Receptor for advanced glycation end-products and ARDS prediction: a multicentre observational study

Matthieu Jabaudon,Jean-Sébastien Faure,Raïko Blondonnet ,Thomas Godet,Bertrand Souweine,Laurence Roszyk,Sophie Cayot,Bruno Pereira,J Pascal ,Loı̈c Blanchon ,Alexandre Lautrette,Nathanaël Eisenmann ,Pauline Berthelin,Thibaut Pranal,Vincent Sapin,Yvan Skrzypczak,Thierry Gillart,Corinne Belville,Russell Chabanne,Jean-Michel Constantin

doi:10.1038/s41598-018-20994-x

Abstract

Acute respiratory distress syndrome (ARDS) prediction remains challenging despite available clinical scores. To assess soluble receptor for advanced glycation end-products (sRAGE), a marker of lung epithelial injury, as a predictor of ARDS in a high-risk population, adult patients with at least one ARDS risk factor upon admission to participating intensive care units (ICUs) were enrolled in a multicentre, prospective study between June 2014 and January 2015. Plasma sRAGE and endogenous secretory RAGE (esRAGE) were measured at baseline (ICU admission) and 24 hours later (day one). Four AGER candidate single nucleotide polymorphisms (SNPs) were also assayed because of previous reports of functionality (rs1800625, rs1800624, rs3134940, and rs2070600). The primary outcome was ARDS development within seven days. Of 500 patients enrolled, 464 patients were analysed, and 59 developed ARDS by day seven. Higher baseline and day one plasma sRAGE, but not esRAGE, were independently associated with increased ARDS risk. AGER SNP rs2070600 (Ser/Ser) was associated with increased ARDS risk and higher plasma sRAGE in this cohort, although confirmatory studies are needed to assess the role of AGER SNPs in ARDS prediction. These findings suggest that among at-risk ICU patients, higher plasma sRAGE may identify those who are more likely to develop ARDS.

Highlights

Acute respiratory distress syndrome (ARDS) prediction remains challenging despite available clinical scores
Soluble forms of RAGE include the extracellular domain of membrane RAGE that is cleaved by proteinases[13] and endogenous secretory RAGE, among other forms produced by alternative splicing14,15. soluble receptor for advanced glycation end-products (sRAGE) has good diagnostic value for ARDS and is associated with lung injury severity, the degree of lung epithelial injury, impaired alveolar fluid clearance, and prognosis in ARDS16,17
Because epithelial injury is a major contributor of ARDS pathogenesis, resolution, and prognosis[23,24], we hypothesised that plasma levels of sRAGE and AGER single nucleotide polymorphisms (SNPs) might predict the development of ARDS in a high-risk population of patients admitted to intensive care units (ICUs)

Summary

Introduction

Acute respiratory distress syndrome (ARDS) prediction remains challenging despite available clinical scores. SRAGE has good diagnostic value for ARDS and is associated with lung injury severity, the degree of lung epithelial injury, impaired alveolar fluid clearance, and prognosis in ARDS16,17 It remains unclear whether esRAGE may be involved in ligand binding or may have any functional effects by itself, esRAGE levels were lower in the plasma and alveolar fluid from patients with ARDS than in mechanically ventilated controls without ARDS in a previous study[18]. Because epithelial injury is a major contributor of ARDS pathogenesis, resolution, and prognosis[23,24], we hypothesised that plasma levels of sRAGE and AGER SNPs might predict the development of ARDS in a high-risk population of patients admitted to intensive care units (ICUs). Some of the results of this study have been previously reported in the form of an abstract during the American Thoracic Society International Conference (2017)

Methods

Results

Conclusion