Application of Novel Biomarkers of Renal Health in Cirrhosis Patients to Stratify Risk of Acute Kidney Injury Occurrence and Reversibility

肝硬化患者肾脏健康的新型生物标志物对急性肾损伤发生风险和可逆性的分层

• 批准号: 10525756
• 负责人: Giuseppe Cullaro
• 金额: $ 16.35万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-02 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10525756
• 关键词: Acute Renal Failure with Renal Papillary Necrosis; Address; Adult; Affect; Age; Albumins; American; Award; Biological Markers; Biological Specimen Banks; Biometry; Calibration; California; Cause of Death; Cessation of life; Chronic Kidney Failure; Cirrhosis; Clinical; Clinical Research; Collaborations; Communities; Complication; Coupled; Creatine; Creatinine; Data; Data Analyses; Development; Development Plans; Discrimination; Early Intervention; Enrollment; Equation; Etiology; Evaluation; Fibrosis; Filtration; Foundations; Future; Glomerular Filtration Rate; Goals; Health; Hepatic; Hepatology; Hospitalization; Hour; Impairment; Incidence; Inflammation; Injury; Injury to Kidney; Inpatients; K-Series Research Career Programs; Kidney; Laboratories; Lead; Leadership; Learning; Liver diseases; Longitudinal cohort; Machine Learning; Measurement; Measures; Methodology; Methods; Modeling; Morbidity - disease rate; National Institute of Diabetes and Digestive and Kidney Diseases; Nephrology; Nephrons; Outcome; Patient risk; Patients; Permeability; Population; Prevalence; Prevention strategy; Preventive therapy; Property; Publications; Renal function; Research; Research Personnel; Risk; San Francisco; Serum; Severities; Skeletal Muscle; Statistical Data Interpretation; Structure; Supervision; Techniques; Training; United States; Universities; Urokinase Plasminogen Activator Receptor; aging population; base; biomarker-driven; career; career development; clinical risk; cohort; cost; demographics; hemodynamics; implementation intervention; kidney dysfunction; liver transplantation; mortality; multidisciplinary; non-alcoholic fatty liver disease; novel; novel marker; post gamma-globulins; prevent; proenkephalin; programs; rat KIM-1 protein; risk prediction; risk stratification; skills; statistics; support vector machine; tool; trend

PROJECT SUMMARY/ABSTRACT Cirrhosis is a leading cause of morbidity and mortality among adults in the United States. Acute kidney injury (AKI) is a common, expensive, and lethal complication of cirrhosis. The strongest predictor of AKI in cirrhosis patients, regardless of etiology, is chronic kidney disease (CKD), as measured by estimated glomerular filtration rate (eGFR). Given that there is a rising incidence of both AKI and CKD in this population, there is a developing critical need for clinical tools that identify cirrhosis patients at risk for AKI before its development. This proposal’s three research aims address this need. Leveraging an ongoing cohort with >1000 decompensated cirrhosis patients with >2500 banked biospecimens, these aims will: (1) establish the independent association between renal health biomarkers and AKI and compare the discrimination of novel renal health biomarkers to serum creatinine (sCr) to predict AKI (Aim 1); develop and internally validate a clinical risk tool to identify cirrhosis patients most vulnerable to AKI (Aim 2); explore the association between longitudinal changes in renal health biomarkers on AKI reversibility (Aim 3). I am a hepatologist specializing in liver transplantation at the University of California, San Francisco. Through a pilot award provided by the American Association for the Study of Liver Disease, we have generated the preliminary data needed for this application. These data, coupled with a strong foundation of hepatology and nephrology research (Master of Advanced Studies in Clinical Research, >10 publications), have prepared me for this proposal. However, there are several gaps in my training that this NIDDK K23 Career Development Award will address (e.g., cohort development, advanced statistical techniques). Under the direct supervision of a multidisciplinary team of leaders in nephrology (Hsu, Liu), hepatology (Lai), and biostatistics (McCulloch), I will execute a detailed career development plan to accelerate my path toward 4 career goals outlined in this proposal: (1) to develop a foundation of core nephrological principles; (2) to acquire analytic skills to validate biomarker use; (3) to learn novel methodologies at risk prediction, including machine learning techniques; (4) to expand a cohort and to apply methods of longitudinal data analysis. As part of my 5-year plan, I will actively engage in coursework and structured tutorials in nephrology and biostatistics, and interdisciplinary development and leadership programs. In addition, I will integrate myself into the nephrology research community and establish a network of nephrology researchers for current and future collaboration. RELEVANCE: Identifying a metric that captures which cirrhosis patients are at greatest risk for and least likely to reverse from AKI has important clinical implications—it will allow for the implementation of interventions that prevent the occurrence and halt the progression of a major driver of mortality in this population.

项目总结/摘要 肝硬化是美国成年人发病率和死亡率的主要原因。急性肾损伤 (AKI)是肝硬化的常见、昂贵和致命的并发症。肝硬化阿基的最强预测因子 患者，无论病因如何，都是慢性肾病（CKD），如通过估计的肾小球 滤过率（eGFR）。考虑到该人群中阿基和CKD的发病率都在上升， 迫切需要临床工具，在其发展之前识别有阿基风险的肝硬化患者。 本提案的三个研究目标满足了这一需求。利用正在进行的队列，>1000 失代偿期肝硬化患者>2500个库存生物标本，这些目标将：（1）建立 肾健康生物标志物与阿基之间的独立关联，并比较新的 肾健康生物标志物与血清肌酐（sCr）的比值，以预测阿基（目标1）;开发并内部验证 临床风险工具，用于识别最易发生阿基的肝硬化患者（目标2）;探索 肾脏健康生物标志物对阿基可逆性的纵向变化（目标3）。 我是加州大学旧金山分校的一名肝脏专家，专门从事肝脏移植工作。弗朗西斯科。通过 由美国肝病研究协会提供的试点奖，我们已经产生了 本申请所需的初步数据。这些数据，加上强大的肝病学基础， 肾脏病学研究（临床研究高级研究硕士，>10篇出版物），已经准备好我 对于这个提议。然而，在我的培训中有几个差距，这个NIDDK K23职业发展 奖励将解决（例如，队列发展、先进的统计技术）。的直接监督下 一个由肾脏病学（Hsu，Liu），肝病学（Lai）和生物统计学（McCulloch）领导的多学科团队， 我将执行一个详细的职业发展计划，以加快我的道路，实现4个职业目标概述在这 建议：（1）建立核心肾脏学原则的基础;（2）获得分析技能，以验证 生物标志物的使用;（3）学习风险预测的新方法，包括机器学习技术;（4） 扩大队列并应用纵向数据分析方法。作为我五年计划的一部分，我将积极 从事肾脏学和生物统计学的课程和结构化教程，以及跨学科 发展和领导力计划。此外，我将把自己融入肾脏病学研究 社区，并建立肾脏病学研究人员网络，以进行当前和未来的合作。 相关性：确定一个衡量指标，捕捉哪些肝硬化患者的风险最大，最不可能 逆转阿基具有重要的临床意义-它将允许实施干预措施， 预防这一人群死亡率的主要驱动因素的发生并阻止其发展。