Serum Krebs von den Lungen-6 level predicts disease progression in interstitial lung disease

Abstract

Disease progression (DP) in interstitial lung disease (ILD) is variable and difficult to predict. In previous reports, serum Krebs von den Lungen-6 (KL-6) was suggested to be useful in diagnosing and predicting survival in ILD. The aim of our study was to investigate the usefulness of serum KL-6 as a predictor of DP in ILD. Clinical data of 199 patients with ILD (idiopathic pulmonary fibrosis: 22.8%) were prospectively collected and serum KL-6 levels were measured. DP was defined as a relative decline in forced vital capacity (FVC) ≥ 10%, acute exacerbation, or death during follow-up. The median follow-up period was 11.1 months. The mean age of the subjects was 62.2 years, and 59.8% were male. DP occurred in 21.6% of patients. The progressed group showed lower FVC, lower diffusing capacity for carbon monoxide, lower the minimum oxygen saturation during the 6-minute walk test, higher fibrosis scores on high-resolution computed tomography, and higher KL-6 levels (826.3 vs. 629.0 U/mL; p < 0.001) than those of the non-progressed group. In receiver operating characteristic curve analysis, serum KL-6 levels were a significant predictor of DP in ILD (area under the curve = 0.629, p = 0.009, and the optimal cut-off level was 811 U/mL). In multivariable Cox analysis, high serum KL-6 levels (≥ 800 U/mL) were only independently associated with DP in ILD (HR 2.689, 95% CI 1.445–5.004, P = 0.002). Serum KL-6 levels might be useful to predict DP in patients with ILD.

KL-6 as an Immunological Biomarker Predicts the Severity, Progression, Acute Exacerbation, and Poor Outcomes of Interstitial Lung Disease: A Systematic Review and Meta-Analysis

“…(Mild ILD: n = 335, Severe ILD: n = 223). Mean (SD) concentrations of KL-6 for patients in progressive ILD and non-progressive ILD groups were collected from 12 studies ( 11 , 18 , 25 , 28 , 29 , 31 , 35 , 36 , 38 , 45 , 47 , 53 ). (Progressive ILD: n = 203, Non-progressive ILD: n = 511).…”

“…(AE-ILD: n = 112, Stable ILD: n = 298). Additionally, adjusted HR (95%CI) of estimating the mortality about ILD were collected from 10 studies ( 13 , 15 , 21 , 24 , 26 , 37 , 40 , 42 , 48 , 50 ), and also adjusted HR (95%CI) of estimating progression of ILD were collected from five studies ( 17 , 21 , 28 , 40 , 44 ).…”

Clinical Utility of Circulating Pneumoproteins as Diagnostic and Prognostic Biomarkers in COVID-19: A Systematic Review and Meta-analysis

“…KL-6 is a high molecular weight glycoprotein secreted by type II alveolar and bronchiolar epithelial cells [ 60 , 61 ], which promotes chemotactic activity and anti-apoptotic effects in human lung fibroblasts. SP-A and SP-D are collagen glycoproteins mainly secreted by type II alveolar cells and have an innate immune defense function [ 62 ].…”

Clinical utility of circulating pneumoproteins as diagnostic biomarkers in COVID-19: a systematic review and meta-analysis

“…Krebs von den Lungen-6 (KL-6) is a high molecular weight glycoprotein secreted by type II alveolar and bronchiolar epithelial cells [63][64][65], which promotes chemotactic activity and anti-apoptotic effects in human lung broblasts. Surface protein A (SP-A) and D (SP-D) are collagen glycoproteins mainly secreted by type II alveolar cells and have an innate immune defence function [66].…”