Increased levels of KL-6 and subsequent mortality in patients with interstitial lung diseases

J Intern Med. 2006 Nov;260(5):429-34. doi: 10.1111/j.1365-2796.2006.01704.x.


Objectives: KL-6 is a specific marker in patients with interstitial lung diseases (ILDs); however, the relationship between elevated levels of KL-6 and subsequent mortality is not well defined. To determine if elevated serum levels of KL-6 are associated with increased mortality, and to identify the most suitable cut-off level of KL-6 by which to distinguish between good prognosis and poor prognosis, we evaluated the prognostic significance of serum KL-6 levels in patients with stable-state ILDs.

Methods: Two hundred and nineteen patients diagnosed with ILDs (152 with idiopathic interstitial pneumonia and 67 with collagen disease-associated pulmonary fibrosis) at Tsukuba University Hospital from April 1999 to October 2005 were entered in this study. Serum KL-6 levels in patients with ILDs were measured with a commercially available enzyme immunoassay kit, and these patients were then followed up.

Results: During the follow-up period, 58 of the 219 patients died of respiratory failure. Patients who died during this period had higher levels of KL-6 than did those who did not (P = 0.0004). The receiver operating characteristic curve analysis showed 1000 U mL(-1) as the most suitable cut-off level by which to distinguish between the two groups of patients. The 95% specificity serum KL-6 level with poor outcome was 2750 U mL(-1). In univariate and multivariate analysis, elevated serum KL-6 (>1000 U mL(-1)) in the stable state indicated poor prognosis (P = 0.0005, log-rank test; P = 0.0001, Cox proportional hazard model).

Conclusions: Elevated KL-6 level may provide simple, yet valuable information by which to identify patients with ILDs who are at increased risk for subsequent mortality.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / blood*
  • Female
  • Humans
  • Japan / epidemiology
  • Lung Diseases, Interstitial / blood
  • Lung Diseases, Interstitial / diagnosis
  • Lung Diseases, Interstitial / mortality*
  • Male
  • Middle Aged
  • Mucin-1
  • Mucins / blood*
  • Prognosis
  • Prospective Studies
  • Pulmonary Fibrosis / blood
  • Pulmonary Fibrosis / diagnosis
  • Pulmonary Fibrosis / mortality
  • ROC Curve
  • Sensitivity and Specificity
  • Statistics, Nonparametric
  • Vital Capacity


  • Antigens, Neoplasm
  • MUC1 protein, human
  • Mucin-1
  • Mucins