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Research Article: Trajectory models of serum creatinine and 28-day mortality in critically ill patients with sepsis complicated by type 2 diabetes mellitus: a cohort study

Date Published: 2026-06-23

Abstract:
In critically ill patients with sepsis complicated by type 2 diabetes mellitus (T2DM), renal dysfunction is prevalent; however, the association between dynamic serum creatinine trajectory patterns and short-term mortality risk remains inadequately characterized. This study was conducted using data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The target population comprised adult intensive care unit (ICU) patients with sepsis complicated by T2DM. Group-Based Trajectory Modeling (GBTM) was employed to categorize the patterns of serum creatinine changes within 72 hours following ICU admission. Multivariable Cox proportional hazards models and Kaplan-Meier (K-M) survival curves were constructed to assess the association between trajectory groups and 28-day all-cause mortality, while restricted cubic spline (RCS) curves were utilized to examine the trend of short-term mortality risk in relation to serum creatinine levels. Furthermore, subgroup analyses and mediation effect analysis of continuous renal replacement therapy (CRRT) were performed. A total of 1909 patients were included in the study, with 439 deaths occurring within 28 days, corresponding to a 28-day all-cause mortality rate of approximately 23.0%. Three distinct serum creatinine trajectory patterns were identified: low-stable, moderate-increasing, and persistently high. Compared with the low-stable trajectory group, patients in the moderate-increasing and persistently high groups exhibited significantly elevated 28-day mortality risk, which remained statistically significant following multivariable adjustment, with adjustments for age, gender, temperature, platelet count, albumin, blood urea nitrogen, pH, renal disease, severe liver disease, mechanical ventilation, 24-hour urine output, and the Charlson Comorbidity Index (model 2: HR = 1.50, 95% CI: 1.16-1.93, p = 0.02; model 3: HR = 1.46, 95% CI: 1.04-2.05, p = 0.03). RCS analysis revealed a significant nonlinear association between serum creatinine levels and mortality risk. The subgroup analysis results revealed significant interaction effects across gender and CRRT subgroups. Mediation analysis demonstrated that CRRT may exert a partial mediating effect on the association between creatinine elevation and mortality risk. The early trajectory of serum creatinine changes following ICU admission is independently associated with 28-day mortality in critically ill patients with sepsis complicated by T2DM. Sustained higher serum creatinine levels are significantly associated with an increased risk of mortality.

Introduction:
In critically ill patients with sepsis complicated by type 2 diabetes mellitus (T2DM), renal dysfunction is prevalent; however, the association between dynamic serum creatinine trajectory patterns and short-term mortality risk remains inadequately characterized.

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