Elevated soluble urokinase plasminogen activator receptor (suPAR) predicts mortality in Staphylococcus aureus bacteremia

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.

Soluble urokinase-type plasminogen activator receptor (suPAR) – a possible biomarker for bacteremia in sepsis / Forma solubilă a receptorului pentru activatorul de plasminogen de tip urokinază (suPAR) – un biomarker posibil pentru bacteriemie în sepsis

“…In Staphylococcus aureus bacteremia (SAB), Molkanen identified the predictive capacity of suPAR for mortality, AUC being comparable to the one reported by us (0.754) but the optimal cut-off value for 30-days mortality was inferior (9.25 ng/mL) similar to the ones reported on other two SAB groups; the study reconfirms the prognostic incapacity of CRP and brings edifying data regarding the persistence of elevated suPAR levels for at least 10 days, which could represent an advantage when used clinically (42,47,48). Wittenhagen found that suPAR is an independent and potent predictor for mortality in pneumococcal bacteremia when levels were superior to the cut-off value of 10 ng/mL (42).…”

Soluble urokinase plasminogen activator receptor as a prognostic marker of all-cause and cardiovascular mortality in a black population

“…Similarly, in patients with HIV infection [30], bacterial infections [17,31] and in those who were admitted to an acute medical unit [32], suPAR was higher in the people who died. We further found that suPAR predicted all-cause mortality, which supports previous studies where suPAR predicted renal replacement therapy and mortality [33], as well as mortality during intensive care unit admission [15].…”

“…Previous studies showed an association between suPAR and cardiovascular disease [6][7][8][9], type 1 [10] and type 2 diabetes [7], several types of cancer [7,11,12] and infectious diseases such as HIV [13]. Furthermore, suPAR provides prognostic information of cardiovascular disease risk in the general population beyond the Framingham risk score [14] and also predicts mortality in critically ill patients [15][16][17], independently of other inflammatory markers such as CRP [7]. SuPAR and CRP seem to reflect different pathophysiological pathways of cardiovascular disease risk.…”

Evaluation of Diagnostic Value of Soluble Urokinase-Type Plasminogen Activator Receptor in Sepsis

“…suPAR is detected in low but fairly constant concentrations in plasma of healthy, normal people. Increased plasma concentrations of suPAR have been found in patients with advanced cancers of lung, breast, and colon and inflammatory rheumatic diseases (5) and also in staphylococcal and HIV infection (7,8). suPAR not only is present in human plasma or serum, but can also be found in other body fluids, including urine, cerebrospinal fluid, as well as in pleural, pericardial, and peritoneal fluids (9,10).…”