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Since their discovery, calcineurin inhibitors (CNI) have been considered the first-line immunosuppressive agents, in spite of their known nephrotoxicity. Chronic CNI toxicity (CNIT) may lead to kidney fibrosis, a threatening scenario for graft survival. However, there is still controversy regarding CNIT diagnosis, monitoring and therapeutic management, and their specific effects at the molecular level are not fully known. Aiming to better characterize CNIT patients, in the present study, we collected urine from kidney-transplanted patients treated with CNI who (i) had a normal kidney function, (ii) suffered CNIT, or (iii) presented interstitial fibrosis and tubular atrophy (IFTA). Urinary extracellular vesicles (uEV) were enriched and the proteome was analyzed to get insight into changes happening during CNI. Members of the uroplakin and plakin families were significantly upregulated in the CNIT group, suggesting an important role in CNIT processes. Although biomarkers cannot be asserted from this single pilot study, our results evidence the potential of uEV as a source of non-invasive protein biomarkers for a better detection and monitoring of this renal alteration in kidney-transplanted patients.<\/jats:p>","DOI":"10.3390\/ijms21207569","type":"journal-article","created":{"date-parts":[[2020,10,14]],"date-time":"2020-10-14T08:59:22Z","timestamp":1602665962000},"page":"7569","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Proteomic Characterization of Urinary Extracellular Vesicles from Kidney-Transplanted Patients Treated with Calcineurin Inhibitors"],"prefix":"10.3390","volume":"21","author":[{"given":"Laura","family":"Carreras-Planella","sequence":"first","affiliation":[{"name":"REMAR-IVECAT Group, Can Ruti Campus, Germans Trias i Pujol Health Science Research Institute, 08916 Badalona, Spain"},{"name":"Department of Cell Biology, Physiology and Immunology, Autonomous University of Barcelona, Bellaterra, 08193 Cerdanyola del Vall\u00e8s, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Juega","sequence":"additional","affiliation":[{"name":"REMAR-IVECAT Group, Can Ruti Campus, Germans Trias i Pujol Health Science Research Institute, 08916 Badalona, Spain"},{"name":"Autonomous University of Barcelona, Bellaterra, 08193 Cerdanyola del Vall\u00e8s, Spain"},{"name":"Nephrology Department, Can Ruti Campus, Germans Trias i Pujol University Hospital, 08916 Badalona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Taco","sequence":"additional","affiliation":[{"name":"Autonomous University of Barcelona, Bellaterra, 08193 Cerdanyola del Vall\u00e8s, Spain"},{"name":"Nephrology Department, Can Ruti Campus, Germans Trias i Pujol University Hospital, 08916 Badalona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Ca\u00f1as","sequence":"additional","affiliation":[{"name":"REMAR-IVECAT Group, Can Ruti Campus, Germans Trias i Pujol Health Science Research Institute, 08916 Badalona, Spain"},{"name":"Autonomous University of Barcelona, Bellaterra, 08193 Cerdanyola del Vall\u00e8s, Spain"},{"name":"Nephrology Department, Can Ruti Campus, Germans Trias i Pujol University Hospital, 08916 Badalona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1287-8908","authenticated-orcid":false,"given":"Marcella","family":"Franquesa","sequence":"additional","affiliation":[{"name":"REMAR-IVECAT Group, Can Ruti Campus, Germans Trias i Pujol Health Science Research Institute, 08916 Badalona, Spain"},{"name":"Nephrology Department, Can Ruti Campus, Germans Trias i Pujol University Hospital, 08916 Badalona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Lauzurica","sequence":"additional","affiliation":[{"name":"REMAR-IVECAT Group, Can Ruti Campus, Germans Trias i Pujol Health Science Research Institute, 08916 Badalona, Spain"},{"name":"Nephrology Department, Can Ruti Campus, Germans Trias i Pujol University Hospital, 08916 Badalona, Spain"},{"name":"Instituto de Salud Carlos III, Red de Investigaci\u00f3n Renal (ISCIII-REDinREN RD16\/0009 Feder Funds), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4038-1912","authenticated-orcid":false,"given":"Francesc Enric","family":"Borr\u00e0s","sequence":"additional","affiliation":[{"name":"REMAR-IVECAT Group, Can Ruti Campus, Germans Trias i Pujol Health Science Research Institute, 08916 Badalona, Spain"},{"name":"Department of Cell Biology, Physiology and Immunology, Autonomous University of Barcelona, Bellaterra, 08193 Cerdanyola del Vall\u00e8s, Spain"},{"name":"Autonomous University of Barcelona, Bellaterra, 08193 Cerdanyola del Vall\u00e8s, Spain"},{"name":"Instituto de Salud Carlos III, Red de Investigaci\u00f3n Renal (ISCIII-REDinREN RD16\/0009 Feder Funds), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,14]]},"reference":[{"key":"ref_1","first-page":"299","article-title":"The controversial early history of cyclosporin","volume":"131","author":"Heusler","year":"2001","journal-title":"Swiss Med. 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