Association between urea-to-creatinine ratio trajectories and clinical outcomes in chronic critical illness patients: a retrospective cohort study.

Background: Chronic critical illness (CCI) is characterized by persistent organ dysfunction and profound catabolism, yet reliable biomarkers to monitor catabolic burden are lacking. The urea-to-creatinine ratio (UCR) has been proposed as a biochemical signature of critical illness-associated catabolism. This study aimed to identify longitudinal UCR trajectory patterns in CCI patients and to evaluate their association with mortality. Methods: We conducted a retrospective cohort study using the MIMIC-IV database. Adult patients (≥18 years) who met the criteria of CCI in their first ICU admission period were included. CCI was defined as an ICU length of stay over 14 days and coexists with persistent organ dysfunction at day 14. Patients with serum creatinine > 4 mg/dL at ICU admission, renal replacement therapy, gastrointestinal bleeding, or obstetric admissions were excluded. Daily UCR from ICU days 1-14 was modeled using group-based trajectory modeling (GBTM). Outcomes were 28-day, 90-day, and 365-day mortality after CCI diagnosis. Kaplan-Meier survival curves and Cox proportional hazards models were applied to analyze the association between UCR trajectories and outcomes. Subgroup analyses were conducted to further validate the robustness of the results. Results: A total of 1718 CCI patients were included. Four distinct UCR trajectory groups were identified: trajectory 1 (low-level, stable), trajectory 2 (low-level, slow increase), trajectory 3 (mid-level, slow increase), and trajectory 4 (high-level, rapid increase). Kaplan-Meier analysis showed that mortality increased progressively from trajectory 1 to trajectory 4. In a fully adjusted Cox proportional hazards model, the 28-day, 90-day, and 365-day mortality risks were significantly higher in trajectory 2-4 groups compared with trajectory 1 group. Subgroup analyses revealed a statistically significant interaction between age and UCR trajectory groups. Conclusion: Longitudinal UCR trajectories provide important prognostic information in CCI patients and are independently associated with short- and long-term mortality. Monitoring UCR trends during the early ICU course may facilitate metabolic phenotyping and risk stratification of CCI patients.