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

Blet, Alice Deniau, Benjamin Santos, Karine van Lier, Dirk P T Azibani, Feriel Wittebole, Xavier [UCL] 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 [UCL] Mebazaa, Alexandre AdrenOSS-1 Study Investigators et al.[show all]

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.