Polyomavirus and Mentoring in Renal Transplantation

描述（由申请人提供）： 我这次续约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善肾移植中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的学生，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，提供了多学科的研究和指导。重要的是，我们完成了原始申请“多瘤病毒和肾移植指导”的所有3个特定目标。我们发现，在随机接受他克莫司或环孢素的患者中，尿液和血液中多瘤病毒（BK）的发生率相同。我们发现BK在血液之前出现在尿液中，并且尿液中的水平远远高于血液-尿液中的10亿拷贝/mL与血液中的10 - 100，000拷贝/mL。我们发现，在移植后早期频繁监测，当血液中检测到BK时，停用麦考酚酯或硫唑嘌呤可清除BK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因子，反之亦然。因此，我们报道了几个重要的发现，这些发现改变了移植界对这种令人烦恼的病毒的态度，因为这种病毒没有有效的抗病毒治疗。 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病毒感染进展的风险因素。我们将通过分析来自原始研究的尿液和血浆中储存的DNA来完成这项工作。具体目标2。确定肾移植受者移植前抗体状态对多瘤病毒BK和JC的作用，以及对感染或非感染的抗体应答。我们将通过分析原始研究中储存的血浆来进行分析。第三章.在随机接受他克莫司或环孢霉素作为钙调磷酸酶免疫抑制剂的患者中，确定BK监测策略和检测到BK病毒血症时提前停用免疫抑制剂抗代谢成分的长期结局。为此，我们将分析从我们的电子病历，诊所笔记和医院图表中提取的数据。

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.