Maluf Daniel G, Dumur Catherine I, Suh Jihee L, Scian Mariano J, King Anne L, Cathro Helen, Lee Jae K, Gehrau Ricardo C, Brayman Kenneth L, Gallon Lorenzo, Mas Valeria R
Translational Genomics Transplant Laboratory, Transplant Division, Department of Surgery, University of Virginia, Charlottesville, Virginia, USA.
Department of Pathology, Virginia Commonwealth University, Charlottesville, Virginia, USA.
Kidney Int. 2014 Feb;85(2):439-49. doi: 10.1038/ki.2013.338. Epub 2013 Sep 11.
Noninvasive, cost-effective biomarkers that allow accurate monitoring of graft function are needed in kidney transplantation. Since microRNAs (miRNAs) have emerged as promising disease biomarkers, we sought to establish an miRNA signature in urinary cell pellets comparing kidney transplant patients diagnosed with chronic allograft dysfunction (CAD) with interstitial fibrosis and tubular atrophy and those recipients with normal graft function. Overall, we evaluated 191 samples from 125 deceased donor primary kidney transplant recipients in the discovery, initial validation, and the longitudinal validation studies for noninvasive monitoring of graft function. Of 1733 mature miRNAs studied using microarrays, 22 were found to be differentially expressed between groups. Ontology and pathway analyses showed inflammation as the principal biological function associated with these miRNAs. Twelve selected miRNAs were longitudinally evaluated in urine samples of an independent set of 66 patients, at two time points after kidney transplant. A subset of these miRNAs was found to be differentially expressed between groups early after kidney transplant before histological allograft injury was evident. Thus, a panel of urine miRNAs was identified as potential biomarkers for monitoring graft function and anticipating progression to CAD in kidney transplant patients.
肾移植需要非侵入性、经济高效的生物标志物来准确监测移植物功能。由于微小RNA（miRNA）已成为有前景的疾病生物标志物，我们试图在尿细胞沉淀中建立一种miRNA特征，比较诊断为慢性移植物功能障碍（CAD）且伴有间质纤维化和肾小管萎缩的肾移植患者与移植物功能正常的受者。总体而言，我们在发现、初始验证和纵向验证研究中评估了125名已故供体初次肾移植受者的191份样本，用于移植物功能的非侵入性监测。在使用微阵列研究的1733种成熟miRNA中，发现有22种在组间差异表达。本体论和通路分析表明，炎症是与这些miRNA相关的主要生物学功能。在肾移植后的两个时间点，对独立的66名患者的尿液样本中的12种选定miRNA进行了纵向评估。发现这些miRNA的一个子集在肾移植后早期、组织学上移植物损伤明显之前在组间差异表达。因此，一组尿miRNA被确定为监测肾移植患者移植物功能和预测CAD进展的潜在生物标志物。
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