Suparnostic

Abstract: The soluble form of urokinase-type plasminogen activator receptor (suPAR) is a new inflammatory marker. High suPAR levels have been shown to associate with mortality in cancer and in chronic infections like HIV and tuberculosis, but reports on the role of suPAR in acute bacteremic infections are scarce. To elucidate the role of suPAR in a common bacteremic infection, the serum suPAR levels in 59 patients with Staphylococcus aureus bacteremia (SAB) were measured using the suPARnostic ELISA assay and associations to 1-month mortality and with deep infection focus were analyzed. On day three, after the first positive blood culture for S. aureus, suPAR levels were higher in 19 fatalities (median 12.3; range 5.7-64.6 ng/mL) than in 40 survivors (median 8.4; range 3.7-17.6 ng/mL, p = 0.002). This difference persisted for 10 days. The presence of deep infection focus was not associated with elevated suPAR levels as compared to patients with no deep infection focus. suPAR was found to be prognostic for mortality in receiver operator characteristic (ROC) curve analysis, which was not observed for serum C-reactive protein (CRP); the area under the curve (AUC) for suPAR was 0.754 (95% confidence interval [CI], 0.615-0.894, p = 0.003) and for CRP, it was 0.596 (95% CI, 0.442-0.750, p = 0.253). The optimal suPAR cut-off value in predicting 1-month mortality was 9.25 ng/mL. In conclusion, our study demonstrates that the new promising biomarker, serum suPAR concentration, was able to predict mortality in SAB.

Abstract: OBJECTIVES: To determine mortality among assumed TB negative (aTBneg) individuals in Guinea-Bissau and to investigate whether plasma levels of soluble urokinase receptor (suPAR) can be used to determine post-consultation mortality risk. METHODS: This prospective West-African cohort study included 1007 aTBneg individuals who were enrolled from 2004 to 2006; 4983 age-matched controls were followed for comparison. Plasma suPAR levels were measured using the suPARnostic ELISA. Survival was analysed using Cox regression ROC curves and Kaplan-Meier analysis. RESULTS: After 3 months of follow-up mortality was 21 per 100 person-year-observation (PYO) among aTBneg individuals and three per 100 PYO among the control population [mortality rate ratio (MRR) = 6.92 (95% CI 4.48-10.7)]. SuPAR values ranged between 0.9 and 45 ng/ml in aTBneg individuals. A log-linear relationship was found between suPAR levels <15 ng/ml and mortality. In the log-linear range a 1 ng/ml increase was associated with a 46% increase in the mortality rate: MRR = 1.46 (95% CI 1.34-1.59). The area under the ROC curves was 0.88 for HIV-positive individuals and 0.79 for HIV-negative individuals. CONCLUSIONS: Our study showed a high mortality rate among aTBneg individuals and demonstrated that suPAR measurements can provide prognostic information on mortality among individuals without disease diagnosis. Measuring suPAR is a technically simple method for determining mortality risk in individuals that are assumed to be TB-negative.

Abstract: Background High blood levels of soluble urokinase Plasminogen Activator Receptor (suPAR) are associated with poor outcomes in human immunodeficiency-1 (HIV-1) infected individuals. Research on the clinical value of suPAR in HIV-1 infection led to the development of the suPARnostic® assay for commercial use in 2006. The aim of this study was to: 1) Evaluate the prognostic value of the new suPARnostic® assay and 2) Determine whether polymorphisms in the active promoter of uPAR influences survival and/or suPAR values in HIV-1 patients who are antiretroviral therapy (ART) naive.

Abstract: Introduction The urokinase-type plasminogen activator receptor (uPAR) and its ligand (suPAR) are involved in numerous physiological and pathological pathways. Previous studies have shown that an elevated plasma suPAR level is associated with disease severity and mortality. The aim of this prospective observational study was to determine if the suPAR level was associated with readmission and mortality in the acute medical setting. Methods Plasma suPAR levels were measured in 1,036 patients at admission. Follow-up ranged 3-10 months. Cox proportional hazards model was used to assess the relative contribution of different risk factors to mortality and readmission. The ANOVA test and Pearson's chi-squared test were used to compare suPAR tertile level with various variables. Results The highest suPAR tertile level was significantly associated with mortality within 30 days after discharge, with a 6.66 hazard ratio (HR). Similar associations were found with readmission within the maximum observation period (HR = 2.26) and within 30 days (HR = 2.08), although the latter became insignificant when covariates were included. Conclusions This study confirms previous findings of increased mortality and adds the finding that increased long-term readmission rates are associated with elevated suPAR levels. The present data do, however, not indicate that suPAR may serve as an independent biomarker for increased risk of short-term readmission in the acute medical setting. Funding This study was funded by a grant from ViroGates A/S, the company that produces the suPARnostic assay. Trial registration No: H-B-2009-075.