Plasma sRAGE is independently associated with increased mortality in ARDS: a meta-analysis of individual patient data |
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| Authors: | Matthieu Jabaudon Raiko Blondonnet Bruno Pereira Rodrigo Cartin-Ceba Christoph Lichtenstern Tommaso Mauri Rogier M Determann Tomas Drabek Rolf D Hubmayr Ognjen Gajic Florian Uhle Andrea Coppadoro Antonio Pesenti Marcus J Schultz Marco V Ranieri Helena Brodska Ségolène Mrozek Vincent Sapin Michael A Matthay Jean-Michel Constantin Carolyn S Calfee |
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| Institution: | 1.Department of Perioperative Medicine,CHU Clermont-Ferrand,Clermont-Ferrand Cedex 1,France;2.CNRS, UMR 6293, INSERM U1103, GReD, Université Clermont Auvergne,Clermont-Ferrand,France;3.Biostatistics Unit, Department of Clinical Research and Innovation (DRCI),CHU Clermont-Ferrand,Clermont-Ferrand,France;4.Division of Pulmonary and Critical Care Medicine,Mayo Clinic,Rochester,USA;5.Department of Anesthesiology,Heidelberg University Hospital,Heidelberg,Germany;6.Department of Anesthesia, Critical Care and Emergency, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico,University of Milan,Milan,Italy;7.Department of Intensive Care Medicine,OLVG,Amsterdam,The Netherlands;8.Department of Anesthesiology,University of Pittsburgh School of Medicine,Pittsburgh,USA;9.Department of Emergency Medicine,San Gerardo Hospital,Monza,Italy;10.Department of Intensive Care Medicine, Academic Medical Center,University of Amsterdam,Amsterdam,The Netherlands;11.Mahidol-Oxford Tropical Medicine Research Unit (MORU),Bangkok,Thailand;12.Department of Surgical Sciences, Molinette Hospital, City of Health and Science,University of Turin,Turin,Italy;13.Institute of Clinical Biochemistry and Laboratory Diagnostics, Faculty of Medicine, General University Hospital,Charles University,Prague,Czech Republic;14.Department of Anesthesia and Intensive Care, University Hospital of Toulouse,University Toulouse 3 Paul Sabatier,Toulouse,France;15.Department of Medical Biochemistry and Molecular Biology,CHU Clermont-Ferrand,Clermont-Ferrand,France;16.Division of Pulmonary and Critical Care Medicine, Departments of Medicine and Anesthesia, Cardiovascular Research Institute,University of California San Francisco,San Francisco,USA |
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| Abstract: | PurposeThe soluble receptor for advanced glycation end-products (sRAGE) is a marker of lung epithelial injury and alveolar fluid clearance (AFC), with promising values for assessing prognosis and lung injury severity in acute respiratory distress syndrome (ARDS). Because AFC is impaired in most patients with ARDS and is associated with higher mortality, we hypothesized that baseline plasma sRAGE would predict mortality, independently of two key mediators of ventilator-induced lung injury.MethodsWe conducted a meta-analysis of individual data from 746 patients enrolled in eight prospective randomized and observational studies in which plasma sRAGE was measured in ARDS articles published through March 2016. The primary outcome was 90-day mortality. Using multivariate and mediation analyses, we tested the association between baseline plasma sRAGE and mortality, independently of driving pressure and tidal volume.ResultsHigher baseline plasma sRAGE odds ratio (OR) for each one-log increment, 1.18; 95% confidence interval (CI) 1.01–1.38; P?=?0.04], driving pressure (OR for each one-point increment, 1.04; 95% CI 1.02–1.07; P?=?0.002), and tidal volume (OR for each one-log increment, 1.98; 95% CI 1.07–3.64; P?=?0.03) were independently associated with higher 90-day mortality in multivariate analysis. Baseline plasma sRAGE mediated a small fraction of the effect of higher ΔP on mortality but not that of higher VT.ConclusionsHigher baseline plasma sRAGE was associated with higher 90-day mortality in patients with ARDS, independently of driving pressure and tidal volume, thus reinforcing the likely contribution of alveolar epithelial injury as an important prognostic factor in ARDS. Registration: PROSPERO (ID: CRD42018100241). |
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