{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:25:59Z","timestamp":1778631959084,"version":"3.51.4"},"reference-count":41,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2019,11,5]],"date-time":"2019-11-05T00:00:00Z","timestamp":1572912000000},"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>Medullary sponge kidney (MSK) disease is a rare and neglected kidney condition often associated with nephrocalcinosis\/nephrolithiasis and cystic anomalies in the precalyceal ducts. Little is known about the pathogenesis of this disease, so we addressed the knowledge gap using a proteomics approach. The protein content of microvesicles\/exosomes isolated from urine of 15 MSK and 15 idiopathic calcium nephrolithiasis (ICN) patients was investigated by mass spectrometry, followed by weighted gene co-expression network analysis, support vector machine (SVM) learning, and partial least squares discriminant analysis (PLS-DA) to select the most discriminative proteins. Proteomic data were verified by ELISA. We identified 2998 proteins in total, 1764 (58.9%) of which were present in both vesicle types in both diseases. Among the MSK samples, only 65 (2.2%) and 137 (4.6%) proteins were exclusively found in the microvesicles and exosomes, respectively. Similarly, among the ICN samples, only 75 (2.5%) and 94 (3.1%) proteins were exclusively found in the microvesicles and exosomes, respectively. SVM learning and PLS-DA revealed a core panel of 20 proteins that distinguished extracellular vesicles representing each clinical condition with an accuracy of 100%. Among them, three exosome proteins involved in the lectin complement pathway maximized the discrimination between MSK and ICN: Ficolin 1, Mannan-binding lectin serine protease 2, and Complement component 4-binding protein \u03b2. ELISA confirmed the proteomic results. Our data show that the complement pathway is involved in the MSK, revealing a new range of potential therapeutic targets and early diagnostic biomarkers.<\/jats:p>","DOI":"10.3390\/ijms20215517","type":"journal-article","created":{"date-parts":[[2019,11,7]],"date-time":"2019-11-07T02:48:31Z","timestamp":1573094911000},"page":"5517","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Proteomic Analysis of Urinary Extracellular Vesicles Reveals a Role for the Complement System in Medullary Sponge Kidney Disease"],"prefix":"10.3390","volume":"20","author":[{"given":"Maurizio","family":"Bruschi","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Nephrology, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3740-7598","authenticated-orcid":false,"given":"Simona","family":"Granata","sequence":"additional","affiliation":[{"name":"Renal Unit, Department of Medicine, University\/Hospital of Verona, Piazzale A. Stefani 1, 37126 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Candiano","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Nephrology, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonia","family":"Fabris","sequence":"additional","affiliation":[{"name":"Renal Unit, Department of Medicine, University\/Hospital of Verona, Piazzale A. Stefani 1, 37126 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Petretto","sequence":"additional","affiliation":[{"name":"Laboratory of Mass Spectrometry\u2014Core Facilities, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gian Marco","family":"Ghiggeri","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Dialysis and Transplantation, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Gambaro","sequence":"additional","affiliation":[{"name":"Renal Unit, Department of Medicine, University\/Hospital of Verona, Piazzale A. Stefani 1, 37126 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6004-6196","authenticated-orcid":false,"given":"Gianluigi","family":"Zaza","sequence":"additional","affiliation":[{"name":"Renal Unit, Department of Medicine, University\/Hospital of Verona, Piazzale A. Stefani 1, 37126 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1093\/ndt\/gfs505","article-title":"Medullary sponge kidney: State of the art","volume":"28","author":"Fabris","year":"2013","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1681\/ASN.V781123","article-title":"Medullary sponge kidney associated with congenital hemihypertrophy","volume":"7","author":"Indridason","year":"1996","journal-title":"J. Am. Soc. 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