Polyomavirus and Mentoring in Renal Transplantation

多瘤病毒和肾移植的指导

基本信息

批准号：
7576805
负责人：
Daniel Conlon Brennan
金额：
$ 16.67万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-05-01 至 2013-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7576805
关键词：
Acute Allografting Antibodies Antibody Formation Antimetabolites Azathioprine BK Virus Binding Biopsy Specimen Blood Blood specimen Calcineurin Classification Clinic Clinical Clinical Data Collaborations Communities Computerized Medical Record Control Groups Cyclosporine Cyclosporins Cytomegalovirus DNA Sequence Rearrangement Data Data Analyses Detection Enhancers Enrollment Evaluation Exposure to Faculty Fostering Functional RNA Functional disorder Genome HLA-A gene Hospitals Human Human Herpesvirus 6 Human Herpesvirus 7 Immunosuppression Immunosuppressive Agents Incidence Infection Interdisciplinary Study JC Virus Kidney Kidney Diseases Kidney Transplantation Large T Antigen Literature Maintenance Mentors Molecular Molecular Biology Monitor Multivariate Analysis Mutation Mycophenolate Natural History Outcome Pathogenicity Patients Pharmacotherapy Plasma Polyomavirus Polyomavirus Infections Prevalence Prophylactic treatment Prospective Studies ROC Curve Randomized Renal Tissue Renal function Reporting Research Risk Risk Factors Role Serologic tests Serological Severities Simian virus 40 Source Specimen Structure Students Tacrolimus Time Tissues Training Transplant Recipients Transplantation Treatment Protocols Universities Urine Variant Viral Viral Load result Viremia Virulence Virus Virus Diseases Washington Whole Blood Withdrawal base clinically relevant cohort genome sequencing human disease improved interest mycophenolate mofetil patient oriented prevent promoter prospective response

项目摘要

DESCRIPTION (provided by applicant): My immediate and long-term objectives for this renewal application are the same as my initial application. I aim to continue and to improve Patient-Oriented Research in renal transplantation and to improve the training and mentoring of students, residents, fellows, and junior faculty in Patient-Oriented Research at Washington University. I believe my past mentoring and research endeavors have fostered collaboration that crossed divisional and departmental barriers to provided multidisciplinary research and mentoring. Importantly we accomplished all 3 of our Specific Aims of the original application, "Polyomavirus and Mentoring in Renal Transplantation". We found that the incidence of polyomavirus (BK) in the urine and blood was the same in patients randomized to receive tacrolimus or cyclosporine. We found that BK appears in the urine before the blood and that levels in the urine are far greater in the urine than the blood--a billion copies/mL in urine vs 10-100,000 copies/mL in blood. We found that with frequent monitoring early after transplant that discontinuation of mycophenolate or azathioprine when BK was detected in the blood led to clearance of BK and prevented progression to BK nephropathy. We also found that 3 other viruses CMV, HHV-6 and HHV-7 were not co-factors for polyomavirus infection or vice versa. Thus, we reported several important findings that have changed the transplant community's approach to this vexing virus for which there is no effective anti-viral treatment. The Specific Aims for the proposed study are: Specific Aim 1. To determine whether viral variants of BK occurred and whether these are risk factors that promote progression of BK viral infections in renal transplant patients. We will do this by analyzing stored DNA from the urine and plasma from the original study. Specific Aim 2. To determine the role of pretransplant antibody status to the polyomaviruses, BK and JC, and the antibody response to infection or non-infection in renal transplant recipients. We will do this by analyzing stored plasma from the original study. Specfic Aim 3. To determine the long-term outcomes of a monitoring strategy for BK and preemptive withdrawal of the antimetabolite component of immunosuppression upon detection of BK viremia in patients randomized to receive either tacrolimus or cyclosporine as the calcineurin component of immunosuppression. To do this we will analyze data extracted from our electronic medical record, clinic notes, and hospital charts.

描述（由申请人提供）：我这次续签申请的近期和长期目标与我最初的申请相同。我的目标是继续并改进肾移植领域以患者为导向的研究，并改善华盛顿大学以患者为导向的研究中对学生、住院医生、研究员和初级教师的培训和指导。我相信我过去的指导和研究工作促进了跨越部门和部门障碍的合作，提供多学科研究和指导。重要的是，我们实现了最初申请“多瘤病毒和肾移植指导”的所有 3 个具体目标。我们发现，随机接受他克莫司或环孢素治疗的患者尿液和血液中多瘤病毒（BK）的发病率相同。我们发现 BK 先于血液出现在尿液中，并且尿液中的 BK 水平远高于血液中的水平 - 尿液中为 10 亿拷贝/mL，而血液中为 10-100,000 拷贝/mL。我们发现，通过移植后早期的频繁监测，当血液中检测到 BK 时，停止使用麦考酚酯或硫唑嘌呤会导致 BK 清除，并防止进展为 BK 肾病。我们还发现其他 3 种病毒 CMV、HHV-6 和 HHV-7 不是多瘤病毒感染的辅助因子，反之亦然。因此，我们报告了几项重要的发现，这些发现改变了移植界对这种令人烦恼的病毒的处理方法，因为目前还没有有效的抗病毒治疗方法。拟议研究的具体目标是：具体目标 1. 确定是否发生 BK 病毒变异以及这些变异是否是促进肾移植患者 BK 病毒感染进展的危险因素。我们将通过分析原始研究中储存的尿液和血浆 DNA 来做到这一点。具体目标 2. 确定移植前针对多瘤病毒、BK 和 JC 的抗体状态的作用，以及肾移植受者对感染或非感染的抗体反应。我们将通过分析原始研究中储存的血浆来做到这一点。具体目标 3. 确定 BK 监测策略的长期结果，以及在随机接受他克莫司或环孢素作为免疫抑制钙调神经磷酸酶成分的患者中检测到 BK 病毒血症后预先撤除免疫抑制抗代谢成分的长期结果。为此，我们将分析从电子病历、临床记录和医院图表中提取的数据。