Frontiers in medicine · 2026
LDAR shows more consistent prognostic performance than other albumin-derived indices for 28-day ICU mortality in critically ill patients with urosepsis: evidence from a dual-cohort retrospective study.
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Mu Yi, Tang Hao, Zeng Yan, Wang Qian, Huang Tao, Li Wei, Wu Xiangbo, Pi Shengming
Аннотация
BACKGROUND: Urosepsis remains a leading cause of ICU mortality. Albumin-derived composite indices, which integrate nutritional, inflammatory, and metabolic parameters, hold prognostic promise; however, their comparative performance has not been directly assessed.
METHODS: We conducted a dual-cohort retrospective study using MIMIC-IV (n = 3,060) for derivation and the Affiliated Hospital of Guizhou Medical University (n = 353) for validation. The primary outcome was 28-day ICU mortality in a competing-risks framework with discharge alive as competing event. Six indices-lactate dehydrogenase-to-albumin ratio (LDAR), anion gap-to-albumin ratio (AGAR), glucose-to-albumin ratio (GAR), red cell distribution width-to-albumin ratio (RAR), total bilirubin-to-albumin ratio (TAR), and urea nitrogen-to-albumin ratio (UAR)-were compared via cause-specific Cox and Fine-Gray subdistribution hazard models, cumulative incidence functions, restricted cubic splines (RCS), Kaplan-Meier curves, and ROC/Youden/cNRI analyses. LASSO-selected features trained a multilayer perceptron (MLP), benchmarked against six severity scores; a parsimonious external model (events per variable ≥ 10) was also examined.
RESULTS: In the derivation cohort, logLDAR, RAR, TAR, AGAR, and UAR were independently associated with 28-day ICU mortality in fully adjusted models (HRs = 1.292, 1.147, 1.136, 1.074, and 1.013, respectively; all P < 0.01), whereas logGAR was not. Fine-Gray models corroborated these findings (logLDAR sHR = 1.351, 95% CI: 1.238-1.473). RCS revealed a non-linear logLDAR-mortality relationship (P non-linear = 0.040), with risk accelerating beyond logLDAR > 7. logLDAR yielded the highest AUC (0.638, 95% CI: 0.609-0.667) and cNRI (0.119). External validation confirmed the independent prognostic value of logLDAR (HR = 1.524, 95% CI: 1.225-1.895; Fine-Gray sHR = 1.545, 95% CI: 1.295-1.844), with an external AUC of 0.735 (95% CI: 0.648-0.808), although between-cohort differences in case definitions may partly contribute. The MLP with eight LASSO-selected features achieved an external AUC of 0.762 (95% CI: 0.687-0.840), comparable to SOFA plus logLDAR (AUC = 0.782; DeLong P = 0.512). SHAP analysis ranked logLDAR among the top predictors.
CONCLUSION: Among the six albumin-derived indices, logLDAR demonstrated the most consistent and generalizable prognostic performance for 28-day ICU mortality in urosepsis, reflecting both tissue hypoxia and nutritional-inflammatory depletion, and remained robust under competing-risk adjustment. logLDAR may serve as a simple bedside biomarker for early risk stratification; however, prospective studies are warranted to determine whether interventions targeting its underlying pathways can improve outcomes.
METHODS: We conducted a dual-cohort retrospective study using MIMIC-IV (n = 3,060) for derivation and the Affiliated Hospital of Guizhou Medical University (n = 353) for validation. The primary outcome was 28-day ICU mortality in a competing-risks framework with discharge alive as competing event. Six indices-lactate dehydrogenase-to-albumin ratio (LDAR), anion gap-to-albumin ratio (AGAR), glucose-to-albumin ratio (GAR), red cell distribution width-to-albumin ratio (RAR), total bilirubin-to-albumin ratio (TAR), and urea nitrogen-to-albumin ratio (UAR)-were compared via cause-specific Cox and Fine-Gray subdistribution hazard models, cumulative incidence functions, restricted cubic splines (RCS), Kaplan-Meier curves, and ROC/Youden/cNRI analyses. LASSO-selected features trained a multilayer perceptron (MLP), benchmarked against six severity scores; a parsimonious external model (events per variable ≥ 10) was also examined.
RESULTS: In the derivation cohort, logLDAR, RAR, TAR, AGAR, and UAR were independently associated with 28-day ICU mortality in fully adjusted models (HRs = 1.292, 1.147, 1.136, 1.074, and 1.013, respectively; all P < 0.01), whereas logGAR was not. Fine-Gray models corroborated these findings (logLDAR sHR = 1.351, 95% CI: 1.238-1.473). RCS revealed a non-linear logLDAR-mortality relationship (P non-linear = 0.040), with risk accelerating beyond logLDAR > 7. logLDAR yielded the highest AUC (0.638, 95% CI: 0.609-0.667) and cNRI (0.119). External validation confirmed the independent prognostic value of logLDAR (HR = 1.524, 95% CI: 1.225-1.895; Fine-Gray sHR = 1.545, 95% CI: 1.295-1.844), with an external AUC of 0.735 (95% CI: 0.648-0.808), although between-cohort differences in case definitions may partly contribute. The MLP with eight LASSO-selected features achieved an external AUC of 0.762 (95% CI: 0.687-0.840), comparable to SOFA plus logLDAR (AUC = 0.782; DeLong P = 0.512). SHAP analysis ranked logLDAR among the top predictors.
CONCLUSION: Among the six albumin-derived indices, logLDAR demonstrated the most consistent and generalizable prognostic performance for 28-day ICU mortality in urosepsis, reflecting both tissue hypoxia and nutritional-inflammatory depletion, and remained robust under competing-risk adjustment. logLDAR may serve as a simple bedside biomarker for early risk stratification; however, prospective studies are warranted to determine whether interventions targeting its underlying pathways can improve outcomes.