Diagnostic and prognostic value of neutrophil gelatinase-associated lipocalin, matrix metalloproteinase-9, and tissue inhibitor of matrix metalloproteinases-1 for sepsis in the Emergency Department: an observational study.

Miaomiao Wang,Xin Zhao,Qian Zhang,Guijuan Dong,Chunsheng Li

doi:10.1186/s13054-014-0634-6

Abstract

IntroductionThe aim of this study was to evaluate the early diagnostic, risk stratification and prognostic value of neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), compared with procalcitonin (PCT) and the Mortality in Emergency Department Sepsis (MEDS) score in septic patients in the emergency department (ED).MethodsIn total, 480 consecutive adult patients were enrolled in this study. They fulfilled the systemic inflammatory response syndrome (SIRS) criteria and were admitted to the ED of Beijing Chaoyang Hospital from February 2013 to August 2013. A total of 40 healthy controls comprised the control group. The patients were classified into four groups: SIRS, sepsis, severe sepsis, and septic shock. Serum NGAL, MMP-9, TIMP-1 and PCT were measured, and MEDS score was calculated at enrollment. The prognostic values of NGAL, MMP-9 and TIMP-1 were compared with PCT and MEDS score. A 28-day follow-up was performed for all patients.ResultsThe median levels of serum NGAL and TIMP-1 increased with sepsis severity. The areas under the receiver operating characteristic (AUC) curves of NGAL or TIMP-1 were greater than those of PCT and MEDS score in diagnosing and predicting 28-day mortality, and the AUC of a combination of NGAL and MEDS score or TIMP-1 and MEDS score was more significant. Serum NGAL, MMP-9 and TIMP-1 levels were significantly higher in non-survivors than survivors at 28 days’ follow-up. In addition, the level of NGAL was much higher in septic patients with acute kidney injury (AKI) than those without AKI. NGAL, TIMP-1, MMP-9 and MEDS score were found to be independent predictors of 28-day mortality in septic patients. The levels of serum NGAL and TIMP-1 were positively correlated with PCT and MEDS score in every septic group.ConclusionsNGAL and TIMP-1 are valuable for the risk stratification, early diagnosis and prognostication of sepsis in the ED. NGAL is also a valuable biomarker for prognosis of septic patients with AKI in the ED.

Highlights

The aim of this study was to evaluate the early diagnostic, risk stratification and prognostic value of neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), compared with procalcitonin (PCT) and the Mortality in Emergency Department Sepsis (MEDS) score in septic patients in the emergency department (ED)
Patient demographics There were no significant differences in age and sex among the five groups of enrolled subjects (SIRS, sepsis, severe sepsis, septic shock, and control groups) (Table 1)
Comparison of median levels of NGAL, MMP-9, TIMP-1 and MMP-9/TIMP-1 ratio, and MEDS score The median NGAL, MMP-9, TIMP-1 and MMP-9/ TIMP-1 ratio levels, the PCT levels, and MEDS scores in each group are shown in Table 1 and NGAL, MMP-9, TIMP-1 levels, in each group are shown in Figures 1, 2 and 3

Summary

Introduction

The aim of this study was to evaluate the early diagnostic, risk stratification and prognostic value of neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), compared with procalcitonin (PCT) and the Mortality in Emergency Department Sepsis (MEDS) score in septic patients in the emergency department (ED). Clinical scoring systems are useful tools to evaluate the severity and prognosis of sepsis, most of them are created for ICU patients and may not be applicable to the ED. Finding biomarkers and combining them with the clinical scoring systems for early diagnosis, risk stratification, and evaluation of prognosis of sepsis has great significance. NGAL seems to positively modulate the activity of MMP-9 [9]. It protects MMP-9 from proteolytic degradation and enhances its enzymatic activities by binding and forming the MMP-9/NGAL complex

Objectives

Methods

Results

Conclusion