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

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

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).

Keywords: Community acquired pneumonia; Mortality; Severity; Syndecan-4; suPAR.

Conflict of interest statement

Ethics approval and consent to participate

All subjects provided informed consent. This study was approved by the medical ethics committee of Peking University People's Hospital.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Flowchart of the study population. SCAP severe community-acquired pneumonia
Fig. 2
Fig. 2
Levels of soluble urokinase-type plasminogen activator receptor (suPAR) and syndecan-4 across multiple groups. a, b Levels of suPAR and syndecan-4 in patients with severe community-acquired pneumonia SCAP, patients with non-SCAP, and healthy individuals, respectively. For suPAR, SCAP versus non-SCAP, p < 0.001; non-SCAP versus healthy individuals, p < 0.001. For syndecan-4, SCAP versus healthy individuals, p < 0.001; non-SCAP versus healthy individuals, p < 0.001. c, d Levels of suPAR and syndecan-4 in survivors and non-survivors among patients with SCAP, patients with SCAP who met at least one major criterion (major criteria), and patients with SCAP who met only minor criterion (minor criteria). For suPAR, survivors versus non-survivors, p < 0.001; major criteria versus minor criteria, p = 0.459. For Syndecan-4, survivors versus non-survivors, p = 0.002; major criteria versus minor criteria, p = 0.671. e, f Comparison of suPAR and syndecan-4 in patients with SCAP and non-SCAP for various causative pathogens; p > 0.05 for all comparisons
Fig. 3
Fig. 3
Correlation of soluble urokinase-type plasminogen activator receptor (suPAR) and syndecan-4 levels with multiple scoring systems across 252 patients with community-acquired pneumonia (CAP). r is the correlation coefficient. a, c, e Levels of suPAR were significantly positively correlated with the confusion, urea, respiratory rate, blood pressure, and age ≥65 years old (CURB-65) score (r = 0.399, p < 0.001), Pneumonia Severity Index (PSI) (r = 0.433, p < 0.001), and Acute Physiology and Chronic Health Evaluation II (APACHE II) score (r = 0.496, p < 0.001), respectively. b, d, f Levels of syndecan-4 were significantly negatively correlated with CURB-65 score (r = -0.220, p = 0.001), PSI (r = -0.279, p < 0.001), and APACHE II score (r = -0.184, p = 0.003), respectively
Fig. 4
Fig. 4
Receiver operating characteristic curve analysis of various parameters to discriminate patients with severe community-acquired pneumonia from patients with community-acquired pneumonia. suPAR soluble urokinase-type plasminogen activator receptor, NLR neutrophil/lymphocyte ratio, WBC whole blood leukocyte count, CRP C-reactive protein, PCT procalcitonin, CURB-65 confusion, urea, respiratory rate, blood pressure, and age ≥65 years old score, PSI Pneumonia Severity Index Score, APACHE II Acute Physiology and Chronic Health Evaluation II score, AUC area under the curve
Fig. 5
Fig. 5
Receiver operating characteristic (ROC) curve analysis of various parameters to predict 30-day mortality in patients with SCAP
Fig. 6
Fig. 6
Kaplan–Meier analysis of 30-day mortality in patients with severe community-acquired pneumonia. Analysis was stratified by soluble urokinase-type plasminogen activator receptor (suPAR) (a) and syndecan-4 (b) levels

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