# Impact of acute renal failure on plasmatic levels of cleaved endocan

Alexandre Gaudet, Erika Parmentier, Nathalie de Freitas Caires, Lucie Portier, Sylvain Dubucquoi, Julien Poissy, Thibault Duburcq, Maxence Hureau, Philippe Lassalle, Daniel Mathieu

► To cite this version:

Alexandre Gaudet, Erika Parmentier, Nathalie de Freitas Caires, Lucie Portier, Sylvain Dubucquoi, et al. Impact of acute renal failure on plasmatic levels of cleaved endocan. Critical care (London, England), 2019, Critical care (London, England), 23, pp.55. 10.1186/s13054-019-2349-1. hal-04465032

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# Impact of acute renal failure on plasmatic levels of cleaved endocan

Alexandre Gaudet, Erika Parmentier, Nathalie de Freitas Caires, Lucie Portier, Sylvain Dubucquoi, Julien Poissy, Thibault Duburcq, Maxence Hureau, Philippe Lassalle, Daniel Mathieu

► To cite this version:

Alexandre Gaudet, Erika Parmentier, Nathalie de Freitas Caires, Lucie Portier, Sylvain Dubucquoi, et al. Impact of acute renal failure on plasmatic levels of cleaved endocan. Critical Care, 2019, Critical care (London, England), 23, pp.55. 10.1186/s13054-019-2349-1. hal-04465032

HAL Id: hal-04465032

https://lilloa.hal.science/hal-04465032v1

Submitted on 19 Feb 2024

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

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Distributed under a Creative Commons Attribution 4.0 International License
<figure><img src="image_2.png" /></figure>

# Impact of acute renal failure on plasmatic levels of cleaved endocan

Alexandre Gaudet<fnref n="1" />,<fnref n="2" />,³,⁴*, Erika Parmentier<fnref n="1" />,<fnref n="2" />,³,⁴, Nathalie De Freitas Caires<fnref n="1" />,<fnref n="2" />,³,⁵, Lucie Portier<fnref n="1" />,<fnref n="2" />,³,⁵, Sylvain Dubucquois⁶, Julien Poissy⁴, Thibault Duburcq⁴, Maxence Hureau<fnref n="1" />,<fnref n="2" />,³,⁴, Philippe Lassalle<fnref n="1" />,<fnref n="2" />,³,⁷ and Daniel Mathieu<fnref n="1" />,<fnref n="2" />,³,⁴

Dear Editor,

Recent failures to improve the prognostic of sepsis have underlined the need for a better phenotypical description of septic subjects. In this view, endocan, an endothelial proteoglycan secreted under proinflammatory conditions, has been described as a useful biomarker to early identify patients at higher risk of poor outcomes during the time course of sepsis [1]. More recently, a major catabolite of endocan, p14, has been observed at high plasmatic levels in a series of septic subjects, paving the way for a more accurate prediction of poor outcomes in such patients. However, major variations of p14 were observed between patients in this series, with unknown clinical significance [2]. Furthermore, it is currently unknown whether p14 could undergo renal elimination.

We performed a post hoc analysis based on the data from a previously published prospective cohort of severe septic patients [3]. Ninety-nine patients underwent measurement of p14 on EDTA plasma. Plasmatic endocan cleavage ratio (ECR) was calculated as plasma p14/(endocan + p14) ratio (endocan and p14 being expressed in pmol/mL) on baseline and 24 h, 48

h, and 72 h following ICU admission. Baseline characteristics of patients are exposed in Additional file 1.

In this cohort, ECR on enrolment was correlated with baseline SAPS 2 ($\rho$ = 0.36, 95% CI (0.17–0.53); $p$ < $10^{-3}$) and SOFA ($\rho$ = 0.21 (0–0.39); $p$ = 0.04). Renal SOFA was the only component of SOFA score associated with higher ECR, with median [IQR] baseline ECR observed at 0.38 [0.29–0.61] in patients with baseline renal SOFA > 2 vs 0.28 [0.19–0.36] in patients with baseline renal SOFA $\le$ 2 ($p$ < $10^{-3}$) (Table 1). Over 72 h, patients with a baseline renal SOFA at 4 h had higher median plasmatic ECR than those with baseline renal SOFA < 4 ($p$ < $10^{-3}$) (Fig. 1).

Our results suggest that circulating concentrations of p14 might be influenced by the severity of acute renal failure. Therefore, it could be proposed that, by contrast with endocan, p14 could be eliminated through glomerular filtration, thus suggesting that it should be measured in urine rather than in blood. This discrepancy might be explained by the smaller molecular weight of p14, as well as the absence of polyanionic glycanic chain on its protein core. Further explorations are needed to confirm these hypotheses.

<figure><img src="image_3.png" /></figure>

<footnote>* Correspondence: alexandre.gaudet@chru-lille.fr</footnote>

<footnote n="1">¹Univ. Lille, U1019 – UMR 8204 – CIIL – Center for Infection and Immunity of Lille, F-59000 Lille, France</footnote>

<footnote n="2">²CNRS, UMR 8204, F-59000 Lille, France</footnote>

<footnote>Full list of author information is available at the end of the article</footnote>
LETTER

Open Access

<figure><img src="image_2.png" /></figure>

CrossMark

# Impact of acute renal failure on plasmatic levels of cleaved endocan

Alexandre Gaudet<fnref n="1" />,<fnref n="2" />,³,⁴*, Erika Parmentier<fnref n="1" />,<fnref n="2" />,³,⁴, Nathalie De Freitas Caires<fnref n="1" />,<fnref n="2" />,³,⁵, Lucie Portier<fnref n="1" />,<fnref n="2" />,³,⁵, Sylvain Dubucquois⁶, Julien Poissy⁴, Thibault Duburcq⁴, Maxence Hureau<fnref n="1" />,<fnref n="2" />,³,⁴, Philippe Lassalle<fnref n="1" />,<fnref n="2" />,³,⁷ and Daniel Mathieu<fnref n="1" />,<fnref n="2" />,³,⁴

Dear Editor,

Recent failures to improve the prognostic of sepsis have underlined the need for a better phenotypical description of septic subjects. In this view, endocan, an endothelial proteoglycan secreted under proinflammatory conditions, has been described as a useful biomarker to early identify patients at higher risk of poor outcomes during the time course of sepsis [1]. More recently, a major catabolite of endocan, p14, has been observed at high plasmatic levels in a series of septic subjects, paving the way for a more accurate prediction of poor outcomes in such patients. However, major variations of p14 were observed between patients in this series, with unknown clinical significance [2]. Furthermore, it is currently unknown whether p14 could undergo renal elimination.

We performed a post hoc analysis based on the data from a previously published prospective cohort of severe septic patients [3]. Ninety-nine patients underwent measurement of p14 on EDTA plasma. Plasmatic endocan cleavage ratio (ECR) was calculated as plasma p14/(endocan + p14) ratio (endocan and p14 being expressed in pmol/mL) on baseline and 24 h, 48

h, and 72 h following ICU admission. Baseline characteristics of patients are exposed in Additional file 1.

In this cohort, ECR on enrolment was correlated with baseline SAPS 2 ($\rho$ = 0.36, 95% CI (0.17–0.53); $p$ < $10^{-3}$) and SOFA ($\rho$ = 0.21 (0–0.39); $p$ = 0.04). Renal SOFA was the only component of SOFA score associated with higher ECR, with median [IQR] baseline ECR observed at 0.38 [0.29–0.61] in patients with baseline renal SOFA > 2 vs 0.28 [0.19–0.36] in patients with baseline renal SOFA $\le$ 2 ($p$ < $10^{-3}$) (Table 1). Over 72 h, patients with a baseline renal SOFA at 4 h had higher median plasmatic ECR than those with baseline renal SOFA < 4 ($p$ < $10^{-3}$) (Fig. 1).

Our results suggest that circulating concentrations of p14 might be influenced by the severity of acute renal failure. Therefore, it could be proposed that, by contrast with endocan, p14 could be eliminated through glomerular filtration, thus suggesting that it should be measured in urine rather than in blood. This discrepancy might be explained by the smaller molecular weight of p14, as well as the absence of polyanionic glycanic chain on its protein core. Further explorations are needed to confirm these hypotheses.

<figure><img src="image_3.png" /></figure>

BMC

© The Author(s). 2019 **Open Access** This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

<footnote>* Correspondence: alexandre.gaudet@chru-lille.fr</footnote>

<footnote n="1">¹Univ. Lille, U1019 – UMR 8204 – CIIL – Center for Infection and Immunity of Lille, F-59000 Lille, France</footnote>

<footnote n="2">²CNRS, UMR 8204, F-59000 Lille, France</footnote>

<footnote>Full list of author information is available at the end of the article</footnote>
<table><caption>**Table 1** Endocan cleavage ratio (ECR) according to patients' characteristics</caption><thead><tr><th>Variables</th><th>Absent</th><th>Present</th><th>Spearman ρ (95% CI)</th><th>p</th></tr></thead><tbody><tr><td>Age (years)</td><td></td><td></td><td>0.18 (-0.03-0.37)</td><td>0.08</td></tr><tr><td>Chronic comorbidities</td><td></td><td></td><td></td><td></td></tr><tr><td>COPD</td><td>0.33 [0.21-0.42]</td><td>0.23 [0.18-0.51]</td><td></td><td>0.53</td></tr><tr><td>Smoker</td><td>0.33 [0.21-0.45]</td><td>0.23 [0.18-0.35]</td><td></td><td>0.15</td></tr><tr><td>Cardiomyopathy</td><td>0.3 [0.2-0.42]</td><td>0.33 [0.2-0.45]</td><td></td><td>0.61</td></tr><tr><td>Chronic kidney failure</td><td>0.31 [0.21-0.44]</td><td>0.25 [0.05-0.56]</td><td></td><td>0.7</td></tr><tr><td>Cirrhosis</td><td>0.31 [0.2-0.45]</td><td>0.3 [0.21-0.37]</td><td></td><td>0.63</td></tr><tr><td>Sepsis severity on enrolment</td><td></td><td></td><td></td><td></td></tr><tr><td>Severe sepsis</td><td></td><td>0.29 [0.2-0.41]</td><td></td><td></td></tr><tr><td>Septic shock</td><td></td><td>0.31 [0.2-0.45]</td><td></td><td>0.74</td></tr><tr><td>Site of infection on enrolment</td><td></td><td></td><td></td><td></td></tr><tr><td>Soft tissues</td><td></td><td>0.3 [0.2-0.39]</td><td></td><td></td></tr><tr><td>Respiratory</td><td></td><td>0.33 [0.21-0.45]</td><td></td><td></td></tr><tr><td>Urinary</td><td></td><td>0.31 [0.22-0.53]</td><td></td><td>0.82</td></tr><tr><td>Digestive</td><td></td><td>0.31 [0.24-0.38]</td><td></td><td></td></tr><tr><td>Other</td><td></td><td>0.21 [0.07-0.49]</td><td></td><td></td></tr><tr><td>Biomarkers on enrolment</td><td></td><td></td><td></td><td></td></tr><tr><td>CRP (mg/L)</td><td></td><td></td><td>0 (-0.21-0.2)</td><td>0.96</td></tr><tr><td>PCT (ng/mL)</td><td></td><td></td><td>0.06 (-0.15-0.26)</td><td>0.58</td></tr><tr><td>Prognostic scores on enrolment</td><td></td><td></td><td></td><td></td></tr><tr><td>SAPS 2</td><td></td><td></td><td>0.36 (0.17-0.53)</td><td>&lt; 10<sup>-3</sup></td></tr><tr><td>SOFA</td><td></td><td></td><td>0.21 (0-0.39)</td><td>0.04</td></tr><tr><td>LIPS</td><td></td><td></td><td>0.12 (-0.08-0.32)</td><td>0.22</td></tr><tr><td>Organ SOFA &gt; 2 on enrolment</td><td></td><td></td><td></td><td></td></tr><tr><td>Pulmonary</td><td>0.3 [0.2-0.37]</td><td>0.35 [0.24-0.48]</td><td></td><td>0.19</td></tr><tr><td>Renal</td><td>0.28 [0.19-0.36]</td><td>0.38 [0.29-0.61]</td><td></td><td>&lt; 10<sup>-3</sup></td></tr><tr><td>Hepatic</td><td>0.32 [0.21-0.42]</td><td>0.26 [0.14-0.53]</td><td></td><td>0.75</td></tr><tr><td>Circulatory</td><td>0.23 [0-0.39]</td><td>0.33 [0.23-0.45]</td><td></td><td>0.12</td></tr><tr><td>Neurological</td><td>0.3 [0.2-0.38]</td><td>0.33 [0.24-0.48]</td><td></td><td>0.19</td></tr><tr><td>Hematological</td><td>0.31 [0.2-0.4]</td><td>0.27 [0.12-0.54]</td><td></td><td>0.99</td></tr><tr><td>Mortality</td><td></td><td></td><td></td><td></td></tr><tr><td>Day 28</td><td>0.3 [0.19-0.38]</td><td>0.33 [0.23-0.48]</td><td></td><td>0.4</td></tr><tr><td>ICU discharge</td><td>0.3 [0.2-0.37]</td><td>0.33 [0.23-0.54]</td><td></td><td>0.24</td></tr><tr><td>ICU length of stay (days)</td><td></td><td></td><td>0.16 (-0.04-0.35)</td><td>0.11</td></tr><tr><td>Mechanical ventilation on enrolment</td><td>0.3 [0.19-0.37]</td><td>0.31 [0.23-0.47]</td><td></td><td>0.33</td></tr></tbody></table>

ECR are presented as median [IQR] values according to presence or absence of categorical variables. A Mann-Whitney test was used for comparison between two groups. A Kruskal-Wallis test was used for comparison between three or more groups. Correlations between ECR and continuous variables are described through Spearman ρ (95% CI)

COPD chronic obstructive pulmonary disease, SOFA Sequential Organ Failure Assessment, ICU intensive care unit, SAPS 2 Simplified Acute Physiology Score 2, LIPS Lung Injury Prediction Score
<table><caption>**Table 1** Endocan cleavage ratio (ECR) according to patients' characteristics</caption><thead><tr><th>Variables</th><th>Absent</th><th>Present</th><th>Spearman ρ (95% CI)</th><th>p</th></tr></thead><tbody><tr><td>Age (years)</td><td></td><td></td><td>0.18 (-0.03-0.37)</td><td>0.08</td></tr><tr><td>Chronic comorbidities</td><td></td><td></td><td></td><td></td></tr><tr><td>COPD</td><td>0.33 [0.21-0.42]</td><td>0.23 [0.18-0.51]</td><td></td><td>0.53</td></tr><tr><td>Smoker</td><td>0.33 [0.21-0.45]</td><td>0.23 [0.18-0.35]</td><td></td><td>0.15</td></tr><tr><td>Cardiomyopathy</td><td>0.3 [0.2-0.42]</td><td>0.33 [0.2-0.45]</td><td></td><td>0.61</td></tr><tr><td>Chronic kidney failure</td><td>0.31 [0.21-0.44]</td><td>0.25 [0.05-0.56]</td><td></td><td>0.7</td></tr><tr><td>Cirrhosis</td><td>0.31 [0.2-0.45]</td><td>0.3 [0.21-0.37]</td><td></td><td>0.63</td></tr><tr><td>Sepsis severity on enrolment</td><td></td><td></td><td></td><td></td></tr><tr><td>Severe sepsis</td><td></td><td>0.29 [0.2-0.41]</td><td></td><td></td></tr><tr><td>Septic shock</td><td></td><td>0.31 [0.2-0.45]</td><td></td><td>0.74</td></tr><tr><td>Site of infection on enrolment</td><td></td><td></td><td></td><td></td></tr><tr><td>Soft tissues</td><td></td><td>0.3 [0.2-0.39]</td><td></td><td></td></tr><tr><td>Respiratory</td><td></td><td>0.33 [0.21-0.45]</td><td></td><td></td></tr><tr><td>Urinary</td><td></td><td>0.31 [0.22-0.53]</td><td></td><td>0.82</td></tr><tr><td>Digestive</td><td></td><td>0.31 [0.24-0.38]</td><td></td><td></td></tr><tr><td>Other</td><td></td><td>0.21 [0.07-0.49]</td><td></td><td></td></tr><tr><td>Biomarkers on enrolment</td><td></td><td></td><td></td><td></td></tr><tr><td>CRP (mg/L)</td><td></td><td></td><td>0 (-0.21-0.2)</td><td>0.96</td></tr><tr><td>PCT (ng/mL)</td><td></td><td></td><td>0.06 (-0.15-0.26)</td><td>0.58</td></tr><tr><td>Prognostic scores on enrolment</td><td></td><td></td><td></td><td></td></tr><tr><td>SAPS 2</td><td></td><td></td><td>0.36 (0.17-0.53)</td><td>&lt; 10<sup>-3</sup></td></tr><tr><td>SOFA</td><td></td><td></td><td>0.21 (0-0.39)</td><td>0.04</td></tr><tr><td>LIPS</td><td></td><td></td><td>0.12 (-0.08-0.32)</td><td>0.22</td></tr><tr><td>Organ SOFA &gt; 2 on enrolment</td><td></td><td></td><td></td><td></td></tr><tr><td>Pulmonary</td><td>0.3 [0.2-0.37]</td><td>0.35 [0.24-0.48]</td><td></td><td>0.19</td></tr><tr><td>Renal</td><td>0.28 [0.19-0.36]</td><td>0.38 [0.29-0.61]</td><td></td><td>&lt; 10<sup>-3</sup></td></tr><tr><td>Hepatic</td><td>0.32 [0.21-0.42]</td><td>0.26 [0.14-0.53]</td><td></td><td>0.75</td></tr><tr><td>Circulatory</td><td>0.23 [0-0.39]</td><td>0.33 [0.23-0.45]</td><td></td><td>0.12</td></tr><tr><td>Neurological</td><td>0.3 [0.2-0.38]</td><td>0.33 [0.24-0.48]</td><td></td><td>0.19</td></tr><tr><td>Hematological</td><td>0.31 [0.2-0.4]</td><td>0.27 [0.12-0.54]</td><td></td><td>0.99</td></tr><tr><td>Mortality</td><td></td><td></td><td></td><td></td></tr><tr><td>Day 28</td><td>0.3 [0.19-0.38]</td><td>0.33 [0.23-0.48]</td><td></td><td>0.4</td></tr><tr><td>ICU discharge</td><td>0.3 [0.2-0.37]</td><td>0.33 [0.23-0.54]</td><td></td><td>0.24</td></tr><tr><td>ICU length of stay (days)</td><td></td><td></td><td>0.16 (-0.04-0.35)</td><td>0.11</td></tr><tr><td>Mechanical ventilation on enrolment</td><td>0.3 [0.19-0.37]</td><td>0.31 [0.23-0.47]</td><td></td><td>0.33</td></tr></tbody></table>

ECR are presented as median [IQR] values according to presence or absence of categorical variables. A Mann-Whitney test was used for comparison between two groups. A Kruskal-Wallis test was used for comparison between three or more groups. Correlations between ECR and continuous variables are described through Spearman ρ (95% CI)

COPD chronic obstructive pulmonary disease, SOFA Sequential Organ Failure Assessment, ICU intensive care unit, SAPS 2 Simplified Acute Physiology Score 2, LIPS Lung Injury Prediction Score
<figure><img src="image_4.png" /></figure>

**Fig. 1** a Box plots of plasmatic endocan cleavage ratio (ECR) on enrolment according to baseline renal SOFA. Box plot shows the median (horizontal line) and IQR (25th–75th percentile) (box). The whiskers show the lowest data within 1.5 IQR of the lower quartile and highest data within 1.5 IQR of the upper quartile; data outside 1.5 IQR of the upper or lower quartiles are depicted with a dot. Comparison between subjects with renal SOFA > 2 vs renal SOFA ≤ 2 was performed with the Mann-Whitney test. \*: *p* < 10⁻³. **b** Kinetics of plasmatic ECR median values over 72 h following enrolment according to baseline renal SOFA

## Additional file

**Additional file 1:** Cohort baseline characteristics. Continuous and categorical variables are described as median [interquartile range] and number (percentage), respectively. COPD chronic obstructive pulmonary disease, SOFA Sequential Organ Failure Assessment, ICU Intensive Care Unit SAPS 2 Simplified Acute Physiology Score 2, LIPS Lung Injury Prediction Score (DOC 45 kb)

### Abbreviations

ECR: Endocan cleavage ratio

### Acknowledgements

Not applicable.

### Funding

This work was supported by BPI France (grant number BPI 2012-05-336). This funding was attributed to D. M, representing Lille University Hospital. There was no role of the funding body in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.

### Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

### Authors' contributions

AG and EP designed the whole study, conducted the data analyses, and drafted the manuscript. ND, LP, and SD performed the biological measurements. DM supervised the whole project. All authors read and approved the final manuscript.

### Ethics approval and consent to participate

This study has been approved by the ethics committee of Lille University Hospital (approval number CP03/07). All the participants to this study gave their informed consent prior to enrollment.

### Consent for publication

Not applicable

### Competing interests

The Endomark H1 and DIYEK C1 ELISA kits used in this study were provided by Lunginnov. PL is the cofounder of Lunginnov. ND and LP are staff members of Lunginnov. The remaining authors declare that they have no competing interests.

## Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

### Author details

¹Univ. Lille, U1019 – UMR 8204 – CIIL – Center for Infection and Immunity of Lille, F-59000 Lille, France. ²CNRS, UMR 8204, F-59000 Lille, France. ³INSERM, U1019, F-59000 Lille, France. ⁴CHU Lille, Pôle de Réanimation, Hôpital Roger Salengro, F-59000 Lille, France. ⁵Lunginnov, 1 rue du Pr Calmette, F-59000 Lille, France. ⁶CHU Lille, Institut d'Immunologie, Centre de Biologie Pathologie Génétique, F-59000 Lille, France. ⁷Institut Pasteur de Lille, F-59000 Lille, France.

Received: 24 January 2019 Accepted: 7 February 2019

Published online: 19 February 2019

### References

1. De Freitas Caires N, Gaudet A, Portier L, Tsicopoulos A, Mathieu D, Lassalle P. Endocan, sepsis, pneumonia, and acute respiratory distress syndrome. Crit Care Lond Engl. 2018;22:280.

2. De Freitas Caires N, Legendre B, Parmentier E, Scherpereel A, Tsicopoulos A, Mathieu D, et al. Identification of a 14 kDa endocan fragment generated by cathepsin G, a novel circulating biomarker in patients with sepsis. J Pharm Biomed Anal. 2013;78-79:45-51.

3. Gaudet A, Parmentier E, Dubucquoi S, Poissy J, Duburcq T, Lassalle P, et al. Low endocan levels are predictive of acute respiratory distress syndrome in severe sepsis and septic shock. J Crit Care. 2018;47:121-6.
<figure><img src="image_4.png" /></figure>

**Fig. 1** a Box plots of plasmatic endocan cleavage ratio (ECR) on enrolment according to baseline renal SOFA. Box plot shows the median (horizontal line) and IQR (25th–75th percentile) (box). The whiskers show the lowest data within 1.5 IQR of the lower quartile and highest data within 1.5 IQR of the upper quartile; data outside 1.5 IQR of the upper or lower quartiles are depicted with a dot. Comparison between subjects with renal SOFA > 2 vs renal SOFA ≤ 2 was performed with the Mann-Whitney test. \*: *p* < 10⁻³. **b** Kinetics of plasmatic ECR median values over 72 h following enrolment according to baseline renal SOFA

## Additional file

**Additional file 1:** Cohort baseline characteristics. Continuous and categorical variables are described as median [interquartile range] and number (percentage), respectively. COPD chronic obstructive pulmonary disease, SOFA Sequential Organ Failure Assessment, ICU Intensive Care Unit SAPS 2 Simplified Acute Physiology Score 2, LIPS Lung Injury Prediction Score (DOC 45 kb)

### Abbreviations

ECR: Endocan cleavage ratio

### Acknowledgements

Not applicable.

### Funding

This work was supported by BPI France (grant number BPI 2012-05-336). This funding was attributed to D. M, representing Lille University Hospital. There was no role of the funding body in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.

### Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

### Authors' contributions

AG and EP designed the whole study, conducted the data analyses, and drafted the manuscript. ND, LP, and SD performed the biological measurements. DM supervised the whole project. All authors read and approved the final manuscript.

### Ethics approval and consent to participate

This study has been approved by the ethics committee of Lille University Hospital (approval number CP03/07). All the participants to this study gave their informed consent prior to enrollment.

### Consent for publication

Not applicable

### Competing interests

The Endomark H1 and DIYEK C1 ELISA kits used in this study were provided by Lunginnov. PL is the cofounder of Lunginnov. ND and LP are staff members of Lunginnov. The remaining authors declare that they have no competing interests.

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### Author details

¹Univ. Lille, U1019 – UMR 8204 – CIIL – Center for Infection and Immunity of Lille, F-59000 Lille, France. ²CNRS, UMR 8204, F-59000 Lille, France. ³INSERM, U1019, F-59000 Lille, France. ⁴CHU Lille, Pôle de Réanimation, Hôpital Roger Salengro, F-59000 Lille, France. ⁵Lunginnov, 1 rue du Pr Calmette, F-59000 Lille, France. ⁶CHU Lille, Institut d'Immunologie, Centre de Biologie Pathologie Génétique, F-59000 Lille, France. ⁷Institut Pasteur de Lille, F-59000 Lille, France.

Received: 24 January 2019 Accepted: 7 February 2019

Published online: 19 February 2019

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