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联合中性粒细胞和巨噬细胞生物标志物检测抗中性粒细胞胞浆抗体相关性血管炎的活动性疾病:钙卫蛋白和尿CD163的联合模型

Combining neutrophil and macrophage biomarkers to detect active disease in ANCA vasculitis: a combinatory model of calprotectin and urine CD163.

作者信息

Anton-Pampols Paula, Martínez Valenzuela Laura, Fernández Lorente Loreto, Quero Ramos Maria, Gómez Preciado Francisco, Martín Capón Irene, Morandeira Francisco, Manrique Escola Joaquín, Fulladosa Xavier, Cruzado Josep Maria, Torras Joan, Draibe Juliana

机构信息

Department of Nephrology, Bellvitge University Hospital, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Barcelona, Spain.

Department of Nephrology, Hospital Universitario de Navarra, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.

出版信息

Clin Kidney J. 2022 Dec 7;16(4):693-700. doi: 10.1093/ckj/sfac257. eCollection 2023 Apr.

Abstract

BACKGROUND

CD163 and calprotectin have been proposed as biomarkers of active renal vasculitis. This study aimed to determine whether the combination of serum/urine calprotectin (s/uCalprotectin) and urinary soluble CD163 (suCD163) increases their individual performance as activity biomarkers.

METHODS

We included 138 patients diagnosed with ANCA vasculitis ( = 52 diagnostic phase,  = 86 remission). The study population was divided into the inception ( = 101) and the validation cohorts ( = 37). We determined the s/uCalprotectin and suCD163 concentration using enzyme-linked immunoassay at the diagnostic or at the remission phase. Receiver operating characteristic (ROC) curves were conducted to assess the biomarkers' classificatory values. We elaborated a combinatorial biomarker model in the inception cohort. The ideal cutoffs were used in the validation cohort to confirm the model's accuracy in the distinction between active disease and remission. We added the classical ANCA vasculitis activity biomarkers to the model to increase the classificatory performance.

RESULTS

The concentrations of sCalprotectin and suCD163 were higher in the diagnostic compared with the remission phase ( = .013 and  < .0001). According to the ROC curves, sCalprotectin and suCD163 were accurate biomarkers to discern activity [area under the curve 0.73 (0.59-0.86),  = .015 and 0.88 (0.79-0.97),  < .0001]. The combinatory model with the best performance in terms of sensitivity, specificity and likelihood ratio included sCalprotectin, suCD163 and haematuria. Regarding the inception and the validation cohort, we obtained a sensitivity, specificity and likelihood ratio of 97%, 90% and 9.7, and 78%, 94% and 13, respectively.

CONCLUSIONS

In patients with ANCA vasculitis, a predictive model combining sCalprotectin, suCD163 and haematuria could be useful in detecting active kidney disease.

摘要

背景

CD163和钙卫蛋白已被提议作为活动性肾血管炎的生物标志物。本研究旨在确定血清/尿钙卫蛋白(s/u钙卫蛋白)和尿可溶性CD163(suCD163)的联合使用是否能提高它们作为活动性生物标志物的个体性能。

方法

我们纳入了138例诊断为抗中性粒细胞胞浆抗体(ANCA)血管炎的患者(诊断期52例,缓解期86例)。研究人群分为起始队列(101例)和验证队列(37例)。我们在诊断期或缓解期使用酶联免疫吸附测定法测定s/u钙卫蛋白和suCD163的浓度。绘制受试者工作特征(ROC)曲线以评估生物标志物的分类价值。我们在起始队列中构建了一个组合生物标志物模型。在验证队列中使用理想的临界值来确认该模型在区分活动性疾病和缓解期方面的准确性。我们将经典的ANCA血管炎活动性生物标志物添加到模型中以提高分类性能。

结果

与缓解期相比,诊断期的s钙卫蛋白和suCD163浓度更高(P = 0.013和P < 0.0001)。根据ROC曲线,s钙卫蛋白和suCD163是辨别活动性的准确生物标志物[曲线下面积分别为0.73(0.59 - 0.86),P = 0.015和0.88(0.79 - 0.97),P < 0.0001]。在敏感性、特异性和似然比方面表现最佳的组合模型包括s钙卫蛋白、suCD163和血尿。对于起始队列和验证队列,我们分别获得了97%、90%和9.7,以及78%、94%和13的敏感性、特异性和似然比。

结论

在ANCA血管炎患者中,结合s钙卫蛋白、suCD163和血尿的预测模型可能有助于检测活动性肾脏疾病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b1b/10061427/10f31bf18860/sfac257fig1g.jpg

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