{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T14:13:31Z","timestamp":1786889611563,"version":"build-2736575974"},"reference-count":49,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T00:00:00Z","timestamp":1757030400000},"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>Exosomes are nanosized vesicles that carry intracellular mediators and their abundance in urine opens new and intriguing possibilities in nephrology since they provide a non-invasive insight into kidney diseases. The aim of this review is to examine the main applications of urinary exosomes in nephropathies. Urinary exosomes are isolated through ultrafiltration, ultracentrifugation, precipitation, and immunoaffinity chromatography. After isolation they are characterized through Western blotting, flow cytometry, and, more recently, with mass spectrometry. Through the analysis of urinary exosomes, it has been possible to distinguish patients with IgA nephropathy from healthy controls. Different profiles of expression have been identified between patients with MCD and FSGS. A distinct exosomal composition has been discovered in patients with lupus nephropathy when compared to those without renal involvement. Significant findings have been reported also in patients with monoclonal gammopathy of renal significance, allowing a differential diagnosis between LCDD and amyloidosis. Among kidney transplant recipients, the analysis of urinary exosomes highlighted differences between antibody-mediated rejection and cell-mediated rejection. Urinary exosomes are new non-invasive, promising biomarkers and potential therapeutic options that have already shown interesting results in the nephrological field. Further studies are needed to harness their potential and diffusion.<\/jats:p>","DOI":"10.3390\/ijms26178679","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T14:53:01Z","timestamp":1757083981000},"page":"8679","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Urinary Exosomes in Nephrology: A New Frontier for Diagnosis and Prognosis of Kidney Diseases"],"prefix":"10.3390","volume":"26","author":[{"given":"Costanza","family":"Gaudio","sequence":"first","affiliation":[{"name":"Unit of Nephrology, San Giovanni di Dio Hospital, Department of Medical Specialties, Azienda USL Toscana Centro, 50143 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0034-7274","authenticated-orcid":false,"given":"Emanuele","family":"D\u2019Arpino","sequence":"additional","affiliation":[{"name":"Unit of Nephrology, San Giovanni di Dio Hospital, Department of Medical Specialties, Azienda USL Toscana Centro, 50143 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7015-3330","authenticated-orcid":false,"given":"Simone","family":"Stefani","sequence":"additional","affiliation":[{"name":"Unit of Nephrology, San Giovanni di Dio Hospital, Department of Medical Specialties, Azienda USL Toscana Centro, 50143 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo Maria","family":"Fani","sequence":"additional","affiliation":[{"name":"Unit of Nephrology, San Giovanni di Dio Hospital, Department of Medical Specialties, Azienda USL Toscana Centro, 50143 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppina","family":"Rosso","sequence":"additional","affiliation":[{"name":"Unit of Nephrology, San Giovanni di Dio Hospital, Department of Medical Specialties, Azienda USL Toscana Centro, 50143 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elio","family":"Di Marcantonio","sequence":"additional","affiliation":[{"name":"Unit of Nephrology, San Giovanni di Dio Hospital, Department of Medical Specialties, Azienda USL Toscana Centro, 50143 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Becherelli","sequence":"additional","affiliation":[{"name":"Unit of Nephrology, San Giovanni di Dio Hospital, Department of Medical Specialties, Azienda USL Toscana Centro, 50143 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianmarco","family":"Caselli","sequence":"additional","affiliation":[{"name":"Unit of Nephrology, San Giovanni di Dio Hospital, Department of Medical Specialties, Azienda USL Toscana Centro, 50143 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Merciai","sequence":"additional","affiliation":[{"name":"Unit of Nephrology, San Giovanni di Dio Hospital, Department of Medical Specialties, Azienda USL Toscana Centro, 50143 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Fortunato","sequence":"additional","affiliation":[{"name":"Unit of Nephrology, San Giovanni di Dio Hospital, Department of Medical Specialties, Azienda USL Toscana Centro, 50143 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicoletta","family":"Scopetani","sequence":"additional","affiliation":[{"name":"Unit of Nephrology, San Giovanni di Dio Hospital, Department of Medical Specialties, Azienda USL Toscana Centro, 50143 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Rosati","sequence":"additional","affiliation":[{"name":"Unit of Nephrology, San Giovanni di Dio Hospital, Department of Medical Specialties, Azienda USL Toscana Centro, 50143 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"137","DOI":"10.7326\/0003-4819-139-2-200307150-00013","article-title":"National Kidney Foundation. National Kidney Foundation practice guidelines for chronic kidney disease: Evaluation, classification, and stratification","volume":"139","author":"Levey","year":"2003","journal-title":"Ann. Intern. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1016\/j.ajkd.2003.08.001","article-title":"Approach to renal biopsy","volume":"42","author":"Fogo","year":"2003","journal-title":"Am. J. Kidney Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1038\/ki.2013.512","article-title":"Utility of renal biopsy in the clinical management of renal disease","volume":"85","author":"Dhaun","year":"2014","journal-title":"Kidney Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1097\/00000478-200306000-00012","article-title":"International variation in histologic grading is large, and persistent feedback does not improve reproducibility","volume":"27","author":"Furness","year":"2003","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1053\/j.ajkd.2012.02.330","article-title":"Bleeding complications of native kidney biopsy: A systematic review and meta-analysis","volume":"60","author":"Corapi","year":"2012","journal-title":"Am. J. Kidney Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1056\/NEJMra2308577","article-title":"Genetics of Chronic Kidney Disease","volume":"391","author":"Vivante","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1056\/NEJMoa1806891","article-title":"Diagnostic Utility of Exome Sequencing for Kidney Disease","volume":"380","author":"Groopman","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_8","unstructured":"ERA-EDTA (2021). Registry: ERA-EDTA Registry Annual Report 2019, Amsterdam UMC, location AMC, Department of Medical Informatics."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/nrd3978","article-title":"Extracellular vesicles: Biology and emerging therapeutic opportunities","volume":"12","author":"Andaloussi","year":"2013","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1146\/annurev-physiol-021014-071641","article-title":"Exosomes: Vehicles of intercellular signaling, biomarkers, and vectors of cell therapy","volume":"77","author":"Kourembanas","year":"2015","journal-title":"Annu. Rev. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1093\/labmed\/lmac087","article-title":"Urinary Exosomes: A Promising Biomarker for Disease Diagnosis","volume":"54","author":"Wang","year":"2023","journal-title":"Lab Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.jprot.2018.07.008","article-title":"Changes in the urinary extracellular vesicle proteome are associated with nephronophthisis-related ciliopathies","volume":"192","author":"Stokman","year":"2019","journal-title":"J. Proteom."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1016\/j.bbalip.2013.04.011","article-title":"Molecular lipidomics of exosomes released by PC-3 prostate cancer cells","volume":"1831","author":"Llorente","year":"2013","journal-title":"Biochim. Biophys. Acta."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Agborbesong, E., Bissler, J., and Li, X. (2023). Liquid Biopsy at the Frontier of Kidney Diseases: Application of Exosomes in Diagnostics and Therapeutics. Genes, 14.","DOI":"10.3390\/genes14071367"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Patel, G.K., Khan, M.A., Zubair, H., Srivastava, S.K., Khushman, M., Singh, S., and Singh, A.P. (2019). Comparative analysis of exosome isolation methods using culture supernatant for optimum yield, purity and downstream applications. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-41800-2"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1736935","DOI":"10.1080\/20013078.2020.1736935","article-title":"Unravelling the proteomic landscape of extracellular vesicles in prostate cancer by density-based fractionation of urine","volume":"9","author":"Dhondt","year":"2020","journal-title":"J. Extracell. Vesicles"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e13346","DOI":"10.1111\/apha.13346","article-title":"Urinary extracellular vesicles: Origin, role as intercellular messengers and biomarkers; efficient sorting and potential treatment options","volume":"228","author":"Svenningsen","year":"2019","journal-title":"Acta Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e12038","DOI":"10.1002\/jev2.12038","article-title":"Comparison of urinary extracellular vesicle isolation methods for transcriptomic biomarker research in diabetic kidney disease","volume":"10","author":"Barreiro","year":"2020","journal-title":"J. Extracell. Vesicles"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1267896","DOI":"10.1080\/20013078.2016.1267896","article-title":"Residual urinary extracellular vesicles in ultracentrifugation supernatants after hydrostatic filtration dialysis enrichment","volume":"6","author":"Musante","year":"2017","journal-title":"Extracell. Vesicles"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/978-1-4939-2550-6_15","article-title":"A protocol for exosome isolation and characterization: Evaluation of ultracentrifugation, density-gradient separation, and immunoaffinity capture methods","volume":"Volume 1295","author":"Posch","year":"2015","journal-title":"Proteomic Profiling"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1038\/s41592-020-01034-x","article-title":"Exosome detection via the ultrafast-isolation system: EXODUS","volume":"18","author":"Chen","year":"2021","journal-title":"Nat. Methods"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1038\/s41596-019-0126-x","article-title":"Asymmetric-flow field-flow fractionation technology for exomere and small extracellular vesicle separation and characterization","volume":"14","author":"Zhang","year":"2019","journal-title":"Nat. Protoc."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"106049","DOI":"10.1016\/j.tiv.2025.106049","article-title":"Minimum information for studies of extracellular vesicles (MISEV) as toolbox for rigorous, reproducible and homogeneous studies on extracellular vesicles","volume":"106","author":"Culot","year":"2025","journal-title":"Toxicol. Vitr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s11010-020-03703-z","article-title":"Inside(sight) of tiny communicator: Exosome biogenesis, secretion, and uptake","volume":"467","author":"Jadli","year":"2020","journal-title":"Mol. Cell. Biochem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.semcdb.2017.08.022","article-title":"Biogenesis and function of ESCRT-dependent extracellular vesicles","volume":"74","author":"Juan","year":"2018","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2459","DOI":"10.1002\/pmic.201000443","article-title":"Proteomic analysis of urinary exosomes from patients of early IgA nephropathy and thin basement membrane nephropathy","volume":"11","author":"Moon","year":"2011","journal-title":"Proteomics"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e22226","DOI":"10.1002\/jcla.22226","article-title":"Differential expression of urinary exosomal microRNAs in IgA nephropathy","volume":"32","author":"Min","year":"2017","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1111\/eci.12420","article-title":"Circulating and urinary microRNA profile in focal segmental glomerulosclerosis: A pilot study","volume":"45","author":"Ramezani","year":"2015","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Wang, L., Wang, J., Xu, A., Wei, L., Pei, M., Shen, T., Xian, X., Yang, K., Fei, L., and Pan, Y. (2024). Future embracing: Exosomes driving a revolutionary approach to the diagnosis and treatment of idiopathic membranous nephropathy. J. Nanobiotechnol., 22.","DOI":"10.1186\/s12951-024-02633-y"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Perez-Hernandez, J., Forner, M.J., Pinto, C., Chaves, F.J., Cortes, R., Redon, J., and Alvarez, M.L. (2015). Increased Urinary Exosomal MicroRNAs in Patients with Systemic Lupus Erythematosus. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0138618"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Ramirez-Alvarado, M., Ward, C.J., Huang, B.Q., Gong, X., Hogan, M.C., Madden, B.J., Charlesworth, M.C., Leung, N., and Abraham, E. (2012). Differences in immunoglobulin light chain species found in urinary exosomes in light chain amyloidosis (Al). PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0038061"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1681\/ASN.2020060850","article-title":"Discovery and Validation of a Urinary Exosome mRNA Signature for the Diagnosis of Human Kidney Transplant Rejection","volume":"32","author":"Hurley","year":"2021","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/s13340-023-00686-2","article-title":"Exosomal UMOD gene expression and urinary uromodulin level as early noninvasive diagnostic biomarkers for diabetic nephropathy in type 2 diabetic patients","volume":"15","author":"Barr","year":"2024","journal-title":"Diabetol. Int."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"709","DOI":"10.7754\/Clin.Lab.2018.171031","article-title":"Potential value of urinary exosome-derived let-7c-5p in the diagnosis and progression of type II diabetic nephropathy","volume":"64","author":"Li","year":"2018","journal-title":"Clin. Lab."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1111\/jdi.12753","article-title":"Microribonucleic acid-192 as a specific biomarker for the early diagnosis of diabetic kidney disease","volume":"9","author":"Yang","year":"2017","journal-title":"J. Diabetes Investig."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4360357","DOI":"10.1155\/2017\/4360357","article-title":"Urinary excretion of kidney aquaporins as possible diagnostic biomarker of diabetic nephropathy","volume":"2017","author":"Rossi","year":"2017","journal-title":"J. Diabetes Res."},{"key":"ref_37","unstructured":"Floege, J., Johnson, R.J., and Feehally, J. (2023). Comprehensive Clinical Nephrology, Elsevier. [7th ed.]."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/s41572-020-0196-7","article-title":"Podocytopathies","volume":"6","author":"Kopp","year":"2020","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1053\/j.ajkd.2016.01.030","article-title":"Membranous Nephropathy: A Journey from Bench to Bedside","volume":"68","author":"Francis","year":"2016","journal-title":"Am. J. Kidney Dis."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Garcia-Vives, E., Sol\u00e9, C., Molin\u00e9, T., Vidal, M., Agraz, I., Ordi-Ros, J., and Cort\u00e9s-Hern\u00e1ndez, J. (2020). The urinary exosomal miRNA expression profile is predictive of clinical response in lupus nephritis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041372"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/ki.2015.59","article-title":"Autosomal-dominant polycystic kidney disease (ADPKD): Executive summary from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference","volume":"88","author":"Chapman","year":"2015","journal-title":"Kidney Int."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1681\/ASN.2008060564","article-title":"Characterization of PKD protein-positive exosome-like vesicles","volume":"20","author":"Hogan","year":"2009","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1681\/ASN.2014040354","article-title":"Identification of Biomarkers for PKD1 Using Urinary Exosomes","volume":"26","author":"Hogan","year":"2015","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3079","DOI":"10.1681\/ASN.2015090994","article-title":"Proteomics of Urinary Vesicles Links Plakins and Complement to Polycystic Kidney Disease","volume":"27","author":"Salih","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/nbt.1807","article-title":"Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes","volume":"29","author":"Seow","year":"2011","journal-title":"Nat. Biotechnol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1038\/mt.2010.105","article-title":"A Novel Nanoparticle Drug Delivery System: The Anti-inflammatory Activity of Curcumin Is Enhanced When Encapsulated in Exosomes","volume":"18","author":"Sun","year":"2010","journal-title":"Mol. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2383","DOI":"10.1016\/j.biomaterials.2013.11.083","article-title":"A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy","volume":"35","author":"Tian","year":"2014","journal-title":"Biomaterials"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1038\/mt.2016.90","article-title":"Mesenchymal Stem Cells Deliver Exogenous MicroRNA-let7c via Exosomes to Attenuate Renal Fibrosis","volume":"24","author":"Wang","year":"2016","journal-title":"Mol. Ther."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1186\/s13287-022-03075-9","article-title":"Exosome from indoleamine 2,3-dioxygenase-overexpressing bone marrow mesenchymal stem cells accelerates repair process of ischemia\/reperfusion-induced acute kidney injury by regulating macrophages polarization","volume":"13","author":"Xie","year":"2022","journal-title":"Stem Cell Res. Ther."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/17\/8679\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:41:00Z","timestamp":1760035260000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/17\/8679"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,5]]},"references-count":49,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["ijms26178679"],"URL":"https:\/\/doi.org\/10.3390\/ijms26178679","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,5]]}}}