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Licensed Unlicensed Requires Authentication Published by De Gruyter April 9, 2021

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

Elena Aloisio ORCID logo, Federica Braga ORCID logo, Chiara Puricelli and Mauro Panteghini

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.


Corresponding author: Elena Aloisio, MD, Research Centre for Metrological Traceability in Laboratory Medicine (CIRME), University of Milan, Via GB Grassi 74, 20157Milan, Italy, Phone: +39 02 39042683, Fax: +39 02 39042896, E-mail:

  1. Research funding: None declared.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Not applicable.

  5. Ethical approval: Not applicable.

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Received: 2021-02-12
Accepted: 2021-03-26
Published Online: 2021-04-09
Published in Print: 2021-07-27

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