Serum level of soluble urokinase-type plasminogen activator receptor is a strong and independent predictor of survival in human immunodeficiency virus infection

Abstract

Human immunodeficiency virus-1 (HIV-1) infection has been shown to result in up-regulation of the urokinase-type plasminogen activator receptor (uPAR/CD87) on leukocytes in vitro and in vivo. The objective of this study was to investigate whether this up-regulation is paralleled by higher serum levels of soluble uPAR (suPAR) in patients with advanced HIV-1 disease and whether the serum level of suPAR is predictive of clinical outcome. Using an enzyme-linked immunosorbent assay, the level of suPAR was measured retrospectively in serum samples from 314 patients with HIV-1 infection. By Kaplan-Meier and Cox regression analyses, the serum suPAR levels were correlated to survival with AIDS-related death as the end point. High levels of serum suPAR (greater than median) were associated with poor overall survival, and Kaplan-Meier analysis on patients stratified by suPAR level demonstrated a continuous increase in mortality rates with higher suPAR levels. After adjustment for accepted prognostic markers—including Centers for Disease Control and Prevention–defined clinical stages, CD4 counts, viral load, β2-microglobulin, and age—the prognostic strength of suPAR remained highly significant, indicating that the serum suPAR level is a novel, strong, and independent predictor of survival in HIV-1 infection. This report is the first to demonstrate an important association between the plasminogen activator system and disease progression in HIV-1 infection.

The plasma level of soluble urokinase receptor is elevated in patients with Streptococcus pneumoniae bacteraemia and predicts mortality

“…The present study demonstrated that suPAR levels are highly elevated and of prognostic value in patients with pneumococcal bacteraemia. Elevated suPAR levels have been shown previously to be of prognostic value for patients with various forms of malignant diseases [32][33][34][35][36], as well as with HIV-1 infection [15], urinary tract infection [37], tuberculosis infection [18], and bacterial meningitis [38]. Similarly, increased suPAR levels in the present study were a strong predictor of mortality.…”

Soluble urokinase plasminogen activator receptor (suPAR) is a novel, independent predictive marker of myocardial infarction in HIV‐1‐infected patients: a nested case‐control study

“…suPAR has previously been shown to predict mortality in treatment-na€ ıve HIV-1-infected patients [16]. In HIVpatients initiating ART, mortality was concentrated in the highest suPAR quartile, while patients with a low suPAR level had a low risk of mortality despite low CD4 cell count and low body weight [15].…”

Soluble urokinase‐type plasminogen activator receptor in patients with suspected infection in the emergency room: a prospective cohort study

“…In accordance with our findings, Kofoed et al [19] showed that suPAR predicted outcome in patients with SIRS. Soluble form of the receptor is not a specific marker for bacterial infection or sepsis: an association has also been observed between high suPAR concentrations and mortality in patients with HIV [12,13], tuberculosis [15] and malaria [20]. In a study including 151 patients with SIRS (96 with bacterial infection), it was foundthatCRPandPCT,butnotsuPAR,couldbeused inthe diagnosis ofbacterial sepsis [16]; AUCvalues for CRP, PCT and suPAR were 0.81, 0.72 and 0.50, respectively.…”