Prognostic role of Krebs von den Lungen-6 (KL-6) measurement in idiopathic pulmonary fibrosis: a systematic review and meta-analysis

Abstract

Objectives Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial disease with limited therapeutic options. The measurement of Krebs von den Lungen-6 (KL-6) glycoprotein has been proposed for evaluating the risk of IPF progression and predicting patient prognosis, but the robustness of available evidence is unclear. Methods We searched Medline and Embase databases for peer-reviewed literature from inception to April 2020. Original articles investigating KL-6 as prognostic marker for IPF were retrieved. Considered outcomes were the risk of developing acute exacerbation (AE) and patient survival. Meta-analysis of selected studies was conducted, and quantitative data were uniformed as odds ratio (OR) or hazard ratio (HR) estimates, with corresponding 95% confidence intervals (CI). Results Twenty-six studies were included in the systematic review and 14 were finally meta-analysed. For AE development, the pooled OR (seven studies) for KL-6 was 2.72 (CI 1.22–6.06; p=0.015). However, a high degree of heterogeneity (I2=85.6%) was found among selected studies. Using data from three studies reporting binary data, a pooled sensitivity of 72% (CI 60–82%) and a specificity of 60% (CI 52–68%) were found for KL-6 measurement in detecting insurgence of AE in IPF patients. Pooled HR (seven studies) for mortality prediction was 1.009 (CI 0.983–1.036; p=0.505). Conclusions Although our meta-analysis suggested that IPF patients with increased KL-6 concentrations had a significant increased risk of developing AE, the detection power of the evaluated biomarker is limited. Furthermore, no relationship between biomarker concentrations and mortality was found. Caution is also needed when extending obtained results to non-Asian populations.

Pulmonary Fibrosis as a Result of Acute Lung Inflammation: Molecular Mechanisms, Relevant In Vivo Models, Prognostic and Therapeutic Approaches

“…The Krebs von den Lungen-6 (KL-6) protein, as a high-molecular weight mucin glycoprotein, predominantly expressed on the surface of AEC II and bronchial epithelial cells [ 393 ], was proposed as a biomarker of both ALI/ARDS and pulmonary fibrosis due to its localization and the damage sustained by AECs in both diseases. This fact limits the diagnostic utility of KL-6, but several studies have reported its prognostic potential in pulmonary fibrosis [ 369 , 394 ].…”

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

“…These observations, however, were not statistically significant. The authors of the meta-analysis highlighted inter-assay disagreement, retrospective design in most studies, and lack of validation in non-Asian subjects as major confounding factors [12].…”

Detection of interstitial pneumonia with autoimmune features and idiopathic pulmonary fibrosis are enhanced by involvement of matrix metalloproteinases levels and clinical diagnosis

“…Elevated levels of SP-A, KL-6 have previously been associated with disease progression and reduced survival in IPAF and IPF patients [31,[55][56][57][58][59][60][61][62][63][64]. Given that a high proportion of patients with IPAF have typical radiological or histological patterns of interstitial pneumonia similar to IPF[61, 65-68], we hypothesized that the biomarkers in IPF that predict clinical outcomes are also associated with IPAF.…”