Predictive value of pentraxin-3 on disease severity and mortality risk in patients with hemorrhagic fever with renal syndrome

Abstract

Background: Hemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus is characterized by systemic immunopathological injury. Pentraxin-3 is an acute-phase reactant involved in the processes of inflammation and infection. This study aimed to investigate the levels of plasma pentraxin-3 and evaluate its predictive value on disease severity and mortality risk in patients with HFRS.

Methods: This was a prospective real-world observational study. The concentrations of plasma pentraxin-3 were measured by enzyme linked immunosorbent assay (ELISA) in 105 HFRS patients and 27 healthy controls. We analyzed the clinical relevance between pentraxin-3 and clinical subtyping, hospital stay and conventional laboratory parameters of HFRS patients. Considering the prognosis (death) as the primary endpoint, the levels of pentraxin-3 between survivors and non-survivors were compared, and its association with mortality was assessed by Kaplan-Meier survival analysis. The predictive potency of pentraxin-3 for mortality risk in HFRS patients was evaluated by receiver operating characteristic (ROC) curve analysis.

Results: The levels of pentraxin-3 during the acute phase were increased with the aggravation of the disease, and showed the highest expression in critical-type patients (P < 0.05). Pentraxin-3 demonstrated significant correlations with conventional laboratory parameters (WBC, PLT, AST, ALB, APTT, Fib) and the length of hospital stay. Compared with the survivors, non-survivors showed higher levels of pentraxin-3 and worse expressions of conventional laboratory parameters during the acute phase. The Kaplan-Meier survival curves showed that high levels of pentraxin-3 during the acute phase were significantly associated with the death in HFRS patients. Pentraxin-3 demonstrated significant predictive value for the mortality risk of HFRS patients, with the area under ROC curve (AUC) of 0.753 (95%CI: 0.593 ~ 0.914, P = 0.003).

Conclusions: The detection of plasma pentraxin-3 might be beneficial to the evaluation of disease severity and to the prediction of mortality risk in HFRS patients.

Keywords: Disease severity; Early prediction; Hemorrhagic fever with renal syndrome; Pentraxin-3; Prognosis.

Fig. 1

Levels of plasma pentraxin-3 during the clinical course in patients with HFRS The levels of plasma pentraxin-3 during the acute phase (a) and the convalescent phase (b) were compared by Kruskal-Wallis H test; pairwise comparisons among the five groups were performed using the Nemenyi rank test. The differences of plasma pentraxin-3 between acute phase and convalescent phase of the mild-type (c), the moderate-type (d), the severe-type (e), and the critical-type (f) were compared by Wilcoxon matched-pairs signed-ranks test. The logarithmic value of pentraxin-3 was used in the figure for the reason of the great differences between the groups.* P < 0.05

Fig. 2

The correlation between pentraxin-3 and conventional laboratory parameters. Figure shows the correlation between pentraxin-3 and WBC (a), PLT (b), ALB (c), AST (d), APTT (e), Fib (f). Spearman rank correlation analysis was used to evaluate the correlation between pentraxin-3 and conventional laboratory parameters. Abbreviations: WBC, White blood cells; PLT, Platelet; AST, Aspartate aminotransferase; ALB, Albumin; APTT, Activated partial thromboplastin time; Fib, Fibrinogen

Fig. 3

ROC curves for evaluating the predictive efficacy of pentraxin-3 and conventional laboratory parameters. Figure shows the predictive efficacy of pentraxin-3, AST, PLT, WBC, and ALB for the prognosis (death) in patients with HFRS. Pentraxin-3 showed significant predictive value, with the AUC of 0.753 (P = 0.003). Abbreviations: ROC curve, Receiver operating characteristic curve; AUC, Area under the ROC curve; WBC, White blood cells; PLT, Platelet; AST, Aspartate aminotransferase; ALB, Albumin

Fig. 4

Kaplan-Meier survival curves of pentraxin-3 and conventional laboratory parameters. Figure shows the association of laboratory parameters (pentraxin-3, WBC, PLT, ALB, AST, APTT, Fib, BUN and Cr) with mortality, as well as the death hazard ratio (HR) of each parameter