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

被引：47

作者：

Blet, Alice ^{[1
,2
,3
,4
]}

Deniau, Benjamin ^{[1
,2
]}

Santos, Karine ^{[5
]}

van Lier, Dirk P. T. ^{[6
,7
]}

Azibani, Feriel ^{[2
]}

Wittebole, Xavier ^{[8
]}

Chousterman, Benjamin G. ^{[1
,2
]}

Gayat, Etienne ^{[1
,2
]}

Hartmann, Oliver ^{[9
]}

Struck, Joachim ^{[9
]}

Bergmann, Andreas ^{[5
]}

Antonelli, Massimo ^{[10
]}

Beishuizen, Albertus ^{[11
]}

Constantin, Jean-Michel ^{[12
]}

Damoisel, Charles ^{[1
]}

Deye, Nicolas ^{[2
,13
]}

Di Somma, Salvatore ^{[14
]}

Dugernier, Thierry ^{[15
]}

Francois, Bruno ^{[16
,17
]}

Gaudry, Stephane ^{[18
]}

Huberlant, Vincent ^{[19
]}

Lascarrou, Jean-Baptiste ^{[20
]}

Marx, Gernot ^{[21
]}

Mercier, Emmanuelle ^{[22
,23
]}

Oueslati, Haikel ^{[1
]}

Pickkers, Peter ^{[6
,7
]}

Sonneville, Romain ^{[23
]}

Legrand, Matthieu ^{[24
]}

Laterre, Pierre-Francois ^{[25
]}

Mebazaa, Alexandre ^{[1
,2
]}

机构：

[1] Univ Paris, AP HP Nord, Lariboisiere St Louis Hosp, Dept Anesthesiol,Crit Care & Burn Ctr,DMU Parabol, Paris, France

[2] Univ Paris, INSERM, Cardiovasc Markers Stress Condit MASCOT, UMRS 942, 2 Rue Ambroise Pare, F-75010 Paris, France

[3] Univ Ottawa, Heart Inst, Ottawa, ON, Canada

[4] Univ Ottawa, Ottawa, ON, Canada

[5] 4TEEN4 Pharmaceut GmbH, Hennigsdorf, Germany

[6] Radboud Univ Nijmegen, Med Ctr, Dept Intens Care Med, Geert Grootepl Zuid 10, NL-6500 HB Nijmegen, Netherlands

[7] Radboud Univ Nijmegen, Med Ctr, Radboud Ctr Infect Dis, Nijmegen, Netherlands

[8] Catholic Univ Louvain, St Luc Univ Hosp, Dept Crit Care Med, Brussels, Belgium

[9] SphingoTec GmbH, Hennigsdorf, Germany

[10] Fdn Policlin Univ A Gemelli IRCCS, Dept Anesthesiol & Intens Care Med, Rome, Italy

[11] Med Spectrum Twente, Dept Intens Care, Enschede, Netherlands

[12] Sorbonne Univ, Pitie Salpetriere Hosp, AP HP, Dept Anaesthesiol & Crit Care,DMU,DREAM,GRC 29, Paris, France

[13] Univ Paris Diderot, Lariboisiere Hosp, Dept Med & Toxicol Crit Care, Federat Toxicol,AP HP, Paris, France

[14] St Andrea Hosp, Rome, Italy

[15] Clin St Pierre, Ottignies, Belgium

[16] CHU Dupuytren, ICU Dept, Limoges, France

[17] INSERM, CIC 1435, UMR 1092, Limoges, France

[18] Hop Louis Mourier, Colombes, France

[19] Hop Jolimont, Haine St Paul, Belgium

[20] CHU Nantes, Nantes, France

[21] Univ Klinikum RWTH, Klin Operat Intens Med & Intermediate Care, Aachen, Germany

[22] CHU Tours, Tours, France

[23] Hop Bichat Claude Bernard, Paris, France

[24] Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA

[25] Catholic Univ Louvain, St Luc Univ Hosp, Dept Crit Care Med, Ave Hippocrate 10, B-1200 Brussels, Belgium

来源：

CRITICAL CARE | 2021年 / 25卷 / 01期

基金：

欧盟地平线“2020”;

关键词：

DPP3; Biomarker; Outcome; Sepsis; Septic shock; Organ dysfunction;

D O I：

10.1186/s13054-021-03471-2

中图分类号：

R4 [临床医学];

学科分类号：

1002 ; 100602 ;

摘要：

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<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.ConclusionsAdmission levels and rapid changes in cDPP3 predict outcome during sepsis.Trial Registration ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015.

引用

页数：10

共 9 条

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