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

Abstract

BackgroundCommunity-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.MethodsA 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.ResultssuPAR 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.ConclusionsuPAR 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 registrationClinicalTrials.gov, NCT03093220. Registered on 28 March 2017 (retrospectively registered).

Increased Serum Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR) Levels in FSGS: A Meta-Analysis

“…The soluble urokinase plasminogen activator receptor (suPAR) is a protein circulating in the human blood and body fluids, which is present at low concentration in healthy individuals and high levels in patients with infections, chronic kidney disease (CKD), and other inflammatory disorders [4]. In that, its usefulness as a biomarker has been investigated in various diseases, such as sepsis [5], pneumonia [6], chronic obstructive pulmonary disease (COPD) [7], and kidney diseases including pFSGS [3, 8–10]. Regarding pFSGS, suPAR has been proposed to be a marker for diagnosis and posttransplantation recurrence [1, 11–13].…”

Soluble syndecans: biomarkers for diseases and therapeutic options

“…Again, the authors propose that baseline serum Sdc4 levels were indicative for the prognosis, showing that higher serum levels of Sdc4 were associated with a worse prognosis than lower baseline levels (Sato et al ., ). Sdc4 serum levels were also associated with severe community‐acquired pneumonia, and these increased serum levels were linked to a higher mortality rate (Luo et al ., ).…”

Biomarker suPAR seems a good prognostic factor for community-acquired pneumonia but less prominent for septic shock

“…We read with interest the article by Luo et al [1]. The urokinase-type plasminogen activator system consists of a protease, a receptor urokinase-type plasminogen activator receptor (uPAR), and inhibitors [2].…”

“…Depending on the degree of glycosylation and proteolytic cleavage, soluble urokinase-type plasminogen activator receptor (suPAR) is a circulating protein ranging mostly between 20 and 35 kDa [2]. Luo et al show that suPAR exhibits high accuracy for both diagnosis and prognosis of severe community-acquired pneumonia (CAP) [1]. We would like to make some comments.…”

“…We would like to make some comments. While the area under the curve (AUC) for suPAR in order to accurately differentiate severe CAP (SCAP) from CAP is extremely good (AUC of 0.835 ( p < 0.001) [1], it was reported poor regarding its ability to differentiate severity of sepsis shock (AUC of 0.62) [3]. An explanation could be that nearly half of critically ill patients especially with septic shock have or develop acute kidney injury (AKI) and 20–25% needs renal replacement therapy (RRT) within the first week of their stay [4].…”