Association of longitudinal blood urea nitrogen trajectory with in-hospital and 28-day mortality in acute heart failure with cardiorenal syndrome

BACKGROUND AND OBJECTIVE: Patients with acute heart failure (AHF) complicated by acute cardiorenal syndrome (CRS) demonstrate substantial mortality risk. Conventional blood urea nitrogen (BUN) assessments using single-point measurements inadequately capture the temporal dynamics of renal dysfunction and disease progression. This study investigated the prognostic utility of BUN trajectory patterns for predicting in-hospital and 28-day mortality in AHF patients with CRS. METHODS: We conducted a retrospective cohort study using the Medical Information Mart for Intensive Care IV (MIMIC-IV) database as the derivation cohort and the eICU Collaborative Research Database (eICU-CRD) as the validation cohort. BUN measurements were obtained at baseline (< 24 h), 72 h, and 144 h across both databases. Longitudinal BUN trajectory patterns were identified using latent class growth modeling (LCGM). Multivariable logistic and Cox proportional hazards regression analyses evaluated the association between trajectory groups and in-hospital and 28-day all-cause mortality, respectively. Subgroup and interaction analyses assessed the robustness of trajectory-based predictions across patient characteristics. RESULTS: Among 2931 patients across both cohorts, LCGM identified three distinct BUN trajectory patterns: persistent-low, persistent-moderate, and persistent-high trajectory groups. Restricted cubic spline analysis revealed a linear relationship between baseline BUN levels and both mortality outcomes (P > 0.05 for non-linearity), though with inconsistent predictive performance. Compared with the persistent-high trajectory group, the persistent-low trajectory group demonstrated significantly reduced in-hospital mortality (derivation cohort: OR 0.47, 95% CI 0.27-0.85; validation cohort: OR 0.59, 95% CI 0.38-0.93) and 28-day mortality (derivation cohort: HR 0.56, 95% CI 0.34-0.94; validation cohort: HR 0.66, 95% CI 0.45-0.85). Subgroup analyses indicated enhanced predictive performance of the persistent-low trajectory group in non-diabetic patients across both cohorts. No significant interactions were observed across subgroups, including different acute kidney injury stages. CONCLUSION: BUN trajectory patterns provide independent prognostic information for short-term outcomes in AHF patients with CRS. Persistent-low BUN trajectory are associated with significantly improved survival compared to persistent-high trajectory.