Synovial fluid Lipocalin-2 as a biomarker for chronic prosthetic joint infection: Prospective validation in hip and knee revision arthroplasty.

Diagnosing prosthetic joint infection (PJI) remains challenging, as no single test can definitively confirm or rule out infection. Current diagnostic criteria rely on a combination of clinical, laboratory, and microbiological data. Lipocalin-2 (LCN2) has emerged as a potential biomarker for PJI, particularly in acute cases. However, its diagnostic role in chronic PJI and aseptic failures is not well established. This study aimed to evaluate the diagnostic performance of synovial LCN2 in chronic PJI. We conducted a prospective study of patients undergoing revision total hip or knee arthroplasty between April 2022 and April 2023. Cases were initially classified preoperatively as aseptic or septic according to the European Bone and Joint Infection Society (EBJIS) criteria, based on the tests available before surgery. After surgery, the EBJIS criteria were reapplied to establish the final diagnosis. Synovial LCN2 levels were compared between groups, and diagnostic performance was assessed using receiver operating characteristic (ROC) curve analysis. Of 125 patients undergoing revision surgery, 110 were included in the final analysis after excluding those with insufficient synovial fluid for LCN2 quantification. The median age was 75.0 years (IQR 68.0-81.0), and 65 patients (59.1%) were female. Based on preoperative evaluation, 90 cases (81.8%) were classified as aseptic failures and 20 (18.2%) as chronic PJI. However, according to the EBJIS criteria, 77 cases (70.0%) were ultimately diagnosed as aseptic and 33 (30.0%) as PJI. An LCN2 threshold of 266ng/mL was identified as the optimal cut-off for diagnosing PJI, showing a significant association with both the preoperative diagnosis of infection (p=0.012) and the definitive postoperative diagnosis (p=0.001). Elevated LCN2 levels were also significantly associated with increased serum C-reactive protein (CRP) levels (p=0.02). There were 13 cases with discordant diagnoses: initially considered aseptic but ultimately confirmed as septic. Among these, 9 cases (69.2%) exhibited elevated LCN2 levels. Synovial fluid LCN2 is a promising biomarker for the diagnosis of chronic PJI, especially in cases initially misclassified as aseptic. Its strong association with the final diagnosis of infection highlights its potential to enhance diagnostic accuracy. Further prospective studies are needed to confirm these findings and support the incorporation of LCN2 into routine clinical practice.