Plasma sRAGE is independently associated with increased mortality in ARDS: a meta-analysis of individual patient data

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 ConstantinCarolyn S. Calfee

Research output: Contribution to journalArticle

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Abstract

Purpose: The 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. Methods: We 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. Results: Higher 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. Conclusions: Higher 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).

Original languageEnglish
Pages (from-to)1388-1399
JournalIntensive Care Medicine
Volume44
Issue number9
DOIs
Publication statusPublished - 2018

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Adult Respiratory Distress Syndrome
Meta-Analysis
Mortality
Tidal Volume
Odds Ratio
Lung Injury
Confidence Intervals
Pressure
Multivariate Analysis
Ventilator-Induced Lung Injury
Advanced Glycosylation End Product-Specific Receptor
Observational Studies
Prospective Studies
Wounds and Injuries

Keywords

  • Acute respiratory distress syndrome
  • Biomarker
  • Lung epithelial injury
  • Prognosis
  • Receptor for advanced glycation end-products

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Plasma sRAGE is independently associated with increased mortality in ARDS : a meta-analysis of individual patient data. / Jabaudon, Matthieu; Blondonnet, Raiko; Pereira, Bruno; Cartin-Ceba, Rodrigo; Lichtenstern, Christoph; Mauri, Tommaso; Determann, Rogier M.; Drabek, Tomas; Hubmayr, Rolf D.; Gajic, Ognjen; Uhle, Florian; Coppadoro, Andrea; Pesenti, Antonio; Schultz, Marcus J.; Ranieri, Marco V.; Brodska, Helena; Mrozek, Ségolène; Sapin, Vincent; Matthay, Michael A.; Constantin, Jean Michel; Calfee, Carolyn S.

In: Intensive Care Medicine, Vol. 44, No. 9, 2018, p. 1388-1399.

Research output: Contribution to journalArticle

Jabaudon, M, Blondonnet, R, Pereira, B, Cartin-Ceba, R, Lichtenstern, C, Mauri, T, Determann, RM, Drabek, T, Hubmayr, RD, Gajic, O, Uhle, F, Coppadoro, A, Pesenti, A, Schultz, MJ, Ranieri, MV, Brodska, H, Mrozek, S, Sapin, V, Matthay, MA, Constantin, JM & Calfee, CS 2018, 'Plasma sRAGE is independently associated with increased mortality in ARDS: a meta-analysis of individual patient data', Intensive Care Medicine, vol. 44, no. 9, pp. 1388-1399. https://doi.org/10.1007/s00134-018-5327-1
Jabaudon, Matthieu ; Blondonnet, Raiko ; Pereira, Bruno ; Cartin-Ceba, Rodrigo ; Lichtenstern, Christoph ; Mauri, Tommaso ; Determann, Rogier M. ; Drabek, Tomas ; Hubmayr, Rolf D. ; Gajic, Ognjen ; Uhle, Florian ; Coppadoro, Andrea ; Pesenti, Antonio ; Schultz, Marcus J. ; Ranieri, Marco V. ; Brodska, Helena ; Mrozek, Ségolène ; Sapin, Vincent ; Matthay, Michael A. ; Constantin, Jean Michel ; Calfee, Carolyn S. / Plasma sRAGE is independently associated with increased mortality in ARDS : a meta-analysis of individual patient data. In: Intensive Care Medicine. 2018 ; Vol. 44, No. 9. pp. 1388-1399.
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T1 - Plasma sRAGE is independently associated with increased mortality in ARDS

T2 - a meta-analysis of individual patient data

AU - Jabaudon, Matthieu

AU - Blondonnet, Raiko

AU - Pereira, Bruno

AU - Cartin-Ceba, Rodrigo

AU - Lichtenstern, Christoph

AU - Mauri, Tommaso

AU - Determann, Rogier M.

AU - Drabek, Tomas

AU - Hubmayr, Rolf D.

AU - Gajic, Ognjen

AU - Uhle, Florian

AU - Coppadoro, Andrea

AU - Pesenti, Antonio

AU - Schultz, Marcus J.

AU - Ranieri, Marco V.

AU - Brodska, Helena

AU - Mrozek, Ségolène

AU - Sapin, Vincent

AU - Matthay, Michael A.

AU - Constantin, Jean Michel

AU - Calfee, Carolyn S.

PY - 2018

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N2 - Purpose: The 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. Methods: We 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. Results: Higher 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. Conclusions: Higher 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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KW - Biomarker

KW - Lung epithelial injury

KW - Prognosis

KW - Receptor for advanced glycation end-products

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