Characterization of renal fibrosis in rats with chronic kidney disease by in vivo tomoelastography

NMR Biomed. 2023 Nov;36(11):e5003. doi: 10.1002/nbm.5003. Epub 2023 Jul 16.

Abstract

Chronic kidney disease (CKD) is characterized by structural changes, such as tubular atrophy, renal fibrosis, and glomerulosclerosis, all of which affect the viscoelastic properties of biological tissues. However, detection of renal viscoelasticity changes because diagnostic markers by in vivo elastography lack histopathological validation through animal models. Therefore, we investigated in vivo multiparametric magnetic resonance imaging (mp-MRI), including multifrequency magnetic resonance elastography-based tomoelastography, in the kidneys of 10 rats with adenine-induced CKD and eight healthy controls. Kidney volume (in mm3 ), water diffusivity (apparent diffusion coefficient [ADC] in mm2 /s), shear wave speed (SWS; in m/s; related to stiffness), and wave penetration rate (PR; in m/s; related to inverse viscosity) were quantified by mp-MRI and correlated with histopathologically determined renal fibrosis (collagen area fraction [CAF]; in %). Kidney volume (40% ± 29%, p = 0.009), SWS (11% ± 12%, p = 0.016), and PR (20% ± 15%, p = 0.004) were significantly increased in CKD, which was accompanied by ADC (-24% ± 27%, p = 0.02). SWS, PR, and ADC were correlated with CAF with R = 0.63, 0.75, and -0.5 (all p < 0.05), respectively. In the CKD rats, histopathology showed tubule dilation due to adenine crystal deposition. Collectively, our results suggest that collagen accumulation during CKD progression transforms soft-compliant renal tissue into a more rigid-solid state with reduced water mobility. We hypothesized that tubule dilation-a specific feature of our model-might lead to higher intraluminal pressure, which could also contribute to elevated renal stiffness. Tomoelastography is a promising tool for noninvasively assessing disease progression, detecting biomechanical properties that are sensitive to different pathologic features of CKD.

Keywords: biophysical properties; chronic kidney disease; multifrequency MR elastography; renal fibrosis; viscoelasticity.

MeSH terms

  • Adenine
  • Animals
  • Collagen
  • Elasticity Imaging Techniques* / methods
  • Fibrosis
  • Kidney / diagnostic imaging
  • Kidney / pathology
  • Rats
  • Renal Insufficiency, Chronic* / diagnostic imaging
  • Renal Insufficiency, Chronic* / pathology
  • Water

Substances

  • Water
  • Adenine
  • Collagen