Predicting the burden of renal disease among liver transplant recipients

描述（由申请人提供）：肝移植后慢性肾衰竭（CRF），定义为肾小球滤过率(eGFR) <30 ml/min或终末期肾病（ESRD），是非肾实体器官移植受者移植后主要合并症之一，与死亡率增加和费用高相关。在所有非肾实体器官移植受者中，肝移植（LT）受者与心脏和肺移植受者相比，尽管钙调磷酸酶抑制剂的免疫抑制水平较低，但其术后CRF发生率第二高。终末期肝病患者的肾功能障碍范围各不相同，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）的肝肾综合征引起的全面肾功能衰竭。虽然肝肾综合征患者通常在肝移植后恢复肾功能，但肾脏恢复的时间是可变的。此外，与肾脏恢复相关的因素还没有很好地阐明。另一方面，先前存在肾脏疾病的候选人不太可能在肾移植后恢复肾功能，可能表现出稳定的肾功能或进展到肾移植后的CRF。本建议的总体目标是了解肝移植受体中肝移植后CRF的流行病学。主要的假设是，除了血清肌酐外，还有其他受体、供体和移植因素导致了肝移植后CRF的负担。为了验证这一假设，我有三个目标：目标1：开发和验证一个模型，以预测LT时eGFR为30ml/min的候选人LT后CRF的风险；目的1b：评估肝移植后CRF对肝移植后住院率的影响；目的2：研究预测eGFR <30 ml/min或RRT患者LT后肾脏恢复的因素；目的3：估计终末期肝病模型（MELD）下预测的a)肝移植后CRF率b)肝移植后肾脏恢复率和c)住院率，MELD是一种衡量肝移植候补名单死亡率和当前分配工具的方法，以及其他候补名单死亡率模型。我将使用来自移植接受者科学登记处（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。密歇根大学的有利环境，高评价的公共卫生学院的教学课程，加上经验丰富的导师的优秀指导，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，成为一名独立的，跨学科的临床研究者和器官移植领域的领导者。

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.