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

Abstract

s. 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.

Serum lysyl oxidase-like 2 levels and idiopathic pulmonary fibrosis disease progression

“…Future studies should also consider whether sLOXL2, along with other promising prognostic IPF biomarkers (e.g. matrix metalloproteinase (MMP)1, MMP7, KL-6, periostin, surfactant protein-A and D, CC chemokine ligand 18, vascular endothelial growth factor and YKL-40) [19][20][21][22][23][24][25][26][27][28][29], as well as prognostic scores [30,31] and radiological modalities [32], might have prognostic value for helping physicians and patients anticipate the patient's IPF disease progression. This might include evaluation of serially collected sLOXL2 levels and their relationship to IPF acute exacerbations, which represent a terminal event for many IPF patients [33].…”

Serum biomarkers in idiopathic pulmonary fibrosis

“…Again, as this study was performed prior to 2002, one should bear in mind that the diagnosis of IPF was since then reclassified [1]. Satoh et al reported an increased mortality in patients with an IIP, including patients with IPF, with serum levels of KL-6 > 1000 U/ml at initial measurement [33]. Furthermore, Yokoyama et al reported worse survival of IPF patients with KL-6 levels > 1000U/ml at time of presentation, in a retrospective study of a total of 27 patients [34].…”

Comparison of pulmonary thin section CT findings and serum KL-6 levels in patients with sarcoidosis

“…It has also been reported that KL-6 induces chemotaxis of human fibroblasts in vitro, suggesting that it may have a pathological role in fibrosing lung disease [21]. Therefore, measurement of serum KL-6 is now widely accepted as a diagnostic marker for monitoring the activity of interstitial lung diseases, such as idiopathic interstitial pneumonia, and for the long-term management of various interstitial diseases [1,2,[7][8][9][10][11]13].…”

“…Several investigators have also reported that KL-6 is a useful serum marker to confirm diagnosis and for long-term management in patients with diffuse pulmonary diseases, particularly interstitial lung diseases. Patients with idiopathic pulmonary fibrosis or non-specific interstitial pneumonia showed significantly elevated KL-6 levels [8][9][10][11][12][13].…”