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

International audienceAcute 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. Acute respiratory distress syndrome (ARDS) still carries a high mortality rate 1,2 , and a major challenge in targeting the prevention and early treatment of ARDS is the inability to accurately predict which patients will develop the syndrome 3-6. The Lung Injury Prediction Score (LIPS) was developed to identify patients at high risk of developing ARDS; however, its positive predictive value is limited (0.14-0.23) 7. To improve prediction, one method may be to combine clinical data with plasma biomarkers that reflect the pathogenesis of ARDS such as angiopoietin-2 (Ang-2), a marker of lung endothelial injury 8. In contrast, the soluble receptor for advanced gly-cation end-products (sRAGE), a marker of lung epithelial injury 9 , may predict ARDS more accurately in selected at-risk patients, e.g. after cardiac surgery 10 , severe trauma 11 , or after major surgery 12. Soluble forms of RAGE (sRAGE) include the extracellular domain of membrane RAGE that is cleaved by proteinases 13 and endogenous secretory RAGE (esRAGE), among other forms produced by alternative splicing 14,15. 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 ARDS 16,17. Although 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. In addition, and although not yet ready for clinical use, genomic applications could facilitate better prediction