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Polyomavirus and Mentoring in Renal Transplantation

多瘤病毒和肾移植的指导

基本信息

批准号：
7468232
负责人：
Daniel Conlon Brennan
金额：
$ 16.82万
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/7468232
关键词：
Acute 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 DNA Sequence Rearrangement Data Data Analyses Detection Enhancers Evaluation Exposure to Faculty Fostering Functional RNA Genome HLA-A Antigens HLA-A gene HLA-A2 Antigen Hospitals Human Human Herpesvirus 6 Human Herpesvirus 7 Immunosuppression Incidence Infection Interdisciplinary Study JC Virus Kidney Kidney Diseases Kidney Transplantation Large T Antigen Literature Maintenance Mentors Molecular Monitor Multivariate Analysis Mutation Mycophenolate Outcome Pathogenicity Patients Pharmacotherapy Plasma Polyomavirus Polyomavirus Infections Prevalence Randomized Rate Renal function Reporting Research Risk Risk Factors Role Serological Severities Simian virus 40 Structure Students Tacrolimus Therapeutic immunosuppression Training Transplant Recipients Transplantation Treatment Protocols Universities Urine Variant Viral Viral Load result Viremia Virulence Virus Virus Diseases Washington Withdrawal blood lead clinically relevant cohort genome sequencing human disease improved interest mycophenolate mofetil patient oriented research prevent promoter prospective

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）：