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Predicting the burden of renal disease among liver transplant recipients

预测肝移植受者的肾脏疾病负担

基本信息

批准号：
8848809
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
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-06-01 至 2017-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8848809
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

项目摘要

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）：肝移植后慢性肾功能衰竭（CRF），定义为估计肾小球滤过率（eGFR）<30ml/min或终末期肾病（ESRD），是非肾实体器官移植受者中主要的移植后并发症之一，与死亡率增加和费用高昂相关。在所有非肾实体器官移植受者中，肝移植 (LT) 受者的 LT 后 CRF 发生率位居第二，尽管与心脏和肺移植受者相比，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。尽管患有肝肾综合征的患者通常在 LT 后恢复其肾功能，但肾脏恢复的时间是可变的。此外，与肾脏恢复相关的因素尚未得到很好的阐明。另一方面，已有肾脏疾病的候选人在 LT 后不太可能恢复其肾功能，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，除了血清肌酐之外，还有其他受体、供体和移植因素导致 LT 后 CRF 的负担。为了检验这一假设，我有三个目标：目标 1：开发并验证一个模型，以预测 LT 时 eGFR e 30ml/min 的候选人发生 LT 后 CRF 的风险；目标 1b：评估 LT 后 CRF 对 LT 后住院率的贡献；目标 2：检查 eGFR <30 ml/min 或接受 RRT 的候选者 LT 后肾脏恢复的预测因素；目标 3：估计终末期肝病 (MELD) 模型下的预测 a) LT 后 CRF 率 b) LT 后肾脏恢复率和 c) 住院率，该模型是候补名单死亡率和当前 LT 分配工具的衡量标准，以及替代候补名单死亡率模型。我将使用来自移植受者科学登记处 (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、备受好评的公共卫生学院的教学课程、经验丰富的导师的出色指导以及大型国家临床 (SRTR) 和管理 (CMS) 数据库的使用将为我提供坚实的基础，并帮助我实现长期职业目标，成为器官移植领域的独立、跨学科临床研究者和领导者。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Predictors of mortality in patients with hepatocellular carcinoma undergoing transarterial chemoembolization.

DOI：
10.1007/s10620-014-3247-7
发表时间：
2014-11
期刊：
DIGESTIVE DISEASES AND SCIENCES
影响因子：
3.1
作者：
Barman, Pranab M.;Sharma, Pratima;Krishnamurthy, Venkat;Willatt, Jonathon;McCurdy, Heather;Moseley, Richard H.;Su, Grace L.
通讯作者：
Su, Grace L.

Interferon-free treatment regimens for hepatitis C: are we there yet?

丙型肝炎的无干扰素治疗方案：我们到了吗？

DOI：
10.1053/j.gastro.2011.10.020
发表时间：
2011
期刊：
Gastroenterology
影响因子：
29.4
作者：
Sharma,Pratima;Lok,AnnaS
通讯作者：
Lok,AnnaS

Immunological dysfunction during or after antiviral therapy for recurrent hepatitis C reduces graft survival.

DOI：
10.1007/s12072-013-9436-1
发表时间：
2013-10
期刊：
HEPATOLOGY INTERNATIONAL
影响因子：
6.6
作者：
Sharma, Pratima;Hosmer, Amy;Appelman, Henry;McKenna, Barbara;Jafri, Mohammad S.;Sullivan, Patricia;Fontana, Robert J.;Lok, Anna S.
通讯作者：
Lok, Anna S.

Upper GI bleeding in a post-liver transplant patient. Hepatic artery pseudoaneurysm.

肝移植后患者的上消化道出血。