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Intensive Care Medicine

, Volume 39, Issue 11, pp 1945–1952 | Cite as

Hospital mortality prognostication in sepsis using the new biomarkers suPAR and proADM in a single determination on ICU admission

  • B. SuberviolaEmail author
  • A. Castellanos-Ortega
  • A. Ruiz Ruiz
  • M. Lopez-Hoyos
  • M. Santibañez
Original

Abstract

Purpose

The soluble form of the urokinase-type plasminogen activator receptor (suPAR) and proadrenomedullin (proADM) are two new and promising sepsis biomarkers. We assessed the prognostic value of a single determination of proADM and suPAR, comparing them with C-reactive protein (CRP) and procalcitonin (PCT), and evaluating whether their addition to severity scores (APACHE II and SOFA) could improve their prognostic accuracy.

Methods

A single-centre prospective observational study conducted in an adult intensive care department at Marques de Valdecilla University Hospital in Spain. APACHE II and SOFA scores, CRP, PCT, suPAR and proADM levels on the day of ICU admission were collected.

Results

A total of 137 consecutive septic patients were studied. The best area under the curve (AUC) for the prediction of in-hospital mortality was for APACHE II (0.82) and SOFA (0.75) scores. The ROC curve for suPAR yielded an AUC of 0.67, higher than proADM (0.62), CRP (0.50) and PCT (0.44). Significant dose-response trends were found between hospital mortality and suPAR (OR Q4 = 4.83, 95 % CI 1.60–14.62) and pro-ADM (OR Q4 = 3.00, 95 % CI 1.06–8.46) quartiles. Non-significant associations were found for PCT and CRP. The combination of severity scores and each biomarker did not provide superior AUCs.

Conclusions

SuPAR and, to a lesser extent, proADM levels on ICU admission were better tools in prognosticating in-hospital mortality than CRP or PCT. However, neither of the two new biomarkers has been demonstrated to be excessively useful in the current setting. The prognostic accuracy was better for severity scores than for any of the biomarkers.

Keywords

Sepsis Biomarkers SuPAR Proadrenomedullin Procalcitonin Mortality 

Supplementary material

134_2013_3056_MOESM1_ESM.doc (26 kb)
Supplementary material (DOC 26 kb)
134_2013_3056_MOESM2_ESM.doc (100 kb)
Supplementary material (DOC 100 kb)

References

  1. 1.
    Martin GS, Mannino DM, Eaton S, Moss M (2003) The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 348:1546–1554PubMedCrossRefGoogle Scholar
  2. 2.
    Knaus WA, Draper EA, Wagner DP, Zimmerman JE (1985) APACHE II: a severity of disease classification system. Crit Care Med 13:818–829PubMedCrossRefGoogle Scholar
  3. 3.
    Vincent JL, Opal SM, Marshall JC (2010) Ten reasons why we should NOT use severity scores as entry criteria for clinical trials or in our treatment decisions. Crit Care Med 38:283–287PubMedCrossRefGoogle Scholar
  4. 4.
    Becker KL, Snider R, Nylen ES (2008) Procalcitonin assay in systemic inflammation, infection, and sepsis: clinical utility and limitations. Crit Care Med 36:941–952PubMedCrossRefGoogle Scholar
  5. 5.
    Schuetz P, Christ-Crain M, Müller B (2009) Procalcitonin and other biomarkers to improve assessment and antibiotic stewardship in infections—hope for hype? Swiss Med Wkly 139:318–326PubMedGoogle Scholar
  6. 6.
    Antonelli M, Azoulay E, Bonten M, Chastre J, Citerio G, Conti G, De Backer D, Gerlach H, Hedenstierna G, Joannidis M, Macrae D, Mancebo J, Maggiore SM, Mebazaa A, Preiser JC, Pugin J, Wernerman J, Zhang H (2011) Year in review in Intensive Care Medicine 2010: II. Pneumonia and infections, cardiovascular and hemodynamics, organization, education, haematology, nutrition, ethics and miscellanea. Intensive Care Med 37:196–213PubMedCrossRefGoogle Scholar
  7. 7.
    Povoa P, Teixeira-Pinto AM, Carneiro AH, Portuguese Community-Acquired Sepsis Study Group SACiUCI (2011) C-reactive protein, an early marker of community-acquired sepsis resolution: a multi-centre prospective observational study. Crit Care 15:R169PubMedCrossRefGoogle Scholar
  8. 8.
    Ostrowski SR, Ullum H, Goka BQ, Høyer-Hansen G, Obeng-Adjei G, Pedersen BK, Akanmori BD, Kurtzhals JA (2005) Plasma concentrations of soluble urokinase-type plasminogen activator receptor are increased in patients with malaria and are associated with a poor clinical or a fatal outcome. J Infect Dis 191:1331–1341PubMedCrossRefGoogle Scholar
  9. 9.
    Rabna P, Andersen A, Wejse C, Oliveira I, Gomes VF, Haaland MB, Aaby P, Eugen-Olsen J (2012) Utility of the plasma level of suPAR in monitoring risk of mortality during TB treatment. PLoS One 7:e43933PubMedCrossRefGoogle Scholar
  10. 10.
    Huttunen R, Syrjänen J, Vuento R, Hurme M, Huhtala H, Laine J, Pessi T, Aittoniemi J (2011) 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 270:32–40PubMedCrossRefGoogle Scholar
  11. 11.
    Giamarellos-Bourboulis EJ, Norrby-Teglund A, Mylona V, Savva A, Tsangaris I, Dimopoulou I, Mouktaroudi M, Raftogiannis M, Georgitsi M, Linnér A, Adamis G, Antonopoulou A, Apostolidou E, Chrisofos M, Katsenos C, Koutelidakis I, Kotzampassi K, Koratzanis G, Koupetori M, Kritselis I, Lymberopoulou K, Mandragos K, Marioli A, Sundén-Cullberg J, Mega A, Prekates A, Routsi C, Gogos C, Treutiger CJ, Armaganidis A, Dimopoulos G (2012) Risk assessment in sepsis: a new prognostication rule by APACHE II score and serum soluble urokinase plasminogen activator receptor. Crit Care 16:R149PubMedCrossRefGoogle Scholar
  12. 12.
    Koch A, Voigt S, Kruschinski C, Sanson E, Dückers H, Horn A, Yagmur E, Zimmermann H, Trautwein C, Tacke F (2011) 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 15:R63PubMedCrossRefGoogle Scholar
  13. 13.
    Hirata Y, Mitaka C, Sato K, Nagura T, Tsunoda Y, Amaha K, Marumo F (1996) Increased circulating adrenomedullin, a novel vasodilatory peptide, in sepsis. J Clin Endocrinol Metab 81:1449–1453PubMedCrossRefGoogle Scholar
  14. 14.
    Guignant C, Voirin N, Venet F, Poitevin F, Malcus C, Bohé J, Lepape A, Monneret G (2009) Assessment of pro-vasopressin and pro-adrenomedullin as predictors of 28-day mortality in septic shock patients. Intensive Care Med 35:1859–1867PubMedCrossRefGoogle Scholar
  15. 15.
    Stolz D, Christ-Crain M, Morgenthaler NG, Miedinger D, Leuppi J, Müller C, Bingisser R, Struck J, Müller B, Tamm M (2008) Plasma pro-adrenomedullin but not plasma pro-endothelin predicts survival in exacerbations of COPD. Chest 134:263–272PubMedCrossRefGoogle Scholar
  16. 16.
    Christ-Crain M, Morgenthaler NG, Struck J, Harbarth S, Bergmann A, Müller B (2005) Mid-regional pro-adrenomedullin as a prognostic marker in sepsis: an observational study. Crit Care 9:R816–R824PubMedCrossRefGoogle Scholar
  17. 17.
    Huang DT, Angus DC, Kellum JA, Pugh NA, Weissfeld LA, Struck J, Delude RL, Rosengart MR, Yealy DM (2009) Mid-regional proadrenomedullin as a prognostic tool in community-acquired pneumonia. Chest 136:823–831PubMedCrossRefGoogle Scholar
  18. 18.
    Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G, International Sepsis Definitions Conference (2003) 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Intensive Care Med 29:530–538PubMedCrossRefGoogle Scholar
  19. 19.
    Vincent JL, de Mendonça A, Cantraine F, Moreno R, Takala J, Suter PM, Sprung CL, Colardyn F, Blecher S (1998) Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on “sepsis-related problems” of the European Society of Intensive Care Medicine. Crit Care Med 26:1793–1800PubMedCrossRefGoogle Scholar
  20. 20.
    Giamarellos–Bourboulis EJ, Mega A, Grecka P, Scarpa N, Koratzanis G, Thomopoulos G, Giamarellou H (2002) Procalcitonin: a marker to clearly differentiate systemic inflammatory response syndrome and sepsis in the critically ill patient? Intensive Care Med 28:1351–1356PubMedCrossRefGoogle Scholar
  21. 21.
    Pettila V, Hynninen M, Takkunen O, Kuusela P, Valtonen M (2002) Predictive value of procalcitonin and interleukin 6 in critically ill patients with suspected sepsis. Intensive Care Med 28:1220–1225PubMedCrossRefGoogle Scholar
  22. 22.
    Suberviola B, Castellanos-Ortega A, González-Castro A, García-Astudillo LA, Fernández-Miret B (2012) Prognostic value of procalcitonin, C-reactive protein and leukocytes in septic shock. Med Intensiva 36:177–184PubMedCrossRefGoogle Scholar
  23. 23.
    Boussekey N, Leroy O, Alfandari S, Devos P, Georges H, Guery B (2006) Procalcitonin kinetics in the prognosis of severe community-acquired pneumonia. Intensive Care Med 32:469–472PubMedCrossRefGoogle Scholar
  24. 24.
    Jensen JU, Heslet L, Jensen TH, Espersen K, Steffensen P, Tvede M (2006) Procalcitonin increase in early identification of critically ill patients at high risk of mortality. Crit Care Med 34:2596–2602PubMedCrossRefGoogle Scholar
  25. 25.
    Silvestre J, Povoa P, Coelho L, Almeida E, Moreira P, Fernandes A, Mealha R, Sabino H (2009) Is C-reactive protein a good prognostic marker in septic patients? Intensive Care Med 35:909–913PubMedCrossRefGoogle Scholar
  26. 26.
    Yilmaz G, Köksal I, Karahan SC, Mentese A (2011) The diagnostic and prognostic significance of soluble urokinase plasminogen activator receptor in systemic inflammatory response syndrome. Clin Biochem 44:1227–1230PubMedCrossRefGoogle Scholar
  27. 27.
    Mölkänen T, Ruotsalainen E, Thorball CW, Järvinen A (2011) Elevated soluble urokinase plasminogen activator receptor (suPAR) predicts mortality in Staphylococcus aureus bacteremia. Eur J Clin Microbiol Infect Dis 30:1417–1424PubMedCrossRefGoogle Scholar
  28. 28.
    Wittenhagen P, Kronborg G, Weis N, Nielsen H, Obel N, Pedersen SS, Eugen-Olsen J (2004) The plasma level of soluble urokinase receptor is elevated in patients with Streptococcus pneumoniae bacteraemia and predicts mortality. Clin Microbiol Infect 10:409–415PubMedCrossRefGoogle Scholar
  29. 29.
    Savva A, Raftogiannis M, Baziaka F, Routsi C, Antonopoulou A, Koutoukas P, Tsaganos T, Kotanidou A, Apostolidou E, Giamarellos-Bourboulis EJ, Dimopoulos G (2011) Soluble urokinase plasminogen activator receptor (suPAR) for assessment of disease severity in ventilator-associated pneumonia and sepsis. J Infect 63:344–350PubMedCrossRefGoogle Scholar
  30. 30.
    Backes Y, Van der Sluijs KF, Mackie DP, Tacke F, Koch A, Tenhunen JJ, Schultz MJ (2012) Usefulness of suPAR as a biological marker in patients with systemic inflammation or infection: a systematic review. Intensive Care Med 38:1418–1428PubMedCrossRefGoogle Scholar
  31. 31.
    Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G, International Sepsis Definitions Conference (2013) SuPAR and PAI-1 in critically ill, mechanically ventilated patients. Intensive Care Med 39:489–496CrossRefGoogle Scholar
  32. 32.
    Backes Y, Van der Sluijs KF, Tuip de Boer AM, Hofstra JJ, Vlaar AP, Determann RM, Knape P, Mackie DP, Schultz MJ (2011) Soluble urokinase-type plasminogen activator receptor levels in patients with burn injuries and inhalation trauma requiring mechanical ventilation: an observational cohort study. Crit Care 15:R270PubMedCrossRefGoogle Scholar
  33. 33.
    Ostrowski SR, Katzenstein TL, Pedersen M, Høyer-Hansen G, Gerstoft J, Pedersen BK, Ullum H (2006) Plasma levels of intact and cleaved urokinase receptor decrease in HIV-1-infected patients initiating highly active antiretroviral therapy. Scand J Immunol 63:478–486PubMedCrossRefGoogle Scholar
  34. 34.
    Sidenius N, Sier CF, Ullum H, Pedersen BK, Lepri AC, Blasi F, Eugen-Olsen J (2000) Serum level of soluble urokinase-type plasminogen activator receptor is a strong and independent predictor of survival in human immunodeficiency virus infection. Blood 96:4091–4095PubMedGoogle Scholar
  35. 35.
    Fevang B, Eugen-Olsen J, Yndestad A, Brosstad F, Beiske K, Aukrust P, Frøland SS (2009) Enhanced levels of urokinase plasminogen activator and its soluble receptor in common variable immunodeficiency. Clin Immunol 131:438–446PubMedCrossRefGoogle Scholar
  36. 36.
    Antonelli M, Azoulay E, Bonten M, Chastre J, Citerio G, Conti G, De Backer D, Gerlach H, Hedenstierna G, Joannidis M, Macrae D, Mancebo J, Maggiore SM, Mebazaa A, Preiser JC, Pugin J, Wernerman J, Zhang H (2010) Year in review in Intensive Care Medicine 2009: I. Pneumonia and infections, sepsis, outcome, acute renal failure and acid base, nutrition and glycaemic control. Intensive Care Med 36:196–209PubMedCrossRefGoogle Scholar
  37. 37.
    Cook NR (2010) Methods for evaluating novel biomarkers: a new paradigm. Int J Clin Pract 64:1723–1727PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg and ESICM 2013

Authors and Affiliations

  • B. Suberviola
    • 1
    Email author
  • A. Castellanos-Ortega
    • 1
  • A. Ruiz Ruiz
    • 1
  • M. Lopez-Hoyos
    • 2
  • M. Santibañez
    • 3
  1. 1.Intensive Care DepartmentUniversity Hospital Marques de Valdecilla-IFIMAVSantanderSpain
  2. 2.Department of ImmunologyUniversity Hospital Marques de Valdecilla-IFIMAVSantanderSpain
  3. 3.IFIMAV-Fundacion Marques de ValdecillaUniversity of Cantabria, School of NursingSantanderSpain

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