A26-14 U-shaped Association Between Plasma Ninj1 Levels and Clinical Outcomes in Patients With Pneumonia-induced Acute Respiratory Failure

Rationale Ninjurin-1 (NINJ1) is a transmembrane protein that plays a pivotal role in mediating plasma membrane rupture during multiple forms of regulated cell death, including apoptosis, pyroptosis, necroptosis, and ferroptosis. Previous studies have demonstrated an association between elevated serum NINJ1 levels and cardiovascular diseases such as atrial fibrillation and acute ischemic stroke. However, the relationship between circulating NINJ1 levels and outcomes in critically ill patients with pneumonia-induced acute respiratory failure remains unclear. Methods This prospective observational study enrolled 79 intensive care unit (ICU) patients with pneumonia-induced acute respiratory failure who required either invasive or noninvasive positive pressure ventilatory support. Plasma NINJ1 levels were measured within 48 hours of ICU admission using an ELISA assay. Clinical parameters, including Sequential Organ Failure Assessment (SOFA), Acute Physiology and Chronic Health Evaluation II (APACHE II), and Simplified Acute Physiology Score II (SAPS II) scores, were recorded. The primary objective was to examine the association between plasma NINJ1 levels and hospital mortality. The secondary objective was to evaluate the relationship between plasma NINJ1 levels and other clinical variables during hospitalization. Results Among the 79 enrolled patients, the median age was 77 years (IQR 69-83), and 72.2% were male. The median plasma NINJ1 concentration was 199 pg/mL (IQR 132-340). On day 1 of ICU admission, the median APACHE II, SAPS II, and SOFA scores were 20 (IQR 16-26), 48 (IQR 38-59), and 7 (IQR 4-9), respectively. Plasma NINJ1 levels showed no significant correlation with APACHE II (p = 0.357), SAPS II (p = 0.142) , or SOFA (p = 0.248) scores. However, plasma NINJ1 levels were significantly associated with white blood cell count (p = 0.018) and creatinine (p = 0.022) on day 1 of ICU admission. Although NINJ1 levels were not associated with 30-day (p = 0.725), 60-day (p = 0.435), or in-hospital mortality (p = 0.346) when analyzed as continuous variables, stratification by quartiles revealed that both lower and higher NINJ1 levels were associated with increased 60-day mortality (p = 0.021), demonstrating a U-shaped relationship between plasma NINJ1 and mortality. Conclusions Plasma NINJ1 levels exhibited a U-shaped association with 60-day mortality in patients with pneumonia-induced acute respiratory failure. Larger cohort studies are warranted to confirm these findings.