Research Centre for Metrological Traceability in Laboratory Medicine (CIRME), University of Milan, Milan, Italy.
Clin Chem Lab Med. 2021 Apr 9;59(8):1400-1408. doi: 10.1515/cclm-2021-0199. Print 2021 Jul 27.
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.
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).
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 (I=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).
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.
特发性肺纤维化（IPF）是一种进行性间质性疾病，治疗选择有限。Krebs von den Lungen-6（KL-6）糖蛋白的测量已被提议用于评估 IPF 进展的风险和预测患者预后，但可用证据的稳健性尚不清楚。
我们检索了 Medline 和 Embase 数据库，以获取自成立至 2020 年 4 月的同行评审文献。检索了调查 KL-6 作为 IPF 预后标志物的原始文章。考虑的结局是发生急性加重（AE）的风险和患者生存。对选定的研究进行了荟萃分析，并将定量数据统一为优势比（OR）或风险比（HR）估计值，以及相应的 95%置信区间（CI）。
系统评价纳入了 26 项研究，最终有 14 项进行了荟萃分析。对于 AE 发展，KL-6 的汇总 OR（七项研究）为 2.72（CI 1.22-6.06；p=0.015）。然而，选定研究之间存在高度异质性（I=85.6%）。使用三项报告二项数据的研究的数据，发现 KL-6 测量在检测 IPF 患者 AE 发作方面的汇总敏感性为 72%（CI 60-82%），特异性为 60%（CI 52-68%）。用于预测死亡率的汇总 HR（七项研究）为 1.009（CI 0.983-1.036；p=0.505）。
尽管我们的荟萃分析表明，KL-6 浓度升高的 IPF 患者发生 AE 的风险显著增加，但评估生物标志物的检测能力有限。此外，未发现生物标志物浓度与死亡率之间存在关系。在将获得的结果扩展到非亚洲人群时也需谨慎。
