Krebs von den Lungen-6 as a Potential Predictive Biomarker in Fibrosing Interstitial Lung Diseases

Respiration. 2023;102(8):591-600. doi: 10.1159/000531945. Epub 2023 Aug 16.

Abstract

Background: As fibrosing interstitial lung diseases (fILDs) are associated with high mortality, monitoring of disease activity under treatment is highly relevant. Krebs von den Lungen-6 (KL-6) is associated with the presence and severity of different fILDs, mainly in Asian patient populations.

Objectives: Our aim was to evaluate KL-6 as a predictive biomarker in fILDs in Caucasian patients.

Methods: Consecutive patients with fILDs were recruited prospectively and serum concentrations of KL-6 were measured at baseline (BL), after 6 and 12 months (6 Months, 12 Months). Clinical characteristics including pulmonary function tests were assessed at 6-monthly visits and correlated with KL-6 BL levels as well as with KL-6 level changes.

Results: A total of 47 fILD patients were included (mean age: 65 years, 68% male). KL-6 levels at BL were significantly higher in fILD patients than in healthy controls (n = 44, mean age: 45, 23% male) (ILD: 1,757 ± 1960 U/mL vs. control: 265 ± 107 U/mL, p < 0.0001). However, no differences were noted between ILD subgroups. KL-6 decreased significantly under therapy (6M∆BL-KL6: -486 ± 1,505 mean U/mL, p = 0.032; 12M∆BL-KL6: -547 ± 1,782 mean U/mL, p = 0.041) and KL-6 level changes were negatively correlated with changes in pulmonary function parameters (forced vital capacity [FVC]: r = -0.562, p < 0.0001; DLCOSB: r = -0.405, p = 0.013). While neither absolute KL-6 levels at BL nor KL-6 level changes were associated with ILD progression (FVC decline ≥10%, DLCOSB decline ≥15% or death), patients with a stable FVC showed significantly decreasing KL-6 levels (p = 0.022).

Conclusions: A decline of KL-6 under therapy correlated with a clinically relevant stabilization of lung function. Thus, KL-6 might serve as a predictive biomarker, which however must be determined by larger prospective cohorts.

Keywords: Interstitial lung disease; Krebs von den Lungen-6; Predictive biomarker.

MeSH terms

  • Aged
  • Biomarkers
  • Female
  • Humans
  • Lung
  • Lung Diseases, Interstitial* / diagnosis
  • Male
  • Middle Aged
  • Mucin-1
  • Prospective Studies
  • Vital Capacity

Substances

  • Mucin-1
  • Biomarkers