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肾移植后早期尿中IP-10表达可预测移植肾短期和长期功能。

Early post-transplant urinary IP-10 expression after kidney transplantation is predictive of short- and long-term graft function.

作者信息

Matz M, Beyer J, Wunsch D, Mashreghi M-F, Seiler M, Pratschke J, Babel N, Volk H-D, Reinke P, Kotsch K

机构信息

Institute of Medical Immunology, Universitätsmedizin Charité Campus Mitte, Berlin, Germany.

出版信息

Kidney Int. 2006 May;69(9):1683-90. doi: 10.1038/sj.ki.5000343.

Abstract

The early identification of renal transplant recipients at enhanced risk of developing acute and subclinical rejection would allow individualized adjustment of immunosuppression before functional graft injury occurs and would exclude these patients from drug-weaning studies. Protein and reverse transcriptase-polymerase chain reaction-based analyses of candidate markers in urine open the opportunity to closely monitor kidney-transplanted patients non-invasively. The chemokine interferon-inducible protein 10 (IP-10; CXCL10) might be an interesting candidate to uncover ongoing immune processes within the graft. Urine samples from kidney-transplanted recipients were retrospectively analyzed for IP-10 mRNA and protein expression. IP-10 levels were correlated with the incidence of acute rejection episodes proven by histology and long-term graft function assessed by the glomerular filtration rate 6 months post transplantation. IP-10 expression in urine identified patients with ongoing acute rejection episodes several days before a biopsy was indicated by rising serum creatinine levels. Most importantly, elevated levels of urinary IP-10 protein within the first four postoperative weeks were predictive of graft function at 6 months even in the absence of acute rejection. These data reveal a correlation between elevated IP-10 expression in urine at early time points post-transplantation and intragraft immune activation that leads to acute rejection and compromised long-term graft function.

摘要

早期识别出有发生急性和亚临床排斥反应高风险的肾移植受者,将能够在移植肾功能受损之前对免疫抑制进行个体化调整,并可将这些患者排除在撤药研究之外。基于蛋白质和逆转录酶-聚合酶链反应的尿液中候选标志物分析,为非侵入性密切监测肾移植患者提供了机会。趋化因子干扰素诱导蛋白10(IP-10;CXCL10)可能是揭示移植肾内正在进行的免疫过程的一个有趣候选物。对肾移植受者的尿液样本进行回顾性分析,以检测IP-10 mRNA和蛋白表达。IP-10水平与经组织学证实的急性排斥反应发生率以及移植后6个月通过肾小球滤过率评估的长期移植肾功能相关。在活检因血清肌酐水平升高而被提示前几天,尿液中的IP-10表达可识别出正在发生急性排斥反应的患者。最重要的是,即使在没有急性排斥反应的情况下,术后前四周尿液中IP-10蛋白水平升高也可预测6个月时的移植肾功能。这些数据揭示了移植后早期尿液中IP-10表达升高与移植肾内免疫激活之间的相关性,而这种免疫激活会导致急性排斥反应和长期移植肾功能受损。

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