The diagnostic utility and tendency of the soluble receptor for advanced glycation end products (sRAGE) in exudative pleural effusion

Abstract

Background: The soluble receptor for advanced glycation end products (sRAGE) may have an inflammatory or homeostatic function in lung tissue. The aim of this study was to assess the usefulness of sRAGE as a diagnostic marker for exudative pleural effusions, which are common manifestations of a variety of diseases.

Methods: Patients with an undiagnosed pleural effusion were prospectively enrolled between January 2013 and January 2015. Samples of blood and pleural fluid were centrifuged and the supernatant stored at -70 °C. The levels of sRAGE in serum and pleural fluid were determined using a commercially available enzyme-linked immunosorbent assay (ELISA) kit.

Results: In total 47 patients, 21 patients were diagnosed with a tuberculous effusion, and the groups diagnosed with parapneumonic or malignant effusions comprised 13 patients each. The serum sRAGE levels for tuberculosis were significantly elevated [median, 1,291 pg/mL; interquartile range (IQR), 948-1,711 pg/mL] when compared with those for both pneumonia (median, 794 pg/mL; IQR, 700-1,255 pg/mL) and lung cancer (median, 886 pg/mL; IQR, 722-1,285 pg/mL) (P=0.029). The pleural sRAGE levels for pneumonia (median, 1,763 pg/mL; IQR, 1,262-4,431 pg/mL) were lower than those for both tuberculosis (median, 5,081 pg/mL; IQR, 3,300-6,004 pg/mL) and lung cancer (median, 4,936 pg/mL; IQR, 3,282-7,018 pg/mL) (P=0.009) The receiver operating characteristic (ROC) curve analysis selected 896 pg/mL as the best cutoff value in the sRAGE serum level for tuberculosis [sensitivity, 86%; specificity 58%; area under the curve (AUC) =0.727, P=0.008]. For the pleural effusion sRAGE level, the ROC curve analysis selected 2,231 pg/mL as the best cutoff value for pneumonia (sensitivity, 91%; specificity, 62%, AUC =0.792, P=0.002).

Conclusions: Among patients with exudative effusion, pleural and serum sRAGE measurements may be useful supportive diagnostic tools in the evaluation of ambiguous pleural effusion. Furthermore, the behavior of sRAGE in the serum and pleural fluid of various pulmonary diseases suggests that sRAGE may be linked to the chronic process of lung damage and inflammation rather than acute bacterial infection.

Keywords: Pleural effusion; receptor for advanced glycation end products (RAGE); tuberculosis.

Figure 1

Boxplot of (A) serum and (B) pleural soluble receptor for advanced glycation end products (sRAGE) levels by diagnostic category.

Figure 2

Receiver operating characteristic curve of (A) serum sRAGE levels comparing patients with pleural effusions caused by tuberculosis to those with pleural effusions attributable to other causes. The area under the curve (AUC) was 0.73 (95% confidence interval, 0.58–0.88); (B) pleural sRAGE levels comparing patients with pleural effusions caused by pneumonia to those with pleural effusions attributable to other causes. The AUC was 0.79 (95% confidence interval, 0.64–0.94).