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Soluble Urokinase Plasminogen Activator Receptor: A New Biomarker in the Pediatric Intensive Care Unit

The Indian Journal of Pediatrics volume 83, pages 661–669 (2016)Cite this article

Abstract

Objective

To evaluate the value of soluble urokinase plasminogen activator receptor (suPAR) in diagnosing sepsis and predicting mortality in critically ill children.

Methods

In a prospective cohort study, 69 critically ill children admitted into the pediatric intensive care unit (PICU) were randomly enrolled in addition to 15 healthy children as a control group. Clinical examination was performed, including calculation of the Pediatric Risk of Mortality (PRISM) and Pediatric Index of Mortality2 (PIM2). suPAR was measured in patients at admission as well as in the controls. Patients were followed up for 30 d.

Results

suPAR level was significantly higher among the total patient cohort compared to controls (p < 0.0001). suPAR was also significantly higher among patients with sepsis compared to both controls (p < 0.0001) and patients without sepsis (p < 0.0001). Furthermore, suPAR level was significantly elevated in non-survivors compared to survivors (p 0.008). Receiver operating characteristic curve (ROC curve) analysis revealed an area under the curve (AUC) of 0.80 for suPAR for diagnosis of sepsis while C-reactive protein (CRP) had an AUC of 0.82. Regarding the prognosis, suPAR had an AUC of 0.69 for prediction of mortality, whereas the AUC for PRISM, PIM2, and CRP were 0.82, 0.81, and 0.77 respectively.

Conclusions

suPAR has both a diagnostic and a prognostic value for critically ill children. However, it does not seem to be superior to the classic laboratory markers and clinical scoring systems.

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References

  1. Wiens MO, Kumbakumba E, Kissoon N, Ansermino JM, Ndamira A, Larson CP. Pediatric sepsis in the developing world: challenges in defining sepsis and issues in post-discharge mortality. Clin Epidemiol. 2012;4:319–25.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Randolph AG, McCulloh RJ. Pediatric sepsis: important considerations for diagnosing and managing severe infections in infants, children, and adolescents. Virulence. 2014;5:179–89.

    Article  PubMed  Google Scholar 

  3. Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM consensus conference committee. American college of chest physicians/society of critical care medicine. Chest. 1992;101:1644–55.

    CAS  Article  PubMed  Google Scholar 

  4. Goldstein B, Giroir B, Randolph A. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med. 2005;6:2–8.

    Article  PubMed  Google Scholar 

  5. Loonen AJ, de Jager CP, Tosserams J, et al. Biomarkers and molecular analysis to improve blood stream infection diagnostics in an emergency care unit. PLoS One. 2014;9:e87315.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Henriquez-Camacho C, Losa J. Biomarkers for sepsis. Biomed Res Int. 2014;2014:547818.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Madsen CD, Ferraris GM, Andolfo A, Cunningham O, Sidenius N. uPAR induced cell adhesion and migration: vitronectin provides the key. J Cell Biol. 2007;177:927–39.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. Huai Q, Mazar AP, Kuo A, et al. Structure of human urokinase plasminogen activator in complex with its receptor. Science. 2006;311:656–9.

    CAS  Article  PubMed  Google Scholar 

  9. Thunø M, Macho B, Eugen-Olsen J. suPAR the molecular crystal ball. Dis Markers. 2009;27:157–72.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Eugen-Olsen J, Gustafson P, Sidenius N, et al. 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. 2002;6:686–92.

    CAS  PubMed  Google Scholar 

  11. Pliyev BK, Menshikov MY. Release of the soluble urokinase-type plasminogen activator receptor (suPAR) by activated neutrophils in rheumatoid arthritis. Inflammation. 2010;33:1–9.

    CAS  Article  PubMed  Google Scholar 

  12. Donadello K, Scolletta S, Covajes C, Vincent JL. suPAR as a prognostic biomarker in sepsis. BMC Med. 2012;10:2.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. Pollack MM, Ruttimann UE, Getson PR. Pediatric risk of mortality score. Crit Care Med. 1988;16:1110–6.

    CAS  Article  PubMed  Google Scholar 

  14. Slater A, Shann F, Pearson G. PIM 2: a revised version of the paediatric index of mortality. Intensive Care Med. 2003;29:278–85.

    Article  PubMed  Google Scholar 

  15. Perch M, Kofoed P, Fischer TK, et al. Serum levels of soluble urokinase plasminogen activator receptor is associated with parasitemia in children with acute plasmodium falciparum malaria infection. Parasite Immunol. 2004;26:207–11.

    CAS  Article  PubMed  Google Scholar 

  16. Siahanidou T, Margeli A, Tsirogianni C, et al. Clinical value of plasma soluble urokinase-type plasminogen activator receptor levels in term neonates with infection or sepsis: a prospective study. Mediat Inflamm. 2014;2014:375702.

    Article  Google Scholar 

  17. Hoenigl M, Raggam RB, Wagner J, et al. Diagnostic accuracy of soluble urokinase plasminogen activator receptor (suPAR) for prediction of bacteremia in patients with systemic inflammatory response syndrome. Clin Biochem. 2013;46:225–9.

    CAS  Article  PubMed  Google Scholar 

  18. Koch A, Voigt S, Kruschinski C, et al. Circulating soluble urokinase plasminogen activator receptor is stably elevated during the first week of treatment in the intensive care unit and predicts mortality in critically ill patients. Crit Care. 2011;15:R63.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Wrotek A, Pawlik K, Jackowska T. Soluble receptor for urokinase plasminogen activator in community-acquire pneumonia in children. Adv Exp Med Biol. 2013;788:329–34.

    CAS  Article  PubMed  Google Scholar 

  20. Kofoed K, Andersen O, Kronborg G, et al. Use of plasma C-reactive protein, procalcitonin, neutrophils, macrophage migration inhibitory factor, soluble urokinase-type plasmnogen activator receptor, and soluble triggering receptor expressed on myeloid cells-1 in combination to diagnose infections: a prospective study. Crit Care. 2007;11:R38.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Huttunen R, Syrjanen J, Vuento R, et al. Plasma level of soluble urokinase-type plasminogen activator receptor as a predictor of disease severity and case fatality in patients with bacteraemia: a prospective cohort study. J Intern Med. 2011;270:32–40.

    CAS  Article  PubMed  Google Scholar 

  22. Donadello K, Scolletta S, Taccone FS, et al. Soluble urokinase-type plasminogen activator receptor as a prognostic biomarker in critically ill patients. J Crit Care. 2014;29:144–9.

    CAS  Article  PubMed  Google Scholar 

  23. Yilmaz G, Mentese A, Kaya S, Uzun A, Karahan SC, Koksal I. The diagnostic and prognostic significance of soluble urokinase plasminogen activator receptor in Crimean-Congo hemorrhagic fever. J Clin Virol. 2011;50:209–11.

    CAS  Article  PubMed  Google Scholar 

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Acknowledgments

The authors thank Dr/ Fady M. El-Gendy, Head of the Pediatric Department, Faculty of Medicine, Menoufia University for helpful discussions.

Contributions

Muhammad S. El-Mekkawy and Nagwan Y. Saleh designed the study, analyzed the data, and wrote the manuscript. Ahmed A. Sonbol performed the suPAR measurements. Dr. Fady M. El-Gendy, Head of the Pediatric Department, Faculty of Medicine, Menoufia University will act as guarantor for the paper.

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Affiliations

  1. Department of Pediatrics, Menoufia University, Menoufia, Egypt

    Muhammad S. El-Mekkawy & Nagwan Y. Saleh

  2. Department of Clinical Pathology, Menoufia University, Menoufia, Egypt

    Ahmed A. Sonbol

Authors
  1. Muhammad S. El-Mekkawy
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  2. Nagwan Y. Saleh
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  3. Ahmed A. Sonbol
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Corresponding author

Correspondence to Muhammad S. El-Mekkawy.

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El-Mekkawy, M.S., Saleh, N.Y. & Sonbol, A.A. Soluble Urokinase Plasminogen Activator Receptor: A New Biomarker in the Pediatric Intensive Care Unit. Indian J Pediatr 83, 661–669 (2016). https://doi.org/10.1007/s12098-016-2063-9

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  • DOI: https://doi.org/10.1007/s12098-016-2063-9

Keywords

  • Soluble urokinase plasminogen activator receptor
  • Sepsis biomarker
  • Intensive care unit
  • Children
  • Systemic inflammatory response syndrome