{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T17:35:48Z","timestamp":1788975348074,"version":"build-2803163510"},"reference-count":31,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T00:00:00Z","timestamp":1744329600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Extracellular vesicles (EVs) have a key role in intercellular communication. We hypothesized that EVs are biomarkers of nephropathy or kidney allograft rejection. We screened patients with chronic kidney disease (CKD) and kidney transplant (KT) recipients. We measured the urine and plasma levels of total EVs overall and EV subpopulations (positive for podocalyxin, aquaporin-1, CD133, CD144, CD19, CD3, CD16, CD56, or CD41). We included 92 patients with CKD, 70 KT recipients, and 33 healthy volunteers. In CKD, the total urine EV concentration was correlated positively with the estimated glomerular filtration rate (eGFR), but none of the subpopulations was identified as a potential biomarker of nephropathy. Among the KT recipients, 30 had good allograft function and 40 had allograft disease (13 with antibody-mediated rejections (ABMR), 12 with T-cell-mediated rejection (TCMR), and 15 with allograft dysfunction). Patients with ABMR had low plasma levels of EVs derived from B-cells, T-cells, and endothelium (p = 0.003, 0.009, and 0.005, respectively). Patients with TCMR had a low urine level of EVs derived from endothelium (p = 0.05). EVs derived from B-cells, T-cells, and endothelium might be biomarkers of kidney allograft rejection. However, we did not identify biomarkers of nephropathy in CKD.<\/jats:p>","DOI":"10.3390\/ijms26083635","type":"journal-article","created":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T10:05:51Z","timestamp":1744365951000},"page":"3635","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Quantification of Urine and Plasma Levels of Extracellular Vesicles in a Cohort of Kidney Transplant Recipients and Chronic Kidney Disease Patients"],"prefix":"10.3390","volume":"26","author":[{"given":"Valentine","family":"Jacob","sequence":"first","affiliation":[{"name":"HEMATIM UR-UPJV 4666, C.U.R.S, University of Picardie Jules Verne, F-80000 Amiens, France"},{"name":"Laboratory of Histocompatibility, Amiens University Hospital, F-80000 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4487-9101","authenticated-orcid":false,"given":"Quentin","family":"de Berny","sequence":"additional","affiliation":[{"name":"Department of Nephrology Dialysis Transplantation, Amiens University Hospital, F-80000 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3898-4389","authenticated-orcid":false,"given":"Fran\u00e7ois","family":"Brazier","sequence":"additional","affiliation":[{"name":"Department of Nephrology Dialysis Transplantation, Amiens University Hospital, F-80000 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Presne","sequence":"additional","affiliation":[{"name":"Department of Nephrology Dialysis Transplantation, Amiens University Hospital, F-80000 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7251-5332","authenticated-orcid":false,"given":"Julien","family":"Lion","sequence":"additional","affiliation":[{"name":"HEMATIM UR-UPJV 4666, C.U.R.S, University of Picardie Jules Verne, F-80000 Amiens, France"},{"name":"Laboratory of Histocompatibility, Amiens University Hospital, F-80000 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3342-1288","authenticated-orcid":false,"given":"Hakim","family":"Ouled-Haddou","sequence":"additional","affiliation":[{"name":"HEMATIM UR-UPJV 4666, C.U.R.S, University of Picardie Jules Verne, F-80000 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1718-5083","authenticated-orcid":false,"given":"Val\u00e9rie","family":"Metzinger-Le Meuth","sequence":"additional","affiliation":[{"name":"HEMATIM UR-UPJV 4666, C.U.R.S, University of Picardie Jules Verne, F-80000 Amiens, France"},{"name":"INSERM UMRS 1148, Laboratory for Vascular Translational Science (LVTS), UFR SMBH, University of Sorbonne Paris Nord, F-93000 Bobigny, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Choukroun","sequence":"additional","affiliation":[{"name":"Department of Nephrology Dialysis Transplantation, Amiens University Hospital, F-80000 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7636-8480","authenticated-orcid":false,"given":"Laurent","family":"Metzinger","sequence":"additional","affiliation":[{"name":"HEMATIM UR-UPJV 4666, C.U.R.S, University of Picardie Jules Verne, F-80000 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Guillaume","sequence":"additional","affiliation":[{"name":"HEMATIM UR-UPJV 4666, C.U.R.S, University of Picardie Jules Verne, F-80000 Amiens, France"},{"name":"Laboratory of Histocompatibility, Amiens University Hospital, F-80000 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1093\/biosci\/biv084","article-title":"Extracellular Vesicles: Composition, Biological Relevance, and Methods of Study","volume":"65","author":"Zaborowski","year":"2015","journal-title":"Bioscience"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"27066","DOI":"10.3402\/jev.v4.27066","article-title":"Biological properties of extracellular vesicles and their physiological functions","volume":"4","author":"Siljander","year":"2015","journal-title":"J. Extracell. Vesicles"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1186\/s12964-023-01251-9","article-title":"Advances in biological functions and applications of apoptotic vesicles","volume":"21","author":"Zou","year":"2023","journal-title":"Cell Commun. Signal"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"24641","DOI":"10.3402\/jev.v3.24641","article-title":"Routes and mechanisms of extracellular vesicle uptake","volume":"3","author":"Mulcahy","year":"2014","journal-title":"J. Extracell. Vesicles"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e12404","DOI":"10.1002\/jev2.12404","article-title":"Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches","volume":"13","author":"Welsh","year":"2024","journal-title":"J. Extracell. Vesicles"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"194","DOI":"10.23876\/j.krcp.20.209","article-title":"Extracellular vesicles in kidneys and their clinical potential in renal diseases","volume":"40","author":"Lee","year":"2021","journal-title":"Kidney Res. Clin. Pract."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Jeon, J.S., Kim, E., Bae, Y.U., Yang, W.M., Lee, H., Kim, H., Noh, H., Han, D.C., Ryu, S., and Kwon, S.H. (2020). microRNA in Extracellular Vesicles Released by Damaged Podocytes Promote Apoptosis of Renal Tubular Epithelial Cells. Cells, 9.","DOI":"10.3390\/cells9061409"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1432206","DOI":"10.1080\/20013078.2018.1432206","article-title":"Podocyte-derived microparticles promote proximal tubule fibrotic signaling via p38 MAPK and CD36","volume":"7","author":"Munkonda","year":"2018","journal-title":"J. Extracell. Vesicles"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1590\/1414-431X20132964","article-title":"Extracellular vesicles: Structure, function, and potential clinical uses in renal diseases","volume":"46","author":"Borges","year":"2013","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_10","first-page":"e15005","article-title":"Reduced urinary release of AQP1- and AQP2-bearing extracellular vesicles in patients with advanced chronic kidney disease","volume":"9","author":"Sonoda","year":"2021","journal-title":"Physiol. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"F193","DOI":"10.1152\/ajprenal.00304.2019","article-title":"Aquaporins in the kidney: Physiology and pathophysiology","volume":"318","author":"Su","year":"2020","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"F584","DOI":"10.1152\/ajprenal.00184.2017","article-title":"Characterization of urinary exosomal release of aquaporin-1 and -2 after renal ischemia-reperfusion in rats","volume":"314","author":"Asvapromtada","year":"2018","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Sonoda, H., Oshikawa-Hori, S., and Ikeda, M. (2019). An Early Decrease in Release of Aquaporin-2 in Urinary Extracellular Vesicles After Cisplatin Treatment in Rats. Cells, 8.","DOI":"10.3390\/cells8020139"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"F553","DOI":"10.1152\/ajprenal.00056.2013","article-title":"Urinary exosomal Wilms\u2019 tumor-1 as a potential biomarker for podocyte injury","volume":"305","author":"Zhou","year":"2013","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Dimuccio, V., Ranghino, A., Pratic\u00f2 Barbato, L., Fop, F., Biancone, L., Camussi, G., and Bussolati, B. (2014). Urinary CD133+ extracellular vesicles are decreased in kidney transplanted patients with slow graft function and vascular damage. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0104490"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1186\/s12967-021-03030-x","article-title":"Urinary small extracellular vesicles derived CCL21 mRNA as biomarker linked with pathogenesis for diabetic nephropathy","volume":"19","author":"Feng","year":"2021","journal-title":"J. Transl. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2542","DOI":"10.1016\/j.ajpath.2018.07.017","article-title":"Urinary Exosomes and Exosomal CCL2 mRNA as Biomarkers of Active Histologic Injury in IgA Nephropathy","volume":"188","author":"Feng","year":"2018","journal-title":"Am. J. Pathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1093\/ndt\/gfv337","article-title":"Effects of lipid-lowering treatment on circulating microparticles in patients with diabetes mellitus and chronic kidney disease","volume":"31","author":"Almquist","year":"2016","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1093\/ndt\/gfy027","article-title":"Phosphatidylserine on microparticles and associated cells contributes to the hypercoagulable state in diabetic kidney disease","volume":"33","author":"Yu","year":"2018","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Georgatzakou, H.T., Pavlou, E.G., Papageorgiou, E.G., Papassideri, I.S., Kriebardis, A.G., and Antonelou, M.H. (2020). The Multi-Faced Extracellular Vesicles in the Plasma of Chronic Kidney Disease Patients. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.00227"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.trim.2014.06.006","article-title":"Early posttransplant changes in circulating endothelial microparticles in patients with kidney transplantation","volume":"31","author":"Qamri","year":"2014","journal-title":"Transpl. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Woud, W.W., Hesselink, D.A., Hoogduijn, M.J., Baan, C.C., and Boer, K. (2022). Direct detection of circulating donor-derived extracellular vesicles in kidney transplant recipients. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-26580-6"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2235","DOI":"10.1097\/TP.0000000000001572","article-title":"Plasma C4d+ Endothelial Microvesicles Increase in Acute Antibody-Mediated Rejection","volume":"101","author":"Tower","year":"2017","journal-title":"Transplantation"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"13368","DOI":"10.1073\/pnas.0403453101","article-title":"Identification and proteomic profiling of exosomes in human urine","volume":"101","author":"Pisitkun","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"11041","DOI":"10.1021\/acsnano.7b05083","article-title":"Integrated Kidney Exosome Analysis for the Detection of Kidney Transplant Rejection","volume":"11","author":"Park","year":"2017","journal-title":"ACS Nano"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1093\/ndt\/gfac259","article-title":"Identification of a serum and urine extracellular vesicle signature predicting renal outcome after kidney transplant","volume":"38","author":"Burrello","year":"2023","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Carmona, A., Guerrero, F., Buendia, P., Obrero, T., Aljama, P., and Carracedo, J. (2017). Microvesicles Derived from Indoxyl Sulfate Treated Endothelial Cells Induce Endothelial Progenitor Cells Dysfunction. Front. Physiol., 8.","DOI":"10.3389\/fphys.2017.00666"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3719","DOI":"10.1016\/j.transproceed.2013.08.079","article-title":"Urinary exosomes as a source of kidney dysfunction biomarker in renal transplantation","volume":"45","author":"Alvarez","year":"2013","journal-title":"Transplant. Proc."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Sigdel, T.K., Ng, Y.W., Lee, S., Nicora, C.D., Qian, W.J., Smith, R.D., Camp, D.G., and Sarwal, M.M. (2015). Perturbations in the urinary exosome in transplant rejection. Front. Med., 1.","DOI":"10.3389\/fmed.2014.00057"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.kint.2023.10.016","article-title":"Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: Known knowns and known unknowns","volume":"105","author":"Levin","year":"2024","journal-title":"Kidney Int."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Jacob, V., Lambour, A., Swinyard, B., Zerbib, Y., Diouf, M., Soudet, S., Brochot, E., Six, I., Maizel, J., and Slama, M. (2023). Annexin-V positive extracellular vesicles level is increased in severe COVID-19 disease. Front. Med., 10.","DOI":"10.3389\/fmed.2023.1186122"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/8\/3635\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:13:04Z","timestamp":1760029984000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/8\/3635"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,11]]},"references-count":31,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["ijms26083635"],"URL":"https:\/\/doi.org\/10.3390\/ijms26083635","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,11]]}}}