{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:36:40Z","timestamp":1772138200454,"version":"3.50.1"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T00:00:00Z","timestamp":1731369600000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["2023-01807"],"award-info":[{"award-number":["2023-01807"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Swedish Heart and Lung Foundation","award":["20230371"],"award-info":[{"award-number":["20230371"]}]},{"name":"Independent Research Fund Denmark\u2014Sapere Aude","award":["1052-00035B"],"award-info":[{"award-number":["1052-00035B"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Knowledge of which medications may lead to acute kidney injury (AKI) is limited, relying mostly on spontaneous reporting in pharmacovigilance systems. We here conducted an exploratory drug-wide association study (DWAS) to screen for associations between dispensed drugs and AKI risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using two large Danish and Swedish data linkages, we identified AKI hospitalizations occurring between April 1997 and December 2021 in Denmark and between March 2007 and December 2021 in Sweden. We used a case-time control design comparing drug dispensing in the 3 months prior to the AKI with earlier periods for the same patient. Odds ratios (ORs) for the association between each drug and AKI were estimated using conditional logistic regression and adjusting for the presence of comorbidities. We sought replication of signals in both health systems and explored the plausibility of findings through pharmacovigilance system analysis in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database, appearance in the RESCUE list of medications that report AKI as a side effect, PubMed evidence review and causality assessment through direct acyclic graphs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We included 20\u2009622 adults in Denmark and 13\u2009852 in Sweden hospitalized for AKI. In total, 16 unique medications were identified in both cohorts as associated to increased AKI occurrence. Of these, 10 medications had higher reporting ORs in the FAERS database, 9 were listed by RESCUE, and 7 appearing in PubMed. This analysis identified some medications with known AKI risks (i.e. likely true positives such as furosemide, penicillin, spironolactone and omeprazole), medications that may have initiated in response to conditions that lead to AKI (i.e. false positives like metoclopramide provided to treat nausea\/vomiting) and other candidates (e.g. opioids) that warrant further evaluation in subsequent studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This hypothesis-generating study identifies medications with potential involvement in AKI that require confirmation and validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ckj\/sfae338","type":"journal-article","created":{"date-parts":[[2024,11,10]],"date-time":"2024-11-10T23:14:05Z","timestamp":1731280445000},"source":"Crossref","is-referenced-by-count":3,"title":["Drug use and acute kidney injury: a Drug-Wide Association Study (DWAS) in Denmark and Sweden"],"prefix":"10.1093","volume":"18","author":[{"given":"Alessandro","family":"Bosi","sequence":"first","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet , Stockholm ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars Christian","family":"Lund","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology, Pharmacy and Environmental Medicine, Department of Public Health, University of Southern , Odense ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3157-1127","authenticated-orcid":false,"given":"Viyaasan","family":"Mahalingasivam","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet , Stockholm ,","place":["Sweden"]},{"name":"Department of Non-Communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine , London,","place":["UK"]},{"name":"Department of Nephrology & Transplantation, Barts Health NHS Trust , London ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faizan","family":"Mazhar","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet , Stockholm ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian Fynbo","family":"Christiansen","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology, Department of Clinical Medicine , , Aarhus ,","place":["Denmark"]},{"name":"Aarhus University and Aarhus University Hospital , , Aarhus ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5226-6685","authenticated-orcid":false,"given":"Arvid","family":"Sj\u00f6lander","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet , Stockholm ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9314-5679","authenticated-orcid":false,"given":"Anton","family":"Potteg\u00e5rd","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology, Pharmacy and Environmental Medicine, Department of Public Health, University of Southern , Odense ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4763-2024","authenticated-orcid":false,"given":"Juan Jesus","family":"Carrero","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet , Stockholm ,","place":["Sweden"]},{"name":"Division of Nephrology, Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital , Stockholm ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,11,11]]},"reference":[{"key":"2025020409380079100_bib1","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/ki.2013.153","article-title":"Raising awareness of acute kidney injury: a global perspective of a silent killer","volume":"84","author":"Lewington","year":"2013","journal-title":"Kidney Int"},{"key":"2025020409380079100_bib2","doi-asserted-by":"publisher","first-page":"3365","DOI":"10.1681\/ASN.2004090740","article-title":"Acute kidney injury, mortality, length of stay, and costs in hospitalized patients","volume":"16","author":"Chertow","year":"2005","journal-title":"J Am Soc Nephrol"},{"key":"2025020409380079100_bib3","doi-asserted-by":"publisher","first-page":"70","DOI":"10.12788\/jhm.2683","article-title":"Cost of acute kidney injury in hospitalized patients","volume":"12","author":"Silver","year":"2017","journal-title":"J Hosp Med"},{"key":"2025020409380079100_bib4","doi-asserted-by":"publisher","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":"Mehta","year":"2004","journal-title":"Kidney Int"},{"key":"2025020409380079100_bib5","doi-asserted-by":"publisher","first-page":"1411","DOI":"10.1007\/s00134-015-3934-7","article-title":"Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study","volume":"41","author":"Hoste","year":"2015","journal-title":"Intensive Care Med"},{"key":"2025020409380079100_bib6","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1038\/ki.2012.208","article-title":"Acute kidney injury and chronic kidney disease: an integrated clinical syndrome","volume":"82","author":"Chawla","year":"2012","journal-title":"Kidney Int"},{"key":"2025020409380079100_bib7","doi-asserted-by":"publisher","first-page":"e756","DOI":"10.1542\/peds.2013-0794","article-title":"Electronic health record identification of nephrotoxin exposure and associated acute kidney injury","volume":"132","author":"Goldstein","year":"2013","journal-title":"Pediatrics"},{"key":"2025020409380079100_bib8","doi-asserted-by":"publisher","first-page":"1897","DOI":"10.2215\/CJN.00150118","article-title":"Pharmacology behind common drug nephrotoxicities","volume":"13","author":"Perazella","year":"2018","journal-title":"Clin J Am Soc Nephrol"},{"key":"2025020409380079100_bib9","doi-asserted-by":"publisher","first-page":"1482","DOI":"10.2215\/CJN.00710113","article-title":"World incidence of AKI: a meta-analysis","volume":"8","author":"Susantitaphong","year":"2013","journal-title":"Clin J Am Soc Nephrol"},{"key":"2025020409380079100_bib10","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1159\/000441887","article-title":"Acute kidney injury in Asia","volume":"2","author":"Yang","year":"2016","journal-title":"Kidney Dis (Basel)"},{"key":"2025020409380079100_bib11","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1038\/sj.ki.5002743","article-title":"The RIFLE criteria and mortality in acute kidney injury: a systematic review","volume":"73","author":"Ricci","year":"2008","journal-title":"Kidney Int"},{"key":"2025020409380079100_bib12","doi-asserted-by":"publisher","first-page":"c179","DOI":"10.1159\/000339789","article-title":"KDIGO clinical practice guidelines for acute kidney injury","volume":"120","author":"Khwaja","year":"2012","journal-title":"Nephron Clin Pract"},{"key":"2025020409380079100_bib13","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1136\/jamia.1998.0050305","article-title":"Identifying adverse drug events: development of a computer-based monitor and comparison with chart review and stimulated voluntary report","volume":"5","author":"Jha","year":"1998","journal-title":"J Am Med Inform Assoc"},{"key":"2025020409380079100_bib14","doi-asserted-by":"publisher","first-page":"563","DOI":"10.2147\/CLEP.S179083","article-title":"The Danish health care system and epidemiological research: from health care contacts to database records","volume":"11","author":"Schmidt","year":"2019","journal-title":"Clin Epidemiol"},{"key":"2025020409380079100_bib15","first-page":"798","article-title":"Data resource profile: the Danish National Prescription Registry","volume":"46","author":"Potteg\u00e5rd","year":"2017","journal-title":"Int J Epidemiol"},{"key":"2025020409380079100_bib16","doi-asserted-by":"publisher","first-page":"449","DOI":"10.2147\/CLEP.S91125","article-title":"The Danish National Patient Registry: a review of content, data quality, and research potential","volume":"7","author":"Schmidt","year":"2015","journal-title":"Clin Epidemiol"},{"key":"2025020409380079100_bib17","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1111\/joim.13418","article-title":"The Stockholm CREAtinine Measurements (SCREAM) project: fostering improvements in chronic kidney disease care","volume":"291","author":"Carrero","year":"2022","journal-title":"J Intern Med"},{"key":"2025020409380079100_bib18","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1093\/ckj\/sfv117","article-title":"The Stockholm CREAtinine Measurements (SCREAM) project: protocol overview and regional representativeness","volume":"9","author":"Runesson","year":"2016","journal-title":"Clin Kidney J"},{"key":"2025020409380079100_bib19","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1007\/s10654-016-0117-y","article-title":"Registers of the Swedish total population and their use in medical research","volume":"31","author":"Ludvigsson","year":"2016","journal-title":"Eur J Epidemiol"},{"key":"2025020409380079100_bib20","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1186\/1471-2458-11-450","article-title":"External review and validation of the Swedish national inpatient register","volume":"11","author":"Ludvigsson","year":"2011","journal-title":"BMC Public Health"},{"key":"2025020409380079100_bib21","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1097\/00001648-199505000-00010","article-title":"The case-time-control design","volume":"6","author":"Suissa","year":"1995","journal-title":"Epidemiology"},{"key":"2025020409380079100_bib22","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1177\/0081175019862259","article-title":"A general and robust estimation method for the case-time-control design","volume":"49","author":"Sj\u00f6lander","year":"2019","journal-title":"Sociol Methodol"},{"key":"2025020409380079100_bib23","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1007\/s40264-024-01423-7","article-title":"The REporting of A disproportionality analysis for DrUg Safety Signal Detection Using Individual Case Safety Reports in PharmacoVigilance (READUS-PV): explanation and elaboration","volume":"47","author":"Fusaroli","year":"2024","journal-title":"Drug Saf"},{"key":"2025020409380079100_bib24","doi-asserted-by":"publisher","first-page":"2549","DOI":"10.1093\/ckj\/sfad160","article-title":"Acute kidney injury associated with nephrotoxic drugs in critically ill patients: a multicenter cohort study using electronic health record data","volume":"16","author":"Yasrebi-De Kom","year":"2023","journal-title":"Clin Kidney J"},{"key":"2025020409380079100_bib25","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1111\/j.1365-2044.2009.06228.x","article-title":"Benefits and risks of furosemide in acute kidney injury","volume":"65","author":"Ho","year":"2010","journal-title":"Anaesthesia"},{"key":"2025020409380079100_bib26","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.1007\/s40264-022-01238-4","article-title":"Medicine-induced acute kidney injury findings from spontaneous reporting systems, sequence symmetry analysis and a case-control study with a focus on medicines used in primary care","volume":"45","author":"Roughead","year":"2022","journal-title":"Drug Saf"},{"key":"2025020409380079100_bib27","doi-asserted-by":"publisher","first-page":"101464","DOI":"10.1016\/j.redox.2020.101464","article-title":"Molecular pathways driving omeprazole nephrotoxicity","volume":"32","author":"Fontecha-Barriuso","year":"2020","journal-title":"Redox Biol"},{"key":"2025020409380079100_bib28","doi-asserted-by":"publisher","first-page":"e76","DOI":"10.1038\/psp.2013.52","article-title":"Medication-wide association studies","volume":"2","author":"Ryan","year":"2013","journal-title":"CPT Pharmacometrics Syst Pharmacol"},{"key":"2025020409380079100_bib29","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1093\/jnci\/65.4.723","article-title":"Initial screening for carcinogenicity of commonly used drugs","volume":"65","author":"Friedman","year":"1980","journal-title":"J Natl Cancer Inst"},{"key":"2025020409380079100_bib30","first-page":"1165","article-title":"Screening for possible drug carcinogenicity: second report of findings","volume":"71","author":"Friedman","year":"1983","journal-title":"J Natl Cancer Inst"},{"key":"2025020409380079100_bib31","first-page":"5736","article-title":"Screening prescription drugs for possible carcinogenicity: eleven to fifteen years of follow-up","volume":"49","author":"Selby","year":"1989","journal-title":"Cancer Res"},{"key":"2025020409380079100_bib32","doi-asserted-by":"publisher","first-page":"1821","DOI":"10.1007\/s10552-009-9375-2","article-title":"Screening pharmaceuticals for possible carcinogenic effects: initial positive results for drugs not previously screened","volume":"20","author":"Friedman","year":"2009","journal-title":"Cancer Causes Control"},{"key":"2025020409380079100_bib33","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1158\/2767-9764.CRC-22-0026","article-title":"Identification of drug-cancer associations: a nationwide screening study","volume":"2","author":"Kristensen","year":"2022","journal-title":"Cancer Res Commun"},{"key":"2025020409380079100_bib34","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1158\/1055-9965.EPI-20-1028","article-title":"Drug use and cancer risk: a drug-wide association study (DWAS) in Norway","volume":"30","author":"St\u00f8er","year":"2021","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"2025020409380079100_bib35","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1158\/1055-9965.EPI-20-1612","article-title":"Drug-wide association study (DWAS): challenges and opportunities","volume":"30","author":"Wang","year":"2021","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"2025020409380079100_bib36","doi-asserted-by":"publisher","DOI":"10.4135\/9781412993869","volume-title":"Fixed Effects Regression Models","author":"Allison","year":"2009"},{"key":"2025020409380079100_bib37","doi-asserted-by":"publisher","first-page":"e8525","DOI":"10.1136\/bmj.e8525","article-title":"Concurrent use of diuretics, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers with non-steroidal anti-inflammatory drugs and risk of acute kidney injury: nested case-control study","volume":"346","author":"Lapi","year":"2013","journal-title":"BMJ"},{"key":"2025020409380079100_bib38","doi-asserted-by":"publisher","first-page":"874","DOI":"10.3389\/fphar.2019.00874","article-title":"Risk evaluation for acute kidney injury induced by the concomitant use of valacyclovir, analgesics, and renin-angiotensin system inhibitors: the detection of signals of drug-drug interactions","volume":"10","author":"Inaba","year":"2019","journal-title":"Front Pharmacol"},{"key":"2025020409380079100_bib39","doi-asserted-by":"publisher","first-page":"1865","DOI":"10.1111\/bcp.13634","article-title":"Identifying signals of interest when screening for drug-outcome associations in health care data","volume":"84","author":"Potteg\u00e5rd","year":"2018","journal-title":"Br J Clin Pharmacol"}],"container-title":["Clinical Kidney Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ckj\/advance-article-pdf\/doi\/10.1093\/ckj\/sfae338\/60597627\/sfae338.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ckj\/article-pdf\/18\/1\/sfae338\/60597627\/sfae338.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ckj\/article-pdf\/18\/1\/sfae338\/60597627\/sfae338.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T04:38:17Z","timestamp":1738643897000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ckj\/article\/doi\/10.1093\/ckj\/sfae338\/7890807"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,11]]},"references-count":39,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1,7]]}},"URL":"https:\/\/doi.org\/10.1093\/ckj\/sfae338","relation":{"is-part-of":[{"id-type":"doi","id":"10.69622\/27160149.v1","asserted-by":"object"},{"id-type":"doi","id":"10.69622\/27160149.v2","asserted-by":"object"},{"id-type":"doi","id":"10.69622\/27160149","asserted-by":"object"}]},"ISSN":["2048-8505","2048-8513"],"issn-type":[{"value":"2048-8505","type":"print"},{"value":"2048-8513","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,1]]},"published":{"date-parts":[[2024,11,11]]},"article-number":"sfae338"}}