Clinical relevance of cleaved RAGE plasma levels as a biomarker of disease severity and functional outcome in aneurysmal subarachnoid hemorrhage

Background Cleaved receptor for advanced glycation end-products (cRAGE) has been introduced as a new inflammatory marker. We clarified the associations between cRAGE levels, disease severity and functional outcome in aneurysmal subarachnoid hemorrhage (aSAH). Methods: In this prospective, observational study, plasma levels of total soluble RAGE (sRAGE) and endogenous secretory RAGE (esRAGE) were quantified in 108 aSAH patients and 108 controls. The level of cRAGE was calculated by subtracting the level of esRAGE from that of sRAGE. World Federation of Neurological Surgeons (WFNS) score, modified Fisher score, and Hunt Hess (HH) score were recorded to assess aSAH severity. Relationship between plasma cRAGE levels and 6-month poor outcome (Glasgow Outcome Scale score of 1-3) was assess using multivariate analysis. Results: Plasma cRAGE levels were significantly higher in patients than in controls. Its levels were significantly correlated with WNFS score, modified Fisher score and HH score of patients. Plasma cRAGE emerged as an independent predictor for 6-month poor outcome. Area under receiver operating characteristic curve (AUC) of this biomarker was similar to those of WNFS score, modified Fisher score and HH score. Moreover, it significantly improved AUCs of WNFS score, modified Fisher score and HH score. Conclusions: Plasma cRAGE levels are highly associated with the severity and poor prognosis in aSAH.