{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:19:18Z","timestamp":1787235558033,"version":"build-2736575974"},"reference-count":39,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T00:00:00Z","timestamp":1755734400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012165","name":"Key Technologies Research and Development Program","doi-asserted-by":"publisher","award":["2022YFC2009800"],"award-info":[{"award-number":["2022YFC2009800"]}],"id":[{"id":"10.13039\/501100012165","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Natural Science Foundation of Changsha","award":["kq2403030"],"award-info":[{"award-number":["kq2403030"]}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2024JJ6659"],"award-info":[{"award-number":["2024JJ6659"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sepsis patients exhibit complex clinical conditions, frequently complicated with metabolic dysregulation. Cardiovascular-Kidney-Metabolic Syndrome (C-K-M) is classified as below: stage 0, no C-K-M risk factors; stage 1, excess or dysfunctional adiposity; stage 2, metabolic risk factors (hypertriglyceridemia, hypertension, diabetes, metabolic syndrome) or moderate- to high-risk chronic kidney disease; stage 3, subclinical cardiovascular diseases (CVD) in C-K-M syndrome or risk equivalents (high predicted CVD risk or very high-risk chronic kidney diseases); and stage 4, clinical CVD in C-K-M syndrome. While high-risk patients defined by C-K-M criteria often have poor outcomes, studies seldom have classified these patients into subtypes based on metabolic profiles. Serum phosphate, recently recognized as a potential metabolic and organ function marker, has unclear dynamic trajectories and prognostic significance across high-risk CKM-sepsis subgroups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>This study aimed to evaluate the association between serum phosphate trajectories and clinical prognosis, specifically 28-day mortality, among high-risk C-K-M-sepsis patients and across various subgroups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We extracted data for high-risk C-K-M-Sepsis patients from the MIMIC-IV database. After developing a simplified C-K-M staging system, we used unsupervised consensus clustering to identify four metabolic phenotypes. Serum phosphate trajectories during the first seven ICU days were summarized by daily earliest measurements. Associations between phosphate trajectory clusters and 28-day ICU mortality were examined using multivariable logistic regression, inverse probability weighting (IPW) derived from propensity scores, and doubly robust estimation. Subgroup analyses stratified by age, sex, and key comorbidities were conducted, and results were visualized as forest plots.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Multivariate analysis revealed that trajectory Group 3 (persistently high serum phosphate) had significantly increased mortality risk (OR=2.909, 95% CI: 2.121\u20132.991, p\u2009&lt;\u20090.001). Elevated risk was prominent in younger (&lt;65 years) and male subgroups. Comorbidity analysis identified CVA and COPD as significant risk factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec005\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Serum phosphate trajectory patterns significantly correlate with 28-day mortality in high-risk CKM-sepsis patients, highlighting potential distinct metabolic phenotypes. Early intervention targeting serum phosphate levels may improve prognosis in high-risk subgroups.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0330497","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T17:27:03Z","timestamp":1755797223000},"page":"e0330497","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Targeting serum phosphate trajectory stratification to improve outcomes in high-risk Cardiovascular-Kidney-Metabolic-Sepsis cohorts"],"prefix":"10.1371","volume":"20","author":[{"given":"Jinwei","family":"Dai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenye","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nianzhe","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoxin","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4753-661X","authenticated-orcid":true,"given":"Zhihong","family":"Zuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,8,21]]},"reference":[{"issue":"8","key":"pone.0330497.ref001","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1007\/s00018-022-04490-0","article-title":"Metabolic reprogramming consequences of sepsis: adaptations and contradictions","volume":"79","author":"J Liu","year":"2022","journal-title":"Cell Mol Life Sci"},{"key":"pone.0330497.ref002","article-title":"Sepsis: pathophysiology and clinical management","volume":"353","author":"JE Gotts","year":"2016","journal-title":"BMJ"},{"issue":"20","key":"pone.0330497.ref003","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1161\/CIR.0000000000001184","article-title":"Cardiovascular-Kidney-Metabolic Health: A Presidential Advisory From the American Heart Association","volume":"148","author":"CE Ndumele","year":"2023","journal-title":"Circulation"},{"key":"pone.0330497.ref004","doi-asserted-by":"crossref","first-page":"1513212","DOI":"10.3389\/fcvm.2024.1513212","article-title":"Association of cardiovascular-kidney-metabolic index with all-cause mortality during hospitalization in critically ill patients: a retrospective cohort study from MIMIC IV2.2","volume":"11","author":"X Qu","year":"2024","journal-title":"Front Cardiovasc Med"},{"issue":"6","key":"pone.0330497.ref005","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1097\/SHK.0000000000002119","article-title":"Analysis Of The Relationship Between Early Serum Phosphate Levels And Short-Term Mortality In Septic Patients: A Retrospective Study Based On Mimic-IV","volume":"59","author":"X Xu","year":"2023","journal-title":"Shock"},{"issue":"6","key":"pone.0330497.ref006","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1213\/ANE.0000000000002077","article-title":"Analysis of hypo- and hyperphosphatemia in an intensive care unit cohort","volume":"124","author":"M Broman","year":"2017","journal-title":"Anesth Analg"},{"issue":"3","key":"pone.0330497.ref007","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1084\/jem.61.3.319","article-title":"Renal damage following the ingestion of a diet containing an excess of inorganic phosphate","volume":"61","author":"EM Mackay","year":"1935","journal-title":"J Exp Med"},{"issue":"2","key":"pone.0330497.ref008","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1172\/JCI100422","article-title":"Studies Of Calcium And Phosphorus Metabolism: XIV. The Relation of Acid-Base Balance to Phosphate Balance Following Ingestion of Phosphates","volume":"11","author":"WT Salter","year":"1932","journal-title":"J Clin Invest"},{"issue":"2","key":"pone.0330497.ref009","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1113\/jphysiol.1926.sp002349","article-title":"The r\u00f4le of the phosphates in carbohydrate metabolism in skeletal muscle: Part II. A comparison between the muscles of normal, fatigued and depancreatised animals","volume":"62","author":"F Beattie","year":"1926","journal-title":"J Physiol"},{"key":"pone.0330497.ref010","doi-asserted-by":"crossref","first-page":"1371000","DOI":"10.3389\/fcvm.2024.1371000","article-title":"Correlation between serum phosphate and all-cause mortality in critically ill patients with coronary heart disease accompanied by chronic kidney disease: a retrospective study using the MIMIC-IV database","volume":"11","author":"M He","year":"2024","journal-title":"Front Cardiovasc Med"},{"issue":"12","key":"pone.0330497.ref011","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.2215\/CJN.00810110","article-title":"Serum phosphate and mortality in patients with chronic kidney disease","volume":"5","author":"H Eddington","year":"2010","journal-title":"Clin J Am Soc Nephrol"},{"issue":"3","key":"pone.0330497.ref012","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1097\/TA.0000000000003271","article-title":"Association between the initial serum phosphate level and 30-day mortality in blunt trauma patients","volume":"91","author":"DW Kim","year":"2021","journal-title":"J Trauma Acute Care Surg"},{"issue":"5","key":"pone.0330497.ref013","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1177\/0885066618762753","article-title":"Impact of Serum Phosphate in Mechanically Ventilated Patients With Severe Sepsis and Septic Shock","volume":"35","author":"CJ Miller","year":"2020","journal-title":"J Intensive Care Med"},{"issue":"1","key":"pone.0330497.ref014","doi-asserted-by":"crossref","first-page":"21869","DOI":"10.1038\/s41598-023-49170-6","article-title":"Association of serum phosphate and changes in serum phosphate with 28-day mortality in septic shock from MIMIC-IV database","volume":"13","author":"W Nan","year":"2023","journal-title":"Sci Rep"},{"key":"pone.0330497.ref015","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.freeradbiomed.2020.01.024","article-title":"The pathogenesis of CKD complications; Attack of dysregulated iron and phosphate metabolism","volume":"157","author":"T Nakanishi","year":"2020","journal-title":"Free Radic Biol Med"},{"issue":"5","key":"pone.0330497.ref016","doi-asserted-by":"crossref","first-page":"76","DOI":"10.5527\/wjn.v10.i5.76","article-title":"Serum phosphate and chronic kidney and cardiovascular disease: Phosphorus potential implications in general population","volume":"10","author":"VD Raikou","year":"2021","journal-title":"World J Nephrol"},{"issue":"11","key":"pone.0330497.ref017","doi-asserted-by":"crossref","DOI":"10.3390\/jpm11111132","article-title":"Machine learning consensus clustering approach for patients with lactic acidosis in intensive care units","volume":"11","author":"P Pattharanitima","year":"2021","journal-title":"J Pers Med"},{"issue":"1","key":"pone.0330497.ref018","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s13054-025-05256-3","article-title":"Clinical subtypes in critically ill patients with sepsis: validation and parsimonious classifier model development","volume":"29","author":"RBE van Amstel","year":"2025","journal-title":"Crit Care"},{"key":"pone.0330497.ref019","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.freeradbiomed.2020.08.009","article-title":"Ferritinophagy-mediated ferroptosis is involved in sepsis-induced cardiac injury","volume":"160","author":"N Li","year":"2020","journal-title":"Free Radic Biol Med"},{"issue":"22","key":"pone.0330497.ref020","doi-asserted-by":"crossref","first-page":"662","DOI":"10.21037\/atm.2019.10.79","article-title":"Utilization of echocardiography during septic shock was associated with a decreased 28-day mortality: a propensity score-matched analysis of the MIMIC-III database","volume":"7","author":"P Lan","year":"2019","journal-title":"Ann Transl Med"},{"key":"pone.0330497.ref021","doi-asserted-by":"crossref","first-page":"10293","DOI":"10.2147\/IJGM.S345050","article-title":"Origin of Sepsis Associated with the Short-Term Mortality of Patients: A Retrospective Study Using the eICU Collaborative Research Database","volume":"14","author":"Q Li","year":"2021","journal-title":"Int J Gen Med"},{"key":"pone.0330497.ref022","doi-asserted-by":"crossref","first-page":"697884","DOI":"10.3389\/fmed.2021.697884","article-title":"ICU-Mortality in Old and Very Old Patients Suffering From Sepsis and Septic Shock","volume":"8","author":"RR Bruno","year":"2021","journal-title":"Front Med (Lausanne)"},{"issue":"1","key":"pone.0330497.ref023","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s12871-021-01239-3","article-title":"Association between normalized lactate load and mortality in patients with septic shock: an analysis of the MIMIC-III database","volume":"21","author":"H Chen","year":"2021","journal-title":"BMC Anesthesiol"},{"issue":"5","key":"pone.0330497.ref024","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1111\/ijlh.13925","article-title":"Red cell distribution width and in-hospital mortality in septic shock: A public database research","volume":"44","author":"Q Ding","year":"2022","journal-title":"Int J Lab Hematol"},{"key":"pone.0330497.ref025","doi-asserted-by":"crossref","first-page":"5595042","DOI":"10.1155\/2021\/5595042","article-title":"Prognostic Value of Blood Urea Nitrogen\/Creatinine Ratio for Septic Shock: An Analysis of the MIMIC-III Clinical Database","volume":"2021","author":"D Han","year":"2021","journal-title":"Biomed Res Int"},{"issue":"6","key":"pone.0330497.ref026","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1038\/s41569-020-00492-2","article-title":"Pathophysiology of sepsis-induced cardiomyopathy","volume":"18","author":"SM Hollenberg","year":"2021","journal-title":"Nat Rev Cardiol"},{"issue":"5","key":"pone.0330497.ref027","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1007\/s15010-024-02265-2","article-title":"Chronic kidney disease and risk of bloodstream infections and sepsis: a 17-year follow-up of the population-based Tr\u00f8ndelag Health Study in Norway","volume":"52","author":"KV Liyanarachi","year":"2024","journal-title":"Infection"},{"issue":"12","key":"pone.0330497.ref028","article-title":"Sepsis-Associated Acute Kidney Injury: Pathophysiology and Treatment Modalities","volume":"16","author":"MG Aguilar","year":"2024","journal-title":"Cureus"},{"issue":"1","key":"pone.0330497.ref029","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1186\/s13613-024-01377-0","article-title":"Organ crosstalk and dysfunction in sepsis","volume":"14","author":"A Borges","year":"2024","journal-title":"Ann Intensive Care"},{"issue":"5","key":"pone.0330497.ref030","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.cmet.2024.02.013","article-title":"Physiologic disruption and metabolic reprogramming in infection and sepsis","volume":"36","author":"K Willmann","year":"2024","journal-title":"Cell Metab"},{"issue":"1","key":"pone.0330497.ref031","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.injury.2022.10.024","article-title":"Association between admission serum phosphate and risk of acute kidney injury in critically ill patients with rhabdomyolysis: A retrospective study based on MIMIC-\u2162","volume":"54","author":"T Wen","year":"2023","journal-title":"Injury"},{"key":"pone.0330497.ref032","doi-asserted-by":"crossref","first-page":"728887","DOI":"10.3389\/fmed.2022.728887","article-title":"Effect of Serum Phosphate on the Prognosis of Septic Patients: A Retrospective Study Based on MIMIC-IV Database","volume":"9","author":"Z Li","year":"2022","journal-title":"Front Med (Lausanne)"},{"issue":"1","key":"pone.0330497.ref033","doi-asserted-by":"crossref","first-page":"300060519831896","DOI":"10.1177\/0300060519831896","article-title":"The relationship and threshold of serum phosphate with regard to the 28-day mortality risk in sepsis patients undergoing continuous renal replacement therapy","volume":"48","author":"H Wang","year":"2020","journal-title":"J Int Med Res"},{"issue":"13","key":"pone.0330497.ref034","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1056\/NEJM197709292971307","article-title":"Hyperphosphatemia in lactic acidosis","volume":"297","author":"LR O\u2019Connor","year":"1977","journal-title":"N Engl J Med"},{"key":"pone.0330497.ref035","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1177\/0004563214521399","article-title":"Phosphate homeostasis and disorders","volume":"51","author":"P Manghat","year":"2014","journal-title":"Ann Clin Biochem"},{"key":"pone.0330497.ref036","article-title":"Lactic Acidosis M","author":"S Baddam","year":"2025","journal-title":"StatPearls. Treasure Island (FL)"},{"issue":"12","key":"pone.0330497.ref037","article-title":"A non-linear positive relationship between serum phosphate and clinical outcomes in sepsis","volume":"8","author":"C Guo","year":"2022","journal-title":"Heliyon"},{"issue":"11","key":"pone.0330497.ref038","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.2215\/CJN.02610319","article-title":"Serum Phosphate and Microvascular Function in a Population-Based Cohort","volume":"14","author":"C Ginsberg","year":"2019","journal-title":"Clin J Am Soc Nephrol"},{"issue":"20","key":"pone.0330497.ref039","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1161\/CIR.0000000000001186","article-title":"A Synopsis of the Evidence for the Science and Clinical Management of Cardiovascular-Kidney-Metabolic (CKM) Syndrome: A Scientific Statement From the American Heart Association","volume":"148","author":"CE Ndumele","year":"2023","journal-title":"Circulation"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0330497","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T17:27:11Z","timestamp":1755797231000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0330497"}},"subtitle":[],"editor":[{"given":"Amirmohammad","family":"Khalaji","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,8,21]]},"references-count":39,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8,21]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0330497","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,21]]}}}