Hemodynamic and Vascular Stressor Exposure and Outcomes Among Inpatient Hospitalization with Chronic Kidney Disease: A Nationwide Study

Background: Hospitalized adults with chronic kidney disease (CKD) experience high morbidity and mortality. Acute inpatient events frequently occur in combination, yet most studies evaluate individual conditions in isolation. Acute hemodynamic and vascular stressors may represent interacting physiological stressors that define heterogeneous patterns of inpatient risk. Methods: Acute hemodynamic stressors (sepsis, shock, acute decompensated heart failure, and mechanical ventilation) and vascular stressors (acute myocardial infarction, major bleeding, stroke, pulmonary embolism, and deep vein thrombosis) were identified using ICD-10-CM and ICD-10-PCS codes. Stressor burden was defined as the number of stressors (0, 1, 2, or ≥3). Hospitalizations were categorized into mutually exclusive domains: none, hemodynamic only, vascular only, or both. Survey-weighted multivariable regression models examined associations with mortality, acute kidney injury (AKI), length of stay (LOS), and hospital charges. Prespecified sensitivity analyses excluded inter-hospital transfers, and interaction analyses assessed modification by age. Results: Among 1,062,813 CKD hospitalizations, 66.1% experienced at least one acute stressor. Increasing stressor burden demonstrated a marked dose–response relationship with mortality, with adjusted odds ratios of 2.15 (95% CI: 2.08–2.23), 7.36 (95% CI: 7.09–7.64), and 31.65 (95% CI: 30.40–32.95) for 1, 2, and ≥3 stressors, respectively. Increasing stressor burden was also associated with higher odds of AKI, longer LOS, and greater hospital charges. Significant dose–response relationships were observed for all outcomes (all P-trend < 0.001). Isolated hemodynamic stressors were associated with greater mortality risk than isolated vascular stressors (aOR: 4.97 vs. 2.15), while hospitalizations experiencing both domains had the greatest risk (aOR: 13.10, 95% CI: 12.52–13.71). These findings were robust in sensitivity analyses excluding inter-hospital transfers. The relative increase in mortality associated with higher stressor burden was greater among patients younger than 65 years than among older adults (P for interaction <0.001). Conclusions: Acute hemodynamic and vascular stressors define heterogeneous patterns of inpatient risk among hospitalized adults with CKD. Both cumulative stressor burden and stressor domain are strongly associated with mortality, AKI, and resource utilization, with robust dose–response relationships that highlight acute physiological stress as an important determinant of inpatient outcomes in CKD.