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Critical Care
Published in: Critical Care 1/2019

Open Access 01-12-2019 | Acute Kidney Injury | Research

Plasma receptor interacting protein kinase-3 levels are associated with acute respiratory distress syndrome in sepsis and trauma: a cohort study

Authors: Michael G. S. Shashaty, John P. Reilly, Hilary E. Faust, Caitlin M. Forker, Caroline A. G. Ittner, Peggy X. Zhang, Meghan J. Hotz, David Fitzgerald, Wei Yang, Brian J. Anderson, Daniel N. Holena, Paul N. Lanken, Jason D. Christie, Nuala J. Meyer, Nilam S. Mangalmurti

Published in: Critical Care | Issue 1/2019

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Abstract

Background

Necroptosis, a form of programmed cell death mediated by receptor interacting serine/threonine-protein kinase-3 (RIPK3), is implicated in murine models of acute respiratory distress syndrome (ARDS). We hypothesized that plasma RIPK3 concentrations in sepsis and trauma would be associated with ARDS development and that plasma RIPK3 would reflect changes in lung tissue RIPK3 in a murine model of systemic inflammation.

Methods

We utilized prospective cohort studies of critically ill sepsis (n = 120) and trauma (n = 180) patients and measured plasma RIPK3 at presentation and 48 h. Patients were followed for 6 days for ARDS by the Berlin definition. We used multivariable logistic regression to determine the association of plasma RIPK3 with ARDS in each cohort, adjusting for confounders. In mice, we determined whether plasma and lung tissue RIPK3 levels rise concomitantly 4 h after injection with lipopolysaccharide and ZVAD-FMK, an apoptosis inhibitor.

Results

The change in plasma RIPK3 from presentation to 48 h (ΔRIPK3) was associated with ARDS in sepsis (OR 1.30, 95% CI 1.03–1.63, per ½ standard deviation) and trauma (OR 1.79, 95% CI 1.33–2.40). This association was not evident for presentation RIPK3 levels. Secondary analyses showed similar findings for the association of ΔRIPK3 with acute kidney injury and 30-day mortality. Mice injected with lipopolysaccharide and ZVAD-FMK had significantly higher plasma (p < 0.001) and lung (p = 0.005) RIPK3 than control mice.

Conclusions

The change in plasma RIPK3 from presentation to 48 h in both sepsis and trauma patients is independently associated with ARDS, and plasma RIPK3 may reflect RIPK3 activity in lung tissue.
Appendix
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Metadata
Title
Plasma receptor interacting protein kinase-3 levels are associated with acute respiratory distress syndrome in sepsis and trauma: a cohort study
Authors
Michael G. S. Shashaty
John P. Reilly
Hilary E. Faust
Caitlin M. Forker
Caroline A. G. Ittner
Peggy X. Zhang
Meghan J. Hotz
David Fitzgerald
Wei Yang
Brian J. Anderson
Daniel N. Holena
Paul N. Lanken
Jason D. Christie
Nuala J. Meyer
Nilam S. Mangalmurti
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2019
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-019-2482-x

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