Accurate Measurement of Renal Function in Cirrhosis

描述(申请人提供)：随着慢性乙肝和丙型肝炎在美国的流行日益严重，肝硬变的发病率不断上升，导致发病率和死亡率显著上升。可供移植的肝脏数量有限，这意味着对这些宝贵资源的适当分配比以往任何时候都更加关键。肾功能障碍是导致肝硬变患者死亡率的最重要的危险因素之一，这一点体现在移植患者的MELD优先评分中包括了血清肌酐(Cr)，然而，在肝硬变患者中，肾功能的测量非常不准确。基于肌酐和最近的胱抑素C(CysC)的GFR估计者高估了肾功能，导致临床管理不善和次优的移植优先顺序。在过去的十年中，我们开发了3D磁共振成像和分析工具，用于测量肾小球滤过率(GFR)，使用低剂量的Gd造影剂，并在不到10分钟的额外MR检查时间内完成。由于有发展为肝细胞癌的倾向，肝硬变患者要接受常规的影像检查；在影像检查中，MRI被证明对早期恶性肿瘤最敏感。我们认为，在常规的肝脏MRI中，可以获得准确的GFR测量来确定肝硬变患者的肾脏状态。我们使用改进的2D方案进行的初步MR GFR测量显示，在肝硬变患者中与参考的99mTC-DTPA清除值非常一致。广泛的长期目标：开发和测试一种易于实施的方法，用于准确测量常规肝脏MRI检查的肝硬变患者的肾功能。具体目的/方法：(1)建立和完善一种快速测量单个肾脏和总肾小球滤过率(GFR)的MRI方法，该方法可与常规的肝脏MR检查相结合。对15名受试者，我们将比较两种方法定量Gd浓度的准确性，进行Gd剂量优化研究，并检查分析的间隔模型的稳健性。(2)在197例肝硬变患者中，验证快速磁共振肾小球滤过率方法与参考核素清除法测定单肾和总肾小球滤过率的准确性。我们将比较MR GFR估计值与传统的基于Cr和CysC的估计值(3)，以开发和提供用户友好的图形用户界面，以便能够在标准的、常见的计算机平台上快速(&lt；5分钟)分析MR肾图数据。在其结论中，我们的研究很有可能表明，磁共振肾成像可以快速准确地提供GFR的准确测量，并且添加到常规肝脏MRI中时，增加的成本可以忽略不计。该项目将通过改善对肝硬变患者的管理，提高风险分层和基于MELD的肝移植优先顺序的准确性，通过准确监测肾功能来降低移植后的发病率和死亡率，并对更广泛的肾病风险患者群体产生重大影响，从而对人类健康产生重大影响。 公共卫生相关性：拟议的项目将对改善慢性肝炎和肝硬变等肝病患者的医疗保健具有重要意义，在这些患者中，肾脏疾病通常会发展，但经常被低估。利用我们提出的新的磁共振成像(MRI)技术，可以比现有方法更准确地测量肾功能，并可以将其整合到肝癌的常规MRI筛查方案中，而增加的时间和成本可以忽略不计。这一更准确的衡量方法的潜在影响包括更好地管理肝硬变患者和改进移植的优先顺序，以及更广泛地说，改善对更广泛的有患肾病风险的患者的诊断。

DESCRIPTION (provided by applicant): With the worsening epidemic of chronic hepatitis B and C infections in the U.S., the rising incidence of cirrhosis is causing significant and growing morbidity and mortality. The limited number of livers available for transplantation means appropriate allocation of these precious resources is more critical than ever. Renal dysfunction is one of the most important risk factors for mortality in cirrhotics, as reflected by the inclusion of serum creatinine (Cr) in the MELD priority score for transplantation, and yet measures of renal function are highly inaccurate in cirrhosis. Estimators of GFR based on Cr and, more recently, cystatin C (CysC), overestimate renal function, leading to clinical mismanagement and suboptimal transplant prioritization. Over the past decade, we have developed 3D MR imaging and analysis tools for measuring glomerular filtration rate (GFR) using low doses of Gd contrast material and in less than 10 min of additional MR table time. Because of their propensity to develop hepatocellular carcinoma, cirrhotic patients undergo routine imaging for screening; of the imaging tests, MRI has proven most sensitive for early malignancy. We propose that during routine liver MRI, accurate measurements of GFR can be obtained for determining renal status in cirrhotic patients. Our preliminary MR GFR measurements, using a modified 2D protocol, show close agreement with reference 99mTc-DTPA clearance values in cirrhotics. Broad long term objectives: To develop and test an easily- implementable method for accurately measuring renal function in cirrhotic patients undergoing routine liver MRI. Specific Aims/Methods: (1) To develop and refine a fast MRI method to measure single kidney and total glomerular filtration rate (GFR) that can be performed in conjunction with routine screening liver MR exams. With 15 subjects, we will compare accuracy of two methods for quantifying Gd concentration, perform a Gd dose optimization study, and examine the robustness of compartmental models of analysis. (2) To validate the accuracy of fast MR GFR methods compared with reference radionuclide clearance methods for single kidney and total GFR in a cirrhotic population of 197 subjects. We will compare MR GFR estimates with conventional Cr and CysC-based estimates (3) To develop and offer for public use a user-friendly graphical user interface to enable rapid (< 5 min) analysis of MR renography data on standard, commonly available computer platforms. At its conclusion, our study is highly likely to show that MR renography can provide accurate measures of GFR quickly and accurately, and with negligible added costs when added to routine liver MRI. This project would have a high impact on human health by improving the management of cirrhotic patients, increasing the accuracy of risk stratification and MELD-based liver transplantation prioritization, and by reducing post-transplantation morbidity and mortality through the accurate monitoring of renal function, in addition to significant implications for the broader population of patients at risk for renal disease. PUBLIC HEALTH RELEVANCE: The proposed project will be important for improving the health care of patients with liver diseases such as chronic hepatitis and cirrhosis, in whom kidney disease commonly develops but is frequently underdiagnosed. With the novel magnetic resonance imaging (MRI) technique that we propose, kidney function can be measured more accurately than available with existing methods, and can be integrated into the routine MRI screening protocol for liver cancer with negligible added time and costs. Potential implications of this more accurate measurement include better management of cirrhotic patients and improved prioritization for transplants as well as, more broadly, improved diagnosis of the broader population of patients who are at risk for developing kidney disease.