Soluble Receptor for Advanced Glycation End-Products Predicts Impaired Alveolar Fluid Clearance in Acute Respiratory Distress Syndrome

Am J Respir Crit Care Med. 2015 Jul 15;192(2):191-9. doi: 10.1164/rccm.201501-0020OC.


Rationale: Levels of the soluble form of the receptor for advanced glycation end-products (sRAGE) are elevated during acute respiratory distress syndrome (ARDS) and correlate with severity and prognosis. Alveolar fluid clearance (AFC) is necessary for the resolution of lung edema but is impaired in most patients with ARDS. No reliable marker of this process has been investigated to date.

Objectives: To verify whether sRAGE could predict AFC during ARDS.

Methods: Anesthetized CD-1 mice underwent orotracheal instillation of hydrochloric acid. At specified time points, lung injury was assessed by analysis of blood gases, alveolar permeability, lung histology, AFC, and plasma/bronchoalveolar fluid measurements of proinflammatory cytokines and sRAGE. Plasma sRAGE and AFC rates were also prospectively assessed in 30 patients with ARDS.

Measurements and main results: The rate of AFC was inversely correlated with sRAGE levels in the plasma and the bronchoalveolar fluid of acid-injured mice (Spearman's ρ = -0.73 and -0.69, respectively; P < 10(-3)), and plasma sRAGE correlated with AFC in patients with ARDS (Spearman's ρ = -0.59; P < 10(-3)). Similarly, sRAGE levels were significantly associated with lung injury severity, and decreased over time in mice, whereas AFC was restored and lung injury resolved.

Conclusions: Our results indicate that sRAGE levels could be a reliable predictor of impaired AFC during ARDS, and should stimulate further studies on the pathophysiologic implications of RAGE axis in the mechanisms leading to edema resolution. Clinical trial registered with (NCT 00811629).

Trial registration: NCT00811629.

Keywords: acid aspiration; alveolar epithelium; animal model; lung injury resolution; pulmonary edema.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / blood
  • Bronchoalveolar Lavage Fluid
  • Cytokines / blood
  • Disease Models, Animal
  • Female
  • Humans
  • Lung / physiopathology
  • Male
  • Mice
  • Middle Aged
  • Prospective Studies
  • Pulmonary Alveoli / physiopathology*
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic / blood*
  • Respiratory Distress Syndrome / blood*
  • Respiratory Distress Syndrome / physiopathology*


  • Biomarkers
  • Cytokines
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic

Associated data