Polyomavirus and Mentoring in Renal Transplantation

多瘤病毒和肾移植的指导

• 批准号: 8261838
• 负责人: Daniel Conlon Brennan
• 金额: $ 17.26万
• 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 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8261838
• 关键词: Allografting; Antibodies; Antibody Formation; Antimetabolites; Azathioprine; BK Virus; Blood; Calcineurin; Clinic; Collaborations; Communities; Computerized Medical Record; Cyclosporine; Cytomegalovirus; DNA; Data Analyses; Detection; Enrollment; Faculty; Fostering; Functional disorder; Hospitals; Human Herpesvirus 6; Human Herpesvirus 7; Immunosuppression; Immunosuppressive Agents; Incidence; Infection; Interdisciplinary Study; Kidney Diseases; Kidney Transplantation; Literature; Mentors; Molecular Biology; Monitor; Mycophenolate; Natural History; Outcome; Patients; Plasma; Polyomavirus; Polyomavirus Infections; Prophylactic treatment; Prospective Studies; ROC Curve; Randomized; Regimen; Renal Tissue; Reporting; Research; Risk Factors; Role; Serologic tests; Serological; Source; Specimen; Students; Tacrolimus; Time; Tissues; Training; Transplant Recipients; Transplantation; Universities; Urine; Variant; Viral; Viremia; Virus; Virus Diseases; Washington; Whole Blood; Withdrawal; base; improved; patient oriented research; prevent; prospective; response

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）： 我对此续签应用程序的直接和长期目标与我的初始申请相同。我的目标是继续并改善以患者为导向的肾脏移植研究，并改善华盛顿大学的学生，居民，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努力促进了合作，跨越了分区和部门的障碍，提供了多学科研究和指导。重要的是，我们完成了原始应用的所有特定目标，“多瘤病毒和肾移植中的指导”。我们发现，在随机接受他克莫司或环孢菌素的患者中，多瘤病毒（BK）的发生率相同。我们发现，BK出现在血液之前的尿液中，尿液中的水平比血液高得多，尿液中的十亿份/mL vs 10-100,000拷贝/ml的血液。我们发现，在移植后频繁进行频繁监测，当在血液中检测到BK时，在血液中检测到BK清除并阻止向BK肾病的进展时，霉酚酸盐或硫唑嘌呤的停用。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共同因素，反之亦然。因此，我们报道了一些重要的发现，这些发现改变了移植社区对这种烦恼的病毒的方法，没有有效的抗病毒治疗。 拟议研究的具体目的是： 具体目的1。确定BK病毒变异是否发生，以及这些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的尿液和血浆中的DNA来做到这一点。具体目的2。确定对多瘤病毒（BK和JC）的移植前抗体状态以及对肾移植受体中感染或不感染的抗体反应的作用。我们将通过分析原始研究中的存储等离​​子体来做到这一点。 Specfic Aim 3。确定BK监测策略的长期结果，并在发现随机接受他克莫司或环孢霉素作为免疫抑制剂的钙调氨酸成分的患者中发现BK病毒血症后的抗代谢物成分。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。

项目成果

Neutralization serotyping of BK polyomavirus infection in kidney transplant recipients.

• DOI: 10.1371/journal.ppat.1002650
• 发表时间: 2012
• 期刊: PLoS pathogens
• 影响因子: 6.7
• 作者: Pastrana DV;Brennan DC;Cuburu N;Storch GA;Viscidi RP;Randhawa PS;Buck CB
• 通讯作者: Buck CB

Obesity and cardiac risk after kidney transplantation: experience at one center and comprehensive literature review.

• DOI: 10.1097/tp.0b013e31817ef0f9
• 发表时间: 2008-07-27
• 期刊: Transplantation
• 影响因子: 6.2
• 作者: Lentine KL;Rocca-Rey LA;Bacchi G;Wasi N;Schmitz L;Salvalaggio PR;Abbott KC;Schnitzler MA;Neri L;Brennan DC
• 通讯作者: Brennan DC

Thymoglobulin induction dosing strategies in a low-risk kidney transplant population: three or four days?

低风险肾移植人群的胸腺球蛋白诱导给药策略：三天还是四天？

• DOI: 10.1155/2010/957549
• 发表时间: 2010
• 期刊: Journal of transplantation
• 影响因子: 2.5
• 作者: Hardinger,KarenL;Rasu,RafiaS;Skelton,Rebecca;Miller,BrentW;Brennan,DanielC
• 通讯作者: Brennan,DanielC

Iron deficiency anemia and iron losses after renal transplantation.

• DOI: 10.1111/j.1432-2277.2008.00814.x
• 发表时间: 2009-04
• 期刊: Transplant international : official journal of the European Society for Organ Transplantation
• 作者: Zheng S;Coyne DW;Joist H;Schuessler R;Godboldo-Brooks A;Ercole P;Brennan DC
• 通讯作者: Brennan DC

Urinary microbiome of kidney transplant patients reveals dysbiosis with potential for antibiotic resistance.

肾移植患者的尿液微生物组揭示了生态失调，可能存在抗生素耐药性。

• DOI: 10.1016/j.trsl.2016.08.008
• 发表时间: 2017
• 期刊: Translational research : the journal of laboratory and clinical medicine
• 作者: Rani,Asha;Ranjan,Ravi;McGee,HalvorS;Andropolis,KalistaE;Panchal,DiptiV;Hajjiri,Zahraa;Brennan,DanielC;Finn,PatriciaW;Perkins,DavidL
• 通讯作者: Perkins,DavidL