Is Pleural Fluid Presepsin a Reliable Diagnostic Biomarker for Pleural Effusions?

Background/Objectives: Biochemical markers used in the diagnostic evaluation of pleural effusions are limited in both number and diagnostic accuracy. Presepsin has shown promise in bacterial infections. This study aimed to evaluate the diagnostic utility of pleural fluid presepsin for differentiating transudative from exudative pleural effusions. Methods: In this prospective observational study, presepsin concentrations were measured in pleural fluid obtained during diagnostic thoracentesis. Patients were classified according to Light’s criteria and final clinical diagnosis. Receiver operating characteristic (ROC) analysis was performed to assess diagnostic performance, while multivariable logistic regression identified independent predictors of exudative pleural effusions. Associations between presepsin concentrations and mortality, infectious etiology, and pleural fluid culture positivity were also analyzed. Results: Eighty-eight patients were included, comprising 48 (54.5%) exudative and 40 (45.5%) transudative pleural effusions. Median pleural fluid presepsin concentrations were significantly higher in transudative than in exudative effusions (410.79 vs. 368.64 pg/mL, p = 0.010). A conventional model based on routinely available clinical and laboratory variables yielded an AUC of 0.797, which increased to 0.807 after adding pleural fluid presepsin (ΔAUC = 0.010; DeLong p = 0.606). Pleural fluid presepsin showed limited discrimination for infectious effusions (AUC = 0.618) and provided no significant incremental diagnostic value beyond routine biomarkers. Conclusions: Pleural fluid presepsin showed limited diagnostic performance and did not provide incremental diagnostic information beyond routinely available biomarkers for either transudative–exudative or infectious–noninfectious classification. The unexpectedly higher concentrations in transudative effusions remain observational and cannot be attributed to a specific biological mechanism.