DISCOVERY OF NOVEL URINARY PROTEOMIC BIOMARKERS IN KIDNEY TRANSPLANTATION

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 具体目标 具体目标1：发现用于诊断急性肾移植排斥反应（AR）的非侵入性尿液生物标志物。 为了检验以下假设，即与移植物功能稳定（STA）的患者相比，儿童和成人AR患者的尿液中存在可用作诊断蛋白质/肽生物标志物的特征肽和蛋白质，将使用LC-FTICR测定尿蛋白，并通过免疫测定（ELISA）进行验证。 具体目标二：鉴定用于诊断慢性移植物肾病（CAN）和钙调神经磷酸酶抑制剂肾毒性（CNIT）的非侵入性尿液生物标志物。 将通过高灵敏度LC-MS分析从移植物稳定（STA）、CAN和CNIT的肾移植患者中连续采集并进行临床注释的尿液标本，并通过免疫测定法（ELISA）进行验证。 具体目标3：对侵袭性BK病毒感染，特别是肾移植患者中BK病毒肾病（BKVJN）特异性的蛋白质和肽特征的鉴定。 将对从患有（i）单独BK尿症、（ii）BK尿症和BK病毒血症以及（iii）BK尿症、BK病毒血症和BKVN的肾移植患者采集的三组不同尿液进行蛋白质和肽的质谱分析。

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.