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.
Similar content being viewed by others
References
Conterno LO, Wey SB, Castelo A (1998) Risk factors for mortality in Staphylococcus aureus bacteremia. Infect Control Hosp Epidemiol 19(1):32–37
Benfield T, Espersen F, Frimodt-Møller N et al (2007) Increasing incidence but decreasing in-hospital mortality of adult Staphylococcus aureus bacteraemia between 1981 and 2000. Clin Microbiol Infect 13(3):257–263
Mylotte JM, Tayara A (2000) Staphylococcus aureus bacteremia: predictors of 30-day mortality in a large cohort. Clin Infect Dis 31(5):1170–1174
Fowler VG Jr, Olsen MK, Corey GR et al (2003) Clinical identifiers of complicated Staphylococcus aureus bacteremia. Arch Intern Med 163(17):2066–2072
Fätkenheuer G, Preuss M, Salzberger B et al (2004) Long-term outcome and quality of care of patients with Staphylococcus aureus bacteremia. Eur J Clin Microbiol Infect Dis 23(3):157–162
Ruotsalainen E, Järvinen A, Koivula I et al (2006) Levofloxacin does not decrease mortality in Staphylococcus aureus bacteraemia when added to the standard treatment: a prospective and randomized clinical trial of 381 patients. J Intern Med 259(2):179–190
Pierrakos C, Vincent JL (2010) Sepsis biomarkers: a review. Crit Care 14(1):R15
Yan SB, Helterbrand JD, Hartman DL, Wright TJ, Bernard GR (2001) Low levels of protein C are associated with poor outcome in severe sepsis. Chest 120(3):915–922
Hatzistilianou M (2010) Diagnostic and prognostic role of procalcitonin in infections. ScientificWorldJournal 10:1941–1946
Black S, Kushner I, Samols D (2004) C-reactive protein. J Biol Chem 279(47):48487–48490
Póvoa P (2002) C-reactive protein: a valuable marker of sepsis. Intensive Care Med 28(3):235–243
Póvoa P, Coelho L, Almeida E et al (2006) Early identification of intensive care unit-acquired infections with daily monitoring of C-reactive protein: a prospective observational study. Crit Care 10(2):R63
Lobo SM, Lobo FR, Bota DP et al (2003) C-reactive protein levels correlate with mortality and organ failure in critically ill patients. Chest 123(6):2043–2049
Silvestre J, Póvoa P, Coelho L et al (2009) Is C-reactive protein a good prognostic marker in septic patients? Intensive Care Med 35(5):909–913
Blasi F, Carmeliet P (2002) uPAR: a versatile signalling orchestrator. Nat Rev Mol Cell Biol 3(12):932–943
Plesner T, Behrendt N, Ploug M (1997) Structure, function and expression on blood and bone marrow cells of the urokinase-type plasminogen activator receptor, uPAR. Stem Cells 15(6):398–408
Huai Q, Mazar AP, Kuo A et al (2006) Structure of human urokinase plasminogen activator in complex with its receptor. Science 311(5761):656–659
De Witte H, Sweep F, Brünner N et al (1998) Complexes between urokinase-type plasminogen activator and its receptor in blood as determined by enzyme-linked immunosorbent assay. Int J Cancer 77(2):236–242
Sier CF, Sidenius N, Mariani A et al (1999) Presence of urokinase-type plasminogen activator receptor in urine of cancer patients and its possible clinical relevance. Lab Invest 79(6):717–722
Garcia-Monco JC, Coleman JL, Benach JL (2002) Soluble urokinase receptor (uPAR, CD 87) is present in serum and cerebrospinal fluid in patients with neurologic diseases. J Neuroimmunol 129(1–2):216–223
Ostrowski SR, Piironen T, Høyer-Hansen G et al (2005) High plasma levels of intact and cleaved soluble urokinase receptor reflect immune activation and are independent predictors of mortality in HIV-1-infected patients. J Acquir Immune Defic Syndr 39(1):23–31
Fevang B, Eugen-Olsen J, Yndestad A et al (2009) Enhanced levels of urokinase plasminogen activator and its soluble receptor in common variable immunodeficiency. Clin Immunol 131(3):438–446
Sidenius N, Sier CF, Ullum H et al (2000) Serum level of soluble urokinase-type plasminogen activator receptor is a strong and independent predictor of survival in human immunodeficiency virus infection. Blood 96(13):4091–4095
Eugen-Olsen J, Gustafson P, Sidenius N et al (2002) The serum level of soluble urokinase receptor is elevated in tuberculosis patients and predicts mortality during treatment: a community study from Guinea-Bissau. Int J Tuberc Lung Dis 6(8):686–692
Sier CF, Sidenius N, Mariani A et al (1999) Presence of urokinase-type plasminogen activator receptor in urine of cancer patients and its possible clinical relevance. Lab Invest 79(6):717–722
Sier CF, Stephens R, Bizik J et al (1998) The level of urokinase-type plasminogen activator receptor is increased in serum of ovarian cancer patients. Cancer Res 58(9):1843–1849
Thunø M, Macho B, Eugen-Olsen J (2009) suPAR: the molecular crystal ball. Dis Markers 27(3):157–172
Florquin S, van den Berg JG, Olszyna DP et al (2001) Release of urokinase plasminogen activator receptor during urosepsis and endotoxemia. Kidney Int 59(6):2054–2061
Wittenhagen P, Kronborg G, Weis N et al (2004) The plasma level of soluble urokinase receptor is elevated in patients with Streptococcus pneumoniae bacteraemia and predicts mortality. Clin Microbiol Infect 10(5):409–415
Perch M, Kofoed P, Fischer TK et al (2004) Serum levels of soluble urokinase plasminogen activator receptor is associated with parasitemia in children with acute Plasmodium falciparum malaria infection. Parasite Immunol 26(5):207–211
Kofoed K, Andersen O, Kronborg G et al (2007) Use of plasma C-reactive protein, procalcitonin, neutrophils, macrophage migration inhibitory factor, soluble urokinase-type plasminogen activator receptor, and soluble triggering receptor expressed on myeloid cells-1 in combination to diagnose infections: a prospective study. Crit Care 11(2):R38
Jackson GG, Arana-Sialer JA, Andersen BR, Grieble HG, McCabe WR (1962) Profiles of pyelonephritis. Arch Intern Med 110:63–75
Mermel LA, Farr BM, Sherertz RJ et al (2001) Guidelines for the management of intravascular catheter-related infections. Clin Infect Dis 32(9):1249–1272
Ruotsalainen E, Sammalkorpi K, Laine J et al (2006) Clinical manifestations and outcome in Staphylococcus aureus endocarditis among injection drug users and nonaddicts: a prospective study of 74 patients. BMC Infect Dis 6:137
Møller HJ, Moestrup SK, Weis N et al (2006) Macrophage serum markers in pneumococcal bacteremia: prediction of survival by soluble CD163. Crit Care Med 34(10):2561–2566
Schneider UV, Nielsen RL, Pedersen C et al (2007) The prognostic value of the suPARnostic ELISA in HIV-1 infected individuals is not affected by uPAR promoter polymorphisms. BMC Infect Dis 7:134
Rabna P, Andersen A, Wejse C et al (2009) High mortality risk among individuals assumed to be TB-negative can be predicted using a simple test. Trop Med Int Health 14(9):986–994
Lomholt AF, Christensen IJ, Høyer-Hansen G et al (2010) Prognostic value of intact and cleaved forms of the urokinase plasminogen activator receptor in a retrospective study of 518 colorectal cancer patients. Acta Oncol 49(6):805–811
Andersen O, Eugen-Olsen J, Kofoed K, Iversen J, Haugaard SB (2008) Soluble urokinase plasminogen activator receptor is a marker of dysmetabolism in HIV-infected patients receiving highly active antiretroviral therapy. J Med Virol 80(2):209–216
Stephens RW, Pedersen AN, Nielsen HJ et al (1997) ELISA determination of soluble urokinase receptor in blood from healthy donors and cancer patients. Clin Chem 43(10):1868–1876
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Mölkänen, T., Ruotsalainen, E., Thorball, C.W. et al. Elevated soluble urokinase plasminogen activator receptor (suPAR) predicts mortality in Staphylococcus aureus bacteremia. Eur J Clin Microbiol Infect Dis 30, 1417–1424 (2011). https://doi.org/10.1007/s10096-011-1236-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10096-011-1236-8