Lactate-to-Albumin Ratio Predicts Mortality in Patients with Sepsis-Associated ARDS: A Dual-Cohort Retrospective Study

Lactate-to-Albumin Ratio Predicts Mortality in Patients with Sepsis-Associated ARDS: A Dual-Cohort Retrospective Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Lactate-to-Albumin Ratio Predicts Mortality in Patients with Sepsis-Associated ARDS: A Dual-Cohort Retrospective Study Guodian Liang, Guangyan Liu, Yi Xiao, Liang Feng, Wenkai Xiao, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9115115/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Background: Sepsis-associated acute respiratory distress syndrome (ARDS) is a common and highly fatal complication in the intensive care unit. The lactate-to-albumin ratio (LAR), a composite biomarker that integrates information on tissue perfusion, oxidative stress, and inflammatory status, has been demonstrated to correlate with prognosis in various critical illnesses. However, its prognostic value in the specific population of patients with sepsis-associated ARDS has not yet been systematically validated in large-scale cohorts. Method: This study was a retrospective cohort analysis based on 5,240 patients from the MIMIC-IV database (primary cohort) and 396 patients hospitalized at the Affiliated Hospital of Guangdong Medical University (validation cohort). All patients were stratified into four groups (Q1–Q4) according to the quartiles of their first LAR value measured within 24 hours of admission. A multivariable Cox proportional hazards regression model was used to evaluate the association between LAR and 28-day all-cause mortality. Restricted cubic spline (RCS) analysis, Kaplan–Meier survival curves, and subgroup analyses were further employed to validate its independent predictive value and robustness. Result: In the multivariable-adjusted models, elevated LAR was independently associated with an increased risk of 28-day mortality (primary cohort: HR = 1.09, 95% CI 1.05–1.13, P < 0.001; validation cohort: HR = 2.87, 95% CI 1.21–6.82, P = 0.017). Restricted cubic spline analysis suggested a nonlinear positive association between LAR and mortality, and Kaplan–Meier curves demonstrated a significant decrease in survival with increasing LAR quartiles (log-rank P < 0.001). Subgroup analysis indicated that the predictive value of LAR was generally consistent across patients with different clinical characteristics. Conclusion: In patients with sepsis-associated ARDS, an elevated LAR early after admission is an independent risk factor for 28-day all-cause mortality. As an easily accessible composite index, LAR may integrate dual pathophysiological information reflecting both hypoxic stress and systemic inflammation/catabolic state. This facilitates early identification of high-risk patients and underscores its potential clinical utility as a prognostic biomarker. Health sciences/Biomarkers Health sciences/Diseases Health sciences/Medical research Health sciences/Risk factors Sepsis acute respiratory distress syndrome lactate‑to‑albumin ratio mortality prognosis intensive care Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers invited by journal 30 Mar, 2026 Editor assigned by journal 24 Mar, 2026 Editor invited by journal 24 Mar, 2026 Submission checks completed at journal 22 Mar, 2026 First submitted to journal 22 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9115115","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":614667496,"identity":"1bc31a21-d6e1-4bd0-a381-6378c0d52a4e","order_by":0,"name":"Guodian Liang","email":"","orcid":"","institution":"Affiliated Hospital of Guangdong Medical University","correspondingAuthor":false,"prefix":"","firstName":"Guodian","middleName":"","lastName":"Liang","suffix":""},{"id":614667497,"identity":"28ef02b4-a35e-4364-9264-160713acf2ff","order_by":1,"name":"Guangyan Liu","email":"","orcid":"","institution":"Affiliated Hospital of Guangdong Medical University","correspondingAuthor":false,"prefix":"","firstName":"Guangyan","middleName":"","lastName":"Liu","suffix":""},{"id":614667498,"identity":"9070095b-2dd6-47e1-a672-db71fd37da4b","order_by":2,"name":"Yi Xiao","email":"","orcid":"","institution":"Affiliated Hospital of Guangdong Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yi","middleName":"","lastName":"Xiao","suffix":""},{"id":614667499,"identity":"d6796c88-79ea-451e-87af-2e567581f612","order_by":3,"name":"Liang Feng","email":"","orcid":"","institution":"Affiliated Hospital of Guangdong Medical University","correspondingAuthor":false,"prefix":"","firstName":"Liang","middleName":"","lastName":"Feng","suffix":""},{"id":614667500,"identity":"fa412f31-9059-4562-8d34-f90566457e99","order_by":4,"name":"Wenkai Xiao","email":"","orcid":"","institution":"Affiliated Hospital of Guangdong Medical University","correspondingAuthor":false,"prefix":"","firstName":"Wenkai","middleName":"","lastName":"Xiao","suffix":""},{"id":614667502,"identity":"e9a76e6e-7330-41c6-80b3-fe7e43cf4659","order_by":5,"name":"Yang Zhu","email":"","orcid":"","institution":"Affiliated Hospital of Guangdong Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yang","middleName":"","lastName":"Zhu","suffix":""},{"id":614667503,"identity":"ed135b9c-d3c3-46e5-8527-0d7091a17bb1","order_by":6,"name":"Sini Chen","email":"","orcid":"","institution":"Affiliated Hospital of Guangdong Medical University","correspondingAuthor":false,"prefix":"","firstName":"Sini","middleName":"","lastName":"Chen","suffix":""},{"id":614667504,"identity":"3ead64f0-734f-4f08-b346-deb385d6b6e8","order_by":7,"name":"Jingying Lin","email":"","orcid":"","institution":"Affiliated Hospital of Guangdong Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jingying","middleName":"","lastName":"Lin","suffix":""},{"id":614667505,"identity":"d4a34d77-fb6d-4e9a-8da9-996c0e9e37b4","order_by":8,"name":"Yingying Zeng","email":"","orcid":"","institution":"Affiliated Hospital of Guangdong Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yingying","middleName":"","lastName":"Zeng","suffix":""},{"id":614667506,"identity":"d61d1880-eb59-43e0-8700-c02a1fdea9f2","order_by":9,"name":"Feng Chen","email":"","orcid":"","institution":"Affiliated Hospital of Guangdong Medical University","correspondingAuthor":false,"prefix":"","firstName":"Feng","middleName":"","lastName":"Chen","suffix":""},{"id":614667507,"identity":"3a38c89c-daab-4ae8-9e85-472b786f3132","order_by":10,"name":"Ji Chen","email":"","orcid":"","institution":"Affiliated Hospital of Guangdong Medical University","correspondingAuthor":false,"prefix":"","firstName":"Ji","middleName":"","lastName":"Chen","suffix":""},{"id":614667508,"identity":"cd61792e-86d6-4025-9306-28ef1cda18c9","order_by":11,"name":"Jia Zhao","email":"","orcid":"","institution":"Affiliated Hospital of Guangdong Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jia","middleName":"","lastName":"Zhao","suffix":""},{"id":614667509,"identity":"1ed3027c-457f-421b-b934-e3dbda6501d5","order_by":12,"name":"Yuanli Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4klEQVRIiWNgGAWjYDACCRiDnYHxQUKFDSlamBmYDR6cSSNNC5vkw7ZDhHXIz25+9vBr22F5c2Yes4oEtgMM/O3dCXi1MM45Zm4s23bYcGczj9mNBJ47DBJnzm7Aq4VZIsFMWrLtMOOGwyAtEs8YDCRy8Wthk0j/BtJiD9JSkGBwmLAWHokcM8mPbYcTQVoYEhKI0CIhkVMmzXAuPXnDYbZiiYQDaTwE/SI/I32b5I8ya9sNx5s3fvz5z0aOv70XvxYQYOZlA1EcBmCXElQOAow//oAo9gdEqR4Fo2AUjIKRBwDDXEhm7DuGLAAAAABJRU5ErkJggg==","orcid":"","institution":"Affiliated Hospital of Guangdong Medical University","correspondingAuthor":true,"prefix":"","firstName":"Yuanli","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2026-03-13 13:09:48","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9115115/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9115115/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106093471,"identity":"cb774d4c-39c8-4d83-ba21-10912fe045fb","added_by":"auto","created_at":"2026-04-03 11:37:30","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1000329,"visible":true,"origin":"","legend":"","description":"","filename":"Liang.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9115115/v1_covered_0ebbaefe-f976-43c3-84ab-09e80e293d91.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Lactate-to-Albumin Ratio Predicts Mortality in Patients with Sepsis-Associated ARDS: A Dual-Cohort Retrospective Study","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Sepsis, acute respiratory distress syndrome, lactate‑to‑albumin ratio, mortality, prognosis, intensive care","lastPublishedDoi":"10.21203/rs.3.rs-9115115/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9115115/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground:\u003c/h2\u003e \u003cp\u003eSepsis-associated acute respiratory distress syndrome (ARDS) is a common and highly fatal complication in the intensive care unit. The lactate-to-albumin ratio (LAR), a composite biomarker that integrates information on tissue perfusion, oxidative stress, and inflammatory status, has been demonstrated to correlate with prognosis in various critical illnesses. However, its prognostic value in the specific population of patients with sepsis-associated ARDS has not yet been systematically validated in large-scale cohorts.\u003c/p\u003e\u003ch2\u003eMethod:\u003c/h2\u003e \u003cp\u003eThis study was a retrospective cohort analysis based on 5,240 patients from the MIMIC-IV database (primary cohort) and 396 patients hospitalized at the Affiliated Hospital of Guangdong Medical University (validation cohort). All patients were stratified into four groups (Q1\u0026ndash;Q4) according to the quartiles of their first LAR value measured within 24 hours of admission. A multivariable Cox proportional hazards regression model was used to evaluate the association between LAR and 28-day all-cause mortality. Restricted cubic spline (RCS) analysis, Kaplan\u0026ndash;Meier survival curves, and subgroup analyses were further employed to validate its independent predictive value and robustness.\u003c/p\u003e\u003ch2\u003eResult:\u003c/h2\u003e \u003cp\u003eIn the multivariable-adjusted models, elevated LAR was independently associated with an increased risk of 28-day mortality (primary cohort: HR\u0026thinsp;=\u0026thinsp;1.09, 95% CI 1.05\u0026ndash;1.13, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; validation cohort: HR\u0026thinsp;=\u0026thinsp;2.87, 95% CI 1.21\u0026ndash;6.82, P\u0026thinsp;=\u0026thinsp;0.017). Restricted cubic spline analysis suggested a nonlinear positive association between LAR and mortality, and Kaplan\u0026ndash;Meier curves demonstrated a significant decrease in survival with increasing LAR quartiles (log-rank P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Subgroup analysis indicated that the predictive value of LAR was generally consistent across patients with different clinical characteristics.\u003c/p\u003e\u003ch2\u003eConclusion:\u003c/h2\u003e \u003cp\u003eIn patients with sepsis-associated ARDS, an elevated LAR early after admission is an independent risk factor for 28-day all-cause mortality. As an easily accessible composite index, LAR may integrate dual pathophysiological information reflecting both hypoxic stress and systemic inflammation/catabolic state. This facilitates early identification of high-risk patients and underscores its potential clinical utility as a prognostic biomarker.\u003c/p\u003e","manuscriptTitle":"Lactate-to-Albumin Ratio Predicts Mortality in Patients with Sepsis-Associated ARDS: A Dual-Cohort Retrospective Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-01 23:08:57","doi":"10.21203/rs.3.rs-9115115/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewersInvited","content":"","date":"2026-03-30T14:29:22+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-24T14:25:16+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-03-24T07:42:51+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-22T19:34:59+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2026-03-22T12:42:07+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e7ec053c-a33e-4faa-afcb-735573a7f144","owner":[],"postedDate":"April 1st, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":65404902,"name":"Health sciences/Biomarkers"},{"id":65404903,"name":"Health sciences/Diseases"},{"id":65404904,"name":"Health sciences/Medical research"},{"id":65404905,"name":"Health sciences/Risk factors"}],"tags":[],"updatedAt":"2026-04-01T23:08:57+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-01 23:08:57","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9115115","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9115115","identity":"rs-9115115","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}