Prognostic value of baseline serum KL-6 for mortality risk in patients with idiopathic pulmonary fibrosis receiving antifibrotic therapy: A retrospective cohort study.

BackgroundAntifibrotic therapy slows disease progression in idiopathic pulmonary fibrosis (IPF), but substantial prognostic heterogeneity persists among treated patients. Serum Krebs von den Lungen-6 (KL-6) is a biomarker of alveolar epithelial injury, but its prognostic value in IPF patients receiving antifibrotic therapy is not well established.ObjectivesThis study aimed to investigate factors associated with all-cause mortality during follow-up in IPF patients receiving antifibrotic therapy and to evaluate the clinical value of baseline serum KL-6 levels in prognostic assessment.DesignThis was a single-center retrospective cohort study.MethodsPatients diagnosed with IPF who received antifibrotic therapy between July 2022 and November 2024 were consecutively enrolled. Baseline clinical data and serum KL-6 levels were collected. Cox proportional hazards regression was used to identify factors associated with mortality risk, and receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cut-off value of KL-6.ResultsA total of 126 patients with IPF receiving antifibrotic therapy were included. During a median follow-up of 21 months, 24 patients (19.0%) died. Non-survivors had significantly higher baseline KL-6 levels (P = 0.002), a higher prevalence of chronic obstructive pulmonary disease and cardiovascular disease, and lower baseline lymphocyte counts and percentage of predicted forced vital capacity (FVC% pred) compared with survivors. Multivariable Cox regression showed that cardiovascular disease (HR = 5.15, 95% CI: 1.86-14.24), lymphocyte count (HR = 0.50, 95% CI: 0.27-0.93), FVC% pred (HR = 0.98, 95% CI: 0.96-0.99), and baseline KL-6 level (per 100 U/mL increment, HR = 1.05, 95% CI: 1.02-1.07) were independently associated with all-cause mortality. ROC analysis identified an optimal KL-6 cut-off value of 746 U/mL. Patients with high KL-6 were associated with a markedly increased risk of death (HR = 7.57, 95% CI: 1.78-32.2).ConclusionsIn IPF patients receiving antifibrotic therapy, elevated baseline serum KL-6 level is independently associated with increased all-cause mortality. A cut-off value of 746 U/mL may help identify high-risk patients, and combining KL-6 with comorbidity burden, immune status, and lung function could facilitate individualized risk stratification.