Accurate Measurement of Renal Function in Cirrhosis

描述（由申请人提供）：随着慢性乙型肝炎和丙型肝炎感染在美国的日益流行，肝硬化的发病率不断上升，导致发病率和死亡率显著上升。可用于移植的肝脏数量有限，这意味着这些宝贵资源的适当分配比以往任何时候都更加关键。肾功能不全是肝硬化患者死亡最重要的危险因素之一，血清肌酐（Cr）被纳入MELD移植优先评分反映了这一点，但肝硬化患者的肾功能测量非常不准确。基于Cr和最近的胱抑素C （CysC）的GFR估算器高估了肾功能，导致临床管理不善和移植优先级不理想。在过去的十年中，我们开发了3D磁共振成像和分析工具，使用低剂量的Gd造影剂，在不到10分钟的额外MR表时间内测量肾小球滤过率（GFR）。由于肝硬化患者有发展为肝细胞癌的倾向，因此他们要接受常规影像学检查；在影像学检查中，MRI已被证明对早期恶性肿瘤最敏感。我们建议，在常规的肝脏MRI中，可以获得准确的GFR测量，以确定肝硬化患者的肾脏状态。我们的初步MR GFR测量，使用改进的2D方案，显示与参考99mTc-DTPA清除值在肝硬化中非常一致。广泛的长期目标：开发和测试一种易于实施的方法，用于准确测量肝硬化患者常规肝脏MRI的肾功能。具体目的/方法：(1)开发和完善一种快速MRI方法来测量单肾和总肾小球滤过率（GFR），该方法可以与常规筛查肝脏MR检查一起进行。在15名受试者中，我们将比较两种定量Gd浓度方法的准确性，进行Gd剂量优化研究，并检验分析的室室模型的稳健性。(2)在197例肝硬化人群中，与参考放射性核素清除方法相比，验证快速MR GFR方法对单肾和总GFR的准确性。我们将MR GFR估算值与传统Cr和基于cysc的估算值进行比较(3)开发并提供一个用户友好的图形用户界面供公众使用，以便在标准的、常用的计算机平台上快速（< 5分钟）分析MR renography数据。综上所述，我们的研究极有可能表明MR肾造影术可以快速准确地提供GFR的准确测量，并且在常规肝脏MRI的基础上增加的成本可以忽略不计。该项目将通过改善对肝硬化患者的管理，提高风险分层和基于meld的肝移植优先排序的准确性，以及通过准确监测肾功能降低移植后发病率和死亡率，对人类健康产生重大影响，此外还将对更广泛的有肾脏疾病风险的患者群体产生重大影响。

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.