Kidney Week

Abstract: FR-PO912

Evaluating Renal Fibrosis Using Diffusion Tensor Imaging (DTI)-MRI

Session Information

• CKD: Epidemiology, Risk Factors, Prevention - II
  November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2201 CKD (Non-Dialysis): Epidemiology‚ Risk Factors‚ and Prevention

Authors

• Avraham, Shimrit, Genentech Inc, South San Francisco, California, United States

Shimrit Avraham,

• Virgincar, Rohan S., Genentech Inc, South San Francisco, California, United States

Rohan S. Virgincar,

• Webster, Joshua, Genentech Inc, South San Francisco, California, United States

Joshua Webster,

• Brightbill, Hans David, Genentech Inc, South San Francisco, California, United States

Hans David Brightbill,

• Korin, Ben, Genentech Inc, South San Francisco, California, United States

Ben Korin,

• Shaw, Andrey S., Genentech Inc, South San Francisco, California, United States

Andrey S. Shaw,

• Xie, Luke, Genentech Inc, South San Francisco, California, United States

Luke Xie,

Background

The estimated glomerular filtration rate (eGFR) is the standard method to determine kidney function. However, GFR measurements can differ based on the patient sex, age, ethnicity, background, and measurement variability. MRI can potentially allow renal structure and function to be assessed in real-time and noninvasively.

Methods

Here, we used diffusion tensor imaging MRI (DTI-MRI) to reveal details about kidney architecture. We characterized normal mouse kidneys and three chronic kidney disease (CKD) mouse models: TLR-7 enhanced lupus, calcium oxalate, and the nephrotoxic nephritis (NTN) model of glomerular injury, to evaluate disease progression.

Results

Using DTI-MRI, we were able to detect changes associated with inflammation and interstitial fibrosis and found that MRI diffusivities can distinguish renal injuries in CKD models. In all of the models, we identified decreased axial diffusivity (AD) and fractional anisotropy (FA) over time correlated with histological increased destruction of glomeruli and fibrosis of the kidney. While the TLR-7 enhanced lupus and the calcium oxalate models develop marked inflammation that can interfere with the DTI-MRI signal, the NTN model, which has separate and time-dependent inflammatory and fibrotic stages, allowed us to follow fibrotic processes from early-stage to severe fibrosis. Interestingly, the most significant changes in DTI-MRI were at the cortical-medullary junction and included decreases in FA, apparent diffusion coefficient (ADC), AD, and radial diffusivity (RD). This finding was supported by Masson’s trichrome staining, which revealed that most of the fibrosis was also in this same region. This suggests that fibrosis may be more anatomically focused.

Conclusion

Taken together, our results show that DTI-MRI is sensitive to inflammation and fibrosis and has the potential to detect early changes of CKD before significant functional decline, demonstrating the advantages of DTI-MRI over traditional measurements.

Funding

• Commercial Support