Soluble form of the receptor for advanced glycation end products is a marker of acute lung injury but not of severe sepsis in critically ill patients

Objectives: Levels of the soluble form of the receptor for advanced glycation end products (sRAGE) are elevated during acute lung injury. However, it is not known whether this increase is linked to its involvement in alveolar epithelium injury or in systemic inflammation. Whether sRAGE is a marker of acute lung injury and acute respiratory distress syndrome, regardless of associated severe sepsis or septic shock, remains unknown in the intensive care unit setting. Design: Prospective, observational, clinical study. Setting: Intensive care unit of an academic medical center. Patients: A total of 64 consecutive subjects, divided into four groups: acute lung injury/acute respiratory distress syndrome (n = 15); acute lung injury/acute respiratory distress syndrome plus severe sepsis/septic shock (n = 18); severe sepsis/septic shock (n = 16); and mechanically ventilated controls (n = 15). Interventions: None. Measurements and Main Results: Plasma sRAGE levels were measured at baseline and on days 3, 6, and 28 (or at intensive care unit discharge, whichever occurred first). Baseline plasma levels of sRAGE were significantly higher in patients with acute lung injury/acute respiratory distress syndrome, with (median, 2951 pg/mL) or without (median, 3761 pg/mL) severe sepsis, than in patients with severe sepsis (median, 488 pg/mL) only and in mechanically ventilated controls (median, 525 pg/mL). Levels of sRAGE were correlated with acute lung injury/acute respiratory distress syndrome severity and decreased over time but were not associated with outcome. Lower baseline plasma sRAGE was associated with focal loss of aeration based on computed tomography lung morphology. Conclusions: sRAGE levels were elevated during acute lung injury/acute respiratory distress syndrome, regardless of the presence or absence of severe sepsis. The plasma level of sRAGE was correlated with clinical and radiographic severity in acute respiratory distress syndrome patients and decreased over time, suggesting resolution of the injury to the alveolar epithelium. Further study is warranted to test the clinical utility of this biomarker in managing such patients and to better understand its relationship with lung morphology during acute lung injury/acute respiratory distress syndrome. (Crit Care Med 2011; 39: 480-488)