Effluent decoy receptor 2 as a novel biomarker of peritoneal fibrosis in peritoneal dialysis patients

Effluent decoy receptor 2 as a novel biomarker of peritoneal fibrosis in peritoneal dialysis patients
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流出物诱饵受体 2 作为腹膜透析患者腹膜纤维化的新型生物标志物

DOI:
10.1177/08968608211067866
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发表时间:
2022-02
期刊:
Perit Dial Int
影响因子:
--
通讯作者:
Jia Chen
Jia Chen
中科院分区:
其他
文献类型:
--
作者:
Jie Yang;Mingyu Cai;Jinfang Wan;Liming Wang;Jia Luo;Xue Li;Wenjiang Gong;Yani He;Jia Chen

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背景:腹膜纤维化(PF)是腹膜透析(PD)的常见并发症,但缺乏特异性和敏感性的PF生物标志物。本研究旨在确定使用流出物诱饵受体2(eDcR 2)作为PD患者PF的生物标志物。方法:收集PD患者248例,分别于PD开始时(30例)和停止时(33例)采集腹膜标本。采用酶联免疫法测定eDcR 2,计算eDcR 2-AR出现率。检测DcR 2 mRNA和蛋白水平。分析eDcR 2水平与腹膜功能、组织学参数和DcR 2表达的相关性。接受者工作特征(ROC)分析用于评估eDcR 2对PF的诊断性能,PF定义为中皮下厚度150 µm或以上。确定DcR 2与间皮细胞标志物、成纤维细胞标志物和纤维化标志物的共定位。结果如下:eDcR 2-AR水平与PD持续时间、D/P Cr值、腹膜Kt/V和腹膜损伤评分相关(r = 0.638,p < 0.001)。DcR 2主要在腹膜成纤维细胞中表达,与α-SMA、波形蛋白、I型胶原和纤连蛋白共定位,但不与E-钙粘蛋白共定位。腹膜DcR 2表达与eDcR 2-AR呈正相关。ROC曲线分析显示eDcR 2检测PF的曲线下面积为0.907(敏感性为78.6%,特异性为100%),最佳临界值为392.5 pg/min。结论:eDcR 2-AR水平是一种潜在的评估PD患者PF的生物标志物。流出液DcR 2主要来源于腹膜成纤维细胞,DcR 2阳性细胞可加速PF,提示其可能是潜在的治疗靶点。
Background: Peritoneal fibrosis (PF) is a common complication of peritoneal dialysis (PD), but a specific and sensitive biomarker for PF is lacking. The present study aimed to determine the use of effluent decoy receptor 2 (eDcR2) as a biomarker for PF in PD patients. Methods: PD patients (n = 248) were recruited, and peritoneal specimens were collected at PD initiation (n = 30) and cessation (n = 33). Enzyme-linked immunoassay was used to measure eDcR2 and the eDcR2 appearance rate (eDcR2-AR) was calculated. The levels of DcR2 mRNA and protein were determined. The correlation of eDcR2 level with peritoneal function, histological parameters and DcR2 expression were analysed. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic performance of eDcR2 for PF, which was defined as a submesothelial thickness 150 µm or more. Co-localisation of DcR2 with a mesothelial marker, fibroblast markers and fibrotic markers were determined. Results: The eDcR2-AR level correlated with PD duration, D/P Cr values, peritoneal Kt/V and peritoneal injury scores, especially submesothelial thickness (r = 0.638, p < 0.001). DcR2 was primarily expressed in peritoneal fibroblasts, and co-localised with α-SMA, vimentin, collagen I and fibronectin, but not with E-cadherin. Peritoneal DcR2 expression had a positive correlation with eDcR2-AR. ROC analysis indicated eDcR2 had an area under the curve of 0.907 for detection of PF (sensitivity: 78.6%, specificity: 100%) and the best cut-off value was 392.5 pg/min. Conclusion: The eDcR2-AR level is a potential biomarker for assessing PF in PD patients. Effluent DcR2 was mainly derived from peritoneal fibroblasts and DcR2-positive cells may accelerate PF, suggesting that it may be a potential therapeutic target.
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期刊: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
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