Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Feb 1;12(3):1173.
doi: 10.3390/jcm12031173.

Serum KL-6 as a Biomarker of Progression at Any Time in Fibrotic Interstitial Lung Disease

Lutz B Jehn  1 , Ulrich Costabel  1 , Eda Boerner  1 , Julia Wälscher  1 , Dirk Theegarten  2 , Christian Taube  1 , Francesco Bonella  1
Affiliations

Serum KL-6 as a Biomarker of Progression at Any Time in Fibrotic Interstitial Lung Disease

Lutz B Jehn et al. J Clin Med. .

Abstract

The development of a progressive phenotype of interstitial lung disease (ILD) is still unpredictable. Whereas tools to predict mortality in ILD exist, scores to predict disease progression are missing. The aim of this study was to investigate whether baseline serum KL-6 as an established marker to assess disease activity in ILD, alone or in combination with clinical variables, could improve stratification of ILD patients according to progression risk at any time. Consecutive patients with fibrotic ILD, followed at our institution between 2008 and 2015, were investigated. Disease progression was defined as relative decline of ≥10% in forced vital capacity (FVC) or ≥15% in diffusing capacity of the lung for carbon monoxide (DLco)% from baseline at any time. Serum KL-6 was measured using an automated immunoassay (Fujirebio Europe, Gent, Belgium). A stepwise logistic regression was performed to select variables to be included in the score. A total of 205 patients (49% idiopathic pulmonary fibrosis (IPF), 51% fibrotic nonspecific interstitial pneumonia (NSIP)) were included, of them 113 (55%) developed disease progression during follow up. Male gender (G) and serum KL-6 strata (K) were significant predictors of progression at regression analysis and were included in the GK score. A threshold of 2 GK score points was best for discriminating patients at high risk versus low risk to develop disease progression at any time. Serum KL-6 concentration, alone or combined in a simple score with gender, allows an effective stratification of ILD patients for risk of disease progression at any time.

Keywords: KL-6; biomarker; fibrotic ILD; progressive ILD.

PubMed Disclaimer

Conflict of interest statement

L.B.J. reports travel costs reimbursement from Boehringer Ingelheim (BI) not related to the present work. U.C., C.T. and E.B. report no conflict of interest. J.W. reports travel costs reimbursement from BI and Novartis; speaker honoraria from MSD, BI and Roche, and advisory fees from Novartis not related to the present work. D.T. reports speaker honoraria from BI not related to the present work. F.B. reports speaker honoraria and advisory fees from Fujirebio Inc. related to the present work, speaker honoraria and travel costs reimbursement from BI and Roche, and advisory fees from BI, Roche, Bristol Myers Squibb, Galapagos, GlaxoSmithKline and Takeda not related to the present work.

Figures

Figure A1
Figure A1
Distribution of baseline serum KL-6 concentrations in the studied subjects according to GAP stage. Dots represent single patients. Red lines represent median and red cross the mean values.
Figure 1
Figure 1
Distribution of baseline serum KL-6 concentrations in the studied subjects. Dots represent single patients. Red line represents the median and red cross the mean values. Significance of the comparisons is shown in the graphic.
Figure 2
Figure 2
Kaplan–Meier analysis for the risk of disease progression at any time by serum KL-6 levels baseline strata. Significance (Log rank p) is shown in the graphic.
Figure 3
Figure 3
Comparison of GK Score versus KL-6 for prediction of disease progression by using ROC curve analysis. Significance of the comparison is shown in the graphic. PPV, NPV and AUC are indicated in the text of the results.
Figure 4
Figure 4
Kaplan–Meier analysis for: (A) serum KL-6 at cut-off >1300 U/mL and (B) GK score at cut-off >2 points to separate patients at high risk (HR) and at low risk (LR) of disease progression. Higher score values indicate a higher risk for disease progression. Significance (Log rank p) is shown in the graphic.
See this image and copyright information in PMC

References

    1. Cottin V., Wollin L., Fischer A., Quaresma M., Stowasser S., Harari S. Fibrosing interstitial lung diseases: Knowns and unknowns. Eur. Respir. Rev. 2019;28:180100. doi: 10.1183/16000617.0100-2018. - DOI - PMC - PubMed
    1. Kolb M., Vašáková M. The natural history of progressive fibrosing interstitial lung diseases. Respir. Res. 2019;20:57. doi: 10.1186/s12931-019-1022-1. - DOI - PMC - PubMed
    1. Brown K.K., Martinez F.J., Walsh S.L., Thannickal V.J., Prasse A., Schlenker-Herceg R., Goeldner R.-G., Clerisme-Beaty E., Tetzlaff K., Cottin V., et al. The natural history of progressive fibrosing interstitial lung diseases. Eur. Respir. J. 2020;55:2000085. doi: 10.1183/13993003.00085-2020. - DOI - PMC - PubMed
    1. Wijsenbeek M., Cottin V. Spectrum of Fibrotic Lung Diseases. N. Engl. J. Med. 2020;383:958–968. doi: 10.1056/NEJMra2005230. - DOI - PubMed
    1. Raghu G., Remy-Jardin M., Richeldi L., Thomson C.C., Inoue Y., Johkoh T., Kreuter M., Lynch D.A., Maher T.M., Martinez F.J., et al. Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am. J. Respir. Crit. Care Med. 2022;205:e18–e47. doi: 10.1164/rccm.202202-0399ST. - DOI - PMC - PubMed