Adriamycin-induced nephropathy in rats: Functional and cellular effects characterized by MRI

Abstract

Purpose: To assess with magnetic resonance imaging (MRI) adriamycin-induced nephropathy in living rats, an established model for proteinuric renal disease was used. Materials and Methods: Functional 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-β123 (TGF-β1,2,3) antibody, 1D11, started 1 week after adriamycin. Histology was performed at week 6 post-adriamycin. Results: Tracer 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 × 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. Conclusion: MRI provides longitudinal functional and cellular (macrophage infiltration) information that correlates with nephropathy development in adriamycin-challenged rats.