Adriamycin-Induced Nephropathy in Rats: Functional and Cellular Effects Characterized by MRI

PurposeTo assess with magnetic resonance imaging (MRI) adriamycin-induced nephropathy in living rats, an established model for proteinuric renal disease was used. Materials and MethodsFunctional information of contrast agent clearance was obtained with dynamic contrast-enhanced (DCE) imaging following intravenous Gd-DOTA administration. Perfusion data were obtained with a bolus tracking technique comprising intravenous injection of superparamagnetic iron oxide (SPIO) nanoparticles. Cellular information was derived from anatomical images acquired 24 hours after SPIO. Treatment with the transforming growth factor-(123) (TGF-(1,2,3)) antibody, 1D11, started 1 week after adriamycin. Histology was performed at week 6 post-adriamycin. ResultsTracer washout rates derived by DCE-MRI decreased by 65.5% with respect to baseline at week 6 post-adriamycin. The impaired kidney function agreed with glomerulopathy, nephropathy and fibrosis revealed histologically (picrosirius collagen staining in adriamycin-treated rats increased by 125.8% [P=0.005] with respect to controls). Perfusion was reduced by 16.1%. Images acquired 24 hours after SPIO presented contrast changes that correlated inversely with the histologically determined iron content (R=-0.74, P=2.6 x 10(-4)). In adriamycin-challenged animals, iron was found in macrophages and in sclerotic tubuli, only in areas where macrophages were present. Treatment with 1D11 did not improve the adriamycin-induced renal injury. ConclusionMRI provides longitudinal functional and cellular (macrophage infiltration) information that correlates with nephropathy development in adriamycin-challenged rats. J. Magn. Reson. Imaging 2014. (c) 2014 Wiley Periodicals, Inc. J. Magn. Reson. Imaging 2015;41:829-840. (c) 2014 Wiley Periodicals, Inc.