parameters and circulating anti-HLA DSA to predict allograft rejection in the first year post-transplantation. Thus, our results open avenues for specifically designed studies to demonstrate the clinical relevance and implementation of other candidate non-invasive biomarkers in kidney transplantation practice. The EU-TRAIN study was funded by the European Union’s Horizon 2020 research and innovation program under grant agreement no. 754995. VG received grants from the French-Speaking Society of Transplantation and the French Foundation for Medical Research. RD was supported by the EU-TRAIN study and the ANR project KTD-innov (ANR-17-RHUS-0010) thanks to the French Government financial support managed by the National Research Agency (ANR) within “Investments into the Future” program. OA received a grant from the Foundation Bettencourt-Schueller. 2025-10-24T08:54:27Z 2025-10-24T08:54:27Z 2025-10-24T08:54:27Z 2025-02-17T13:28:06Z 2025-02-17T13:28:06Z 2024-11 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/11351/12604 Kidney International;106(5) https://doi.org/10.1016/j.kint.2024.07.027 info:eu-repo/grantAgreement/EC/H2020/754995 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess Elsevier Scientia