DISCOVERY OF NOVEL URINARY PROTEOMIC BIOMARKERS IN KIDNEY TRANSPLANTATION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 具体目标 具体目的1：发现诊断急性肾移植排斥反应的非侵入性尿液生物标志物。为了验证儿童和成人AR患者尿中有标志性多肽和蛋白质可作为诊断蛋白/多肽生物标志物的假设，以移植物功能稳定(STA)患者为对照，采用LC-FTICR检测尿蛋白，并用免疫分析(ELISA)进行验证。 具体目的2：鉴定诊断慢性移植物肾病(CAN)和钙调神经磷酸酶抑制物肾毒性(CNIT)的非侵入性尿液生物标志物。连续采集和临床批注的肾移植患者的稳定移植物(STA)患者的尿标本，CAN和CNIT，将用高灵敏度的LC-MS进行检测，并通过免疫分析(ELISA)进行验证。 具体目标3：鉴定肾移植患者侵袭性BK病毒感染，特别是BK病毒肾病(BKVJN)的特异性蛋白质和多肽特征。将对肾移植患者收集的三组不同尿液进行蛋白质和多肽的质谱分析，这些尿液包括：(I)单纯BK vyuria、(Ii)bk vyuria和bk病毒血症，以及(Iii)bk vyuria、bk病毒血症和bkvn。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Specific Aims Specific Aim 1: Discovery of non-invasive urinary biomarkers for diagnosis of acute kidney transplant rejection (AR). To test the hypothesis that there are signature peptides and proteins which can serve as diagnostic protein/peptide biomarkers in urine of pediatric and adult patients with AR, compared to patients with stable graft function (STA), urinary proteins will be assayed by the use of LC-FTICR and validated by immunoassay (ELISA). Specific Aim 2: Identification of non-invasive urinary biomarkers for diagnosis of chronic allograft nephropathy (CAN) and calcineurin inhibitor nephrotoxicity (CNIT). Serially collected and clinically annotated urine specimens from renal transplant patients with stable graft (STA), CAN and CNIT, will be assayed by high sensitivity LC-MS and validated by immunoassay (ELISA). Specific Aim 3: Identification of protein and peptide signatures specific for invasive BK viral infection, specifically BK virus nephropathy (BKVJN) in kidney transplant patients. Mass spectrometric analysis of proteins and peptides will be conducted on three different sets of urine collected from renal transplant patients with (i) BK vyuria alone, (ii) BK vyuria and BK viremia, and (iii) BK vyuria, BK viremia and BKVN.