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Published in: Critical Care 1/2018

Open Access 01-12-2018 | Research

Serum suPAR and syndecan-4 levels predict severity of community-acquired pneumonia: a prospective, multi-centre study

Authors: Qiongzhen Luo, Pu Ning, Yali Zheng, Ying Shang, Bing Zhou, Zhancheng Gao

Published in: Critical Care | Issue 1/2018

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Abstract

Background

Community-acquired pneumonia (CAP) is a major cause of death worldwide and occurs with variable severity. There are few studies focused on the expression of soluble urokinase-type plasminogen activator receptor (suPAR) and syndecan-4 in patients with CAP.

Methods

A prospective, multi-centre study was conducted between January 2014 and December 2016. A total of 103 patients with severe CAP (SCAP), 149 patients with non-SCAP, and 30 healthy individuals were enrolled. Clinical data were recorded for all enrolled patients. Serum suPAR and syndecan-4 levels were determined by quantitative enzyme-linked immunosorbent assay. The t test and Mann–Whitney U test were used to compare between two groups; one-way analysis of variance and the Kruskal–Wallis test were used to compare multiple groups. Correlations were assessed using Pearson and Spearman tests. Area under the curve (AUCs), optimal threshold values, sensitivity, and specificity were calculated. Survival curves were constructed and compared by log-rank test. Regression analyses assessed the effect of multiple variables on 30-day survival.

Results

suPAR levels increased in all patients with CAP, especially in severe cases. Syndecan-4 levels decreased in patients with CAP, especially in non-survivors. suPAR and syndecan-4 levels were positively and negatively correlated with severity scores, respectively. suPAR exhibited high accuracy in predicting SCAP among patients with CAP with an AUC of 0.835 (p < 0.001). In contrast, syndecan-4 exhibited poor diagnostic value for predicting SCAP (AUC 0.550, p = 0.187). The AUC for predicting mortality in patients with SCAP was 0.772 and 0.744 for suPAR and syndecan-4, respectively; the respective prediction threshold values were 10.22 ng/mL and 6.68 ng/mL. Addition of both suPAR and syndecan-4 to the Pneumonia Severity Index significantly improved their prognostic accuracy, with an AUC of 0.885. Regression analysis showed that suPAR ≥10.22 ng/mL and syndecan-4 ≤ 6.68 ng/mL were reliable independent markers for prediction of 30-day survival.

Conclusion

suPAR exhibits high accuracy for both diagnosis and prognosis of SCAP. Syndecan-4 can reliably predict mortality in patients with SCAP. Addition of both suPAR and syndecan-4 to a clinical scoring method could improve prognostic accuracy.

Trial registration

ClinicalTrials.gov, NCT03093220. Registered on 28 March 2017 (retrospectively registered).
Literature
1.
go back to reference Prina E, Ranzani OT, Torres A. Community-acquired pneumonia. Lancet. 2015;386:1097–108.PubMed Prina E, Ranzani OT, Torres A. Community-acquired pneumonia. Lancet. 2015;386:1097–108.PubMed
2.
go back to reference Musher DM, Thorner AR. Community-acquired pneumonia. N Engl J Med. 2014;371:1619–28.PubMed Musher DM, Thorner AR. Community-acquired pneumonia. N Engl J Med. 2014;371:1619–28.PubMed
3.
go back to reference Chalmers JD. Identifying severe community-acquired pneumonia: moving beyond mortality. Thorax. 2015;70:515–6.PubMed Chalmers JD. Identifying severe community-acquired pneumonia: moving beyond mortality. Thorax. 2015;70:515–6.PubMed
4.
go back to reference Fine MJ, Auble TE, Yealy DM, Hanusa BH, Weissfeld LA, Singer DE, Coley CM, Marrie TJ, Kapoor WN. A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med. 1997;336:243–50.PubMed Fine MJ, Auble TE, Yealy DM, Hanusa BH, Weissfeld LA, Singer DE, Coley CM, Marrie TJ, Kapoor WN. A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med. 1997;336:243–50.PubMed
5.
go back to reference Gibot S, Cravoisy A, Levy B, Bene MC, Faure G, Bollaert PE. Soluble triggering receptor expressed on myeloid cells and the diagnosis of pneumonia. N Engl J Med. 2004;350:451–8.PubMed Gibot S, Cravoisy A, Levy B, Bene MC, Faure G, Bollaert PE. Soluble triggering receptor expressed on myeloid cells and the diagnosis of pneumonia. N Engl J Med. 2004;350:451–8.PubMed
6.
go back to reference Bello S, Lasierra AB, Mincholé E, Fandos S, Ruiz MA, Vera E, de Pablo F, Ferrer M, Menendez R, Torres A. Prognostic power of proadrenomedullin in community-acquired pneumonia is independent of aetiology. Eur Respir J. 2012;39:1144–55.PubMed Bello S, Lasierra AB, Mincholé E, Fandos S, Ruiz MA, Vera E, de Pablo F, Ferrer M, Menendez R, Torres A. Prognostic power of proadrenomedullin in community-acquired pneumonia is independent of aetiology. Eur Respir J. 2012;39:1144–55.PubMed
7.
go back to reference Krüger S, Ewig S, Giersdorf S, Hartmann O, Suttorp N, Welte T; German Competence Network for the Study of Community Acquired Pneumonia (CAPNETZ) Study Group. Cardiovascular and inflammatory biomarkers to predict short- and long-term survival in community-acquired pneumonia: Results from the German Competence Network, CAPNETZ. Am J Respir Crit Care Med. 2010;182:1426-34.PubMed Krüger S, Ewig S, Giersdorf S, Hartmann O, Suttorp N, Welte T; German Competence Network for the Study of Community Acquired Pneumonia (CAPNETZ) Study Group. Cardiovascular and inflammatory biomarkers to predict short- and long-term survival in community-acquired pneumonia: Results from the German Competence Network, CAPNETZ. Am J Respir Crit Care Med. 2010;182:1426-34.PubMed
8.
go back to reference Manetti M, Rosa I, Milia AF, Guiducci S, Carmeliet P, Ibba-Manneschi L, Matucci-Cerinic M. Inactivation of urokinase-type plasminogen activator receptor (uPAR) gene induces dermal and pulmonary fibrosis and peripheral microvasculopathy in mice: a new model of experimental scleroderma? Ann Rheum Dis. 2014;73:1700–9.PubMed Manetti M, Rosa I, Milia AF, Guiducci S, Carmeliet P, Ibba-Manneschi L, Matucci-Cerinic M. Inactivation of urokinase-type plasminogen activator receptor (uPAR) gene induces dermal and pulmonary fibrosis and peripheral microvasculopathy in mice: a new model of experimental scleroderma? Ann Rheum Dis. 2014;73:1700–9.PubMed
9.
go back to reference Kobayashi N, Ueno T, Ohashi K, Yamashita H, Takahashi Y, Sakamoto K, Manabe S, Hara S, Takashima Y, Dan T, Pastan I, Miyata T, Kurihara H, Matsusaka T, Reiser J, Nagata M. Podocyte injury-driven intracapillary plasminogen activator inhibitor type 1 accelerates podocyte loss via uPAR-mediated β1-integrin endocytosis. Am J Physiol Renal Physiol. 2015;308:F614–26.PubMedPubMedCentral Kobayashi N, Ueno T, Ohashi K, Yamashita H, Takahashi Y, Sakamoto K, Manabe S, Hara S, Takashima Y, Dan T, Pastan I, Miyata T, Kurihara H, Matsusaka T, Reiser J, Nagata M. Podocyte injury-driven intracapillary plasminogen activator inhibitor type 1 accelerates podocyte loss via uPAR-mediated β1-integrin endocytosis. Am J Physiol Renal Physiol. 2015;308:F614–26.PubMedPubMedCentral
10.
go back to reference Genua M, D'Alessio S, Cibella J, Gandelli A, Sala E, Correale C, Spinelli A, Arena V, Malesci A, Rutella S, Ploplis VA, Vetrano S, Danese S. The urokinase plasminogen activator receptor (uPAR) controls macrophage phagocytosis in intestinal inflammation. Gut. 2015;64:589–600.PubMed Genua M, D'Alessio S, Cibella J, Gandelli A, Sala E, Correale C, Spinelli A, Arena V, Malesci A, Rutella S, Ploplis VA, Vetrano S, Danese S. The urokinase plasminogen activator receptor (uPAR) controls macrophage phagocytosis in intestinal inflammation. Gut. 2015;64:589–600.PubMed
11.
go back to reference Mazzieri R, Pietrogrande G, Gerasi L, Gandelli A, Colombo P, Moi D, Brombin C, Ambrosi A, Danese S, Mignatti P, Blasi F, D'Alessio S. Urokinase receptor promotes skin tumor formation by preventing epithelial cell activation of Notch1. Cancer Res. 2015;75:4895–909.PubMed Mazzieri R, Pietrogrande G, Gerasi L, Gandelli A, Colombo P, Moi D, Brombin C, Ambrosi A, Danese S, Mignatti P, Blasi F, D'Alessio S. Urokinase receptor promotes skin tumor formation by preventing epithelial cell activation of Notch1. Cancer Res. 2015;75:4895–909.PubMed
12.
go back to reference Matzkies LM, Raggam RB, Flick H, Rabensteiner J, Feierl G, Hoenigl M, Prattes J. Prognostic and diagnostic potential of suPAR levels in pleural effusion. J Infect. 2017;75:465–7.PubMed Matzkies LM, Raggam RB, Flick H, Rabensteiner J, Feierl G, Hoenigl M, Prattes J. Prognostic and diagnostic potential of suPAR levels in pleural effusion. J Infect. 2017;75:465–7.PubMed
13.
14.
go back to reference Choi S, Chung H, Hong H, Kim SY, Kim SE, Seoh JY, Moon CM, Yang EG, Oh ES. Inflammatory hypoxia induces syndecan-2 expression through IL-1β-mediated FOXO3a activation in colonic epithelia. FASEB J. 2017;31:1516–30.PubMed Choi S, Chung H, Hong H, Kim SY, Kim SE, Seoh JY, Moon CM, Yang EG, Oh ES. Inflammatory hypoxia induces syndecan-2 expression through IL-1β-mediated FOXO3a activation in colonic epithelia. FASEB J. 2017;31:1516–30.PubMed
15.
go back to reference Brauer R, Ge L, Schlesinger SY, Birkland TP, Huang Y, Parimon T, Lee V, McKinney BL, McGuire JK, Parks WC, Chen P. Syndecan-1 attenuates lung injury during influenza infection by potentiating c-met signaling to suppress epithelial apoptosis. Am J Respir Crit Care Med. 2016;194:333–44.PubMedPubMedCentral Brauer R, Ge L, Schlesinger SY, Birkland TP, Huang Y, Parimon T, Lee V, McKinney BL, McGuire JK, Parks WC, Chen P. Syndecan-1 attenuates lung injury during influenza infection by potentiating c-met signaling to suppress epithelial apoptosis. Am J Respir Crit Care Med. 2016;194:333–44.PubMedPubMedCentral
16.
go back to reference Cassinelli G, Zaffaroni N, Lanzi C. The heparanase/heparan sulfate proteoglycan axis: a potential new therapeutic target in sarcomas. Cancer Lett. 2016;382:245–54.PubMed Cassinelli G, Zaffaroni N, Lanzi C. The heparanase/heparan sulfate proteoglycan axis: a potential new therapeutic target in sarcomas. Cancer Lett. 2016;382:245–54.PubMed
17.
go back to reference Santoso A, Kikuchi T, Tode N, Hirano T, Komatsu R, Damayanti T, Motohashi H, Yamamoto M, Kojima T, Uede T, Nukiwa T, Ichinose M. Syndecan 4 mediates Nrf2-dependent expansion of bronchiolar progenitors that protect against lung inflammation. Mol Ther. 2016;24:41–52.PubMed Santoso A, Kikuchi T, Tode N, Hirano T, Komatsu R, Damayanti T, Motohashi H, Yamamoto M, Kojima T, Uede T, Nukiwa T, Ichinose M. Syndecan 4 mediates Nrf2-dependent expansion of bronchiolar progenitors that protect against lung inflammation. Mol Ther. 2016;24:41–52.PubMed
18.
go back to reference Niederman MS, Mandell LA, Anzueto A, Bass JB, Broughton WA, Campbell GD, Dean N, File T, Fine MJ, Gross PA, Martinez F, Marrie TJ, Plouffe JF, Ramirez J, Sarosi GA, Torres A, Wilson R, Yu VL; American Thoracic Society. Guidelines for the management of adults with community-acquired pneumonia. Diagnosis, assessment of severity, antimicrobial therapy, and prevention. Am J Respir Crit Care Med. 2001;163:1730–54.PubMed Niederman MS, Mandell LA, Anzueto A, Bass JB, Broughton WA, Campbell GD, Dean N, File T, Fine MJ, Gross PA, Martinez F, Marrie TJ, Plouffe JF, Ramirez J, Sarosi GA, Torres A, Wilson R, Yu VL; American Thoracic Society. Guidelines for the management of adults with community-acquired pneumonia. Diagnosis, assessment of severity, antimicrobial therapy, and prevention. Am J Respir Crit Care Med. 2001;163:1730–54.PubMed
19.
go back to reference Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, Dowell SF, File TM Jr, Musher DM, Niederman MS, Torres A, Whitney CG; Infectious Diseases Society of America; American Thoracic Society. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44 Suppl 2:S27–72. Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, Dowell SF, File TM Jr, Musher DM, Niederman MS, Torres A, Whitney CG; Infectious Diseases Society of America; American Thoracic Society. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44 Suppl 2:S27–72.
20.
go back to reference Capelastegui A, España PP, Quintana JM, Areitio I, Gorordo I, Egurrola M, Bilbao A. Validation of a predictive rule for the management of community-acquired pneumonia. Eur Respir J. 2006;27:151–7.PubMed Capelastegui A, España PP, Quintana JM, Areitio I, Gorordo I, Egurrola M, Bilbao A. Validation of a predictive rule for the management of community-acquired pneumonia. Eur Respir J. 2006;27:151–7.PubMed
21.
go back to reference Spindler C, Ortqvist A. Prognostic score systems and community-acquired bacteraemic pneumococcal pneumonia. Eur Respir J. 2006;28:816–23.PubMed Spindler C, Ortqvist A. Prognostic score systems and community-acquired bacteraemic pneumococcal pneumonia. Eur Respir J. 2006;28:816–23.PubMed
22.
go back to reference Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985;13:818–29.PubMed Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985;13:818–29.PubMed
23.
go back to reference 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. Risk assessment in sepsis: a new prognostication rule by APACHE II score and serum soluble urokinase plasminogen activator receptor. Crit Care. 2012;16(4):R149.PubMedPubMedCentral 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. Risk assessment in sepsis: a new prognostication rule by APACHE II score and serum soluble urokinase plasminogen activator receptor. Crit Care. 2012;16(4):R149.PubMedPubMedCentral
24.
go back to reference Rudolf F, Wagner AJ, Back FM, Gomes VF, Aaby P, Østergaard L, Eugen-Olsen J, Wejse C. Tuberculosis case finding and mortality prediction: added value of the clinical TBscore and biomarker suPAR. Int J Tuberc Lung Dis. 2017;21:67–72.PubMed Rudolf F, Wagner AJ, Back FM, Gomes VF, Aaby P, Østergaard L, Eugen-Olsen J, Wejse C. Tuberculosis case finding and mortality prediction: added value of the clinical TBscore and biomarker suPAR. Int J Tuberc Lung Dis. 2017;21:67–72.PubMed
25.
go back to reference Rasmussen LJ, Knudsen A, Katzenstein TL, Gerstoft J, Obel N, Jørgensen NR, Kronborg G, Benfield T, Kjaer A, Eugen-Olsen J, Lebech AM. Soluble urokinase plasminogen activator receptor (suPAR) is a novel, independent predictive marker of myocardial infarction in HIV-1-infected patients: a nested case-control study. HIV Med. 2016;17:350–7.PubMed Rasmussen LJ, Knudsen A, Katzenstein TL, Gerstoft J, Obel N, Jørgensen NR, Kronborg G, Benfield T, Kjaer A, Eugen-Olsen J, Lebech AM. Soluble urokinase plasminogen activator receptor (suPAR) is a novel, independent predictive marker of myocardial infarction in HIV-1-infected patients: a nested case-control study. HIV Med. 2016;17:350–7.PubMed
26.
go back to reference Savva A, Raftogiannis M, Baziaka F, Routsi C, Antonopoulou A, Koutoukas P, Tsaganos T, Kotanidou A, Apostolidou E, Giamarellos-Bourboulis EJ, Dimopoulos G. Soluble urokinase plasminogen activator receptor (suPAR) for assessment of disease severity in ventilator-associated pneumonia and sepsis. J Infect. 2011;63:344–50.PubMed Savva A, Raftogiannis M, Baziaka F, Routsi C, Antonopoulou A, Koutoukas P, Tsaganos T, Kotanidou A, Apostolidou E, Giamarellos-Bourboulis EJ, Dimopoulos G. Soluble urokinase plasminogen activator receptor (suPAR) for assessment of disease severity in ventilator-associated pneumonia and sepsis. J Infect. 2011;63:344–50.PubMed
27.
go back to reference Wittenhagen P, Kronborg G, Weis N, Nielsen H, Obel N, Pedersen SS, Eugen-Olsen J. The plasma level of soluble urokinase receptor is elevated in patients with Streptococcus pneumoniae bacteraemia and predicts mortality. Clin Microbiol Infect. 2004;10:409–15.PubMed Wittenhagen P, Kronborg G, Weis N, Nielsen H, Obel N, Pedersen SS, Eugen-Olsen J. The plasma level of soluble urokinase receptor is elevated in patients with Streptococcus pneumoniae bacteraemia and predicts mortality. Clin Microbiol Infect. 2004;10:409–15.PubMed
28.
go back to reference Kofoed K, Andersen O, Kronborg G, Tvede M, Petersen J, Eugen-Olsen J, Larsen K. 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. 2007;11:R38.PubMedPubMedCentral Kofoed K, Andersen O, Kronborg G, Tvede M, Petersen J, Eugen-Olsen J, Larsen K. 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. 2007;11:R38.PubMedPubMedCentral
29.
go back to reference Nikaido T, Tanino Y, Wang X, Sato S, Misa K, Fukuhara N, Sato Y, Fukuhara A, Uematsu M, Suzuki Y, Kojima T, Tanino M, Endo Y, Tsuchiya K, Kawamura I, Frevert CW, Munakata M. Serum syndecan-4 as a possible biomarker in patients with acute pneumonia. J Infect Dis. 2015;212:1500–8.PubMed Nikaido T, Tanino Y, Wang X, Sato S, Misa K, Fukuhara N, Sato Y, Fukuhara A, Uematsu M, Suzuki Y, Kojima T, Tanino M, Endo Y, Tsuchiya K, Kawamura I, Frevert CW, Munakata M. Serum syndecan-4 as a possible biomarker in patients with acute pneumonia. J Infect Dis. 2015;212:1500–8.PubMed
30.
go back to reference Derman BA, Macklis JN, Azeem MS, Sayidine S, Basu S, Batus M, Esmail F, Borgia JA, Bonomi P, Fidler MJ. Relationships between longitudinal neutrophil to lymphocyte ratios, body weight changes, and overall survival in patients with non-small cell lung cancer. BMC Cancer. 2017;17:141.PubMedPubMedCentral Derman BA, Macklis JN, Azeem MS, Sayidine S, Basu S, Batus M, Esmail F, Borgia JA, Bonomi P, Fidler MJ. Relationships between longitudinal neutrophil to lymphocyte ratios, body weight changes, and overall survival in patients with non-small cell lung cancer. BMC Cancer. 2017;17:141.PubMedPubMedCentral
31.
go back to reference Curbelo J, Luquero Bueno S, Galván-Román JM, Ortega-Gómez M, Rajas O, Fernández-Jiménez G, Vega-Piris L, Rodríguez-Salvanes F, Arnalich B, Díaz A, Costa R, de la Fuente H, Lancho Á, Suárez C, Ancochea J, Aspa J. Inflammation biomarkers in blood as mortality predictors in community-acquired pneumonia admitted patients: Importance of comparison with neutrophil count percentage or neutrophil-lymphocyte ratio. PLoS One. 2017;12, e0173947.PubMedPubMedCentral Curbelo J, Luquero Bueno S, Galván-Román JM, Ortega-Gómez M, Rajas O, Fernández-Jiménez G, Vega-Piris L, Rodríguez-Salvanes F, Arnalich B, Díaz A, Costa R, de la Fuente H, Lancho Á, Suárez C, Ancochea J, Aspa J. Inflammation biomarkers in blood as mortality predictors in community-acquired pneumonia admitted patients: Importance of comparison with neutrophil count percentage or neutrophil-lymphocyte ratio. PLoS One. 2017;12, e0173947.PubMedPubMedCentral
32.
go back to reference Benites-Zapata VA, Hernandez AV, Nagarajan V, Cauthen CA, Starling RC, Tang WH. Usefulness of neutrophil-to-lymphocyte ratio in risk stratification of patients with advanced heart failure. Am J Cardiol. 2015;115:57–61.PubMed Benites-Zapata VA, Hernandez AV, Nagarajan V, Cauthen CA, Starling RC, Tang WH. Usefulness of neutrophil-to-lymphocyte ratio in risk stratification of patients with advanced heart failure. Am J Cardiol. 2015;115:57–61.PubMed
33.
go back to reference Koch A, Voigt S, Kruschinski C, Sanson E, Dückers H, Horn A, Yagmur E, Zimmermann H, Trautwein C, Tacke F. 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.PubMedPubMedCentral Koch A, Voigt S, Kruschinski C, Sanson E, Dückers H, Horn A, Yagmur E, Zimmermann H, Trautwein C, Tacke F. 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.PubMedPubMedCentral
34.
go back to reference Hoenigl M, Raggam RB, Wagner J, Valentin T, Leitner E, Seeber K, Zollner-Schwetz I, Krammer W, Prüller F, Grisold AJ, Krause R. 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.PubMed Hoenigl M, Raggam RB, Wagner J, Valentin T, Leitner E, Seeber K, Zollner-Schwetz I, Krammer W, Prüller F, Grisold AJ, Krause R. 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.PubMed
35.
go back to reference Suberviola B, Castellanos-Ortega A, Ruiz Ruiz A, Lopez-Hoyos M, Santibañez M. Hospital mortality prognostication in sepsis using the new biomarkers suPAR and proADM in a single determination on ICU admission. Intensive Care Med. 2013;39:1945–52.PubMed Suberviola B, Castellanos-Ortega A, Ruiz Ruiz A, Lopez-Hoyos M, Santibañez M. Hospital mortality prognostication in sepsis using the new biomarkers suPAR and proADM in a single determination on ICU admission. Intensive Care Med. 2013;39:1945–52.PubMed
36.
go back to reference Mölkänen T, Ruotsalainen E, Thorball CW, Järvinen A. Elevated soluble urokinase plasminogen activator receptor (suPAR) predicts mortality in Staphylococcus aureus bacteremia. Eur J Clin Microbiol Infect Dis. 2011;30:1417–24.PubMed Mölkänen T, Ruotsalainen E, Thorball CW, Järvinen A. Elevated soluble urokinase plasminogen activator receptor (suPAR) predicts mortality in Staphylococcus aureus bacteremia. Eur J Clin Microbiol Infect Dis. 2011;30:1417–24.PubMed
37.
go back to reference Huttunen R, Syrjänen J, Vuento R, Hurme M, Huhtala H, Laine J, Pessi T, Aittoniemi J. 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.PubMed Huttunen R, Syrjänen J, Vuento R, Hurme M, Huhtala H, Laine J, Pessi T, Aittoniemi J. 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.PubMed
38.
go back to reference Jalkanen V, Yang R, Linko R, Huhtala H, Okkonen M, Varpula T, Pettilä V, Tenhunen J, FINNALI Study Group. SuPAR and PAI-1 in critically ill, mechanically ventilated patients. Intensive Care Med. 2013;39:489–96.PubMed Jalkanen V, Yang R, Linko R, Huhtala H, Okkonen M, Varpula T, Pettilä V, Tenhunen J, FINNALI Study Group. SuPAR and PAI-1 in critically ill, mechanically ventilated patients. Intensive Care Med. 2013;39:489–96.PubMed
39.
go back to reference Murciano JC, Higazi AA, Cines DB, Muzykantov VR. Soluble urokinase receptor conjugated to carrier red blood cells binds latent pro-urokinase and alters its functional profile. J Control Release. 2009;139:190–6.PubMedPubMedCentral Murciano JC, Higazi AA, Cines DB, Muzykantov VR. Soluble urokinase receptor conjugated to carrier red blood cells binds latent pro-urokinase and alters its functional profile. J Control Release. 2009;139:190–6.PubMedPubMedCentral
40.
go back to reference Tanino Y, Chang MY, Wang X, Gill SE, Skerrett S, McGuire JK, Sato S, Nikaido T, Kojima T, Munakata M, Mongovin S, Parks WC, Martin TR, Wight TN, Frevert CW. Syndecan-4 regulates early neutrophil migration and pulmonary inflammation in response to lipopolysaccharide. Am J Respir Cell Mol Biol. 2012;47:196–202.PubMedPubMedCentral Tanino Y, Chang MY, Wang X, Gill SE, Skerrett S, McGuire JK, Sato S, Nikaido T, Kojima T, Munakata M, Mongovin S, Parks WC, Martin TR, Wight TN, Frevert CW. Syndecan-4 regulates early neutrophil migration and pulmonary inflammation in response to lipopolysaccharide. Am J Respir Cell Mol Biol. 2012;47:196–202.PubMedPubMedCentral
41.
go back to reference Ishiguro K, Kadomatsu K, Kojima T, Muramatsu H, Iwase M, Yoshikai Y, Yanada M, Yamamoto K, Matsushita T, Nishimura M, Kusugami K, Saito H, Muramatsu T. Syndecan-4 deficiency leads to high mortality of lipopolysaccharide-injected mice. J Biol Chem. 2001;276:47483–8.PubMed Ishiguro K, Kadomatsu K, Kojima T, Muramatsu H, Iwase M, Yoshikai Y, Yanada M, Yamamoto K, Matsushita T, Nishimura M, Kusugami K, Saito H, Muramatsu T. Syndecan-4 deficiency leads to high mortality of lipopolysaccharide-injected mice. J Biol Chem. 2001;276:47483–8.PubMed
42.
go back to reference Theilade S, Lyngbaek S, Hansen TW, Eugen-Olsen J, Fenger M, Rossing P, Jeppesen JL. Soluble urokinase plasminogen activator receptor levels are elevated and associated with complications in patients with type 1 diabetes. J Intern Med. 2015;277:362–71.PubMed Theilade S, Lyngbaek S, Hansen TW, Eugen-Olsen J, Fenger M, Rossing P, Jeppesen JL. Soluble urokinase plasminogen activator receptor levels are elevated and associated with complications in patients with type 1 diabetes. J Intern Med. 2015;277:362–71.PubMed
43.
go back to reference Kirkegaard-Klitbo DM, Langkilde A, Mejer N, Andersen O, Eugen-Olsen J, Benfield T. Soluble urokinase plasminogen activator receptor is a predictor of incident non-AIDS comorbidity and all-cause mortality in human immunodeficiency virus type 1 infection. J Infect Dis. 2017;216:819–23.PubMed Kirkegaard-Klitbo DM, Langkilde A, Mejer N, Andersen O, Eugen-Olsen J, Benfield T. Soluble urokinase plasminogen activator receptor is a predictor of incident non-AIDS comorbidity and all-cause mortality in human immunodeficiency virus type 1 infection. J Infect Dis. 2017;216:819–23.PubMed
44.
go back to reference Koller L, Stojkovic S, Richter B, Sulzgruber P, Potolidis C, Liebhart F, Mörtl D, Berger R, Goliasch G, Wojta J, Hülsmann M, Niessner A. Soluble urokinase-type plasminogen activator receptor improves risk prediction in patients with chronic heart failure. JACC Heart Fail. 2017;5:268–77.PubMed Koller L, Stojkovic S, Richter B, Sulzgruber P, Potolidis C, Liebhart F, Mörtl D, Berger R, Goliasch G, Wojta J, Hülsmann M, Niessner A. Soluble urokinase-type plasminogen activator receptor improves risk prediction in patients with chronic heart failure. JACC Heart Fail. 2017;5:268–77.PubMed
Metadata
Title
Serum suPAR and syndecan-4 levels predict severity of community-acquired pneumonia: a prospective, multi-centre study
Authors
Qiongzhen Luo
Pu Ning
Yali Zheng
Ying Shang
Bing Zhou
Zhancheng Gao
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2018
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-018-1943-y

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