Plasma suPAR as a prognostic biological marker for ICU mortality in ARDS patients

Abstract

Purpose: We investigated the prognostic value of plasma soluble urokinase plasminogen activator receptor (suPAR) on day 1 in patients with the acute respiratory distress syndrome (ARDS) for intensive care unit (ICU) mortality and compared it with established disease severity scores on day 1. Methods: suPAR was determined batchwise in plasma obtained within 24 h after admission. Results: 632 ARDS patients were included. Significantly (P = 0.02) higher median levels of suPAR were found with increasing severity of ARDS: 5.9 ng/ml [IQR 3.1-12.8] in mild ARDS (n = 82), 8.4 ng/ml .0] in moderate ARDS (n = 333), and 9.0 ng/ml .0] in severe ARDS (n = 217). Non-survivors had higher median levels of suPAR [12.5 ng/ml (IQR 5.1-19.5) vs. 7.4 ng/ml (3.9-13.6), P \ 0.001]. The area under the receiver operator characteristic curve (ROC-AUC) for mortality of suPAR (0.62) was lower than the ROC-AUC of the APACHE IV score (0.72, P = 0.007), higher than that of the ARDS definition classification (0.53, P = 0.005), and did not differ from that of the SOFA score (0.68, P = 0.07) and the oxygenation index (OI) (0.58, P = 0.29). Plasma suPAR did not improve the discrimination of the established disease severity scores, but did improve net reclassification of the APACHE score (29 %), SOFA score (23 %), OI (38 %), and Berlin definition classification (39 %). Conclusion: As a single biological marker, the prognostic value for death of plasma suPAR in ARDS patients is low. Plasma suPAR, however, improves the net reclassification, suggesting a potential role for suPAR in ICU mortality prediction models.

Identification and validation of distinct biological phenotypes in patients with acute respiratory distress syndrome by cluster analysis

“…All patients with ARDS from whom plasma that was obtained on the day of diagnosis of ARDS was available in the biobank were eligible for the present study. Part of this cohort was described earlier, albeit with a different scientific question, and the definitions are equal to those used in that study 28. ARDS was defined according to the criteria stated by the American-European Consensus Conference on ARDS:29 that is, the diagnosis required an acute onset of symptoms, the presence of bilateral infiltrates on chest radiography, a pulmonary artery wedge pressure <18 mm Hg and/or the absence of signs of left ventricular dysfunction, and a pO 2 in arterial blood to fraction of inspired oxygen ratio (PaO 2 /FiO 2 ) ≤ 200.…”

External validation confirms the legitimacy of a new clinical classification of ARDS for predicting outcome

“…Consecutive adult patients admitted to the mixed intensive care units (ICU) of two university hospitals in the Netherlands and 14 hospitals in Brazil were prospectively screened for the incidence of moderate and severe ARDS [1,4,5]. In short, patients were classified into four groups based on PaO 2 /FiO 2 and PEEP measured at onset of clinical symptoms and 24 h later (Table 1).…”

Focus on ARDS

“…Also, the lack of association between the sTM levels and genetic variants reported in this latter study suggests that the increased levels of sTM may reflect severity of endothelial damage rather than genetic heterogeneity [10]. Finally, the prognostic value of plasma soluble urokinase plasminogen activator receptor (suPAR) was recently assessed in a series of 632 ARDS patients, and increased levels of plasma suPAR were significantly associated with ICU mortality [11]. Altogether, these promising endothelial biomarkers may guide the development of future strategies targeting endothelial stabilization, Right ventricular dysfunction may reflect the presence of lung vascular dysfunction during ARDS.…”