1593: Association of Plasma Angiopoetin-2 With Acute Kidney Injury and Multiorgan Dysfunction in Ards

Introduction: Endothelial dysfunction contributes to the pathogenesis of acute kidney injury (AKI) and multi-organ dysfunction in critical illness. We previously identified higher angiopoietin-2 (Angpt2), a marker of endothelial activation, as a risk factor for adverse outcomes in septic patients. We aimed to validate these findings in an independent ARDS cohort. Methods: We analyzed data from the EDEN trial, which randomized 1000 ARDS patients to trophic or full enteral feeding. Baseline plasma Angpt2 was available for 889 patients. Associations between higher Angpt2 and persistent severe AKI were assessed by multivariable regression adjusted for age, gender, and APACHE III. Secondary outcomes included any AKI, stage 2/3 AKI, acute kidney disease (AKD), hepatic dysfunction (bilirubin >2. 0 mg/dL), thrombocytopenia (platelets < 100 x10⁹/L), 28-day organ failure-free days, ARDS severity, and mortality. Analyses were stratified by sepsis status. Results: In all ARDS patients, higher plasma Angpt2 levels were independently associated with the development persistent severe AKI (OR 2. 2, 95% CI 1. 4–3. 5, p=0. 001), development of any AKI in patients enrolled within 24 hours of admission (OR 4. 7, 1. 5–15. 7, p=0. 009), stage 2/3 AKI in the first 3 days of randomization (OR 2. 7, 95% CI 1. 8–3. 9, p< 0. 001), AKD (OR 2. 95, 1. 9–4. 8, p< 0. 001), and fewer 28-day organ failure–free days (IRR 0. 86, 0. 82–0. 90, p< 0. 001). For extra-renal organ dysfunction, elevated Angpt2 was associated with hepatic dysfunction (OR 1. 8, 1. 2–2. 8, p=0. 003) and thrombocytopenia (OR 1. 8, 1. 3–2. 5, p< 0. 001) specifically in patients with sepsis-associated ARDS, but these associations were not observed in non-septic ARDS. Angpt2 was not significantly associated with ARDS severity or mortality. Conclusions: Elevated Angpt2 at enrollment was associated with persistent severe AKI, AKD, and fewer organ failure-free days in all patients with ARDS. The association between Angpt2 and hepatic dysfunction or thrombocytopenia was specific to patients with sepsis-associated ARDS. These findings reinforce the central role of endothelial dysfunction in sepsis-related multi-organ dysfunction and suggest Angpt2 as a promising biomarker and potential therapeutic target in critically ill patients.