Faculty Collaboration Database

Plasma receptor interacting protein kinase-3 levels are associated with acute respiratory distress syndrome in sepsis and trauma: a cohort study. Crit Care 2019 Jun 28;23(1):235

Date

06/30/2019

Pubmed ID

31253195

Pubmed Central ID

PMC6599265

DOI

10.1186/s13054-019-2482-x

Scopus ID

2-s2.0-85068191079 (requires institutional sign-in at Scopus site)   28 Citations

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.

Author List

Shashaty MGS, Reilly JP, Faust HE, Forker CM, Ittner CAG, Zhang PX, Hotz MJ, Fitzgerald D, Yang W, Anderson BJ, Holena DN, Lanken PN, Christie JD, Meyer NJ, Mangalmurti NS

Author

Daniel N. Holena MD Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Biomarkers
Cohort Studies
Critical Illness
Female
Humans
Logistic Models
Male
Middle Aged
Prospective Studies
Receptor-Interacting Protein Serine-Threonine Kinases
Sepsis
Severity of Illness Index
Wounds and Injuries