Noninvasive diagnosis of BKV nephropathy

BKV肾病的无创诊断

• 批准号: 7220537
• 负责人: MANIKKAM SUTHANTHIRAN
• 金额: $ 35.84万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-15 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7220537
• 关键词: Acute; Adrenal Cortex Hormones; Adult; BK Virus; Biopsy; CD3 Antigens; CXC chemokine IP-10; CXCR3 gene; Capsid Proteins; Cells; Childhood; Clinical Trials; Cohort Studies; Development; Diagnosis; Diagnostic; Diagnostic tests; Differential Diagnosis; Elevation; Enrollment; Functional disorder; HLA-DR Antigens; Immunosuppression; Intercellular adhesion molecule 1; Interferon Type II; Interferons; Investigation; Kidney; Kidney Diseases; Kidney Transplantation; MS4A1 gene; Measurement; Measures; Messenger RNA; Molecular Profiling; National Institute of Allergy and Infectious Disease; Outcome; Patients; Protease Inhibitor; RNA; Randomized; Research Personnel; Risk Factors; Sensitivity and Specificity; Specimen; Steroids; Testing; Therapeutic immunosuppression; Time; Transforming Growth Factors; Transplantation; Tumor Necrosis Factor Ligand Superfamily Member 6; Urine; Viral; base; cohort; comparative trial; functional outcomes; graft failure; granulysin; granzyme B; heme oxygenase-1; kidney allograft; noninvasive diagnosis; perforin; prognostic; programs; prospective; trial comparing; urinary

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.

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测试，可预测、诊断和预后 BK 病毒相关肾病。 拟议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 (VP1) mRNA 的测量）可预测、诊断和预后 BKV 肾病。拟议调查的具体目标是： 具体目标 1. 在一项大型多中心研究中，证明尿细胞 BKV VP1 mRNA 水平作为 BKV 肾病高度敏感（>90%）和特异性（>90%）无创诊断测试的有效性。 具体目标 2. 为了检验这一假设，在一项前瞻性队列研究中，诊断 BKV 肾病时评估的尿细胞 mRNA 谱可预测同种异体移植肾的功能结果。 具体目标 3. 通过测量连续尿液样本中的 BKV VP1 mRNA 水平来评估 BKV 复制，并测试 BKV VP1 mRNA 水平的升高是否预测： (a) 同种异体移植肾功能； (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探讨，研究对象不仅包括成人，还有儿童同种异体肾移植受者。 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 肾病发展的危险因素，因为研究队列将由参与 NIAID 赞助的多中心随机、平行组试验的儿科患者组成，该试验比较类固醇基于无类固醇免疫抑制的免疫抑制。