Accurate Measurement of Renal Function in Cirrhosis

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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.