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: 8463163
• 负责人: PRATIMA SHARMA
• 金额: $ 15.3万
• 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/8463163
• 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; public health relevance; 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（由申请人提供）：肝移植后慢性肾衰竭（CRF），定义为估计肾小球滤过率（eGFR）<30 ml/min或终末期肾病（ESRD），是非肾实体器官移植受者中与死亡率增加和费用高相关的主要移植后并发症之一。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，尽管钙调磷酸酶抑制剂的免疫抑制水平较低，但肝移植（LT）受者的LT后CRF发生率第二高。终末期肝病候选患者的肾功能不全范围从既存肾病导致的血清肌酐轻微升高到需要肾脏替代治疗（RRT）的肝肾综合征导致的全面肾衰竭不等。虽然肝肾综合征患者通常在LT后恢复肾功能，但肾功能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，既存肾脏疾病的候选人在LT后不太可能恢复肾功能，并且可能表现出稳定的肾功能或进展为LT后CRF。该提案的首要目标是了解LT接受者中LT后CRF的流行病学。主要假设是，除了血清肌酐外，还有其他受体、供体和移植因素导致LT后CRF的负担。为了验证这一假设，我有三个目标：目标1：开发并验证一个模型，以预测LT时eGFR <30 ml/min的候选人中LT后CRF的风险;目标1b：评估LT后CRF在LT后住院率中的作用;目标2：检查预测eGFR <30 ml/min或接受RRT的候选人中LT后肾脏恢复的因素;目标3：估计预测的a）LT后CRF率B）LT后肾脏恢复率和c）终末期肝病模型（MELD）下的住院率，MELD是一种衡量等待名单死亡率和LT当前分配工具的指标，以及替代等待名单死亡率模型。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计划的国家数据进行这些研究。密歇根大学的有利环境，来自高度评价的公共卫生学院的教学课程，结合经验导师的优秀指导，以及访问大型国家临床（SRTR）和行政（CMS）数据库将为我提供坚实的基础，并帮助我实现我的长期职业目标，成为一个独立的，跨学科的，临床研究者和器官移植领域的领导者。