SP37
CHARACTERISATION OF RENAL FIBROSIS THROUGH MAGNETIC
RESONANCE IMAGING USING AN ELASTIN SPECIFIC CONTRAST AGENT
Saha S1, Newbury L1, Phinikaridou A2, Botnar R2, Hendry B1, Sharpe C1
1- Renal Sciences, King’s College London
2- Imaging Sciences, King’s College London
INTRODUCTION
Tubulointerstitial fibrosis is the histological finding which best correlates with chronic kidney
disease (CKD). CKD is currently diagnosed by raised serum creatinine concentrations.
Undetected fibrosis can occur before serum creatinine becomes raised making early detection
impossible without an invasive renal biopsy. The development of a longitudinal and noninvasive method to evaluate fibrosis would identify those at risk and would allow early
interventions aimed at reducing the degree of fibrosis.
A new MRI technique using an elastin-specific magnetic resonance contrast agent (ESMA) has
demonstrated that the degree of atherosclerotic plaque burden through it’s up regulated elastin
expression can be quantified using ESMA in mice.
We aim to demonstrate that elastin is up regulated in the unilateral ureteric obstruction (UUO)
fibrosis model and then demonstrate that ESMA can provide a non-invasive assessment of renal
fibrosis in rodents with UUO.
METHOD
4 Male Wistar rats underwent UUO through ligation. 16 days post obstruction, each rat
underwent MRI scanning using a 3T scanner. 2 rats received the widely available Gadolinium
(DTPA) intravenously (0.2mmol/kg) which acted as a non-specific control and had MRI scans
performed pre-contrast and at 1 hour and 24 hours post contrast. The remaining 2 rats received
the Gadolinium–ESMA intravenously at the same dose and had MRI scans at the same time
points. Each series of scans had T1 mapping performed and subsequent image analysis provided
the relaxation value (R1) to ascertain the degree of binding of ESMA to elastin.
UUO & sham-operated kidney sections were stained with Miller picric acid to determine the
presence of elastin. Western blot looking for Tropoelastin was also performed.
RESULTS
Both Miller picric acid staining and western blot analysis for Tropoelastin confirmed the
marked up regulated presence of elastin in the UUO model of kidney fibrosis.
The MRI analysis of the ESMA and DTPA scans showed a 2-fold difference in their R1 values
obtained from the cortex of the obstructed kidneys at the 1-hour time point. Furthermore,
analysis of the fall in the R1 values after 24 hours in the obstructed kidneys, when residual
binding to ESMA might affect the R1 value, showed a 30% difference between the ESMA and
Gadolinium DTPA.
CONCLUSION
Elastin deposition is up regulated in renal fibrosis. The MRI study has shown a difference in R1
values between the ESMA injected animals compared to those receiving DTPA at both the 1hour post contrast time point but also at 24 hours. This suggests that the ESMA is able to
differentiate itself from the non-specific DTPA contrast agent and provides support for further
study in greater numbers and in other models to confirm that renal fibrosis can be determined
through MRI scanning with the ESMA contrast agent.