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Published in: Critical Care 1/2021

01-12-2021 | Septicemia | Research

Monitoring circulating dipeptidyl peptidase 3 (DPP3) predicts improvement of organ failure and survival in sepsis: a prospective observational multinational study

Authors: Alice Blet, Benjamin Deniau, Karine Santos, Dirk P. T. van Lier, Feriel Azibani, Xavier Wittebole, Benjamin G. Chousterman, Etienne Gayat, Oliver Hartmann, Joachim Struck, Andreas Bergmann, Massimo Antonelli, Albertus Beishuizen, Jean-Michel Constantin, Charles Damoisel, Nicolas Deye, Salvatore Di Somma, Thierry Dugernier, Bruno François, Stephane Gaudry, Vincent Huberlant, Jean-Baptiste Lascarrou, Gernot Marx, Emmanuelle Mercier, Haikel Oueslati, Peter Pickkers, Romain Sonneville, Matthieu Legrand, Pierre-François Laterre, Alexandre Mebazaa, AdrenOSS-1 Study Investigators

Published in: Critical Care | Issue 1/2021

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Abstract

Background

Dipeptidyl peptidase 3 (DPP3) is a cytosolic enzyme involved in the degradation of various cardiovascular and endorphin mediators. High levels of circulating DPP3 (cDPP3) indicate a high risk of organ dysfunction and mortality in cardiogenic shock patients.

Methods

The aim was to assess relationships between cDPP3 during the initial intensive care unit (ICU) stay and short-term outcome in the AdrenOSS-1, a prospective observational multinational study in twenty-four ICU centers in five countries. AdrenOSS-1 included 585 patients admitted to the ICU with severe sepsis or septic shock. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by the Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use and need for renal replacement therapy. cDPP3 levels were measured upon admission and 24 h later.

Results

Median [IQR] cDPP3 concentration upon admission was 26.5 [16.2–40.4] ng/mL. Initial SOFA score was 7 [5–10], and 28-day mortality was 22%. We found marked associations between cDPP3 upon ICU admission and 28-day mortality (unadjusted standardized HR 1.8 [CI 1.6–2.1]; adjusted HR 1.5 [CI 1.3–1.8]) and between cDPP3 levels and change in renal and liver SOFA score (p = 0.0077 and 0.0009, respectively). The higher the initial cDPP3 was, the greater the need for organ support and vasopressors upon admission; the longer the need for vasopressor(s), mechanical ventilation or RRT and the higher the need for fluid load (all p < 0.005). In patients with cDPP3 > 40.4 ng/mL upon admission, a decrease in cDPP3 below 40.4 ng/mL after 24 h was associated with an improvement of organ function at 48 h and better 28-day outcome. By contrast, persistently elevated cDPP3 at 24 h was associated with worsening organ function and high 28-day mortality.

Conclusions

Admission levels and rapid changes in cDPP3 predict outcome during sepsis.
Trial Registration ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015.
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Metadata
Title
Monitoring circulating dipeptidyl peptidase 3 (DPP3) predicts improvement of organ failure and survival in sepsis: a prospective observational multinational study
Authors
Alice Blet
Benjamin Deniau
Karine Santos
Dirk P. T. van Lier
Feriel Azibani
Xavier Wittebole
Benjamin G. Chousterman
Etienne Gayat
Oliver Hartmann
Joachim Struck
Andreas Bergmann
Massimo Antonelli
Albertus Beishuizen
Jean-Michel Constantin
Charles Damoisel
Nicolas Deye
Salvatore Di Somma
Thierry Dugernier
Bruno François
Stephane Gaudry
Vincent Huberlant
Jean-Baptiste Lascarrou
Gernot Marx
Emmanuelle Mercier
Haikel Oueslati
Peter Pickkers
Romain Sonneville
Matthieu Legrand
Pierre-François Laterre
Alexandre Mebazaa
AdrenOSS-1 Study Investigators
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2021
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-021-03471-2

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