Predicting the burden of renal disease among liver transplant recipients

预测肝移植受者的肾脏疾病负担

• 批准号: 8661169
• 负责人: PRATIMA SHARMA
• 金额: $ 15.34万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8661169
• 关键词: Calcineurin inhibitor; Cessation of life; Chronic Kidney Failure; Clinical; Clinical Investigator; Comorbidity; Creatinine; Data; Databases; Donor person; End stage renal failure; Environment; Epidemiology; Equation; Event; Foundations; Functional disorder; Glomerular Filtration Rate; Goals; Heart; Hepatorenal Syndrome; Hospitalization; Immunosuppression; Incidence; Individual; Kidney; Kidney Diseases; Kidney Failure; Kidney Transplantation; Liver; Liver diseases; Lung; Measures; Mentors; Methods; Michigan; Modeling; Modification; Organ Transplantation; Outcome; Prevention; Public Health; Public Health Schools; Recovery; Recurrence; Registries; Renal Replacement Therapy; Renal function; Resources; Risk; Risk Factors; Serum; Social Security; Solid; Staging; Survival Analysis; Techniques; Testing; Time; Transplant Recipients; Transplantation; United States Centers for Medicare and Medicaid Services; Universities; Validation; career; cost; improved; indexing; liver transplantation; models and simulation; modifiable risk; mortality; programs; simulation; skills; tool

DESCRIPTION (provided by applicant): Post-liver transplant chronic renal failure (CRF), defined as estimated glomerular filtration rate (eGFR) <30 ml/min or end-stage renal disease (ESRD), is one of the major post-transplant co-morbidities among non-renal solid organ transplant recipients associated with increased mortality and high costs. Among all non-renal solid organ transplant recipients, liver transplant (LT) recipients have the second highest incidence of post-LT CRF despite the lower level of immunosuppression by calcineurin inhibitors, compared to heart and lung transplant recipients. The spectrum of renal dysfunction in the end-stage liver disease candidates varies from slight elevation in serum creatinine from pre-existing renal disease to full blown renal failure from hepatorenal syndrome requiring renal replacement therapy (RRT). Although candidates with hepatorenal syndrome usually recover their renal function after LT, the timing of renal recovery is variable. Moreover, the factors associated with renal recovery are not very well elucidated. On the other hand, candidates with pre-existing kidney disease are unlikely to recover their renal function after LT and may demonstrate stable renal function or progression to post-LT CRF. The overarching goal of this proposal is to understand the epidemiology of post- LT CRF among LT recipients. The main hypothesis is that there are other recipient, donor and transplant factors besides serum creatinine that contribute to the burden of post-LT CRF. To test this hypothesis, I have three aims: Aim 1: To develop and validate a model to predict the risk of post-LT CRF among candidates with eGFR e 30ml/min at LT; Aim 1b: To evaluate the contribution of post-LT CRF reflected in post-LT hospitalization rates; Aim 2: To examine the factors predicting renal recovery after LT among candidates with eGFR <30 ml/min or on RRT; Aim 3: To estimate the predicted a) post-LT CRF rates b) renal recovery rates after LT and c) hospitalization rates under the Model for end-stage Liver Disease (MELD), a measure of waitlist mortality and current allocation tool for LT, and alternative waitlist mortality models. I will use national data from the Scientific Registry of Transplant Recipients (SRTR) and the Centers for Medicare and Medicaid Services (CMS) ESRD Program to conduct these studies. The conducive environment at the University of Michigan, didactic coursework from the highly rated School of Public Health, combined with excellent mentoring from experiential mentors, and access to large national clinical (SRTR) and administrative (CMS) databases will provide me with a strong foundation and aid me in achieving my long term career goal to become an independent, interdisciplinary, clinical investigator and leader in the field of organ transplantation.

描述(申请人提供)：肝移植后慢性肾功能衰竭(CRF)，定义为估计的肾小球滤过率(EGFR)和30毫升/分钟或终末期肾病(ESRD)，是非肾脏实体器官移植受者移植后的主要并发症之一，与死亡率和高昂的费用有关。在所有非肾实体器官移植受者中，与心脏和肺移植受者相比，肝移植(LT)受者术后CRF的发生率第二高，尽管钙调神经磷酸酶抑制剂的免疫抑制水平较低。终末期肝病候选患者的肾功能障碍谱各不相同，从先前存在的肾脏疾病引起的血清肌酐轻微升高，到需要肾脏替代治疗(RRT)的肝肾综合征所致的全面肾功能衰竭。尽管患有肝肾综合征的患者通常会在肝移植后恢复肾功能，但肾功能恢复的时间是不同的。此外，与肾脏恢复相关的因素也没有得到很好的阐明。另一方面，患有既往肾脏疾病的考生不太可能在肝移植后恢复肾功能，并可能表现出稳定的肾功能或进展为肝移植后CRF。这项建议的首要目标是了解移植后慢性肾功能衰竭在肝移植受者中的流行病学。主要的假设是，除了血肌酐之外，还有其他受者、供者和移植因素对移植后CRF的负担起作用。为了验证这一假设，我有三个目标：目标1：建立和验证一个模型来预测在肝移植中EGFR e为30ml/min的受试者移植后CRF的风险；目标1b：评估移植后CRF在术后住院率中的贡献；目标2：检验预测肾移植后肾功能恢复的因素。目的3：评估预测的肝移植后CRF发生率，b)肝移植后肾功能恢复率，c)终末期肝病模型(MELD)下的住院率，肝移植等待名单死亡率的测量和当前分配工具，以及替代等待名单死亡率模型。我将使用来自移植受者科学登记(SRTR)和医疗保险和医疗补助服务中心(CMS)ESRD计划的国家数据来进行这些研究。密歇根大学有利的环境，高评价的公共卫生学院的授课，加上经验导师的出色指导，以及大型国家临床(SRTR)和行政(CMS)数据库的访问，将为我提供坚实的基础，并帮助我实现我的长期职业目标，成为器官移植领域的一名独立的、跨学科的临床研究员和领导者。