title: Adriamycin-induced nephropathy in rats: functional and cellular effects characterized by MRI.
abstract: OBJECTIVE
  To assess with magnetic resonance imaging (MRI) adriamycin-induced nephropathy in living rats, an established model for proteinuric renal disease was used.
  
  
  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.
  
  
  CONCLUSIONS
  MRI provides longitudinal functional and cellular (macrophage infiltration) information that correlates with nephropathy development in adriamycin-challenged rats.
authors.affiliation: Novartis Institutes for BioMedical Research, Analytical Sciences and Imaging, Basel, Switzerland; University of Basel, Biocenter, Basel, Switzerland.
authors.forename: Christine
authors.initials: C
authors.lastname: Egger
authors.forename: Catherine
authors.initials: C
authors.lastname: Cannet
authors.forename: Christelle
authors.initials: C
authors.lastname: Gérard
authors.forename: Corinne
authors.initials: C
authors.lastname: Debon
authors.forename: Nadine
authors.initials: N
authors.lastname: Stohler
authors.forename: Andrew
authors.initials: A
authors.lastname: Dunbar
authors.forename: Bruno
authors.initials: B
authors.lastname: Tigani
authors.forename: Jianping
authors.initials: J
authors.lastname: Li
authors.forename: Nicolau
authors.initials: N
authors.lastname: Beckmann
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000378:metabolism; D004195:Disease Models, Animal; D004317:Doxorubicin; D005290:Ferric Compounds / Q000378:metabolism; D006571:Heterocyclic Compounds / Q000378:metabolism; D007089:Image Enhancement; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology; D007674:Kidney Diseases / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D009942:Organometallic Compounds / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism
chemical_list: D003287:Contrast Media; D005290:Ferric Compounds; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; C000499:ferric oxide; D004317:Doxorubicin; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate
keywords: adriamycin (doxorubicin); fibrosis; kidney; macrophage; magnetic resonance imaging; regulatory T cells (Treg)