Micro-CT imaging and structural analysis of glomeruli in a model of Adriamycin-induced nephropathy

Abstract

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 × 10 μm3) 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: 8,298 ± 221, Adriamycin: 6,781 ± 630 (mean ± SE)] and right kidney (control: 7,317 ± 367, Adriamycin: 5,522 ± 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 to 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 they provide an imaging tool to investigate diverse interventions and therapeutic drugs.

Novel multimodal MRI and MicroCT imaging approach to quantify angiogenesis and 3D vascular architecture of biomaterials

“…However, this did not reveal any disadvantages in the presentation of the vascular architecture by MicroCT measurement. Similar to studies performed in mice and rats, heterogenous perfusion was observed especially in smaller blood vessels, which has been described as one of the major limitations of MicroFil 53–56 . Another limitation is the resolution of the MicroCT scanner.…”

Glomerular Volume and Glomerulosclerosis at Different Depths within the Human Kidney

“…5 In certain animal models, deep glomeruli are larger than superficial glomeruli, 628 and glomeruli of intermediate depth. 9,10 Several human autopsy studies of glomerular volume have also concluded that deep glomeruli are larger, 11213 although one study has found superficial glomeruli to be larger in older adults. 14 Age-related glomerulosclerosis appears to occur predominantly in the superficial cortex.…”

A Stereological Study of the Toxic Effects of Cerium Oxide during Pregnancy on Kidney Tissues in Neonatal NMRI Mice

“…Increased glomeruli volume, as representative of the renal and functional units of the kidney, can compensate for lost glomeruli function, adapt to new conditions, and remove toxins from the body [55,56]. Glomeruli undergo hyperfiltration to control the conditions and maintain filtration, resulting in an increase in glomerular volume [57].…”