Noninvasive diagnosis of BKV nephropathy

描述（由申请人提供）：拟议项目的总体目标是开发一种非侵入性诊断试验，用于预测、诊断和预后BK病毒相关肾病。 拟定研究的主要假设是尿细胞信使RNA（mRNA）谱（包括BKV病毒衣壳蛋白1（VP 1）mRNA的测量）可预测、诊断和预后BKV肾病。拟议调查的具体目的是： 具体目标1。 在一项大型多中心研究中，记录尿细胞BKV VP 1 mRNA水平作为BKV肾病高灵敏度（>90%）和特异性（>90%）非侵入性诊断试验的有效性。 具体目标2。为了验证这一假设，在一项前瞻性队列研究中，在诊断BKV肾病时评估尿细胞mRNA谱可预测肾移植功能结局。 具体目标3。通过测量连续尿液标本中BKV VP 1 mRNA水平评价BKV复制，并检测BKV VP 1 mRNA水平升高是否预测：（a）肾移植功能;（B）BKV肾病的发生。 将在成人和儿童肾移植受者的前瞻性队列研究中探索BKV复制和BKV肾病的发展。 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BKV肾病发展的风险因素，因为研究队列将由入组NIAID申办的多中心随机、平行组试验的儿科患者组成，该试验比较基于类固醇的免疫抑制与不含类固醇的免疫抑制。

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.