Pleural Fluid suPAR Levels Predict the Need for Invasive Management in Parapneumonic Effusions

Abstract

Rationale: Parapneumonic effusions have a wide clinical spectrum. The majority settle with conservative management but some progress to complex collections requiring intervention. For decades, physicians have relied on pleural fluid pH to determine the need for chest tube drainage despite a lack of prospective validation and no ability to predict the requirement for fibrinolytics or thoracic surgery.Objectives: To study the ability of suPAR (soluble urokinase plasminogen activator receptor), a potential biomarker of pleural fluid loculation, to predict the need for invasive management compared with conventional fluid biomarkers (pH, glucose, and lactate dehydrogenase) in parapneumonic effusions.Methods: Patients presenting with pleural effusions were prospectively recruited to an observational study with biological samples stored at presentation. Pleural fluid and serum suPAR levels were measured using the suPARnostic double-monoclonal antibody sandwich ELISA on 93 patients with parapneumonic effusions and 47 control subjects (benign and malignant effusions).Measurements and Main Results: Pleural suPAR levels were significantly higher in effusions that were loculated versus nonloculated parapneumonic effusions (median, 132 ng/ml vs. 22 ng/ml; P , 0.001). Pleural suPAR could more accurately predict the subsequent insertion of a chest tube with an area under the curve (AUC) of 0.93 (95% confidence interval, 0.89-0.98) compared with pleural pH (AUC 0.82; 95% confidence interval, 0.73-0.90). suPAR was superior to the combination of conventional pleural biomarkers (pH, glucose, and lactate dehydrogenase) when predicting the referral for intrapleural fibrinolysis or thoracic surgery (AUC 0.92 vs. 0.76).Conclusions: Raised pleural suPAR was predictive of patients receiving more invasive management of parapneumonic effusions and added value to conventional biomarkers. These results need validation in a prospective multicenter trial.

The Contribution of the Urokinase Plasminogen Activator and the Urokinase Receptor to Pleural and Parenchymal Lung Injury and Repair: A Narrative Review

“…High affinity binding to its ligand, uPA, primarily involves domain I, while requiring the structural integrity of all three domains [ 86 ]. Although a splice variant of the PLAUR gene can generate a soluble uPAR construct [ 87 ], soluble uPAR is also generated by cleavage of cell-surface uPAR and occurs in serum and other biologic fluids, including pleural effusions [ 88 , 89 ]. suPAR can be generated by cleavage of the GPI-anchor of uPAR at the cell surface by enzymes such as phospholipase C [ 90 ].…”

“…In a recent study, pleural fluid suPAR levels were found to correlate with the requirement for invasive management in parapneumonic pleural effusions [ 89 ]. This work extends prior work showing that elevated levels of suPAR occur in a range of biologic fluids in infectious, autoimmune and neoplastic diseases, as previously reviewed [ 88 ].…”

Diagnostics in Pleural Disease

“…In the context of pleural infection, PF soluble urokinase Plasminogen Activator Receptor (suPAR) has been shown to be potentially of use in predicting the need for tube thoracostomy in parapneumonic effusions, though prospective validation in a multicentre trial setting is awaited [33].…”

From Bedside to the Bench—A Call for Novel Approaches to Prognostic Evaluation and Treatment of Empyema

“…While patient mortality is negligible, the rate of IPFT failure in pediatric empyema remains around 15% ( Sonnappa et al, 2006 ; St Peter et al, 2009 ; Livingston et al, 2016b ; Long et al, 2016 ; Derderian et al, 2020 ). Defining reliable molecular predictors of treatment failure ( Arnold et al, 2012020 ; Derderian et al, 2020 ; Khemasuwan et al, 2018 ; Livingston et al, 2016a ) would therefore likely increase the efficacy of IPFT as a therapy for empyema in pediatrics. The striking difference in the efficacy of IPFT in adult and pediatric patients with empyema abrogates the possibility of applying successful pediatric treatments to adults.…”