The urokinase-type plasminogen activator system consists of a protease, a receptor (uPAR) and inhibitors. uPAR was initially characterized as a cofactor for plasminogen activation by its ligand urokinase-type plasminogen activator (uPA or urokinase). Structurally, uPAR is a glycosylphosphatidylinositol (GPI)-anchored membrane glycoprotein encoded by PLAUR gene. It consists of three homologous domains (DI, DII and DIII), each of approximately 90 amino acids. The molecular mass of non-glycosylated uPAR is approximately 35 kDa, whereas glycosylated uPAR has a molecular mass of approximately 60 kDa. Removal of the GPI anchor by phospholipases or extracellular proteolytic cleavage yields a soluble form – soluble urokinase-type plasminogen activator receptor (suPAR). Cleavage of uPAR from the cell can occur both at the GPI-anchor and at the linker region between DI and DII. Thus, suPAR is a circulating protein ranging from 20 to 50 kDa, depending on the degree of glycosylation and proteolytic cleavage. The uPAR has been shown to associate with many signalling molecules and to mediate signal transduction. Chemotaxis-inducing molecules upregulate uPAR in different cell types, including neutrophils, macrophages, lymphocytes, endothelial cells and malignant cells. uPAR promotes the migration and adhesion of leucocytes by binding to β-integrins. Moreover, uPAR has a pivotal role in cell proliferation, angiogenesis and fibrinolysis. After cleavage from the cell surface, soluble uPAR can be measured in the blood and other organic fluids such as urine, saliva, bronchoalveolar lavage (BALF) and cerebrospinal fluid (CSF). In such matrices suPAR, similarly to anchored uPAR, also takes part in various immunological functions, including cell adhesion, migration, chemotaxis, proteolysis, immune activation, tissue remodelling, cell invasion and signal transduction. Elevated levels of suPAR in circulation are considered to be a marker for activation of immune and inflammatory systems. In the acute setting, elevated levels of suPAR have been proposed to be predictive for disease severity in bacteraemia, human immunodeficiency virus infection (HIV), bacterial meningitis, active pulmonary tuberculosis, ventilator-associated pneumonia with sepsis, and in intensive care unit (ICU) patients with or without sepsis. The suPAR was also discovered as a cause of chronic renal disease focal segmental glomerulosclerosis (FSGS). Described in details, suPAR levels were investigated as a predictor of disease severity and mortality in 132 patients with bacteremia caused by Staphylococcus aureus, Streptococcus pneumonia and β-hemolytic streptococcae or Escherichia coli. The best mortality predictive cut-off plasma level was 11 ng/ml; the sensitivity and specificity of suPAR for fatal disease was 83% and 76%, respectively. It was found that HIV-infected patients receiving antiretroviral therapy have an increased risk of various metabolic disorders, which may involve low-grade inflammation and other immunological perturbations. Plasma suPAR, which has been established as a marker of the immunological status of HIV-infected patients, may correlate with important features of dysmetabolism in such patients. From the study performed with CSF samples of 545 patients was found that suPAR, age and type of infection, all add value in predicting mortality among patients with initial diagnosis of meningitis. The diagnostic value of suPAR to identify patients with severe sepsis seems to be similar to that of procalcitonin or interleukin-6. More importantly, suPAR levels was found to be strong predictors of 28-day, 90-day and even 1-year case fatality and allowed a better risk stratification compared to classical inflammatory markers such as procalcitonin, interleukin-6 or C-reactive protein. It has recently been suggested that suPAR has a role in the pathogenesis of focal segmental glomerulosclerosis (FSGS). In vitro and in vivo studies demonstrated that enhanced circulating su
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