Association of Serum Calprotectin Concentrations with Mortality in Critically Ill and Septic Patients.

Nina Haehnsen,Philipp Hohlstein,Jonathan F Brozat,Samira Abu Jhaisha,Ralf Weiskirchen,Alexander Koch,Tom Luedde,Christian Trautwein,Raphael Mohr,Ger Koek,Albrecht Eisert,Sven H Loosen,Frank Tacke,Tobias Puengel,Christoph Roderburg,Theresa H Wirtz,Lukas Buendgens

doi:10.3390/diagnostics10110990

Abstract

Background: Calprotectin is present in the cytosol of neutrophil granulocytes and released upon activation. Fecal calprotectin is applied in the clinical management of inflammatory bowel disease whereas serum calprotectin has been discussed as a biomarker in inflammatory disorders. However, its long-term prognostic relevance in critical illness remains unclear. Our aim was to investigate serum calprotectin concentrations as a prognostic biomarker in critically ill and septic patients. Methods: Serum calprotectin concentrations were analyzed in 165 critically ill patients (108 with sepsis, 57 without sepsis) included in our observational study. Patients were enrolled upon admission to the medical intensive care unit (ICU) of the RWTH Aachen University Hospital. Calprotectin concentrations were compared to 24 healthy controls and correlated with clinical parameters, therapeutic interventions, and survival. Results: Serum calprotectin concentrations were significantly increased in ICU patients as well as in septic patients compared to respective controls (p < 0.001 for ICU patients and p = 0.001 for septic patients). Lower calprotectin concentrations were measured in patients with comorbidities i.e., coronary artery disease. Calprotectin concentrations strongly correlated with the C-reactive protein (p < 0.001) and were closely associated to parameters of mechanical ventilation (i.a. inspiratory oxygen fraction, FiO2; p < 0.001). The overall survival was significantly impaired in septic patients with high baseline calprotectin concentrations (p = 0.036). However, patients with increasing calprotectin serum concentrations within the first week of ICU admission showed an improved overall survival (p = 0.009). Conclusions: In summary, serum calprotectin concentrations are significantly increased in critically ill patients with sepsis. High calprotectin concentrations at ICU admission predict long-term mortality risk, whereas increasing calprotectin concentrations are associated with a favorable long-term outcome.

Highlights

Calprotectin represents a heterodimer of the mammalian proteins S100A8 and S100A9
31.6% of included patients had previously been diagnosed with diabetes mellitus type 2; 10% suffered from malignant disease at the time point of intensive care unit (ICU) admission
We demonstrate that serum concentrations of calprotectin are increased in critically ill patients as well as septic patients at ICU admission compared to controls

Summary

Introduction

Calprotectin represents a heterodimer of the mammalian proteins S100A8 and S100A9. It accounts for 60% of the soluble protein in the cytosol of neutrophil granulocytes and is released by neutrophils upon their activation and turnover [1,2]. Since one of the main sources for S100A8/S100A9 secretion is infection-induced inflammation, calprotectin concentrations in serum were found to be elevated during bacterial infections [7,8,9,10] and indicated complicated courses of disease [11]. Both S100 proteins were identified to participate in innate immunity in a proinflammatory manner as they mediate inflammatory responses by triggering cytokine release and neutrophil recruitment—both essential mechanisms in inflammatory responses and immune defense [12,13]. Our aim was to investigate serum calprotectin concentrations as a prognostic biomarker in critically ill and septic patients

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Methods

Results

Conclusion