Chen D J, Peng W H, Jiang H, Huang H F, Wu J Y, Wang H P, Chen J H
Kidney Disease Center, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.
Zhonghua Yi Xue Za Zhi. 2017 Jan 10;97(2):92-98. doi: 10.3760/cma.j.issn.0376-2491.2017.02.003.
To investigate the relationship between early-stage renal acute rejection(AR) and the level of Fractalkine in urine, explore the diagnostic and noninvasive monitoring value in early stage after transplantation by measurement of urine Fractalkine. Urine samples were examined from renal transplant patients between January 2006 and October 2009. A total of 155 patients were enrolled, including 49 with biopsy-proved AR, 58 patients with stable renal function and no abnormal histological findings, 10 patients with subclinical rejection in protocol biopsy, 9 patients with biopsy-proven acute tubular necrosis and 29 patients with biopsy-proven chronic allograft nephropathy. Additionally, urine samples were also collected from 40 healthy controls. Fractalkine was measured in urine samples using a commercial human Fractalkine enzyme-linked immunosorbent assay (ELISA) kit. Immunohistochemistry for Fractalkine expression was performed on biopsies from renal transplant patients with AR and non-AR. Forty-nine patients with AR excreted urinary Fractalkine at a significantly higher level than levels in patients with stable renal function and healthy controls[(429.1±56.1)vs (94.6±8.4), (84.5±8.9)ng/mmol creatine, both <0.001]. Patients with AR excreted urinary Fractalkine at a significantly higher level than levels in patients with acute tubular necrosis and chronic allograft nephropathy[(429.1±56.1)vs(133.0±9.8), (183.0±18.9)ng/mmol creatine, both <0.001]. Receiver operating characteristic(ROC)curve was constructed to determine the discriminatory power of Fractalkine levels for diagnosis of AR. The area under ROC curve was 0.920(95% : 0.875-0.969, <0.001), which showed that Fractalkine was a suitable marker for the diagnosis of AR. At a cut-off point of 157.5 ng/mmol creatinine, the sensitivity was 83.7% and the specificity was 84.5% (<0.001). The dynamic level of urinary Fractalkine in AR patients within 3 weeks after transplantation fluctuated above 300 ng/mmol creatine, which is remarkably higher than patients with stable renal function (below 200 ng/mmol creatinine). As a noninvasive monitoring method, Fractalkine in urine may be a new approach for detection of AR as well as useful to predict response to antirejection therapy. It has good sensitivity and specificity. Besides, measurement of Fractalkine in urine is a simple, inexpensive method for the routine clinical monitoring after kidney transplantation.
为探讨早期肾急性排斥反应(AR)与尿中Fractalkine水平的关系,通过检测尿Fractalkine探索其在移植后早期的诊断及无创监测价值。收集了2006年1月至2009年10月肾移植患者的尿液样本。共纳入155例患者,包括49例经活检证实为AR的患者、58例肾功能稳定且组织学检查无异常的患者、10例在方案活检中为亚临床排斥反应的患者、9例经活检证实为急性肾小管坏死的患者以及29例经活检证实为慢性移植肾肾病的患者。此外,还收集了40例健康对照者的尿液样本。使用商业化的人Fractalkine酶联免疫吸附测定(ELISA)试剂盒检测尿液样本中的Fractalkine。对有AR和无AR的肾移植患者的活检组织进行Fractalkine表达的免疫组织化学检测。49例AR患者尿中Fractalkine排泄水平显著高于肾功能稳定患者及健康对照者[(429.1±56.1)对(94.6±8.4)、(84.5±8.9)ng/mmol肌酐,均<0.001]。AR患者尿中Fractalkine排泄水平显著高于急性肾小管坏死和慢性移植肾肾病患者[(429.1±56.1)对(133.0±9.8)、(183.0±18.9)ng/mmol肌酐,均<0.001]。构建受试者操作特征(ROC)曲线以确定Fractalkine水平对AR诊断的鉴别能力。ROC曲线下面积为0.920(95%:0.875 - 0.969,<0.001),表明Fractalkine是诊断AR的合适标志物。在肌酐截断值为157.5 ng/mmol时,敏感性为83.7%,特异性为84.5%(<0.001)。移植后3周内AR患者尿Fractalkine的动态水平波动于300 ng/mmol肌酐以上,显著高于肾功能稳定患者(低于200 ng/mmol肌酐)。作为一种无创监测方法,尿中的Fractalkine可能是检测AR的新方法,也有助于预测抗排斥治疗的反应。它具有良好的敏感性和特异性。此外,检测尿中Fractalkine是肾移植后常规临床监测的一种简单、廉价的方法。