{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T23:32:10Z","timestamp":1787959930546,"version":"build-2784847793"},"reference-count":24,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T00:00:00Z","timestamp":1709769600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"\n Introduction<\/jats:title>\n Vancomycin, a commonly prescribed antibiotic particularly in the setting of multi-drug resistant infections, is limited by its nephrotoxicity. Despite its common occurrence, much remains unknown on the clinicopathologic profile as well as the pathogenesis of vancomycin nephrotoxicity. Clinical studies included patients often with severe comorbidities and concomitant polypharmacy confounding the causal pathogenesis. Animal models cannot recapitulate this complex clinical situation. Kidney biopsy was not commonly performed.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n To address this limitation, we studied 36 patients who had renal biopsies for acute kidney injury (AKI) for suspicion of vancomycin nephrotoxicity. Detailed renal biopsy evaluation, meticulous evaluation of clinical profiles, and up-to-date follow-up allowed for a diagnostic categorization of vancomycin nephrotoxicity (VNT) in 25 patients and absence of vancomycin nephrotoxicity (NO-VNT) in 11 patients. For careful comparison of these two groups, we proceeded to compile a clinicopathologic and morphologic profiles characteristic for each group.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Patients with VNT had a characteristic clinical profile including a common clinical background, a high serum trough level of vancomycin, a rapidly developed and severe acute kidney injury, and a recovery of renal function often shortly after discontinuation of vancomycin. This clinical course was correlated with characteristic renal biopsy findings including acute tubulointerstitial nephritis of allergic type, frequent granulomatous inflammation, concomitant and pronounced acute tubular necrosis of nephrotoxic type, and vancomycin casts, in the absence of significant tubular atrophy and interstitial fibrosis. This clinico-pathologic profile was different from that of patients with NO-VNT, highlighting its role in the diagnosis, management and pathogenetic exploration of vancomycin nephrotoxicity<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Vancomycin nephrotoxicity has a distinctive morphologic and clinical profile, which should facilitate diagnosis, guide treatment and prognostication, and confer pathogenetic insights.<\/jats:p>\n <\/jats:sec>","DOI":"10.1371\/journal.pone.0295136","type":"journal-article","created":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T13:57:52Z","timestamp":1709819872000},"page":"e0295136","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":22,"title":["Vancomycin nephrotoxicity: A comprehensive clinico-pathological study"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2396-0739","authenticated-orcid":true,"given":"Rajesh","family":"Nachiappa Ganesh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelina","family":"Edwards","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziad","family":"El Zaatari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lillian","family":"Gaber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Barrios","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luan D.","family":"Truong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,3,7]]},"reference":[{"key":"pone.0295136.ref001","unstructured":"Richard H Drew, George Sakoulas. Vancomycin: Parenteral dosing, monitoring, and adverse effects in adults\u2013In: UpToDate, TW (Ed), UpToDate, Waltham, MA 2020. (Section Editor David C Hooper, Deputy Editor: Elinor L Baron)"},{"key":"pone.0295136.ref002","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.2215\/CJN.11011016","article-title":"Vancomycin and the risk of AKI: Now clearer than Mississippi mud","volume":"11","author":"Thomas D Nolin","year":"2016","journal-title":"Clin J Am Soc Nephrol"},{"key":"pone.0295136.ref003","doi-asserted-by":"crossref","first-page":"2132","DOI":"10.2215\/CJN.05920616","article-title":"Vancomycin and the risk of AKI: A systematic review and meta-analysis","volume":"11","author":"Abhisekh Sinha Ray","year":"2016","journal-title":"Clin J Am Soc Nephrol"},{"key":"pone.0295136.ref004","article-title":"The Nephrotoxicity of Vancomycin","author":"EJ Filippone","year":"2017","journal-title":"Clinical Pharmacology and Therapeutics"},{"key":"pone.0295136.ref005","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1681\/ASN.2016080867","article-title":"Vancomycin associated cast nephropathy","volume":"28","author":"Yosu Luque","year":"2017","journal-title":"J Am Soc Nephrol"},{"issue":"7","key":"pone.0295136.ref006","first-page":"1912","volume":"6","author":"Ngoentra Tantranont","year":"2021","journal-title":"Vancomycin associated tubular casts and vancomycin nephrotoxicity"},{"key":"pone.0295136.ref007","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.ijantimicag.2010.10.013","article-title":"Vancomycin associated nephrotoxicity: a critical appraisal of risk with high dose therapy","volume":"37","author":"Annie Wong Beringer","year":"2011","journal-title":"International journal of antimicrobial agents"},{"issue":"1","key":"pone.0295136.ref008","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mayocp.2018.11.012","article-title":"Navigating the muddy waters of vancomycin nephrotoxicity","volume":"94","author":"EF Barreto","year":"2019","journal-title":"Mayo clinic proceedings"},{"issue":"4","key":"pone.0295136.ref009","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.ijantimicag.2018.12.014","article-title":"The dosing and monitoring of vancomycin\u2013what is the best way forward?","volume":"53","author":"PG Drennan","year":"2019","journal-title":"Journal of antimicrobial agents"},{"key":"pone.0295136.ref010","first-page":"31","article-title":"Vancomycin associated acute kidney injury with a steep rise in serum creatinine","volume":"139","author":"JCQ Velez","year":"2018","journal-title":"Nephron"},{"issue":"9","key":"pone.0295136.ref011","doi-asserted-by":"crossref","first-page":"4277","DOI":"10.1128\/AAC.01674-10","volume":"55","author":"Jill M Butterfield","year":"2011","journal-title":"Antimicrobial agents and Chemotherapy"},{"issue":"11","key":"pone.0295136.ref012","doi-asserted-by":"crossref","first-page":"7073","DOI":"10.1128\/AAC.01185-15","article-title":"Factors impacting unbound vancomycin concentrations in different patient populations","volume":"59","author":"Matthijs Oyaert","year":"2015","journal-title":"Antimicrobial agents and chemotherapy"},{"key":"pone.0295136.ref013","doi-asserted-by":"crossref","first-page":"S35","DOI":"10.1086\/491712","article-title":"The Pharmacokinetic and pharmacodynamic properties of vancomycin","volume":"42","author":"Michael J Rybak","year":"2006","journal-title":"Clinical Infectious diseases"},{"key":"pone.0295136.ref014","unstructured":"Peter F Weller. 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(Section Editor N Franklin Adkinson, Deputy Editor Anna M Feldweg. https:\/\/www.uptodate.com\/contents\/vancomycin-hypersensitivity\/print"},{"issue":"3","key":"pone.0295136.ref015","first-page":"1283","article-title":"Mechanism of vancomycin transport in the kidney: studies in rabbit renal brush border and basolateral membrane vesicles","volume":"259","author":"Paul P Sokol","year":"1991","journal-title":"The journal of Pharmacology and experimental therapeutics"},{"issue":"5","key":"pone.0295136.ref016","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1002\/phar.2388","article-title":"Vancomycin induced kidney injury: Animal models of toxicodynamics, mechanisms of injury, human translation and potential strategies for prevention","volume":"40","author":"Gwendolyn M Pais","year":"2020","journal-title":"Pharmacotherapy"},{"issue":"7","key":"pone.0295136.ref017","first-page":"e00264","article-title":"Incidence of acute kidney injury among patients treated with piperacillin-tazobactam or meropenem in combination with vancomycin","volume":"62","author":"W. Cliff Rutter","year":"2018","journal-title":"Antimicrobials and chemotherapy"},{"issue":"7","key":"pone.0295136.ref018","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1002\/phar.1442","article-title":"Comparison of the incidence of vancomycin induced nephrotoxicity in hospitalized patients with and without concomitant piperacillin-tazobactam","volume":"34","author":"Lindsey D Burgess","year":"2014","journal-title":"Pharmacotherapy"},{"issue":"2","key":"pone.0295136.ref019","first-page":"e02089","article-title":"Nephrotoxicity during vancomycin therapy in combination with piperacillin-tazobactem or cefepime","volume":"61","author":"W. Cliff Rutter","year":"2017","journal-title":"Antimicrobials and Chemotherapy"},{"issue":"2","key":"pone.0295136.ref020","doi-asserted-by":"crossref","first-page":"77","DOI":"10.12788\/jhm.2684","article-title":"Acute kidney injury in patients treated with vancomycin and piperacillin-tazobactam: a retrospective cohort analysis","volume":"12","author":"W Cliff Rutter","year":"2017","journal-title":"J Hosp Med"},{"issue":"1","key":"pone.0295136.ref021","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1089\/sur.2015.104","article-title":"Top Guns: The \u201cMavierck\u201d and \u201cGoose\u201d of empiric therapy","volume":"17","author":"SW Davies","year":"2016","journal-title":"Surg Infect (Larchmt)"},{"issue":"4","key":"pone.0295136.ref022","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1097\/MAJ.0000000000000240","volume":"347","author":"Michael S Gelfand","year":"2014","journal-title":"American Journal of the Medical Sciences"},{"key":"pone.0295136.ref023","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.12659\/AJCR.905214","article-title":"Vancomycin induced leukocytoclastic vasculitis and acute renal failure due to tubulointerstitial nephritis","volume":"18","author":"Chandra Shekar Pingili","year":"2017","journal-title":"American Journal of Case reports"},{"issue":"3","key":"pone.0295136.ref024","doi-asserted-by":"crossref","first-page":"145","DOI":"10.3345\/kjp.2016.59.3.145","article-title":"Acute tubular necrosis as a part of vancomycin induced drug rash with eosinophilia and systemic symptoms syndrome with coincident post-infectious glomerulonephritis","volume":"59","author":"Kyung Min Kim","year":"2016","journal-title":"Korean J Pediatr"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0295136","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T13:58:11Z","timestamp":1709819891000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0295136"}},"subtitle":[],"editor":[{"given":"Fabio","family":"Sallustio","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,3,7]]},"references-count":24,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3,7]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0295136","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,7]]}}}