Presepsin Usefulness as a Diagnostic Test for Sepsis in Intensive Care Unit Patients

Abstract

Sepsis, severe sepsis and septic shock are common conditions, very frequently recognized and handled in the ICU. According to the most recent guidelines, published by the Surviving Sepsis Campaign, early recognition of these conditions and appropriateness of therapy in the initial hours after presentation considerably influences the outcomes of septic patients. Nonetheless, the early stratification of patients with severe sepsis and their prognosis, as well as accurate monitoring of the effects of clinical treatment, is still an unsolved issue. Blood culture is the gold standard method for detecting micro-organisms but it requires too much time for results to be known. CRP is one of the acute phase proteins synthesized by the liver: it has a great sensitivity but a very poor specificity for bacterial infections. Moreover, the evolution of sepsis does not correlate with CRP plasma changes. Procalcitonin (PCT) has gained a significant diagnostic role in this field, because of its close correlation with infections, but it still retains some limitations and false positivity (such as in multiple trauma and burns). CD14 (cluster-of-differentiation) is a glycoprotein expressed on the membrane surface of various cells, including monocytes, macrophages and neutrophils (mCD14) and serves as a specific high-affinity receptor for complexes of lipopolysaccharides (LPSs) and LPS binding protein (LBP). Upon binding of the LBP complex, CD14 activates the toll-like receptor 4 (TLR4)-specific proinflammatory signalling cascade thereby starting the inflammatory reaction of the host against infectious agents. In addition, mCD14 may function as a receptor for peptidoglycan, cell wall component of Gram-positive and Gram-negative bacteria, and other microbial products with similar structures features. CD14 is also found in a circulating soluble (sCD14) state and further cleavage of sCD14, generating a truncated form named sCD14 subtype (sCD14-ST) or presepsin. One of the production mechanisms of presepsin is related to the phagocytosis process and aspartate proteases, including cathepsin D, were one of the lysozomal enzymes that are related to the production of presepsin. So it seems to be a more specific biomarker for the diagnosis of sepsis compared with PCT and CRP. Presepsin is a novel and promising biomarker that has been shown to increase significantly in patients with sepsis, in comparison to the healthy population. Studies pointed out the capability of this biomarker for diagnosing sepsis, assessing the severity of the disease and providing a prognostic evaluation of patient outcome. The aim of this study was to validate the diagnostic role of presepsin for sepsis in intensive care unit patients, alone and compared with serum procalcitonin and C-reactive protein. This study enrolled twenty eight patients with at least two diagnostic criteria for systemic inflammatory response syndrome (SIRS) who were admitted to Ain Shams University Hospitals ICU and had documented or suspected infection, fifteen patients admitted to ICU for any medical cause but with no evidence of infection were enrolled as patient control group and further ten apparently healthy subjects were enrolled as healthy control group. The study was conducted during the period between December 2013 and June 2014. The laboratory work was done in the Clinical Pathology Department, Ain Shams University Hospitals. To detect presepsin we used a new rapid method based on a chemiluminescent enzyme immunoassay. The presepsin values were significantly higher in patients with sepsis than the control groups. The area under the receiver operating characteristics (ROC) curve for discriminating sepsis from non septic conditions for presepsin was greater than the AUC of PCT, CRP or WBC. We suggested cut-off value of presepsin to be 863pg/ml which provided a sensetivity of 85.2% and 86.7% specificity for sepsis diagnosis.