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尿 CXCL13 是抗体介导的肾移植排斥反应的非侵入性生物标志物。

Urinary C‑X‑C motif chemokine 13 is a noninvasive biomarker of antibody‑mediated renal allograft rejection.

机构信息

Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.

出版信息

Mol Med Rep. 2018 Aug;18(2):2399-2406. doi: 10.3892/mmr.2018.9211. Epub 2018 Jun 22.

DOI:10.3892/mmr.2018.9211
PMID:29956754
Abstract

Noninvasive monitoring methods of immune status are preferred by transplant recipients. The present study investigated whether urinary C‑X‑C motif chemokine 13 (CXCL13) had the potential to reflect ongoing immune processes within renal allografts. Using an ELISA assay, the level of urinary CXCL13 was quantified in a total of 146 renal allograft recipients and 40 healthy controls at scheduled intervals and at the time of the indicated or protocol biopsy. The results of the present study revealed that urinary CXCL13/creatinine (Cr) was lower in normal transplants compared with in those with acute tubular necrosis (ATN; P=0.001), chronic allograft nephropathy (CAN; P=0.01), and acute rejection (AR; P<0.0001), which was associated with a good diagnostic performance for AR [area under the curve (AUC)=0.818, P<0.0001). In addition, urinary CXCL13/Cr levels in patients with AR were also higher than that of patients with graft dysfunction but no rejection, including ATN and CAN (P=0.034). Notably, urinary CXCL13 distinguished between acute antibody‑mediated rejection (ABMR) and acute cellular rejection, with an AUC of 0.856. Furthermore, patients with steroid‑resistant AR exhibited significantly increased urinary CXCL13/Cr levels than patients with reversible AR (P=0.001). Additionally, elevated levels of urinary CXCL13/Cr within the first month of transplant were predictive of graft function at 3 and 6 months (P=0.044 and P=0.04, respectively). Collectively, the findings of the present study indicated that the noninvasive investigation of urinary CXCL13/Cr may be valuable for the detection of AR, particularly ABMR. In addition, high urinary CXCL13/Cr levels predicted a poor response to steroid treatment and compromised graft function.

摘要

移植受者更喜欢非侵入性监测免疫状态的方法。本研究探讨了尿 C-X-C 基序趋化因子 13(CXCL13)是否有可能反映肾移植中持续的免疫过程。使用 ELISA 检测法,在预定时间间隔和指定或方案活检时,对总共 146 名肾移植受者和 40 名健康对照者的尿 CXCL13 水平进行了定量检测。本研究结果显示,与急性肾小管坏死(ATN;P=0.001)、慢性移植肾肾病(CAN;P=0.01)和急性排斥反应(AR;P<0.0001)相比,正常移植中的尿 CXCL13/肌酐(Cr)较低,与 AR 的良好诊断性能相关 [曲线下面积(AUC)=0.818,P<0.0001]。此外,AR 患者的尿 CXCL13/Cr 水平也高于无排斥但存在移植物功能障碍的患者,包括 ATN 和 CAN(P=0.034)。值得注意的是,尿 CXCL13 可区分急性抗体介导的排斥反应(ABMR)和急性细胞性排斥反应,AUC 为 0.856。此外,与可逆转 AR 患者相比,类固醇耐药性 AR 患者的尿 CXCL13/Cr 水平显著升高(P=0.001)。此外,移植后第一个月内尿 CXCL13/Cr 水平升高可预测 3 个月和 6 个月时的移植物功能(P=0.044 和 P=0.04)。总之,本研究结果表明,非侵入性检测尿 CXCL13/Cr 可能对检测 AR 具有重要价值,尤其是 ABMR。此外,高尿 CXCL13/Cr 水平预测对类固醇治疗反应差和移植物功能受损。

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