1. Monitoring circulating dipeptidyl peptidase 3 (DPP3) predicts improvement of organ failure and survival in sepsis: a prospective observational multinational study
- Author
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Blet, Alice, Deniau, Benjamin, Santos, Karine, van Lier, Dirk PT, Azibani, Feriel, Wittebole, Xavier, Chousterman, Benjamin G, Gayat, Etienne, Hartmann, Oliver, Struck, Joachim, Bergmann, Andreas, Antonelli, Massimo, Beishuizen, Albertus, Constantin, Jean-Michel, Damoisel, Charles, Deye, Nicolas, Di Somma, Salvatore, Dugernier, Thierry, François, Bruno, Gaudry, Stephane, Huberlant, Vincent, Lascarrou, Jean-Baptiste, Marx, Gernot, Mercier, Emmanuelle, Oueslati, Haikel, Pickkers, Peter, Sonneville, Romain, Legrand, Matthieu, Laterre, Pierre-François, and Mebazaa, Alexandre
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Kidney Disease ,Infectious Diseases ,Hematology ,Clinical Research ,Sepsis ,Infection ,Inflammatory and immune system ,Good Health and Well Being ,Aged ,Biomarkers ,Chi-Square Distribution ,Dipeptidyl-Peptidases and Tripeptidyl-Peptidases ,Female ,Humans ,Intensive Care Units ,Male ,Middle Aged ,Mortality ,Multiple Organ Failure ,Organ Dysfunction Scores ,Proportional Hazards Models ,Prospective Studies ,Statistics ,Nonparametric ,DPP3 ,Biomarker ,Outcome ,Septic shock ,Organ dysfunction ,AdrenOSS-1 Study Investigators ,Medical and Health Sciences ,Emergency & Critical Care Medicine ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundDipeptidyl 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.MethodsThe 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.ResultsMedian [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 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.ConclusionsAdmission levels and rapid changes in cDPP3 predict outcome during sepsis. Trial Registration ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015.
- Published
- 2021