Indian Journal of Critical Care Medicine

Register      Login



Volume / Issue

Online First

Related articles

VOLUME 24 , ISSUE 4 ( April, 2020 ) > List of Articles

Original Article

A Comparative Study of the Diagnostic and Prognostic Utility of Soluble Urokinase-type Plasminogen Activator Receptor and Procalcitonin in Patients with Sepsis and Systemic Inflammation Response Syndrome

Sumit Ray, Ramya Mamidipalli, Atul Kakar, Ridhima Jain, Manvender S Ghalaut, Sangeeta Choudhury

Keywords : Procalcitonin, Sepsis, Soluble urokinase-type plasminogen activator receptor, Systemic inflammation response syndrome

Citation Information : Ray S, Mamidipalli R, Kakar A, Jain R, Ghalaut MS, Choudhury S. A Comparative Study of the Diagnostic and Prognostic Utility of Soluble Urokinase-type Plasminogen Activator Receptor and Procalcitonin in Patients with Sepsis and Systemic Inflammation Response Syndrome. Indian J Crit Care Med 2020; 24 (4):245-251.

DOI: 10.5005/jp-journals-10071-23385

License: CC BY-NC 4.0

Published Online: 00-04-2020

Copyright Statement:  Copyright © 2020; Jaypee Brothers Medical Publishers (P) Ltd.


Introduction: Differentiation between sepsis and systemic inflammation response syndrome (SIRS) remains a diagnostic challenge for clinicians as both may have similar clinical presentation. A quick and accurate diagnostic tool that can discriminate between these two conditions would aid in appropriate therapeutic decision-making. This prospective study was conducted to evaluate the diagnostic and prognostic utility of soluble urokinase-type plasminogen activator receptor (suPAR) and procalcitonin (PCT) in sepsis and SIRS patients. Materials and methods: Eighty-eight patients were enrolled, of which 29 were SIRS and 59 were sepsis patients. The levels of suPAR and PCT were measured on the day of admission (day 1), day 3, and day 7. Results: The levels of suPAR and PCT were significantly higher (p = 0.05 and p < 0.001, respectively) in sepsis group as compared to the SIRS group. The soluble urokinase-type plasminogen activator receptor was a better diagnostic tool in predicting sepsis over PCT [area under curve (AUC) 0.89 vs 0.82] on day 1. The best cutoff for suPAR was 5.58 pg/mL [96% sensitivity and 90% negative predictive value (NPV)] and the best cut-off for PCT was 1.96 ng/mL (93.1% sensitivity and 80% NPV). However, PCT had better prognostic trends (p = 0.006) to identify nonsurvivors in sepsis group. Conclusion: Our findings suggest that both suPAR and PCT can be used as potential test tools to differentiate between SIRS and sepsis. Procalcitonin showed significant prognostic trends to identify nonsurvivors. The soluble urokinase-type plasminogen activator receptor showed better diagnostic potential than PCT on day 1. Clinical significance: Both suPAR and PCT can be used as surrogate biomarkers to distinguish sepsis from SIRS. Procalcitonin showing a significant prognostic trend to identify nonsurvivors can help the clinicians to take relevant clinical decisions. Also, the use of biomarkers like PCT and suPAR could reduce the inappropriate use of antibiotics in noninfective SIRS.

  1. Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United states from 1979 through 2000. N Engl J Med 2003;348(16):1546–1554. DOI: 10.1056/NEJMoa022139.
  2. Engel C, Brunkhorst FM, Bone HG, Brunkhorst R, Gerlach H, Grond S, et al. Epidemiology of sepsis in Germany: results from a national prospective multicenter study. Intensive Care Med 2007;33(4): 606–618. DOI: 10.1007/s00134-006-0517-7.
  3. Dombrovskiy VY, Martin AA, Sunderram J, Paz HL. Rapid increase in hospitalization and mortality rates for severe sepsis in the United States: a trend analysis from 1993 to 2003. Crit Care Med 2007;35(5):1244–1250. DOI: 10.1097/01.CCM.0000261890.41311.E9.
  4. Hall MJ, Williams SN, DeFrances CJ, Golosinskiy A. Inpatient care for septicemia or sepsis: a challenge for patients and hospitals. NCHS Data Brief 2011(62):1–8.
  5. Vincent JL, Rello J, Marshall J, Silva E, Anzueto A, Martin CD, et al. EPIC II group of investigators. International study of the prevalence and outcomes of infection in intensive care units. J Am Med Assoc 2009;302(21):2323–2329. DOI: 10.1001/jama.2009.1754.
  6. Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, 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(6):1644–1655. DOI: 10.1378/chest.101.6.1644.
  7. Anand D, Das S, Bhargava S, Srivastava LM, Garg A, Tyagi N, et al. Procalcitonin as a rapid diagnostic biomarker to differentiate between culture-negative bacterial sepsis and systemic inflammatory response syndrome: a prospective, observational, cohort study. J Crit Care 2015;30(1):218.e7-12. DOI: 10.1016/j.jcrc.2014.08.017.
  8. Høyer-Hansen G, Rønne E, Solberg H, Behrendt N, Ploug M, Lund LR, et al. Urokinase plasminogen activator cleaves its cell surface receptor releasing the ligand-binding domain. J Biol Chem 1992;267(25):18224–18229.
  9. Wilhelm OG, Wilhelm S, Escott GM, Lutz V, Magdolen V, Schmitt M, et al. Cellular glycosylphosphatidylinositol-specific phospholipase D regulates urokinase receptor shedding and cell surface expression. J Cell Physiol 1999;180(2):225–235. DOI: 10.1002/(SICI)1097-4652(199908)180:23.0.CO;2-2.
  10. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). J Am Med Assoc 2016;315(8):801–810. DOI: 10.1001/jama.2016.0287.
  11. Tsalik EL, Jaggers LB, Glickman SW, Langley RJ, van Velkinburgh JC, Park LP, et al. Discriminative value of inflammatory biomarkers for suspected sepsis. J Emerg Med 2012;43(1):97–106. DOI: 10.1016/j.jemermed.2011.05.072.
  12. Liaudat S, Dayer E, Praz G, Bille J, Troillet N. Usefulness of procalcitonin serum level for the diagnosis of bacteremia. Eur J Clin Microbiol Infect Dis 2001;20(8):524–527. DOI: 10.1007/s100960100548.
  13. Chirouze C, Schuhmacher H, Rabaud C, Gil H, Khayat N, Estavoyer JM, et al. Low serum procalcitonin level accurately predicts the absence of bacteremia in adult patients with acute fever. Clin Infect Dis 2002;35(2):156–161. DOI: 10.1086/341023.
  14. Wittenhagen P, Kronborg G, Weis N, Nielsen H, Obel N, Pedersen SS, et al. The plasma level of soluble urokinase receptor is elevated in patients with streptococcus pneumoniae bacteraemia and predicts mortality. Clin Microbiol Infect 2004;10(5):409–415. DOI: 10.1111/j.1469-0691.2004.00850.x.
  15. Huttunen R, Syrjänen J, Vuento R, Hurme M, Huhtala H, Laine J, 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(1):32–40. DOI: 10.1111/j.1365-2796.2011.02363.x.
  16. Langkilde A, Hansen TW, Ladelund S, Linneberg A, Andersen O, Haugaard SB. Increased plasma soluble uPAR level is a risk marker of respiratory cancer in initially cancer-free individuals. Cancer Epidemiol Biomarkers Prev 2011;20(4):609–618. DOI: 10.1158/1055-9965.EPI-10-1009.
  17. Eugen-Olsen J, Gustafson P, Sidenius N, Fischer TK, Parner J, Aaby P, 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(8):686–692.
  18. Savva A, Raftogiannis M, Baziaka F, Antonopoulou A, Koutaukas P, Tsaganos T, et al. Soluble urokinase plasminogen activator receptor (suPAR) for assessment of disease severity in ventilator-associated pneumonia and sepsis. J Infect 2011;63(5):344–350. DOI: 10.1016/j.jinf.2011.07.016.
  19. Koch A, Voigt S, Kruschinski C, Sanson E, Duckers H, Horn A, 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(1):R63. DOI: 10.1186/cc10037.
  20. Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006;34(6):1589–1596. DOI: 10.1097/01.CCM.0000217961.75225.E9.
  21. Backes Y, van der Sluijs KF, Mackie DP, Tacke F, Koch A, Tenhunen JJ, et al. Usefulness of suPAR as a biological marker in patients with systemic inflammation or infection: a systematic review. Intensive Care Med 2012;38(9):1418–1428. DOI: 10.1007/s00134-012- 2613-1.
  22. Sidenius N, Sier CF, Blasi F. Shedding and cleavage of the urokinase receptor (uPAR): identification andcharacterisation of uPAR fragments in vitro and in vivo. FEBS Lett 2000;475(1):52–56. DOI: 10.1016/s0014-5793(00)01624-0.
  23. Jevdjic J, Surbatovic M, Milosavljevic S, Rondovic G, Stanojevic I, Eric S, et al. Galectin-3 in critically ill patients with sepsis and/or trauma: a good predictor of outcome or not? Ser J Exp Clin Res 2017.
  24. Le Moullec JM, Jullienne A, Chenais J, Lasmoles F, Guliana JM, Milhaud G, et al. The complete sequence of human preprocalcitonin. FEBS Lett 1984;167(1):93–97. DOI: 10.1016/0014-5793(84)80839-x.
  25. Assicot M, Gendrel D, Carsin H, Raymond J, Guilbaud J, Bohuon C. High serum procalcitonin concentrations in patients with sepsis and infection. Lancet 1993;341(8844):515–518. DOI: 10.1016/0140-6736(93)90277-n.
  26. Dandona P, Nix D, Wilson MF, Aljada A, Love J, Assicot M, et al. Procalcitonin increase after endotoxin injection in normal subjects. J Clin Endocrinol Metab 1994;79(6):16058. DOI: 10.1210/jcem.79.6.7989463.
  27. Phua J, Koh Y, Du B, Tang YQ, Divatia JV, Tan CC, et al. Management of severe sepsis in patients admitted to Asian intensive care units: prospective cohort study. BMJ 2011;342(jun 13 1):d3245. DOI: 10.1136/bmj.d3245.
  28. Mölkänen T, Ruotsalainen E, Thorball CW, Järvinen A. Elevated soluble urokinase plasminogen activator receptor (suPAR) predictsmortality in staphylococcus aureus bacteremia. Eur J Clin Microbiol Infect Dis 2011;30(11):1417–1424. DOI: 10.1007/s10096-011-1236-8.
  29. Sehestedt T, Lyngbæk S, Eugen-Olsen J, Jeppesen J, Andersen O, Hansen TW, et al. Soluble urokinase plasminogen activator receptor is associated with subclinical organ damage and cardiovascular events. Atherosclerosis 2011;216(1):237–243. DOI: 10.1016/j.atherosclerosis.2011.01.049.
  30. Kofoed K, Eugen-Olsen J, Petersen J, Larsen K, Andersen O. Predicting mortality in patients with systemic inflammatory response syndrome: an evaluation of two prognostic models, two soluble receptors, and a macrophage migration inhibitory factor. Eur J Clin Microbiol Infect Dis 2008;27(5):375–383. DOI: 10.1007/s10096-007-0447-5.
  31. Schultz M, Rasmussen L, Andersen M, Stefansson J, Falkentoft A, Alstrup M, et al. Use of the prognostic biomarker suPAR in the emergency department improves risk stratification but has no effect on mortality: a cluster-randomized clinical trial (TRIAGE III). Scand J Trauma Resusc Emerg Med 2018;26(1):69. DOI: 10.1186/s13049-018-0539-5.
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.