Prognosis prediction by urinary L-FABP in ICU patients admitted from the emergency department: a single-center, historical cohort study

Prognosis prediction by urinary L-FABP in ICU patients admitted from the emergency department: a single-center, historical cohort 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 Research Article Prognosis prediction by urinary L-FABP in ICU patients admitted from the emergency department: a single-center, historical cohort study Hirozumi Okuda, Hideki Asai, Koji Yamamoto, Keita Miyazaki, Hidetada Fukushima, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7161428/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Early risk stratification of critically ill patients is essential for optimizing intensive care unit (ICU) resource allocation and treatment decisions. Urinary liver-type fatty acid-binding protein (L-FABP) is a simple, noninvasive biomarker that may provide real-time information on organ dysfunction. However, its prognostic utility in patients admitted to the ICU from the emergency department remains unclear. Methods This single-center retrospective observational study included patients admitted to the ICU between December 2020 and August 2022. Urinary L-FABP concentrations were measured at ICU admission (T0) and 3 hours later (T3). The primary outcome was 28-day in-hospital mortality. Prognostic performance was assessed using receiver operating characteristic (ROC) curves and Cox proportional hazards models with inverse probability of treatment weighting (IPTW). Results were compared with APACHE II, SOFA scores, and lactate levels. Results A total of 118 patients (median age: 69 years [interquartile range (IQR) 51–82]; 72 males [61.0%]) were included in the final analysis. Urinary L-FABP at T3 showed the highest predictive performance for 28-day mortality (area under the curve [AUC] = 0.873), outperforming APACHE II (AUC = 0.801), SOFA (AUC = 0.753), and lactate (AUC = 0.734). Elevated L-FABP (T3) was independently associated with increased mortality (hazard ratio [HR] = 8.60, 95% confidence interval [CI]: 1.02–72.64, P = 0.047). The T3/T0 ratio showed only modest predictive value (AUC = 0.623). Conclusions Urinary L-FABP levels measured 3 hours after ICU admission were a strong and independent predictor of short-term mortality. Its simplicity and bedside applicability suggest its potential utility not only in ICUs but also in emergency departments and triage decision-making. Liver-type fatty acid-binding protein (L-FABP) Prognosis prediction Intensive Care Unit (ICU) Emergency department admission Figures Figure 1 Figure 2 Figure 3 Background Intensive Care Units (ICUs) provide critical care for patients with life-threatening conditions, and early risk stratification is essential in guiding treatment and optimizing resource allocation. Conventional scoring systems, such as the Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA), are widely used for this purpose [ 1 – 5 ]. While these tools are valuable when appropriately applied, the early phase of ICU admission is often marked by urgency and limited time, making it challenging for clinicians to rely solely on complex and time-consuming scoring systems. In many countries, including Japan, the number of board-certified intensivists is limited, and ICU care is frequently provided in open ICU models [ 6 , 7 ]. In these settings, critically ill patients are managed by various non-intensivist physicians, such as emergency physicians, internists, surgeons, and anesthesiologists, who may have limited time for continuous patient assessment. Therefore, a simple, rapid, and objective prognostic biomarker is highly desirable, especially during the early phase of ICU admission, when clinical decisions must be made quickly under high-pressure conditions. Liver-type fatty acid-binding protein (L-FABP) is a urinary biomarker for detecting acute kidney injury and intestinal ischemia. It is non-invasively measurable and has a short half-life, and reflects systemic inflammation and organ dysfunction in near real-time. Although emerging evidence supports its prognostic value in critically ill patients, little is known about its utility in patients admitted to the ICU from the emergency department. Furthermore, most prior studies have focused on medical ICU patients with chronic conditions. In contrast, our study uniquely evaluates emergency ICU admissions primarily due to acute external causes such as trauma and poisoning, a population that has been underrepresented in L-FABP research. This study aimed to evaluate the prognostic value of urinary L-FABP concentrations measured at ICU admission and 3 hours post-admission, and to compare its performance with that of conventional prognostic indicators such as APACHE II, SOFA scores, and lactate levels. Methods Study design and the primary outcome This single-center, historical cohort study was conducted at the Advanced Emergency and Critical Care Center of Nara Medical University Hospital from December 1, 2020, to August 31, 2022. The primary outcome was all-cause mortality within 28 days of ICU admission. The study protocol was approved by the Ethics Committee of Nara Medical University Hospital (Approval No. 1798) and conducted in accordance with the principles of the Declaration of Helsinki. Inclusion and exclusion criteria All patients admitted to the Intensive Care Unit (ICU) of Nara Medical University Hospital during the study period were screened for eligibility. To avoid collecting specimens solely for research purposes, only patients with a urinary catheter and an indwelling arterial line, both of which were placed as part of standard clinical management, were included. The exclusion criteria were: (1) age < 18 years and (2) known anuria before ICU admission due to chronic kidney disease or maintenance dialysis, and confirmed or suspected COVID-19 infection ( excluded for biosafety reasons related to specimen collection, storage, or handling). Measurement of urinary L-FABP and other variables Urine samples were collected at ICU admission (T0) and 3 hours later (T3). Each sample was placed in a sterile plastic container immediately after collection and stored at − 80°C. Urinary L-FABP concentrations were measured using an enzyme-linked immunosorbent assay (ELISA) kit (L-FABP; CMIC Holdings Co., Ltd., Tokyo, Japan) in batch analyses outsourced to an external laboratory. Hourly urine output was monitored, and all samples used for analysis were confirmed to contain urine excreted within 1 hour of collection. Sample collection was performed by bedside nurses. Clinical data were extracted from electronic medical records and included age, sex, height, weight, comorbidities, laboratory test results, arterial blood gas findings, APACHE II score, SOFA scores, and primary diagnosis. Study outcomes The primary outcome was all-cause mortality within 28 days of ICU admission and its association with urinary L-FABP concentrations measured at T0 and T3. Receiver operating characteristic (ROC) curves were generated for L-FABP levels at both time points, and the area under the curve (AUC) was calculated. These values were compared with conventional prognostic indicators, including the APACHE II, SOFA score, and arterial lactate concentration. Optimal cutoff values for each marker were determined using the Youden Index, and the potential prognostic utility of these markers was assessed. The secondary outcome was the prognostic value of changes in urinary L-FABP levels over time, evaluated using the ratio (T3/T0) of the L-FABP concentration between the two measurements. Statistical Analysis Continuous variables were expressed as medians with interquartile ranges (IQRs), and categorical variables as counts and percentages. Group comparisons for continuous variables were performed using the Mann–Whitney U test. The prognostic performance of each marker was evaluated using ROC curve analysis, and AUC values were calculated for each predictor. The Youden index was used to determine optimal cut-off values. Kaplan–Meier survival curves were generated to compare 28-day survival between groups stratified by the cutoff value, and statistical significance was assessed using the log-rank test. To adjust for potential confounders, a Cox proportional hazards model was constructed using inverse probability of treatment weighting (IPTW) based on propensity scores for age, gender, weight, albumin level, ICU admission time, lactate level, APACHE II scores, and SOFA scores. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to estimate the association between L-FABP levels and 28-day mortality. All statistical analyses were performed using R software (version 4.3.3). A two-tailed p-value of < 0.05 was considered statistically significant. Although a formal sample size calculation was not performed due to the retrospective design, we conducted a post-hoc power analysis. Based on the observed effect size (HR = 8.60), sample size (n = 118), and α = 0.05, the estimated power was approximately 82%. Results From December 1, 2020, to August 31, 2022, 774 patients were admitted to the ICU of the Advanced Emergency and Critical Care Center at Nara Medical University Hospital. Among them, 138 patients who met the inclusion criteria and provided consent were enrolled after excluding those with confirmed or suspected COVID-19 infection. However, 20 cases were excluded due to missing data caused by poor specimen quality (poor specimen storage, no urine available for collection, or difficulty in collection related to early death or emergency surgery). Therefore, 118 patients were included in the final analysis. During the 28-day observation period, 101 patients survived, while 17 died (Fig. 1 ). Compared with survivors, non-survivors had significantly lower body weight, a lower proportion of external causes of disease, lower albumin levels, and shorter ICU admission times (Table 1 ). Clinically, non-survivors had significantly higher APACHE II scores, SOFA scores, and arterial lactate concentrations. Additionally, urinary L-FABP concentrations were significantly higher in non-survivors than in survivors at T0 (median 1006.9 vs 24.23 ng/ml, p < 0.001) and T3 (2921.5 vs. 20.69 ng/ml, p < 0.001). [Figure 1 near here] Table 1 Basic and clinical parameters by survival status Parameters, median [IQR] Survival group n = 101 Death group n = 17 p Physical data Age (years) 65[48–80] 79[75–83] < 0.01 Male, n(%) 61(60.4) 11(64.7) 0.94 Height (cm) 161[154.3–168] 156.5[151–161] 0.09 Body weight(kg) 60.1[50-68.5] 52.6[40-57.8] 0.02 Laboratory data WBC (/µL) 11200[8200–16300] 8900[7500–12000] 0.35 Hb (g/dL) 12.2[10.6–13.8] 12[9.9–12.8] 0.30 CRP (mg/dL) 0.14[0.03–1.55] 1.09[0.18–5.33] 0.07 ALB (g/dL) 3.8[3.3–4.2] 3.2[2.8–3.6] < 0.01 Cre (mg/dL) 0.95[0.73–1.45] 1.3[0.89–1.45] 0.17 Lac (mg/dL) 2.1[1.2–3.5] 5.4[2.2–12.9] < 0.01 L-FABP (at admission) (ng/mL) 24.23[5.95-191.04] 1006.9[134.41–7381] < 0.01 L-FABP (3hours later) (ng/mL) 20.69[7.38-153.96] 2921.5[519.02-6104.5] < 0.01 Scoring data APACHE II score 19[14–27] 34[28–40] < 0.01 SOFA score 7[ 3 – 10 ] 11[ 9 – 13 ] < 0.01 Others External causes, n(%) 65(64.4) 5(29.4) 0.01 Time to ICU admission (min) 113[86–203] 93[82–107] 0.03 WBC: White blood cell count; Hb: Hemoglobin; CRP: C-reactive protein; ALB: Albumin; Cre: Creatinine; Lac: Lactate; L-FABP: Liver-type fatty acid-binding protein; APACHE II: Acute Physiology and Chronic Health Evaluation II; SOFA: Sequential Organ Failure Assessment; ICU: Intensive Care Unit ROC curve analysis for 28-day mortality (Fig. 2 ) showed that urinary L-FABP at T3 had the highest AUC value (0.8733) compared to L-FABP at T0 (0.7851), APACHE Ⅱ (0.8008), SOFA (0.7530), and arterial lactate (0.7338) [Additional File 1]. The optimal cutoff value of L-FABP (T3) determined using the Youden index was 90.815. [Figure 2 near here] Based on the cutoff value (T3), the patients were divided into high (H) and low (L) L-FABP groups. The H group consisted of 44 patients (29 survivors and 15 non-survivors), while the L group included 74 patients (73 survivors and 1 non-survivor). A Kaplan-Meier survival analysis showed a significant difference in 28-day mortality between the groups (log-rank p < 0.01) (Fig. 3 ). [Figure 3 near here] The crude HR for mortality within 28 days after ICU admission in the High L-FABP group was significantly higher than in the Low L-FABP group (HR: 32.35, 95% CI: 4.29–244.0, p < 0.001). After adjusting for confounders using IPTW based on propensity scores for age, gender, weight, albumin level, ICU admission time, lactate level, APACHE II, and SOFA scores, the adjusted HR remained significant (HR: 8.60, 95% CI: 1.02–72.64, P = 0.047) (Table 2 ). Table 2 Hazard Ratio for 28-Day Survival by Urinary L-FABP at 3 Hours after ICU Admission Low L-FABP* (n = 74) High L-FABP† (n = 44) p-value Crude model, HR [95% CI] 1 (reference) 32.35 [4.29–244] < 0.01 IPTW adjusted, HR [95% CI] 1 (reference) 8.60 [1.02–72.64] 0.047 * L-FABP (T3) < 90.815, † L-FABP (T3) ≧ 90.815 L-FABP: Urinary Liver-type fatty acid-binding protein; ICU: Intensive Care Unit; HR: Hazard Ratio; CI: Confidence Interval; IPTW: Inverse Probability of Treatment Weighting In the secondary analysis, the L-FABP ratio (T3/T0) was evaluated using logistic regression to predict 28-day mortality. The Cox proportional hazard ratio was 1.52 (CI: 1.08–2.25, p = 0.0213), and the ROC-AUC (T3/T0) was 0.623 [Additional File 2]. Discussion This study demonstrated that urinary L-FABP concentration, particularly when measured at T3, serves as a strong and independent predictor of 28-day in-hospital mortality in critically ill patients. Among all evaluated indicators, L-FABP (T3) showed the highest area under the ROC curve (AUC = 0.873), outperforming APACHE II (AUC = 0.801), SOFA (AUC = 0.753), and arterial lactate (AUC = 0.734). Furthermore, elevated L-FABP level at T3 was significantly associated with increased mortality in the IPTW-adjusted Cox proportional hazards model (HR = 8.60, 95% CI: 1.02–72.64, p = 0.047), suggesting that this marker offers strong prognostic value even after adjusting for confounders. In contrast, L-FABP levels measured at T0 had a lower predictive performance (AUC = 0.785), indicating that initial levels may not fully reflect the severity of illness or impending physiological deterioration. Moreover, the change in L-FABP levels between T0 and T3, represented by the T3/T0 ratio, demonstrated only modest predictive value (AUC = 0.623; HR = 1.008, 95% CI: 1.006–1.011, p < 0.05), suggesting that the absolute concentration at T3 provides more reliable prognostic information. One possible explanation is that the T3 value reflects not only baseline disease burden but also the patient’s physiological response to early ICU interventions such as fluid resuscitation, mechanical ventilation, or vasopressor support. Previous studies have reported that semiquantitative changes in urinary L-FABP levels within the first 6 hours of ICU admission are related to outcomes; however, the optimal timing and method for evaluating these dynamics remain unclear. Our findings suggest that a single measurement at T3 may offer clinically useful and practical prognostic information, potentially offering an efficient alternative to serial monitoring. Biologically, L-FABP is primarily synthesized in hepatocytes, released into the bloodstream, and subsequently excreted in the urine under conditions of oxidative stress and tissue hypoxia. With a short plasma half-life of approximately 11 minutes [ 8 ], L-FABP reflects dynamic physiological changes and has been recognized as a sensitive marker of acute kidney injury (AKI) [ 9 – 11 ], intestinal ischemia [ 12 ], and systemic inflammatory states [ 13 ]. Unlike other markers that require longer integration periods, L-FABP offers near-real-time insight into cellular injury, making it especially suitable for critical care settings, where patient conditions can deteriorate rapidly. Previous studies have demonstrated that elevated urinary L-FABP levels are associated with both short- and long-term mortality in ICU populations [ 14 – 16 ]. However, most of these studies focused on medical ICU patients or those with chronic comorbidities. In contrast, our study primarily included patients admitted via the emergency department for acute external causes such as trauma. This patient population likely had fewer underlying chronic conditions, thereby reducing confounding and highlighting the role of L-FABP as a marker of acute systemic physiological stress rather than chronic disease burden. Given the heterogeneous and rapidly evolving nature of emergency ICU admissions, biomarkers such as L-FABP, capable of capturing real-time organ dysfunction, may offer particular value in this clinical context. These findings are particularly relevant in open ICU settings, where intensivists may not be consistently available, and critically ill patients are often managed by physicians from diverse specialties such as emergency medicine, internal medicine, surgery, and anesthesiology. In these environments, frequently constrained by time and staffing, simple, rapid, and bedside-accessible biomarkers, such as urinary L-FABP, can support timely risk assessment and facilitate clinical decision-making. Previous studies have shown that 24/7 in-house ICU intensivist models, as seen in high-acuity, high-volume centers where intensive care specialists provide care on a full-time basis, are associated with better patient outcomes compared to ICUs without dedicated intensivist staffing [ 17 ]. These findings suggest that intensivist-led care improves outcomes, likely through the consistent application of evidence-based practices. However, many healthcare institutions worldwide operate under open ICU systems, where access to intensivists is limited. In such contexts, objective and easily interpretable biomarkers such as L-FABP may help bridge the gap by providing real-time assessments of illness severity. Moreover, unlike conventional scoring systems such as APACHE II, which require the integration of multiple clinical variables and time-consuming calculations, urinary L-FABP can be measured from a single-spot urine sample. This noninvasive, rapid, and widely deployable test offers potential utility not only in the ICU but also in emergency departments, general wards, and prehospital settings. By offering a real-time snapshot of a patient’s physiological burden, L-FABP may serve as a triage tool to determine ICU admission or as an objective criterion for patient transfer to higher-level critical care facilities. Its simplicity and portability make it especially attractive for use in resource-limited settings and during early phases of care where time-sensitive decisions are crucial. Future prospective, multicenter studies involving heterogeneous ICU populations, as well as interventional trials evaluating L-FABP-guided triage protocols, are warranted to validate and expand upon these findings. Limitations This study has some limitations. First, it was conducted at a single center, which may limit the generalizability of the findings to other institutions or healthcare systems with different ICU structures, staffing models, and patient populations. Second, the sample size was relatively small (n = 118), partly due to the exclusion of patients with confirmed or suspected COVID-19 during the study period. To ensure safety and prevent infection risk during specimen collection and handling, patients with fever or respiratory symptoms were excluded unless COVID-19 was definitively ruled out. This may have introduced selection bias and reduced the diversity of the study population. Third, most enrolled patients were admitted from the emergency department due to external causes such as trauma, burns, or poisoning. Consequently, patients with endogenous causes, such as sepsis or chronic disease exacerbations, were underrepresented. This imbalance may limit the applicability of our findings to other ICU populations, particularly those dominated by medical rather than surgical or trauma cases. Finally, although we used IPTW to adjust for measured confounders, the observational design leaves room for residual confounding from unmeasured variables. Further multicenter, prospective studies involving larger and more heterogeneous populations are warranted to confirm the prognostic utility of urinary L-FABP and to determine its generalizability across various ICU settings. Conclusions This study demonstrated that urinary L-FABP concentration measured 3 hours after ICU admission is a strong predictor of 28-day mortality, outperforming conventional scoring systems such as APACHE II and SOFA. Given its simplicity, non-invasiveness, and rapid availability, L-FABP may serve as a practical tool for early risk stratification in critically ill patients. Further prospective studies are warranted to validate its broader clinical applicability across different ICU settings. Abbreviations APACHE II: acute physiology and chronic health evaluation II AUC: area under the curve COVID-19: coronavirus disease 2019 HR: hazard ratio ICU: intensive care unit IPTW: inverse probability of treatment weighting IQR: interquartile range Lac: lactate L-FABP: liver-type fatty acid-binding protein ROC: receiver operating characteristic SOFA: sequential organ failure assessment Declarations Ethics approval and consent to participate : This single-center, retrospective, observational study was conducted at the Advanced Emergency and Critical Care Center of Nara Medical University Hospital. This study adhered to the principles of the Declaration of Helsinki and was approved by the Nara Medical University Hospital Ethics Committee (Approval No. 1798). Written informed consent was obtained from all participants. In cases where the patient was unable to provide consent, written consent was obtained from a legally authorized representative, such as an adult family member living with the patient or a relative within the third degree of kinship. Consent for publication : Not applicable. Availability of data and materials : The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests : The authors declare that they have no competing interests. Funding : Not applicable. Authors' contributions : H.O. and H.A. contributed to the conception and design of the study. H.O. and K.S. performed the data analysis. H.O. conducted the literature review. H.O., H.A., K.M., K.Y., and H.F. were responsible for data acquisition. All authors contributed to data interpretation. H.O. drafted the manuscript. All authors read and approved the final manuscript. Acknowledgments : The authors gratefully acknowledge CMIC Holdings Co., Ltd. (Tokyo, Japan) for performing urinary L-FABP measurements on the patient samples at no cost. The company had no role in the design, execution, analysis, or interpretation of this study. We would like to thank Editage (www.editage.jp) for English language editing. References Desai N, Gross J. Scoring systems in the critically ill: uses, cautions, and future directions. BJA Educ. 2019;19:212–8. Rahmatinejad Z, Hoseini B, Rahmatinejad F, Abu-Hanna A, Bergquist R, Pourmand A, et al. Internal validation of the predictive performance of models based on three ED and ICU scoring systems to predict inhospital mortality for intensive care patients referred from the emergency department. Biomed Res Int. 2022;2022:3964063. Moreno-Torres V, Royuela A, Múñez E, Ortega A, Gutierrez Á, Mills P, et al. Better prognostic ability of NEWS2, SOFA and SAPS-II in septic patients. Med Clin (Barc). 2022;159:224–9. Naqvi IH, Mahmood K, Ziaullaha S, Kashif SM, Sharif A. 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Ren Fail. 2021;43:1041–8. Naruse H, Ishii J, Takahashi H, Kitagawa F, Nishimura H, Kawai H, et al. Urinary liver-type fatty-acid-binding protein predicts long-term adverse outcomes in medical cardiac intensive care units. J Clin Med. 2020;9:360. Ha EC, Yang HN, Jo S-K, Cho W-Y, Kim H-K. The role of urinary liver-type fatty acid-binding protein in critically ill patients. J Korean Med Sci. 2013;28:100–5. Masud F, Lam TYC, Fatima S. Is 24/7 in-house intensivist staffing necessary in the intensive care unit? Methodist Debakey Cardiovasc J. 2018;14:134–40. Additional Declarations No competing interests reported. Supplementary Files AdditionalFile1.docx Additional File 1 (.docx) ROC comparison among each model This file provides detailed results of the receiver operating characteristic (ROC) curve analysis comparing the prognostic performance of urinary L-FABP at T0 and T3 with conventional scoring systems (APACHE II, SOFA) and arterial lactate levels in predicting 28-day mortality. AdditionalFile2.docx Additional File 2 (.docx) ROC curve of L-FABP ratio (T3/T0) for 28-day mortality prediction This file presents the receiver operating characteristic (ROC) curve analysis of the urinary L-FABP ratio (T3/T0) for predicting 28-day mortality. The area under the curve (AUC) was 0.623, indicating limited discriminative ability compared to absolute L-FABP values. Cite Share Download PDF Status: Posted Version 1 posted 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. 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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-7161428","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":491368909,"identity":"8a362542-eeea-41a5-b979-189d56a9b5fd","order_by":0,"name":"Hirozumi Okuda","email":"data:image/png;base64,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","orcid":"","institution":"Nara Medical University","correspondingAuthor":true,"prefix":"","firstName":"Hirozumi","middleName":"","lastName":"Okuda","suffix":""},{"id":491368910,"identity":"d48a8f1e-4380-4b92-9461-c896261e2600","order_by":1,"name":"Hideki Asai","email":"","orcid":"","institution":"Nara Medical University","correspondingAuthor":false,"prefix":"","firstName":"Hideki","middleName":"","lastName":"Asai","suffix":""},{"id":491368911,"identity":"b9644b79-b9f3-46e1-b21b-1101a93cea85","order_by":2,"name":"Koji Yamamoto","email":"","orcid":"","institution":"Nara Medical University","correspondingAuthor":false,"prefix":"","firstName":"Koji","middleName":"","lastName":"Yamamoto","suffix":""},{"id":491368912,"identity":"372d495f-2799-48fb-9fa4-dab196dcb7ef","order_by":3,"name":"Keita Miyazaki","email":"","orcid":"","institution":"Nara Medical University","correspondingAuthor":false,"prefix":"","firstName":"Keita","middleName":"","lastName":"Miyazaki","suffix":""},{"id":491368913,"identity":"436f1453-b0d6-4eb7-beab-e8a990fe70d2","order_by":4,"name":"Hidetada Fukushima","email":"","orcid":"","institution":"Nara Medical University","correspondingAuthor":false,"prefix":"","firstName":"Hidetada","middleName":"","lastName":"Fukushima","suffix":""},{"id":491368914,"identity":"c49ee6af-132a-4952-b1ed-794ce4d965c9","order_by":5,"name":"Keigo Saeki","email":"","orcid":"","institution":"Nara Medical University","correspondingAuthor":false,"prefix":"","firstName":"Keigo","middleName":"","lastName":"Saeki","suffix":""}],"badges":[],"createdAt":"2025-07-19 03:08:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7161428/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7161428/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":87827961,"identity":"9159900b-d89d-45ec-ba10-751e1163508d","added_by":"auto","created_at":"2025-07-29 11:59:19","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":9755365,"visible":true,"origin":"","legend":"\u003cp\u003ePatient flow chart of the study\u003c/p\u003e","description":"","filename":"Fig.1.png","url":"https://assets-eu.researchsquare.com/files/rs-7161428/v1/3a8ac6d7b79beab0fec00080.png"},{"id":87826147,"identity":"b649226b-2176-44db-b439-cd9260a20023","added_by":"auto","created_at":"2025-07-29 11:51:19","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1377618,"visible":true,"origin":"","legend":"\u003cp\u003eROC curve for mortality within 28-day prediction by urinary L-FABP at 3 hours after ICU admission. AUC: area under the curve; ICU: intensive care unit; L-FABP: liver-type fatty acid-binding protein; ROC: receiver operating characteristic\u003c/p\u003e","description":"","filename":"Fig.2.png","url":"https://assets-eu.researchsquare.com/files/rs-7161428/v1/f88a8868abbf92d321844a65.png"},{"id":87827962,"identity":"1d9ae1ca-d69d-4e69-8c46-ea65a4b8d0f8","added_by":"auto","created_at":"2025-07-29 11:59:19","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1124643,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier analysis about Survival for 28 days by urinary L-FABP at 3 hours after ICU admission. ICU: intensive care unit; L-FABP: liver-type fatty acid-binding protein\u003c/p\u003e","description":"","filename":"Fig.3.png","url":"https://assets-eu.researchsquare.com/files/rs-7161428/v1/b8ef5961c7e8f9b40807f36c.png"},{"id":88085946,"identity":"69d2e08c-63c1-4bd3-a85d-4d6b9e189d11","added_by":"auto","created_at":"2025-08-01 09:17:14","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":8701128,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7161428/v1/28ae3d6b-2d72-42b2-a902-02f8730dedf4.pdf"},{"id":87826150,"identity":"00610064-4c3f-446e-9561-58576e0cf32e","added_by":"auto","created_at":"2025-07-29 11:51:19","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":229390,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAdditional File 1 (.docx)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eROC comparison among each model\u003c/p\u003e\n\u003cp\u003eThis file provides detailed results of the receiver operating characteristic (ROC) curve analysis comparing the prognostic performance of urinary L-FABP at T0 and T3 with conventional scoring systems (APACHE II, SOFA) and arterial lactate levels in predicting 28-day mortality.\u003c/p\u003e","description":"","filename":"AdditionalFile1.docx","url":"https://assets-eu.researchsquare.com/files/rs-7161428/v1/011dcb769ffe384f15ca74f7.docx"},{"id":87827959,"identity":"eba4f4af-8618-4913-8bc0-ef570e608fc6","added_by":"auto","created_at":"2025-07-29 11:59:19","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":20188,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAdditional File 2 (.docx)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eROC curve of L-FABP ratio (T3/T0) for 28-day mortality prediction\u003c/p\u003e\n\u003cp\u003eThis file presents the receiver operating characteristic (ROC) curve analysis of the urinary L-FABP ratio (T3/T0) for predicting 28-day mortality. The area under the curve (AUC) was 0.623, indicating limited discriminative ability compared to absolute L-FABP values.\u003c/p\u003e","description":"","filename":"AdditionalFile2.docx","url":"https://assets-eu.researchsquare.com/files/rs-7161428/v1/8c530f1b2f4825e6ff68ce8d.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Prognosis prediction by urinary L-FABP in ICU patients admitted from the emergency department: a single-center, historical cohort study","fulltext":[{"header":"Background","content":"\u003cp\u003eIntensive Care Units (ICUs) provide critical care for patients with life-threatening conditions, and early risk stratification is essential in guiding treatment and optimizing resource allocation. Conventional scoring systems, such as the Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA), are widely used for this purpose [\u003cspan additionalcitationids=\"CR2 CR3 CR4\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e–\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. While these tools are valuable when appropriately applied, the early phase of ICU admission is often marked by urgency and limited time, making it challenging for clinicians to rely solely on complex and time-consuming scoring systems.\u003c/p\u003e\u003cp\u003eIn many countries, including Japan, the number of board-certified intensivists is limited, and ICU care is frequently provided in open ICU models [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In these settings, critically ill patients are managed by various non-intensivist physicians, such as emergency physicians, internists, surgeons, and anesthesiologists, who may have limited time for continuous patient assessment. Therefore, a simple, rapid, and objective prognostic biomarker is highly desirable, especially during the early phase of ICU admission, when clinical decisions must be made quickly under high-pressure conditions.\u003c/p\u003e\u003cp\u003eLiver-type fatty acid-binding protein (L-FABP) is a urinary biomarker for detecting acute kidney injury and intestinal ischemia. It is non-invasively measurable and has a short half-life, and reflects systemic inflammation and organ dysfunction in near real-time. Although emerging evidence supports its prognostic value in critically ill patients, little is known about its utility in patients admitted to the ICU from the emergency department. Furthermore, most prior studies have focused on medical ICU patients with chronic conditions. In contrast, our study uniquely evaluates emergency ICU admissions primarily due to acute external causes such as trauma and poisoning, a population that has been underrepresented in L-FABP research.\u003c/p\u003e\u003cp\u003eThis study aimed to evaluate the prognostic value of urinary L-FABP concentrations measured at ICU admission and 3 hours post-admission, and to compare its performance with that of conventional prognostic indicators such as APACHE II, SOFA scores, and lactate levels.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cb\u003eStudy design and the primary outcome\u003c/b\u003e\u003c/p\u003e\u003cp\u003e This single-center, historical cohort study was conducted at the Advanced Emergency and Critical Care Center of Nara Medical University Hospital from December 1, 2020, to August 31, 2022. The primary outcome was all-cause mortality within 28 days of ICU admission. The study protocol was approved by the Ethics Committee of Nara Medical University Hospital (Approval No. 1798) and conducted in accordance with the principles of the Declaration of Helsinki.\u003c/p\u003e\u003cp\u003e\u003cb\u003eInclusion and exclusion criteria\u003c/b\u003e\u003c/p\u003e\u003cp\u003eAll patients admitted to the Intensive Care Unit (ICU) of Nara Medical University Hospital during the study period were screened for eligibility. To avoid collecting specimens solely for research purposes, only patients with a urinary catheter and an indwelling arterial line, both of which were placed as part of standard clinical management, were included. The exclusion criteria were: (1) age \u0026lt; 18 years and (2) known anuria before ICU admission due to chronic kidney disease or maintenance dialysis, and confirmed or suspected COVID-19 infection ( excluded for biosafety reasons related to specimen collection, storage, or handling).\u003c/p\u003e\u003cp\u003e\u003cb\u003eMeasurement of urinary L-FABP and other variables\u003c/b\u003e\u003c/p\u003e\u003cp\u003eUrine samples were collected at ICU admission (T0) and 3 hours later (T3). Each sample was placed in a sterile plastic container immediately after collection and stored at − 80°C. Urinary L-FABP concentrations were measured using an enzyme-linked immunosorbent assay (ELISA) kit (L-FABP; CMIC Holdings Co., Ltd., Tokyo, Japan) in batch analyses outsourced to an external laboratory. Hourly urine output was monitored, and all samples used for analysis were confirmed to contain urine excreted within 1 hour of collection. Sample collection was performed by bedside nurses.\u003c/p\u003e\u003cp\u003eClinical data were extracted from electronic medical records and included age, sex, height, weight, comorbidities, laboratory test results, arterial blood gas findings, APACHE II score, SOFA scores, and primary diagnosis.\u003c/p\u003e\u003cp\u003e\u003cb\u003eStudy outcomes\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe primary outcome was all-cause mortality within 28 days of ICU admission and its association with urinary L-FABP concentrations measured at T0 and T3.\u003c/p\u003e\u003cp\u003eReceiver operating characteristic (ROC) curves were generated for L-FABP levels at both time points, and the area under the curve (AUC) was calculated. These values were compared with conventional prognostic indicators, including the APACHE II, SOFA score, and arterial lactate concentration. Optimal cutoff values for each marker were determined using the Youden Index, and the potential prognostic utility of these markers was assessed.\u003c/p\u003e\u003cp\u003eThe secondary outcome was the prognostic value of changes in urinary L-FABP levels over time, evaluated using the ratio (T3/T0) of the L-FABP concentration between the two measurements.\u003c/p\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eContinuous variables were expressed as medians with interquartile ranges (IQRs), and categorical variables as counts and percentages. Group comparisons for continuous variables were performed using the Mann–Whitney U test. The prognostic performance of each marker was evaluated using ROC curve analysis, and AUC values were calculated for each predictor. The Youden index was used to determine optimal cut-off values.\u003c/p\u003e\u003cp\u003eKaplan–Meier survival curves were generated to compare 28-day survival between groups stratified by the cutoff value, and statistical significance was assessed using the log-rank test. To adjust for potential confounders, a Cox proportional hazards model was constructed using inverse probability of treatment weighting (IPTW) based on propensity scores for age, gender, weight, albumin level, ICU admission time, lactate level, APACHE II scores, and SOFA scores. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to estimate the association between L-FABP levels and 28-day mortality.\u003c/p\u003e\u003cp\u003eAll statistical analyses were performed using R software (version 4.3.3). A two-tailed p-value of \u0026lt; 0.05 was considered statistically significant. Although a formal sample size calculation was not performed due to the retrospective design, we conducted a post-hoc power analysis. Based on the observed effect size (HR = 8.60), sample size (n = 118), and α = 0.05, the estimated power was approximately 82%.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eFrom December 1, 2020, to August 31, 2022, 774 patients were admitted to the ICU of the Advanced Emergency and Critical Care Center at Nara Medical University Hospital. Among them, 138 patients who met the inclusion criteria and provided consent were enrolled after excluding those with confirmed or suspected COVID-19 infection. However, 20 cases were excluded due to missing data caused by poor specimen quality (poor specimen storage, no urine available for collection, or difficulty in collection related to early death or emergency surgery). Therefore, 118 patients were included in the final analysis.\u003c/p\u003e\u003cp\u003eDuring the 28-day observation period, 101 patients survived, while 17 died (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Compared with survivors, non-survivors had significantly lower body weight, a lower proportion of external causes of disease, lower albumin levels, and shorter ICU admission times (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Clinically, non-survivors had significantly higher APACHE II scores, SOFA scores, and arterial lactate concentrations. Additionally, urinary L-FABP concentrations were significantly higher in non-survivors than in survivors at T0 (median 1006.9 vs 24.23 ng/ml, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and T3 (2921.5 vs. 20.69 ng/ml, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e[Figure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e near here]\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBasic and clinical parameters by survival status\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eParameters, median [IQR]\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSurvival group\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;101\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eDeath group\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;17\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePhysical data\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (years)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e65[48\u0026ndash;80]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e79[75\u0026ndash;83]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e61(60.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11(64.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.94\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHeight (cm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e161[154.3\u0026ndash;168]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e156.5[151\u0026ndash;161]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.09\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBody weight(kg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e60.1[50-68.5]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e52.6[40-57.8]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.02\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLaboratory data\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWBC (/\u0026micro;L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11200[8200\u0026ndash;16300]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8900[7500\u0026ndash;12000]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.35\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHb (g/dL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12.2[10.6\u0026ndash;13.8]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12[9.9\u0026ndash;12.8]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.30\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCRP (mg/dL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.14[0.03\u0026ndash;1.55]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.09[0.18\u0026ndash;5.33]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.07\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eALB (g/dL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.8[3.3\u0026ndash;4.2]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.2[2.8\u0026ndash;3.6]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCre (mg/dL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.95[0.73\u0026ndash;1.45]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.3[0.89\u0026ndash;1.45]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.17\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLac (mg/dL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.1[1.2\u0026ndash;3.5]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5.4[2.2\u0026ndash;12.9]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eL-FABP (at admission) (ng/mL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24.23[5.95-191.04]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1006.9[134.41\u0026ndash;7381]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eL-FABP (3hours later) (ng/mL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20.69[7.38-153.96]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2921.5[519.02-6104.5]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eScoring data\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAPACHE II score\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19[14\u0026ndash;27]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e34[28\u0026ndash;40]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSOFA score\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7[\u003cspan additionalcitationids=\"CR4 CR5 CR6 CR7 CR8 CR9\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11[\u003cspan additionalcitationids=\"CR10 CR11 CR12\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eOthers\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eExternal causes, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e65(64.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5(29.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTime to ICU admission\u003c/p\u003e\u003cp\u003e(min)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e113[86\u0026ndash;203]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e93[82\u0026ndash;107]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.03\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eWBC: White blood cell count; Hb: Hemoglobin; CRP: C-reactive protein; ALB: Albumin; Cre: Creatinine; Lac: Lactate; L-FABP: Liver-type fatty acid-binding protein; APACHE II: Acute Physiology and Chronic Health Evaluation II; SOFA: Sequential Organ Failure Assessment; ICU: Intensive Care Unit\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eROC curve analysis for 28-day mortality (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) showed that urinary L-FABP at T3 had the highest AUC value (0.8733) compared to L-FABP at T0 (0.7851), APACHE Ⅱ (0.8008), SOFA (0.7530), and arterial lactate (0.7338) [Additional File 1]. The optimal cutoff value of L-FABP (T3) determined using the Youden index was 90.815.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e[Figure \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e near here]\u003c/p\u003e\u003cp\u003eBased on the cutoff value (T3), the patients were divided into high (H) and low (L) L-FABP groups. The H group consisted of 44 patients (29 survivors and 15 non-survivors), while the L group included 74 patients (73 survivors and 1 non-survivor). A Kaplan-Meier survival analysis showed a significant difference in 28-day mortality between the groups (log-rank p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e[Figure \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e near here]\u003c/p\u003e\u003cp\u003eThe crude HR for mortality within 28 days after ICU admission in the High L-FABP group was significantly higher than in the Low L-FABP group (HR: 32.35, 95% CI: 4.29\u0026ndash;244.0, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). After adjusting for confounders using IPTW based on propensity scores for age, gender, weight, albumin level, ICU admission time, lactate level, APACHE II, and SOFA scores, the adjusted HR remained significant (HR: 8.60, 95% CI: 1.02\u0026ndash;72.64, P\u0026thinsp;=\u0026thinsp;0.047) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eHazard Ratio for 28-Day Survival by Urinary L-FABP at 3 Hours after ICU Admission\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLow L-FABP* (n\u0026thinsp;=\u0026thinsp;74)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eHigh L-FABP\u0026dagger; (n\u0026thinsp;=\u0026thinsp;44)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCrude model, HR [95% CI]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (reference)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e32.35 [4.29\u0026ndash;244]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIPTW adjusted, HR [95% CI]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (reference)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e8.60 [1.02\u0026ndash;72.64]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.047\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e* L-FABP (T3)\u0026thinsp;\u0026lt;\u0026thinsp;90.815, \u0026dagger; L-FABP (T3)\u0026thinsp;≧\u0026thinsp;90.815\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eL-FABP: Urinary Liver-type fatty acid-binding protein; ICU: Intensive Care Unit; HR: Hazard Ratio; CI: Confidence Interval; IPTW: Inverse Probability of Treatment Weighting\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eIn the secondary analysis, the L-FABP ratio (T3/T0) was evaluated using logistic regression to predict 28-day mortality. The Cox proportional hazard ratio was 1.52 (CI: 1.08\u0026ndash;2.25, p\u0026thinsp;=\u0026thinsp;0.0213), and the ROC-AUC (T3/T0) was 0.623 [Additional File 2].\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study demonstrated that urinary L-FABP concentration, particularly when measured at T3, serves as a strong and independent predictor of 28-day in-hospital mortality in critically ill patients. Among all evaluated indicators, L-FABP (T3) showed the highest area under the ROC curve (AUC\u0026thinsp;=\u0026thinsp;0.873), outperforming APACHE II (AUC\u0026thinsp;=\u0026thinsp;0.801), SOFA (AUC\u0026thinsp;=\u0026thinsp;0.753), and arterial lactate (AUC\u0026thinsp;=\u0026thinsp;0.734). Furthermore, elevated L-FABP level at T3 was significantly associated with increased mortality in the IPTW-adjusted Cox proportional hazards model (HR\u0026thinsp;=\u0026thinsp;8.60, 95% CI: 1.02\u0026ndash;72.64, p\u0026thinsp;=\u0026thinsp;0.047), suggesting that this marker offers strong prognostic value even after adjusting for confounders.\u003c/p\u003e\u003cp\u003eIn contrast, L-FABP levels measured at T0 had a lower predictive performance (AUC\u0026thinsp;=\u0026thinsp;0.785), indicating that initial levels may not fully reflect the severity of illness or impending physiological deterioration. Moreover, the change in L-FABP levels between T0 and T3, represented by the T3/T0 ratio, demonstrated only modest predictive value (AUC\u0026thinsp;=\u0026thinsp;0.623; HR\u0026thinsp;=\u0026thinsp;1.008, 95% CI: 1.006\u0026ndash;1.011, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), suggesting that the absolute concentration at T3 provides more reliable prognostic information. One possible explanation is that the T3 value reflects not only baseline disease burden but also the patient\u0026rsquo;s physiological response to early ICU interventions such as fluid resuscitation, mechanical ventilation, or vasopressor support.\u003c/p\u003e\u003cp\u003ePrevious studies have reported that semiquantitative changes in urinary L-FABP levels within the first 6 hours of ICU admission are related to outcomes; however, the optimal timing and method for evaluating these dynamics remain unclear. Our findings suggest that a single measurement at T3 may offer clinically useful and practical prognostic information, potentially offering an efficient alternative to serial monitoring.\u003c/p\u003e\u003cp\u003eBiologically, L-FABP is primarily synthesized in hepatocytes, released into the bloodstream, and subsequently excreted in the urine under conditions of oxidative stress and tissue hypoxia. With a short plasma half-life of approximately 11 minutes [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], L-FABP reflects dynamic physiological changes and has been recognized as a sensitive marker of acute kidney injury (AKI) [\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], intestinal ischemia [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], and systemic inflammatory states [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Unlike other markers that require longer integration periods, L-FABP offers near-real-time insight into cellular injury, making it especially suitable for critical care settings, where patient conditions can deteriorate rapidly.\u003c/p\u003e\u003cp\u003ePrevious studies have demonstrated that elevated urinary L-FABP levels are associated with both short- and long-term mortality in ICU populations [\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. However, most of these studies focused on medical ICU patients or those with chronic comorbidities. In contrast, our study primarily included patients admitted via the emergency department for acute external causes such as trauma. This patient population likely had fewer underlying chronic conditions, thereby reducing confounding and highlighting the role of L-FABP as a marker of acute systemic physiological stress rather than chronic disease burden. Given the heterogeneous and rapidly evolving nature of emergency ICU admissions, biomarkers such as L-FABP, capable of capturing real-time organ dysfunction, may offer particular value in this clinical context.\u003c/p\u003e\u003cp\u003eThese findings are particularly relevant in open ICU settings, where intensivists may not be consistently available, and critically ill patients are often managed by physicians from diverse specialties such as emergency medicine, internal medicine, surgery, and anesthesiology. In these environments, frequently constrained by time and staffing, simple, rapid, and bedside-accessible biomarkers, such as urinary L-FABP, can support timely risk assessment and facilitate clinical decision-making.\u003c/p\u003e\u003cp\u003ePrevious studies have shown that 24/7 in-house ICU intensivist models, as seen in high-acuity, high-volume centers where intensive care specialists provide care on a full-time basis, are associated with better patient outcomes compared to ICUs without dedicated intensivist staffing [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. These findings suggest that intensivist-led care improves outcomes, likely through the consistent application of evidence-based practices. However, many healthcare institutions worldwide operate under open ICU systems, where access to intensivists is limited. In such contexts, objective and easily interpretable biomarkers such as L-FABP may help bridge the gap by providing real-time assessments of illness severity.\u003c/p\u003e\u003cp\u003eMoreover, unlike conventional scoring systems such as APACHE II, which require the integration of multiple clinical variables and time-consuming calculations, urinary L-FABP can be measured from a single-spot urine sample. This noninvasive, rapid, and widely deployable test offers potential utility not only in the ICU but also in emergency departments, general wards, and prehospital settings. By offering a real-time snapshot of a patient\u0026rsquo;s physiological burden, L-FABP may serve as a triage tool to determine ICU admission or as an objective criterion for patient transfer to higher-level critical care facilities. Its simplicity and portability make it especially attractive for use in resource-limited settings and during early phases of care where time-sensitive decisions are crucial. Future prospective, multicenter studies involving heterogeneous ICU populations, as well as interventional trials evaluating L-FABP-guided triage protocols, are warranted to validate and expand upon these findings.\u003c/p\u003e\u003cp\u003e\u003cb\u003eLimitations\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThis study has some limitations. First, it was conducted at a single center, which may limit the generalizability of the findings to other institutions or healthcare systems with different ICU structures, staffing models, and patient populations. Second, the sample size was relatively small (n\u0026thinsp;=\u0026thinsp;118), partly due to the exclusion of patients with confirmed or suspected COVID-19 during the study period. To ensure safety and prevent infection risk during specimen collection and handling, patients with fever or respiratory symptoms were excluded unless COVID-19 was definitively ruled out. This may have introduced selection bias and reduced the diversity of the study population. Third, most enrolled patients were admitted from the emergency department due to external causes such as trauma, burns, or poisoning. Consequently, patients with endogenous causes, such as sepsis or chronic disease exacerbations, were underrepresented. This imbalance may limit the applicability of our findings to other ICU populations, particularly those dominated by medical rather than surgical or trauma cases. Finally, although we used IPTW to adjust for measured confounders, the observational design leaves room for residual confounding from unmeasured variables. Further multicenter, prospective studies involving larger and more heterogeneous populations are warranted to confirm the prognostic utility of urinary L-FABP and to determine its generalizability across various ICU settings.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis study demonstrated that urinary L-FABP concentration measured 3 hours after ICU admission is a strong predictor of 28-day mortality, outperforming conventional scoring systems such as APACHE II and SOFA. Given its simplicity, non-invasiveness, and rapid availability, L-FABP may serve as a practical tool for early risk stratification in critically ill patients. Further prospective studies are warranted to validate its broader clinical applicability across different ICU settings.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAPACHE II: acute physiology and chronic health evaluation II\u003c/p\u003e\n\u003cp\u003eAUC: area under the curve\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCOVID-19: coronavirus disease 2019\u003c/p\u003e\n\u003cp\u003eHR: hazard ratio\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eICU: intensive care unit\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIPTW: inverse probability of treatment weighting\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIQR: interquartile range\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLac: lactate\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eL-FABP: liver-type fatty acid-binding protein\u003c/p\u003e\n\u003cp\u003eROC: receiver operating characteristic\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSOFA: sequential organ failure assessment\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e: This single-center, retrospective, observational study was conducted at the Advanced Emergency and Critical Care Center of Nara Medical University Hospital. This study adhered to the principles of the Declaration of Helsinki and was approved by the Nara Medical University Hospital Ethics Committee (Approval No. 1798). Written informed consent was obtained from all participants. In cases where the patient was unable to provide consent, written consent was obtained from a legally authorized representative, such as an adult family member living with the patient or a relative within the third degree of kinship.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e: Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e: The authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e: H.O. and H.A. contributed to the conception and design of the study. H.O. and K.S. performed the data analysis. H.O. conducted the literature review. H.O., H.A., K.M., K.Y., and H.F. were responsible for data acquisition. All authors contributed to data interpretation. H.O. drafted the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e: The authors gratefully acknowledge CMIC Holdings Co., Ltd. (Tokyo, Japan) for performing urinary L-FABP measurements on the patient samples at no cost. The company had no role in the design, execution, analysis, or interpretation of this study. We would like to thank Editage (www.editage.jp) for English language editing.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eDesai N, Gross J. Scoring systems in the critically ill: uses, cautions, and future directions. BJA Educ. 2019;19:212\u0026ndash;8.\u003c/li\u003e\n\u003cli\u003eRahmatinejad Z, Hoseini B, Rahmatinejad F, Abu-Hanna A, Bergquist R, Pourmand A, et al. Internal validation of the predictive performance of models based on three ED and ICU scoring systems to predict inhospital mortality for intensive care patients referred from the emergency department. Biomed Res Int. 2022;2022:3964063.\u003c/li\u003e\n\u003cli\u003eMoreno-Torres V, Royuela A, M\u0026uacute;\u0026ntilde;ez E, Ortega A, Gutierrez \u0026Aacute;, Mills P, et al. Better prognostic ability of NEWS2, SOFA and SAPS-II in septic patients. Med Clin (Barc). 2022;159:224\u0026ndash;9.\u003c/li\u003e\n\u003cli\u003eNaqvi IH, Mahmood K, Ziaullaha S, Kashif SM, Sharif A. Better prognostic marker in ICU - APACHE II, SOFA or SAP II! Pak J Med Sci. 2016;32:1146\u0026ndash;51.\u003c/li\u003e\n\u003cli\u003eVincent JL, Moreno R. Clinical review: scoring systems in the critically ill. Crit Care. 2010;14:207.\u003c/li\u003e\n\u003cli\u003eSarfati S, Ehrmann S, Vodovar D, Jung B, Aissaoui N, Darreau C, et al. Inadequate intensive care physician supply in France: a point-prevalence prospective study. Ann Intensive Care. 2024;14:92.\u003c/li\u003e\n\u003cli\u003eWatanabe T, Ohsugi K, Suminaga Y, Somei M, Kikuyama K, Mori M, et al. An evaluation of the impact of the implementation of the Tele-ICU: a retrospective observational study. J Intensive Care. 2023;11:9.\u003c/li\u003e\n\u003cli\u003evan de Poll MCG, Derikx JPM, Buurman WA, Peters WH, Roelofs HMJ, Wigmore SJ, et al. Liver manipulation causes hepatocyte injury and precedes systemic inflammation in patients undergoing liver resection. World J Surg. 2007;31:2033\u0026ndash;8.\u003c/li\u003e\n\u003cli\u003eDoi K, Negishi K, Ishizu T, Katagiri D, Fujita T, Matsubara T, et al. Evaluation of new acute kidney injury biomarkers in a mixed intensive care unit. Crit Care Med. 2011;39(:2464\u0026ndash;9.\u003c/li\u003e\n\u003cli\u003eGinga S, Ryo I, Saki Y, Kawashima D, Hoshiyama M, Takahashi Y, et al. Clinical significance of urinary L-FABP in the emergency department. Int J Emerg Med. 2019;12:24.\u003c/li\u003e\n\u003cli\u003eParr SK, Clark AJ, Bian A, Shintani A, Wickersham NE, Ware LB, et al. Urinary L-FABP predicts poor outcomes in critically ill patients with early acute kidney injury. Kidney Int. 2015;87:640\u0026ndash;8.\u003c/li\u003e\n\u003cli\u003eThuijls G, van Wijck K, Grootjans J, Derikx JP, van Bijnen AA, Heineman E, et al. Early diagnosis of intestinal ischemia using urinary and plasma fatty acid binding proteins. Ann Surg. 2011;253:303\u0026ndash;8.\u003c/li\u003e\n\u003cli\u003eKim H, Gil G, Lee S, Kwak A, Jo S, Kim E, et al. Cytokine-like activity of liver type fatty acid binding protein (L-FABP) inducing inflammatory cytokine interleukin-6. Immune Netw. 2016;16:296\u0026ndash;304.\u003c/li\u003e\n\u003cli\u003eGinga S, Ryo I, Saki Y, Hibiki S, Yoshimi N, Masayuki W, et al. Urinary liver-type fatty acid-binding protein variation as a predictive value of short-term mortality in intensive care unit patients. Ren Fail. 2021;43:1041\u0026ndash;8.\u003c/li\u003e\n\u003cli\u003eNaruse H, Ishii J, Takahashi H, Kitagawa F, Nishimura H, Kawai H, et al. Urinary liver-type fatty-acid-binding protein predicts long-term adverse outcomes in medical cardiac intensive care units. J Clin Med. 2020;9:360.\u003c/li\u003e\n\u003cli\u003eHa EC, Yang HN, Jo S-K, Cho W-Y, Kim H-K. The role of urinary liver-type fatty acid-binding protein in critically ill patients. J Korean Med Sci. 2013;28:100\u0026ndash;5.\u003c/li\u003e\n\u003cli\u003eMasud F, Lam TYC, Fatima S. Is 24/7 in-house intensivist staffing necessary in the intensive care unit? Methodist Debakey Cardiovasc J. 2018;14:134\u0026ndash;40.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Liver-type fatty acid-binding protein (L-FABP), Prognosis prediction, Intensive Care Unit (ICU), Emergency department admission","lastPublishedDoi":"10.21203/rs.3.rs-7161428/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7161428/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eEarly risk stratification of critically ill patients is essential for optimizing intensive care unit (ICU) resource allocation and treatment decisions. Urinary liver-type fatty acid-binding protein (L-FABP) is a simple, noninvasive biomarker that may provide real-time information on organ dysfunction. However, its prognostic utility in patients admitted to the ICU from the emergency department remains unclear.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThis single-center retrospective observational study included patients admitted to the ICU between December 2020 and August 2022. Urinary L-FABP concentrations were measured at ICU admission (T0) and 3 hours later (T3). The primary outcome was 28-day in-hospital mortality. Prognostic performance was assessed using receiver operating characteristic (ROC) curves and Cox proportional hazards models with inverse probability of treatment weighting (IPTW). Results were compared with APACHE II, SOFA scores, and lactate levels.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eA total of 118 patients (median age: 69 years [interquartile range (IQR) 51\u0026ndash;82]; 72 males [61.0%]) were included in the final analysis. Urinary L-FABP at T3 showed the highest predictive performance for 28-day mortality (area under the curve [AUC]\u0026thinsp;=\u0026thinsp;0.873), outperforming APACHE II (AUC\u0026thinsp;=\u0026thinsp;0.801), SOFA (AUC\u0026thinsp;=\u0026thinsp;0.753), and lactate (AUC\u0026thinsp;=\u0026thinsp;0.734). Elevated L-FABP (T3) was independently associated with increased mortality (hazard ratio [HR]\u0026thinsp;=\u0026thinsp;8.60, 95% confidence interval [CI]: 1.02\u0026ndash;72.64, P\u0026thinsp;=\u0026thinsp;0.047). The T3/T0 ratio showed only modest predictive value (AUC\u0026thinsp;=\u0026thinsp;0.623).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eUrinary L-FABP levels measured 3 hours after ICU admission were a strong and independent predictor of short-term mortality. Its simplicity and bedside applicability suggest its potential utility not only in ICUs but also in emergency departments and triage decision-making.\u003c/p\u003e","manuscriptTitle":"Prognosis prediction by urinary L-FABP in ICU patients admitted from the emergency department: a single-center, historical cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-29 11:51:14","doi":"10.21203/rs.3.rs-7161428/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c7cc5114-606b-418c-ae58-1ac9f1bfc9b8","owner":[],"postedDate":"July 29th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-08-01T09:08:38+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-29 11:51:14","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7161428","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7161428","identity":"rs-7161428","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}