Noninvasive diagnosis of BKV nephropathy

描述(由申请人提供)：建议项目的总体目标是开发一种非侵入性诊断测试，对BK病毒相关性肾病进行预测、诊断和预后。 这项研究的基本假设是，包括BKV病毒衣壳蛋白1(VP1)mRNA测量在内的尿细胞信使RNA(MRNA)谱可预测、诊断和预测BKV肾病。拟议调查的具体目标是： 具体目的1.在一项大型多中心研究中，证明尿细胞BKV VP1mRNA水平作为诊断BKV肾病的高敏感性(&gt；90%)和特异性(&gt；90%)无创检测的有效性。 具体目的2：在前瞻性队列研究中，对BKV肾病诊断时评估的尿细胞信使核糖核酸谱可预测移植肾功能结果的假设进行检验。 具体目的3.通过测定连续尿样中BKV VP1mRNA水平来评估BKV复制，并检验BKV VP1mRNA水平升高是否可预测：(A)移植肾功能；(B)BKV肾病的发展。BKV复制和BKV肾病的发展将在前瞻性队列研究中进行，研究对象不仅包括成人，还包括接受肾移植的儿童。在儿科研究中，我们还将确定基于皮质类固醇的免疫抑制是否是BKV复制和发展BKV肾病的危险因素，因为研究队列将由NIAID赞助的比较基于类固醇的免疫抑制和非类固醇免疫抑制的多中心随机平行小组试验的儿科患者组成。

DESCRIPTION (provided by applicant): The overall objective of the proposed project is to develop a noninvasive diagnostic test that is predictive, diagnostic and prognostic of BK virus associated nephropathy. The primary hypothesis for the proposed investigation is that urinary cell messenger RNA (mRNA) profiles that include measurement of mRNA for BKV viral capsid protein 1 (VP1) are predictive, diagnostic and prognostic of BKV nephropathy. The Specific Aims of the proposed investigation are: Specific Aim 1. To document, in a large multi-center study, the validity of urinary cell BKV VP1 mRNA level as a highly sensitive (>90%) and specific (>90%) noninvasive diagnostic test for BKV nephropathy. Specific Aim 2. To test the hypothesis, in a prospective cohort study, that urinary cell mRNA profiles, assessed at the time BKV nephropathy is diagnosed, predict renal allograft functional outcome. Specific Aim 3. To evaluate BKV replication by measurement of BKV VP1 mRNA levels in sequential urine specimens and test whether elevations in BKV VP1 mRNA levels predict: (a) renal allograft function; and (b) the development of BKV nephropathy. BKV replication and development of BKV nephropathy will be explored in prospective cohort studies of not only adult but also pediatric recipients of renal allografts. In the pediatric study, we will also determine whether corticosteroid based immunosuppression is a risk factor for BKV replication and development of BKV nephropathy since the study cohort will be composed of pediatric patients enrolled in a NIAID sponsored multi-center randomized, parallel group trial comparing steroid based immunosuppression with steroid-free immunosuppression.