Why high suPAR is not super--diagnostic, prognostic and potential pathogenic properties of a novel biomarker in the ICU

Abstract

The soluble urokinase plasminogen activator receptor (suPAR) has been suggested as a biomarker that reflects immune cell activation. In critically ill patients, several independent investigations have reported elevated suPAR in conditions of systemic inflammatory response syndrome (SIRS), bacteriemia, sepsis, and septic shock, in which high circulating suPAR levels indicated an unfavorable prognosis. In a prospective cohort study in this issue of Critical Care, suPAR levels were detected in bronchoalveolar lavage (BAL) and identified inhalation injury. High systemic levels indicated an adverse prognosis. This study expands our knowledge of the diagnostic power of suPAR, confirms its prognostic value, and raises the demand for future studies investigating the pathogenic involvement of suPAR.

Figure 1

Schematic depiction of soluble urokinase plasminogen activator receptor (suPAR) as a novel biomarker in the intensive care unit. The urokinase plasminogen activator receptor (uPAR) (CD87) is expressed in various populations of immune cells, including neutrophils, monocytes, macrophages, and lymphocytes (upper left corner). uPAR consists of three disulphide-bonded domains (D1, D2, and D3) and is attached to the cell membrane by a glycosyl phosphatidylinositol (GPI) anchor. Domains D1 and D3 represent a composite binding site for uPA. Upon inflammation, the receptor is cleaved from the cell surface at the GPI anchor and is released into various body fluids (upper right corner). Circulating suPAR levels in serum are closely linked to inflammation in patients with type 2 diabetes, cardiovascular (CV) disorders, or cancer. The highest suPAR serum concentrations are found in critically ill patients with systemic inflammatory response syndrome (SIRS) or sepsis, and elevated suPAR values indicate an unfavorable prognosis (lower left corner). This was confirmed by Backes and colleagues [1] in a prospective observational cohort study of 26 intensive care unit patients (11 with and 15 without burn injury). As also demonstrated by the study, suPAR can be detected in bronchoalveolar lavage (BAL) and is indicative of inhalation injury (lower right corner). No data about pulmonary suPAR levels in pneumonia or other conditions of lung injury exist at present.