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Detection and Localization of Proteinuria by Dynamic Contrast-Enhanced Magnetic Resonance Imaging Using MS325

Yantian Zhang^*, Peter L. Choyke^*, Huiyan Lu, Hideko Takahashi, Roslyn B. Mannon, Xiaojie Zhang, Hani Marcos^*, King C.P. Li^* and Jeffrey B. Kopp

^* Department of Radiology, Warren Grant Magnuson Clinical Center and Transplanation Branch, and Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland

Address correspondence to: Dr. Jeffrey Kopp, 10 Center Drive, MSC 1268, National Institutes of Health, Bethesda, MD 20892. Phone: 301-594-3403; Fax: 301-402-0014; E-mail: jbkopp{at}nih.gov

Received for publication November 19, 2004. Accepted for publication March 11, 2005.

After renal transplantation, persistent glomerular disease affecting the native kidneys typically causes albuminuria, at least for a period of time, making it difficult to determine in a noninvasive fashion whether proteinuria originates in the native kidneys or the renal allograft. To address this problem, dynamic contrast-enhanced magnetic resonance imaging (MRI) using gadolinium (Gd)-based albumin-bound blood pool contrast agent (MS325) to localize proteinuria was investigated. Glomerular proteinuria was induced in Sprague-Dawley rats by intravenous injection of puromycin aminonucleoside (PAN), whereas control rats received physiologic saline vehicle. Both groups of animals underwent a 40-min dynamic contrast-enhanced MRI using radio frequency spoiled gradient echo imaging sequence after injection of Gd-labeled MS325. Contrast uptake and clearance curves for cortex and medulla were determined from acquired MR images. Compared with controls, proteinuric rats exhibited significantly lower elimination rate constants. The use of gadopentetate dimeglumine (Gd-DTPA) as a contrast agent showed smaller and less specific differences between proteinuric and control groups. In rats with one proteinuric kidney (PAN-treated) and one normal kidney (transplanted from a normal rat), MRI using MS325 was able to differentiate between the two kidneys. The results suggest that MRI with an albumin-bound blood pool contrast agent may be a useful noninvasive way to localize proteinuria. If this technique can be successfully applied in human patients, it may allow for the localization of proteinuria after kidney transplant and thereby provide a noninvasive way to detect disease affecting the renal allograft.

Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673