Prediction of Chronic Lung Allograft Dysfunction by Serum KL-6 Levels

Purpose: Chronic lung allograft dysfunction (CLAD) is the main long-term complication limiting survival after lung transplantation. Early detection biomarkers could contribute to improve therapeutic and preventive measures. CLAD has 3 main phenotypes: Bronchiolitis obliterans syndrome (BOS), Restrictive allograft syndrome (RAS) and mixed. The mucin KL-6, an antigen produced mainly by damaged type II pneumocytes, has been described as a diagnostic biomarker for RAS. The aim of our study was to assess the utility of serum KL-6 levels to predict CLAD. Methods: This was a longitudinal study in which KL-6 levels were measured in 55 bilateral LT patients pre-LT and at 3, 6, 12, 18 and 24 months after LT. Concurrently, clinical features and pulmonary function were determined. CLAD diagnosis was assessed during a three years follow-up. Results: After LT in those patients with high pre-transplant KL-6 levels a significant drop was observed. From 55 patients 22 developed CLAD (50% BOS and 50% RAS/mixed) and 7 patients were excluded for presenting other lung complications. RAS patients showed higher levels of KL-6 at 24 months when compared with stable patients. A repeatedly measured predictor was applied to develop a predictor model using only samples previous CLAD diagnosis and RAS patients showed significantly higher values than stable patients (p=0.041). RAS-freedom curves were calculated stratifying patients with high KL-6 levels at 6M (>520U/ml) and those with low and curves were significantly different (p=0.026). Conclusion: Serum KL-6 levels might be a useful biomarker for RAS prediction, but should be used with caution as other lung diseases could also rise KL-6 levels. Funded by Societat Catalana de Pneumologia.