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

Egger, Christine and Cannet, Catherine and Gerard Sachot, Christelle and Debon, Corinne and Stohler, Nadine and Meyer, Angelika and Rohner, Daisy and Dunbar, Andrew W. and Tigani, Bruno and Li, Jianping and Beckmann, Nicolau (2015) Adriamycin-induced nephropathy in rats: Functional and cellular effects characterized by MRI. Journal of Magnetic Resonance Imaging, 41 (3). pp. 829-840. ISSN 1522-2586

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.

Item Type: Article
Keywords: Adriamycin (doxorubicin) Fibrosis Kidney Macrophage Magnetic resonance imaging Regulatory T cells (Treg)
Date Deposited: 25 Oct 2017 00:45
Last Modified: 25 Jan 2019 00:46
URI: https://oak.novartis.com/id/eprint/9771

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