Evaluation of gene panel mRNAs in urine samples of kidney transplant recipients as a non-invasive tool of graft function

Evaluation of gene panel mRNAs in urine samples of kidney transplant recipients as a non-invasive tool of graft function
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DOI:
10.2119/2007-00017.mas
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发表时间:
2007-05-01
期刊:
影响因子:
5.7
通讯作者:
Maluf, Daniel G.
Maluf, Daniel G.
中科院分区:
医学2区
文献类型:
--
作者:
Mas, Valeria R.;Mas, Luciana A.;Maluf, Daniel G.

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非侵入性监测可能是有用的肾移植(KT)后,特别是预测急性排斥反应(AR)。目前尚不清楚慢性移植物肾病(CAN)是否也与尿细胞的变化有关。为了鉴定肾移植患者(KTP)中同种异体移植物功能的非侵入性标志物,使用QRT-PCR研究尿液(Ur)样本中AGT、TGF-β 1、EGFR、IFN-γ、TSP-1和IL-10的mRNA水平。对95个KTP和111个Ur样品进行了评价。患者(Pts)分为KT后6个月内(N = 31)和6个月以上(N = 64)。KT后超过6个月的KTP被分类为具有稳定肾功能(SKF)的KTP(N = 32)、具有SKF(肌酸酐< 2 mg/dL)和蛋白尿> 500 mg/24 h的KTP(N = 18)和具有活检证实的CAN的KTP(N = 14)。各组间方差齐性检验显示,KT后6个月内,KTP组尿标本中IL-10 mRNA水平明显降低(P = 0.005)。对于KT后超过6个月的KTR组,KTP伴SKF、KTP伴SKF和蛋白尿以及CAN Pts之间AGT和EGFR mRNA存在统计学差异(P = 0.003和P = 0.01),KTP伴SKF的平均表达更高。TSP-1 mRNA水平在这三组之间也有显著差异(P = 0.04),在CAN Pts中观察到更高的表达。使用随机森林算法,AGT,EGFR和TGF-β 1被确定为CAN,SKF,SKF伴蛋白尿的预测因子。在不同的KTP组的mRNA水平的特征模式,观察表明在尿嘧啶核苷细胞的mRNA水平可能反映同种异体移植功能。
Non-invasive monitoring may be useful after kidney transplantation (KT), particularly for predicting acute rejection (AR). It is less clear whether chronic allograft nephropathy (CAN) is also associated with changes in urine cells. To identify non-invasive markers of allograft function in kidney transplant patients (KTP), mRNA levels of AGT, TGF-beta 1, EGFR, IFN-gamma, TSP-1, and IL-10 in urine (Ur) samples were studied using QRT-PCR. Ninety-five KTP and 111 Ur samples were evaluated. Patients (Pts) were divided as, within six months (N = 31), and with more than six months post-KT (N = 64). KTP with more than six months post-KT were classified as KTP with stable kidney function (SKF) (N = 32), KTP with SKF (creatinine < 2 mg/dL) and proteinuria > 500 mg/24 h (N = 18), and KTP with biopsy proven CAN (N = 14). F-test was used to test for equality of variances between groups, IL-10 mRNA was decreased in Ur samples from KTP with less than six months post-KT (P = 0.005). For KTR groups with more than six months post-KT, AGT and EGFR mRNA were statistically different among KTP with SKF, KTP with SKF and proteinuria, and CAN Pts (P = 0,003, and P = 0.01), with KTP with SKF having higher mean expression. TSP-1 mRNA levels also were significantly different among these three groups (P = 0.04), with higher expression observed in CAN Pts. Using the random forest algorithm, AGT, EGFR, and TGF-beta 1 were identified as predictors of CAN, SKF, SKF with proteinuria. A characteristic pattern of mRNA levels in the different KTP groups was observed indicating that the mRNA levels in Ur cells might reflect allograft function.