Polyomavirus and Mentoring in Renal Transplantation

多瘤病毒和肾移植的指导

• 批准号: 6744323
• 负责人: DANIEL C. BRENNAN
• 金额: $ 13.52万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6744323
• 关键词: FK506; Polyomavirus; artificial immunosuppression; blood chemistry; clinical research; comorbidity; cyclosporines; cytomegalovirus; epidemiology; human herpesvirus 6; human subject; kidney transplantation; opportunistic infections; patient oriented research; polymerase chain reaction; transplant rejection; urinalysis; virus diseases

DESCRIPTION (provided by applicant):Our studies based on Thymoglobulin, cyclosporine, azathioprine and prednisone resulted in a 1-year rejection rate of 4% and 3-year graft survival of 95%. Use of tacrolimus, compared to cyclosporine, has been associated with lower rejection rates and better graft survival. The incidence of polyoma virus infection may increase with tacrolimus. Polyoma virus has a 60-80% seroprevalence in the general population and reactivation after transplant is common. It is an important cause of graft dysfunction with graft loss in 50% of cases. The incidence, natural history, the role of tacrolimus or cyclosporine on the incidence of reactivation; the relationship of viruruia, viremia, invasive disease and renal dysfunction; and whether other viruses are co-factors for polyoma infection are unknown. Thus, this study has 3 Specific Aims. Aim 1: To determine the incidence, natural history and associated factors of polyoma infection from the time of transplant and over 1-year in a large cohort (n=250) of new renal transplant recipients monitored with PCR of urine, plasma, and whole blood weekly for 16 weeks and at months 4, 5, 6, 9 and 12, in patients treated with tacrolimus or cyclosporine. Aim 2: To determine the relationship among tissue, blood and urine polyoma-PCR and renal allograft pathology, by analyzing conventional histopathology, immunohistochemistry, in situ hybridization, and tissue, blood and urine-PCR for polyoma in renal transplant recipients with graft dysfunction. Aim 3: To determine whether active polyoma virus infection is a co-factor in the 10-20% of patients who develop active CMV, HHV-6, or HHV-7 after discontinuation of oral ganciclovir prophylaxis compared to the 80-90% of patients at risk who do not develop CMV disease.The candidate is a patient-oriented researcher and an Established Investigator for the American Heart Association and a Young Investigator for the American Society of Transplantation. He has or currently mentored 13 patient-oriented researchers. This award and project will allow him to improve his own patient-oriented research and mentoring capabilities. It will allow him to increase the number and more formally mentor the patient-oriented training of fellows and junior faculty.

描述（由申请人提供）：我们基于胸腺球蛋白、环孢素、硫唑嘌呤和泼尼松的研究结果显示，1 年排斥率为 4%，3 年移植物存活率为 95%。与环孢菌素相比，使用他克莫司可降低排斥率并提高移植物存活率。使用他克莫司可能会增加多瘤病毒感染的发生率。多瘤病毒在普通人群中的血清阳性率为 60-80%，移植后重新激活很常见。它是移植物功能障碍的重要原因，50%的病例发生移植物丢失。发病率、自然史、他克莫司或环孢素对再激活发生率的作用；病毒尿、病毒血症、侵袭性疾病和肾功能不全的关系；其他病毒是否是多瘤感染的辅助因素尚不清楚。因此，本研究有 3 个具体目标。目标 1：通过对尿液、血浆和全血进行 PCR 监测，确定一大群 (n = 250) 新肾移植受者中从移植时起和超过 1 年多瘤感染的发病率、自然史和相关因素对于接受他克莫司或环孢菌素治疗的患者，每周进行一次血液检查，持续 16 周以及第 4、5、6、9 和 12 个月。目的 2：通过分析移植功能障碍肾移植受者多瘤的常规组织病理学、免疫组织化学、原位杂交以及组织、血液和尿液多瘤 PCR，确定组织、血液和尿液多瘤 PCR 与肾同种异体移植病理学之间的关系。目标 3：确定活动性多瘤病毒感染是否是 10-20% 的患者在停止口服更昔洛韦预防后出现活动性 CMV、HHV-6 或 HHV-7 的辅助因素，而 80-90% 的患者在停止口服更昔洛韦预防后出现活动性 CMV、HHV-6 或 HHV-7有风险但未患 CMV 疾病的患者。候选人是一位以患者为中心的研究人员，也是美国心脏协会的资深研究员和美国心脏协会的年轻研究员移植。他已经或目前指导了 13 名以患者为中心的研究人员。这个奖项和项目将使他能够提高自己以患者为中心的研究和指导能力。这将使他能够增加研究员和初级教师的数量，并更正式地指导以患者为导向的培训。