Elsevier

Clinica Chimica Acta

Volume 414, 24 December 2012, Pages 228-233
Clinica Chimica Acta

Role of S100B protein in urine and serum as an early predictor of mortality after severe traumatic brain injury in adults

https://doi.org/10.1016/j.cca.2012.09.025Get rights and content

Abstract

S100B is a calcium-binding protein released into the blood from astroglial cells due to brain injury. Some authors have described a correlation between S100B serum concentration and severity of brain damage. There is not much information about the accuracy of urinary S100B for predicting outcome after severe traumatic brain injury (TBI). 55 patients with severe TBI were included in the study. Blood and urine samples were drawn to determine S100B levels on admission and on the subsequent 24, 48, 72 and 96 h. S100B concentrations (serum and urine) were significantly higher in patients who were dead a month after the accident compared to survivors. ROC-analysis showed that S100B at 24 h post-severe TBI is a useful tool for predicting mortality (serum: AUC 0.958, urine: AUC 0.778). The best cut-offs for S100B were 0.461 μg/L and 0.025 μg/L (serum and urine respectively), with a sensitivity of 90% for both measurements and a specificity of 88.4% (serum) and 62.8% (urine). We can state that the determination of S100B levels both in urine and serum acts as a sensitive and an effective biomarker for the early prediction of mortality after severe TBI.

Highlights

► Blood and urine samples were drawn on admission and every 24 h up to 4 days. ► Serum and urine S100B levels were higher in patients dead within a month of trauma. ► S100B in serum and urine at 24 h post-severe TBI is useful for predicting mortality. ► S100B acts as a sensitive biomarker for the prediction of mortality after severe TBI.

Introduction

The use of biochemical markers in daily clinical practice to diagnose and monitor diverse diseases or pathologic situations has increased in the last decades [1], [2], [3]. Nevertheless, no biomarkers are currently used in clinical practice as markers for brain damage. Some authors have described a series of biomarkers, including neuron-specific enolase, TAU protein, glial fibrillary astrocytic protein, cell-free DNA and S100B protein as damage markers of the central nervous system [4], [5], [6], [7].

S100B protein is a calcium-binding protein released into the blood from the cytosol of astroglial and Schwann cells due to a lesion to the cephalous [8], [9], [10], [11]. S100B acts in a bimodal manner [12], [13]. Nanomolar concentrations stimulate neurite growth and promote neuron survival. However, micromolar concentrations have the opposite effect and can even induce neuronal apoptosis, leading to the induction of pro-inflammatory cytokines and inflammatory stress-related enzymes [14], [15], [16]. The short biological half-life of S100B (between 30 and 60 min) and its renal clearance (2 h) imply that any persistent elevation of S100B concentration in the blood reflects a continuous active secretion or passive release from damaged tissues [17].

Over the last decade, several research groups have published their results correlating S100B levels in serum to the severity of traumatic brain damage and patient outcome [18], [19], [20]. Bloomfield et al. affirmed that a normal S100B level reliably predicts the absence of significant central nervous system injury, whereas elevations of S100B above certain threshold levels might be able to accurately predict brain death or mortality [19]. In reference to urine there is not much information about the utility of urinary S100B levels. Few research groups have studied urinary S100B as a marker of brain damage and most of them have only focused in pediatric population. Thus, several authors confirm a rise in urinary S100B levels in patients who suffered a TBI compared to controls or patients who did not suffer a TBI [18], [21], [22], [23].

The present study was designed to study the role of serum and urine S100B levels as an early predictor of mortality after severe TBI in adults.

Section snippets

Patients and samples

During eighteen months, fifty-five severe head injury patients admitted to the NeuroCritical Care Unit (NCCU) were prospectively selected for this study. The protocol, carried out in accordance with the Declaration of Helsinki, was approved by the Virgen del Rocío University Hospital Institutional Review Board. TBI patients were eligible based on the following inclusion criteria: aged 14 or over, Glasgow Coma Scale score (GCS)  8 after hemodynamic and metabolic resuscitation, first serum sample

Demographics and clinical characteristics

Fifty-six severe TBI patients were admitted in our NCCU. One family declined participation on the part of their injured relative. A total of 55 patients met the inclusion criteria for the study. Fifty patients were male (91.38%) and five female (8.62%). Mean age was 37.6 (SD ± 16.3). No patient was under 16 years of age. All patients presented with intracranial lesions on an admission head CT scan (TCDB I, n = 0). Ten patients were dead one month after TBI (18.2%). The clinical characteristic and

Discussion

This is the first study carried out on severe TBI in adult population that proves the accuracy of S100B urine levels as an early predictor of a short-term mortality. Moreover, we demonstrated an increase of S100B concentrations both in urine and serum. Our results revealed that patients who died one month after the TBI presented with higher levels of S100B at 24 h after the injury than those who survive. Nevertheless, urine S100B measurement did not prove a better mortality predictor than serum

Conclusion

The determination of both serum and urine S100B levels at 24 h post severe TBI acts as an early predictor of short-term mortality. S100B serum samples showed higher predictive capacity than S100B urine samples. These measurements used as biomarkers for brain damage could guide neurocritical care physicians in decision-making and would provide objective data to transmit accurate information to patients' relatives. Taking into account the ease of urine sampling versus serum sampling, further

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Acknowledgments

The invaluable technical help of laboratory residents, laboratory technicians, residents and nurses from the NCCU is gratefully appreciated. This research was made possible in part by the generous donation of Protein S100B Electrochemiluminescence Assay Kits from Roche Diagnostics, Mannheim, Germany.

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