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纤维化、肾脏组织损伤和炎症的生物标志物可预测肾脏 ANCA 相关性血管炎的严重程度和结局。

Biomarkers of fibrosis, kidney tissue injury and inflammation may predict severity and outcome of renal ANCA - associated vasculitis.

机构信息

Department of Nephrology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czechia.

Nordic Bioscience, Herlev, Denmark.

出版信息

Front Immunol. 2023 Mar 20;14:1122972. doi: 10.3389/fimmu.2023.1122972. eCollection 2023.

Abstract

BACKGROUND

Activity and chronicity of kidney involvement in ANCA-associated vasculitis (AAV) can be currently reliably evaluated only by kidney biopsy. In this study, we measured a panel of serum and urinary biomarkers collected at the time of kidney biopsy and hypothesized that they could reflect specific histopathological parameters in the biopsy and help to predict prognosis.

METHODS

We examined a cohort of 45 patients with AAV and 10 healthy controls. Biomarker levels (DKK-3, CD163, EGF, PRO-C6 and C3M) were measured in this study by ELISA. Biopsies were scored with a scoring system for AAV (focal x crescentic x sclerotic x mixed class) and interstitial fibrosis was quantified.

RESULTS

Levels of urinary DKK-3, CD163, EGF, PRO-C6 and C3M significantly differed among biopsy classes in AAV, with urinary DKK-3 and PRO-C6 levels being highest in the sclerotic class and lowest in the focal class, urinary CD163 levels highest in the crescentic class and urinary C3M levels highest in the focal class. Moreover, the urinary biomarkers were able to discriminate focal biopsy class from the other classes. Urinary DKK-3, EGF, PRO-C6 and C3M levels measured at the time of biopsy were also significantly related to the extent of fibrosis and to the final kidney function at the end of follow-up.

CONCLUSIONS

This small pilot study suggests that selected urinary biomarkers of fibrosis and inflammation may reflect changes in the kidney biopsy and be prognostic of kidney outcome in patients with AAV.

摘要

背景

目前,只有通过肾活检才能可靠地评估抗中性粒细胞胞浆抗体(ANCA)相关性血管炎(AAV)患者肾脏受累的活动度和慢性度。在本研究中,我们检测了一组在肾活检时采集的血清和尿液生物标志物,并假设它们可以反映活检中的特定组织病理学参数,并有助于预测预后。

方法

我们检查了 45 例 AAV 患者和 10 例健康对照者的队列。本研究通过 ELISA 测定了 DKK-3、CD163、EGF、PRO-C6 和 C3M 的生物标志物水平。使用 AAV 评分系统(局灶性 x 新月体性 x 硬化性 x 混合性)对活检进行评分,并对间质纤维化进行定量。

结果

在 AAV 的活检分类中,尿 DKK-3、CD163、EGF、PRO-C6 和 C3M 的水平存在显著差异,其中硬化性分类中的尿 DKK-3 和 PRO-C6 水平最高,局灶性分类中的水平最低,新月体性分类中的尿 CD163 水平最高,局灶性分类中的尿 C3M 水平最高。此外,这些尿液生物标志物可以将局灶性活检分类与其他分类区分开来。活检时测量的尿 DKK-3、EGF、PRO-C6 和 C3M 水平也与纤维化程度以及随访结束时的最终肾功能显著相关。

结论

这项小型初步研究表明,纤维化和炎症的某些尿液生物标志物可能反映了肾活检的变化,并可预测 AAV 患者的肾脏结局。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8c7/10067901/18e3a2a19bce/fimmu-14-1122972-g001.jpg

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