{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T03:55:11Z","timestamp":1788839711715,"version":"build-2803163510"},"reference-count":25,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T00:00:00Z","timestamp":1672963200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery","award":["J011972"],"award-info":[{"award-number":["J011972"]}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["RS-2022-00165597"],"award-info":[{"award-number":["RS-2022-00165597"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Korea University Grant"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\"><jats:title>Background<\/jats:title><jats:p>Drug-induced nephrotoxicity is a relatively common preventable cause of acute kidney injury (AKI), providing early recognition and management. The pharmacokinetics or pharmacodynamics of drug-drug interactions may lead to additive or synergistic toxicity. The influx of new medications or off-label use of medications in the critical care setting can lead to additional nephrotoxicities, often challenging to predict or detect. This study evaluates the patterns of medication utilization, their combinations, and the related associations with AKI.<\/jats:p><\/jats:sec><jats:sec id=\"sec002\"><jats:title>Methods<\/jats:title><jats:p>We utilized correlation-based network analysis (CNA) to investigate the relationship between medications or their combinations with AKI in a large cohort of critically ill patients in a tertiary medical center between 2007 and 2018. Pairwise medication-AKI correlation analysis was performed to evaluate drug synergistic or additive effects. To investigate the inherent nephrotoxicity of medications, we further analyzed medications that were not paired with any other medications within 24 hours before or after their administration time (isolated medication analysis).<\/jats:p><\/jats:sec><jats:sec id=\"sec003\"><jats:title>Results<\/jats:title><jats:p>Among 147,289 ICU admissions, we identified 244 associations among 1,555 unique medication types. In pairwise analysis, 233 significant correlations were found among 13,150,198 medication pair instances. In isolated medication analysis, ten significant AKI associations were noted. When stratified by eGFR level, substantial differences between eGFR&lt;90 vs. eGFR\u226590 patients were observed. This highlights a need to determine eGFR as a risk factor for nephrotoxicity assessment when drug interactions are considered.<\/jats:p><\/jats:sec><jats:sec id=\"sec004\"><jats:title>Conclusions<\/jats:title><jats:p>This large-scale cohort study identified an artificial intelligence model to identify patient-agnostic relationships between medication or their pairs with AKI incidence among critically ill patients. It could be used as a continuous quality assurance tool to monitor drug-associated risk nephrotoxicity.<\/jats:p><\/jats:sec>","DOI":"10.1371\/journal.pone.0279928","type":"journal-article","created":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T18:36:47Z","timestamp":1673030207000},"page":"e0279928","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":19,"title":["Drug-drug interaction and acute kidney injury development: A correlation-based network analysis"],"prefix":"10.1371","volume":"18","author":[{"given":"Wenjun","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin F.","family":"Barreto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingshan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0735-662X","authenticated-orcid":true,"given":"Hyo Kyung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2184-3683","authenticated-orcid":true,"given":"Kianoush","family":"Kashani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,1,6]]},"reference":[{"issue":"6","key":"pone.0279928.ref001","doi-asserted-by":"crossref","first-page":"1780","DOI":"10.1016\/j.transproceed.2004.07.015","article-title":"Pattern of acute renal failure in a tertiary hospital in the United Arab Emirates","volume":"36","author":"B Bernieh","year":"2004","journal-title":"Transplant Proc"},{"issue":"4","key":"pone.0279928.ref002","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1111\/j.1523-1755.2004.00927.x","article-title":"Spectrum of acute renal failure in the intensive care unit: the PICARD experience","volume":"66","author":"RL Mehta","year":"2004","journal-title":"Kidney international"},{"issue":"7","key":"pone.0279928.ref003","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1001\/jama.294.7.813","article-title":"Acute renal failure in critically ill patients: a multinational, multicenter study","volume":"294","author":"S Uchino","year":"2005","journal-title":"JAMA"},{"key":"pone.0279928.ref004","first-page":"1","article-title":"KDIGO Clinical Practice Guideline for Acute Kidney Injury","volume":"2","author":"Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group","year":"2012","journal-title":"Kidney Int"},{"issue":"2","key":"pone.0279928.ref005","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.ccc.2006.02.003","article-title":"Drug-associated renal dysfunction.","volume":"22","author":"SS Taber","year":"2006","journal-title":"Critical care"},{"issue":"18","key":"pone.0279928.ref006","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1056\/NEJMra1613984","article-title":"Acute Kidney Injury in Patients with Cancer","volume":"376","author":"MH Rosner","year":"2017","journal-title":"N Engl J Med"},{"key":"pone.0279928.ref007","first-page":"1","article-title":"Consensus Obtained for the Nephrotoxic Potential of 167 Drugs in Adult Critically Ill Patients Using a Modified Delphi Method.","author":"MP Gray","year":"2022","journal-title":"Drug Saf"},{"issue":"12","key":"pone.0279928.ref008","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1038\/ki.2010.475","article-title":"Drug use and nephrotoxicity in the intensive care unit","volume":"81","author":"MA Perazella","year":"2012","journal-title":"Kidney international"},{"issue":"4","key":"pone.0279928.ref009","doi-asserted-by":"crossref","first-page":"856","DOI":"10.2215\/CJN.08110910","article-title":"Acute kidney injury and increasing nephrotoxic-medication exposure in noncritically-ill children","volume":"6","author":"BS Moffett","year":"2011","journal-title":"Clin J Am Soc Nephrol"},{"issue":"1","key":"pone.0279928.ref010","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.bpa.2003.09.007","article-title":"Acute toxic renal failure.","volume":"18","author":"P. Evenepoel","year":"2004","journal-title":"Best Pract Res Clin Anaesthesiol"},{"key":"pone.0279928.ref011","first-page":"970","article-title":"Drug-induced kidney diseases.","volume":"51","author":"NP Singh","year":"2003","journal-title":"J Assoc Physicians India"},{"issue":"4","key":"pone.0279928.ref012","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1097\/01.aids.0000210610.52836.07","article-title":"Acute renal failure in hospitalized patients with HIV: risk factors and impact on in-hospital mortality","volume":"20","author":"CM Wyatt","year":"2006","journal-title":"AIDS"},{"issue":"1","key":"pone.0279928.ref013","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1097\/CCM.0000000000002769","article-title":"Vancomycin Plus Piperacillin-Tazobactam and Acute Kidney Injury in Adults: A Systematic Review and Meta-Analysis.","volume":"46","author":"MK Luther","year":"2018","journal-title":"Critical care medicine"},{"issue":"9","key":"pone.0279928.ref014","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1007\/s40264-015-0311-y","article-title":"Detection of Drug-Drug Interactions Inducing Acute Kidney Injury by Electronic Health Records Mining.","volume":"38","author":"Y Girardeau","year":"2015","journal-title":"Drug Saf"},{"issue":"1","key":"pone.0279928.ref015","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s40272-016-0205-1","article-title":"Identifying High-Risk Medications Associated with Acute Kidney Injury in Critically Ill Patients: A Pharmacoepidemiologic Evaluation.","volume":"19","author":"MB Slater","year":"2017","journal-title":"Paediatr Drugs"},{"issue":"6","key":"pone.0279928.ref016","doi-asserted-by":"crossref","first-page":"461","DOI":"10.7326\/0003-4819-130-6-199903160-00002","article-title":"A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group","volume":"130","author":"AS Levey","year":"1999","journal-title":"Ann Intern Med"},{"issue":"1","key":"pone.0279928.ref017","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.kint.2016.03.031","article-title":"A sustained quality improvement program reduces nephrotoxic medication-associated acute kidney injury","volume":"90","author":"SL Goldstein","year":"2016","journal-title":"Kidney international"},{"issue":"4","key":"pone.0279928.ref018","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1159\/000167492","article-title":"Nitroprusside-induced acute azotemia.","volume":"7","author":"GM Reid","year":"1987","journal-title":"Am J Nephrol"},{"issue":"3\u20134","key":"pone.0279928.ref019","first-page":"203","article-title":"Renal failure caused by eyedrops containing phenylephrine in a case of retinopathy of prematurity.","volume":"50","author":"K Shinomiya","year":"2003","journal-title":"J Med Invest"},{"issue":"6","key":"pone.0279928.ref020","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1016\/j.jiph.2016.11.007","article-title":"Comparison of the incidence of acute kidney injury during treatment with vancomycin in combination with piperacillin-tazobactam or with meropenem.","volume":"10","author":"MS Al Yami","year":"2017","journal-title":"J Infect Public Health"},{"issue":"Database issue","key":"pone.0279928.ref021","doi-asserted-by":"crossref","first-page":"D901","DOI":"10.1093\/nar\/gkm958","article-title":"DrugBank: a knowledgebase for drugs, drug actions and drug targets","volume":"36","author":"DS Wishart","year":"2008","journal-title":"Nucleic Acids Res"},{"issue":"11","key":"pone.0279928.ref022","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1177\/1060028016657839","article-title":"Drug Class Combination-Associated Acute Kidney Injury","volume":"50","author":"RM Rivosecchi","year":"2016","journal-title":"The Annals of pharmacotherapy"},{"issue":"4","key":"pone.0279928.ref023","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1002\/pds.4960","article-title":"Identifying drug combinations associated with acute kidney injury using association rules method.","volume":"29","author":"PS Nishtala","year":"2020","journal-title":"Pharmacoepidemiol Drug Saf"},{"issue":"12","key":"pone.0279928.ref024","first-page":"e12183","article-title":"Frequency of Exposure of Nephrotoxic Drugs and Drug-Induced Acute Kidney Injury in Pediatric Intensive Care Unit: A Retrospective Review From a Tertiary Care Centre in Pakistan.","volume":"12","author":"R Ahmed","year":"2020","journal-title":"Cureus"},{"key":"pone.0279928.ref025","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.jpeds.2020.08.035","article-title":"Association between Nephrotoxic Drug Combinations and Acute Kidney Injury in the Neonatal Intensive Care Unit","volume":"228","author":"SN Salerno","year":"2021","journal-title":"The Journal of pediatrics"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0279928","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,4]],"date-time":"2023-12-04T05:05:51Z","timestamp":1701666351000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0279928"}},"subtitle":[],"editor":[{"given":"Robert Jeenchen","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,1,6]]},"references-count":25,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1,6]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0279928","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,6]]}}}