Micro-CT imaging and structural analysis of glomeruli in a model of Adriamycin-induced nephropathy.
Authors of this article are:
Xie L Koukos G Barck K Foreman O Lee WP Brendza R Eastham-Anderson J McKenzie BS Peterson A Carano RAD.
A summary of the article is shown below:
Glomeruli number and size are important for determining the pathogenesis of glomerular disease, chronic kidney disease, and hypertension. Moreover, renal injury can occur in specific cortical layers and alter glomerular spatial distribution. In this study, we present a comprehensive structural analysis of glomeruli in a model of Adriamycin (Doxorubicin) nephropathy. Glomeruli are imaged (micro-CT at 10×10×10μm3) in kidney specimens from C57Bl/6 mouse cohorts: control treated with saline (n=9) and Adriamycin treated with 20 mg/kg Adriamycin (n=7). Several indices were examined including glomerular number, glomerular volume, glomerular volume heterogeneity, and spatial density at each glomerulus and in each cortical layer (superficial, midcortical, and juxtamedullary). In the Adriamycin treated animals, glomerular number decreased significantly in the left kidney (control: 8298±221, Adriamycin: 6781±630 [mean±standard error]) and right kidney (control: 7317±367, Adriamycin: 5522±508), and glomerular volume heterogeneity increased significantly in the left kidney (control: 0.642±0.015, Adriamycin: 0.786±0.018) and right kidney (control: 0.739±0.016, Adriamycin: 0.937±0.023). Glomerular spatial density was not affected. Glomerular volume heterogeneity increased significantly in the superficial and midcortical layers of the Adriamycin cohort. Adriamycin did not affect glomerular volume or density metrics in the juxtamedullary region, suggesting a compensatory mechanism of juxtamedullary glomeruli for injury in the outer cortical layers. Left/right asymmetry was observed in kidney size and various glomeruli metrics. The methods presented here can be used to evaluate renal disease models with subtle changes in glomerular endowment locally or across the entire kidney, and provides an imaging tool to investigate diverse interventions and therapeutic drugs.
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