{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T15:32:46Z","timestamp":1785252766426,"version":"3.55.0"},"reference-count":50,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,3,10]],"date-time":"2021-03-10T00:00:00Z","timestamp":1615334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"International Serious Adverse Events Consortium","award":["12-1325"],"award-info":[{"award-number":["12-1325"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background: Vancomycin is commonly used as a first line therapy for gram positive organisms such as methicillin resistant Staphylococcusaureus. Vancomycin-induced acute kidney injury (V-AKI) has been reported in up to 43% of patients, especially in those with higher targeted trough concentrations. The precise mechanism of injury in humans remains elusive, with recent evidence directed towards proximal tubule cell apoptosis. In this study, we investigated the protein contents of urinary exosomes in patients with V-AKI to further elucidate biomarkers of mechanisms of injury and potential responses. Methods: Urine samples from patients with V-AKI who were enrolled in the DIRECT study and matched healthy controls from the UAB-UCSD O\u2019Brien Center Biorepository were included in the analysis. Exosomes were extracted using solvent exclusion principle and polyethylene glycol induced precipitation. Protein identity and quantification was determined by label-free liquid chromatography mass spectrometry (LC\/MS). The mean peak serum creatinine was 3.7 \u00b1 1.4 mg\/dL and time to kidney injury was 4.0 \u00b1 3.0 days. At discharge, 90% of patients demonstrated partial recovery; 33% experienced full recovery by day 28. Proteomic analyses on five V-AKI and 7 control samples revealed 2009 proteins in all samples and 251 proteins significantly associated with V-AKI (Pi-score &gt; 1). The top discriminatory proteins were complement C3, complement C4, galectin-3-binding protein, fibrinogen, alpha-2 macroglobulin, immunoglobulin heavy constant mu and serotransferrin. Conclusion: Urinary exosomes reveal up-regulation of inflammatory proteins after nephrotoxic injury in V-AKI. Further studies are necessary in a large patient sample to confirm these findings for elucidation of pathophysiologic mechanisms and validation of potential injury biomarkers.<\/jats:p>","DOI":"10.3390\/ijms22062784","type":"journal-article","created":{"date-parts":[[2021,3,10]],"date-time":"2021-03-10T02:51:06Z","timestamp":1615344666000},"page":"2784","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Urinary Exosomes Identify Inflammatory Pathways in Vancomycin Associated Acute Kidney Injury"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3187-3264","authenticated-orcid":false,"given":"Linda","family":"Awdishu","sequence":"first","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Le","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan","family":"Amato","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vidhyut","family":"Jani","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soma","family":"Bal","sequence":"additional","affiliation":[{"name":"School of Medicine, University of California, San Diego, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Mills","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marvic","family":"Carrillo-Terrazas","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashita","family":"Tolwani","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Alabama, Birmingham, AL 35233, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjali","family":"Acharya","sequence":"additional","affiliation":[{"name":"Albert Einstein College of Medicine, The Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7058-1697","authenticated-orcid":false,"given":"Jorge","family":"Cerda","sequence":"additional","affiliation":[{"name":"Albany Medical College, Albany, NY 12208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Joy","sequence":"additional","affiliation":[{"name":"Division of Renal Diseases and Hypertension, Skaggs School of Pharmacy and Pharmaceutical, Aurora, CO 80045, USA"},{"name":"School of Medicine, University of Colorado, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Nicoletti","sequence":"additional","affiliation":[{"name":"Mount Sinai School of Medicine, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etienne","family":"Macedo","sequence":"additional","affiliation":[{"name":"School of Medicine, University of California, San Diego, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sucheta","family":"Vaingankar","sequence":"additional","affiliation":[{"name":"School of Medicine, University of California, San Diego, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravindra","family":"Mehta","sequence":"additional","affiliation":[{"name":"School of Medicine, University of California, San Diego, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0680-7994","authenticated-orcid":false,"given":"Satish","family":"RamachandraRao","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, University of Michigan Medical System, Ann Arbor, MI 48109, 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