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Using Contrast-Enhanced MRI to Investigate the Structural Effects of Chronic Kidney Disease

Presenters Name: 
Jillian Hughes
Primary Research Mentor: 
Jennifer Charlton
Secondary Research Mentor: 
Session: 
2
Location: 
South Meeting Room
Grant Program Recipient: 
USOAR Program
Abstract: 

Chronic kidney disease (CKD) affects over 26 million American adults. Its progression can be slowed, though it is difficult to detect in its earliest stages. Our objective is to develop noninvasive, early-use MRI tools to assess the number of nephrons, small units in the kidneys that filter out toxins from the blood, using cationic ferritin-enhanced magnetic resonance imaging (CFE-MRI). In our study, folic acid was injected into healthy male mice to induce CKD, compared to controls that did not receive folic acid. Four weeks after exposure, both groups of mice were given cationic ferritin to enhance contrast among kidney microstructures. Then, all mice were euthanized to have their kidneys analyzed by MRI and histology. Overall, CKD models gained less weight and had wrinkled kidneys with wedge-shaped defects, though there was no difference in kidney to body weight ratio. The amount of nephrons in the CKD group decreased (mean: 9522 CKD vs. 13371 control, p=0.02), and also tended to cluster together on MRI. Within these clusters, the average nephron grew in volume (CKD in cluster: 3.9 vs. controls: 2.4 x10-4 μm3, p=0.02), but those outside of clusters did not. By histologic methods, CKD models contained fewer proximal tubules (CKD: 31% vs. controls: 36%), more atubular glomeruli (CKD: 75% vs controls: 31%, p=0.02), and more fibrotic changes (CKD: 25% vs control: 0%, p=0.01). These unique observations and 3-D kidney view are only possible with CFE-MRI, and enabled us to clearly visualize the nephron loss and histologic changes that occur as CKD progresses.