{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T05:04:22Z","timestamp":1789535062362,"version":"build-2803163510"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The lactate dehydrogenase-to-albumin ratio (LDAR) reflects tissue damage, inflammation, and nutritional status. Its prognostic value in urosepsis remains unexplored. We evaluated LDAR\u2019s association with short-term mortality and developed an LDAR-based prediction model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This retrospective dual-cohort study used MIMIC-IV (n=3,060) and an external cohort (n=370). Exposure was log\n                      <jats:sub>2<\/jats:sub>\n                      -transformed LDAR (logLDAR); outcomes were 28-day intensive care unit (ICU) and in-hospital mortality. Cox regression with three adjustment models, restricted cubic splines (RCS), and Kaplan-Meier curves assessed associations; Fine-Gray models addressed competing risks. DeLong tests compared area under the curve (AUC) of six conventional scores with and without logLDAR. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) quantified incremental value of adding logLDAR; Machine learning selected predictors for a parsimonious model validated internally and externally. decision curve analysis (DCA) evaluated the 7-variable model\u2019s utility.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 3,060 patients, higher logLDAR was associated with significantly elevated 28-day ICU (23.4% vs. 9.02%) and in-hospital (22.1% vs. 8.24%) mortality (both P&amp;lt;0.001). In the primary multivariable-adjusted model, per-unit increases in logLDAR yielded hazard ratios (HRs) of 1.26 (95% CI: 1.17\u20131.36) for ICU mortality and 1.35 (95% CI: 1.25\u20131.45) for in-hospital mortality. Compared with the lowest tertile, the highest tertile showed HRs of 1.79 (1.40\u20132.30) and 2.29 (1.77\u20132.96), respectively. RCS analysis revealed linear dose-response relationships (P&amp;lt;0.001), and the Fine-Gray model confirmed robust associations (subdistribution hazard ratio (sHR)=1.36, 1.27\u20131.46). Adding logLDAR significantly improved the AUCs of all six conventional scores (DeLong P&amp;lt;0.01), with NRI\/IDI showing substantial reclassification improvement (P&amp;lt;0.001). A parsimonious 7-variable model achieved AUCs of 0.674, 0.677, and 0.783 in the internal training, internal validation, and external cohorts, respectively, with adequate calibration (Hosmer-Lemeshow P &amp;gt; 0.05) and DCA demonstrating net clinical benefit. These findings were fully validated in an external real-world cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>LDAR independently predicts short-term mortality in critically ill patients with urosepsis, supplementing conventional severity scores. The parsimonious risk model showed moderate performance with acceptable cross-cohort generalizability.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1891664","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T04:31:10Z","timestamp":1789533070000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Association between lactate dehydrogenase-to-albumin ratio and short-term mortality in critically ill patients with urosepsis: evidence from dual retrospective cohorts"],"prefix":"10.3389","volume":"16","author":[{"given":"Guangyou","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Urology, Xingyi People\u2019s Hospital Affiliatedo Guizhou Medical University","place":["Xing Yi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunyuan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Urology, Xingyi People\u2019s Hospital Affiliatedo Guizhou Medical University","place":["Xing Yi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoming","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Urology, Xingyi People\u2019s Hospital Affiliatedo Guizhou Medical University","place":["Xing Yi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinxin","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Urology, Xingyi People\u2019s Hospital Affiliatedo Guizhou Medical University","place":["Xing Yi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"B35","doi-asserted-by":"publisher","first-page":"8646","DOI":"10.1111\/jan.70493","article-title":"Delayed admission to the intensive care unit is associated with increased mortality risk in critically ill patients: a prospective cohort study","volume":"82","author":"Anagi","year":"2026","journal-title":"J. Adv. Nurs."},{"key":"B9","doi-asserted-by":"publisher","first-page":"8528","DOI":"10.1039\/d4cp00059e","article-title":"Oxidative stress induced conformational changes of human serum albumin","volume":"26","author":"Brahma","year":"2024","journal-title":"Phys. Chem. Chem. Phys."},{"key":"B2","doi-asserted-by":"publisher","first-page":"6260","DOI":"10.1097\/JS9.0000000000002668","article-title":"Unveiling the research advances of sepsis: pathogenesis, precise intervention and clinical perspective","volume":"111","author":"Cheng","year":"2025","journal-title":"Int. J. Surg."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3390\/jcm13020315","article-title":"Lower urinary tract inflammation and infection: key microbiological and immunological aspects","volume":"13","author":"Dickson","year":"2024","journal-title":"J. Clin. Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1111\/j.0894-0959.2004.17603.x","article-title":"Serum albumin: relationship to inflammation and nutrition","volume":"17","author":"Don","year":"2004","journal-title":"Semin. Dial"},{"key":"B3","doi-asserted-by":"publisher","first-page":"837","DOI":"10.3238\/arztebl.2015.0837","article-title":"Urosepsis--Etiology, diagnosis, and treatment","volume":"112","author":"Dreger","year":"2015","journal-title":"Dtsch. Arztebl Int."},{"key":"B17","doi-asserted-by":"publisher","first-page":"2167","DOI":"10.1016\/j.ajem.2016.06.012","article-title":"Prognostic value of neglected biomarker in sepsis patients with the old and new criteria: predictive role of lactate dehydrogenase","volume":"34","author":"Duman","year":"2016","journal-title":"Am. J. Emerg. Med."},{"key":"B14","article-title":"Biochemistry, lactate dehydrogenase","volume-title":"Statpearls","author":"Farhana","year":"2023"},{"key":"B4","doi-asserted-by":"publisher","first-page":"e2013","DOI":"10.1016\/S2214-109X(25)00356-0","article-title":"Global, regional, and national sepsis incidence and mortality, 1990-2021: a systematic analysis","volume":"13","year":"2025","journal-title":"Lancet Glob. Health"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2026.1771448","article-title":"Dynamic changes and prognostic utility of procalcitonin, D-dimer, and lactate dehydrogenase in patients with sepsis and septic shock","volume":"13","author":"Ge","year":"2026","journal-title":"Front. Med. (Lausanne)"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e27560","article-title":"The relationship between lactate dehydrogenase to albumin ratio and all-cause mortality during ICU stays in patients with sepsis: a retrospective cohort study with propensity score matching","volume":"10","author":"Guan","year":"2024","journal-title":"Heliyon"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2024.1398614","article-title":"The association between lactate dehydrogenase to serum albumin ratio and in-hospital mortality in patients with pulmonary embolism: a retrospective analysis of the MIMIC-IV database","volume":"11","author":"Hu","year":"2024","journal-title":"Front. Cardiovasc. Med."},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0105983","article-title":"Hypoalbuminemia is a strong predictor of 30-day all-cause mortality in acutely admitted medical patients: a prospective, observational, cohort study","volume":"9","author":"Jellinge","year":"2014","journal-title":"PloS One"},{"key":"B15","doi-asserted-by":"publisher","first-page":"855","DOI":"10.2174\/1871530320666191230141110","article-title":"The biochemical and clinical perspectives of lactate dehydrogenase: an enzyme of active metabolism","volume":"20","author":"Khan","year":"2020","journal-title":"Endocr. Metab. Immune Disord. Drug Targets"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.64249","article-title":"Beyond the horizon: a comprehensive review of contemporary strategies in sepsis management encompassing predictors, diagnostic tools, and therapeutic advances","volume":"16","author":"Konjety","year":"2024","journal-title":"Cureus"},{"key":"B33","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1186\/s13054-019-2663-7","article-title":"The SOFA score-development, utility and challenges of accurate assessment in clinical trials","volume":"23","author":"Lambden","year":"2019","journal-title":"Crit. Care"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1080\/0886022X.2023.2212080","article-title":"The association between lactate dehydrogenase to serum albumin ratio and the 28-day mortality in patients with sepsis-associated acute kidney injury in intensive care: a retrospective cohort study","volume":"45","author":"Liang","year":"2023","journal-title":"Ren Fail."},{"key":"B10","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.jconrel.2022.05.038","article-title":"Molecular analysis and therapeutic applications of human serum albumin-fatty acid interactions","volume":"348","author":"Linciano","year":"2022","journal-title":"J. Control Release"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2025.1700486","article-title":"The relationship between improved elderly nutritional risk index and short-term all-cause mortality in patients with urinary sepsis: a retrospective cohort study","volume":"12","author":"Liu","year":"2026","journal-title":"Front. Nutr."},{"key":"B13","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1007\/s00415-017-8451-x","article-title":"Significance of admission hypoalbuminemia in acute intracerebral hemorrhage","volume":"264","author":"Morotti","year":"2017","journal-title":"J. Neurol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1186\/s12879-025-10921-7","article-title":"Demographic and regional trends of sepsis mortality in the United States, 1999-2022","volume":"25","author":"Morrissey","year":"2025","journal-title":"BMC Infect. Dis."},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2026.1753403","article-title":"The lactate-to-albumin ratio as a potential biomarker for short-term mortality risk in critically ill patients with urosepsis: a retrospective study with dual-cohort validation","volume":"13","author":"Nie","year":"2026","journal-title":"Front. Nutr."},{"key":"B26","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1080\/14787210.2020.1700794","article-title":"Preventing sepsis development in complicated urinary tract infections","volume":"18","author":"Petrosillo","year":"2020","journal-title":"Expert Rev. Anti Infect. Ther."},{"key":"B31","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1055\/s-0044-1787270","article-title":"Early diagnosis of sepsis: the role of biomarkers and rapid microbiological tests","volume":"45","author":"Plata-Menchaca","year":"2024","journal-title":"Semin. Respir. Crit. Care Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1007\/s11845-019-02118-0","article-title":"The impact of increasing antimicrobial resistance in the treatment of urosepsis","volume":"189","author":"Ryan","year":"2020","journal-title":"Ir. J. Med. Sci."},{"key":"B34","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1186\/s12871-020-00975-2","article-title":"Mortality prediction by SOFA score in ICU-patients after cardiac surgery; comparison with traditional prognostic-models","volume":"20","author":"Schoe","year":"2020","journal-title":"BMC Anesthesiol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1080\/14017431.2020.1762918","article-title":"Serum albumin, cardiometabolic and other adverse outcomes: systematic review and meta-analyses of 48 published observational cohort studies involving 1,492,237 participants","volume":"54","author":"Seidu","year":"2020","journal-title":"Scand. Cardiovasc. J."},{"key":"B1","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1016\/S0140-6736(25)02422-5","article-title":"Sepsis","volume":"407","author":"Singer","year":"2026","journal-title":"Lancet"},{"key":"B19","doi-asserted-by":"publisher","first-page":"100948","DOI":"10.1016\/j.clinsp.2026.100948","article-title":"Lactate dehydrogenase-to-albumin ratio (LAR) predicts mortality in critically ill patients with hypertensive heart failure: a MIMIC-IV database analysis","volume":"81","author":"Tu","year":"2026","journal-title":"Clinics (Sao Paulo)"},{"key":"B28","doi-asserted-by":"publisher","first-page":"119","DOI":"10.3233\/SHTI210549","article-title":"Hands on the medical informatics initiative core data set - lessons learned from converting the MIMIC-IV","volume":"283","author":"Ulrich","year":"2021","journal-title":"Stud. Health Technol. Inform."},{"key":"B30","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1186\/s12879-024-09319-8","article-title":"Nomogram predictive model for in-hospital mortality risk in elderly ICU patients with urosepsis","volume":"24","author":"Wei","year":"2024","journal-title":"BMC Infect. Dis."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2025.1623109","article-title":"Significant adverse prognostic events in patients with urosepsis: a machine learning based model development and validation study","volume":"15","author":"Wei","year":"2025","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2026.1709663","article-title":"Red cell distribution width to albumin ratio predicts short-term mortality in urosepsis: a dual-cohort study","volume":"13","author":"Yu","year":"2026","journal-title":"Front. Nutr."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2026.1724997","article-title":"Prognostic value of the creatinine-to-albumin ratio for 28-day mortality in patients with sepsis and diabetes: integrating renal and nutritional status in the ICU","volume":"13","author":"Zhou","year":"2026","journal-title":"Front. Nutr."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.1186\/s40001-025-03492-5","article-title":"Lactate dehydrogenase and short-term mortality in ICU patients with ischemic stroke: a single-center retrospective analysis of MIMIC-IV","volume":"30","author":"Zhou","year":"2025","journal-title":"Eur. J. Med. Res."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1891664\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T04:31:19Z","timestamp":1789533079000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1891664\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,16]]},"references-count":35,"alternative-id":["10.3389\/fcimb.2026.1891664"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2026.1891664","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,16]]},"article-number":"1891664"}}