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Neutrophil gelatinase-associated lipocalin (NGAL) is produced in the bronchial and alveolar cells of inflamed lungs and is regarded as a potential prognostic biomarker in various respiratory diseases. However, there are no studies on patients with acute respiratory distress syndrome (ARDS). NGAL levels in serum and bronchoalveolar lavage (BAL) were measured at baseline and on day 7 in 110 patients with ARDS. Baseline NGAL levels were significantly higher in ARDS patients than in healthy controls (serum 25 [14.5–41] vs. 214 [114.5–250.3] ng/mL; BAL 90 [65–115] vs. 211 [124–244] ng/mL). In ARDS, baseline NGAL levels in serum and BAL were significantly higher in non-survivors than in survivors (p < 0.001 and p = 0.021, respectively). Baseline NGAL levels showed a fair predictive power for intensive care unit (ICU) mortality (serum area under the curve (AUC) 0.747, p < 0.001; BAL AUC 0.768, p < 0.001). In a multivariate Cox regression analysis, the baseline serum NGAL level (> 240 ng/mL) was significantly associated with ICU mortality (hazard ratio [HR] 5.39, 95% confidence interval [CI] 2.67–10.85, p < 0.001). In particular, day 7 NGAL was significantly correlated with day 7 driving pressure (serum r = 0.388, BAL r = 0.702), and 28 ventilator-free days (serum r = − 0.298, BAL r = − 0.297). Baseline NGAL has good prognostic value for ICU mortality in patients with ARDS. NGAL can be a biomarker for ventilator requirement, as it may be indicative of potential alveolar epithelial injury.