Tracking kidney volume in mice with polycystic kidney disease by magnetic resonance imaging

Abstract

Polycystic kidney disease is characterized by the progressive enlargement of kidneys due to expanding fluid-filled cysts with the rate of renal volume increase held to be a marker of disease progression. Magnetic resonance imaging (MRI) is used to monitor changes in renal volume in patients with polycystic kidney disease; however, it has not been effectively used in mice to monitor changes in kidney volume during drug treatment studies. We used a powerful 9.4-T horizontal bore magnetic resonance scanner to track changes in kidney volume in pcy/pcy mice, an ortholog of nephronophthisis type 3. Mice were sequentially scanned from 4 to 30 weeks of age and kidney volumes determined from high-resolution images. Kidney volume and maximal cross-sectional surface area correlated positively with kidney weight and the histologic determination of surface area. The increase in kidney volume was exponential up to 20 weeks of age, after which there was a plateau consistent with the replacement of normal parenchyma by fibrotic tissue. Our study demonstrates that MRI accurately determines the rate of kidney volume increase in mice with polycystic kidney disease and hence may be useful in assessing the effectiveness of therapeutic agents to slow disease progression.

Screening for Kidney Diseases

“…Magnetic resonance imaging has been shown to be a more sensitive biomarker of disease progression than either serum creatinine or estimated GFR. Magnetic resonance imaging is already being used as a surrogate outcome to increases in creatinine in clinical trials (42,43). It is thought that if we can intervene before the rise in serum creatinine, therapies can have a greater chance of success.…”

Noninvasive Monitoring and Evaluation of the Renal Structure and Function in a Mouse Model of Unilateral Ureteral Occlusion Using Microcomputed Tomography

“…9 In addition, Almajdub et al 10 regards mouse kidney phenotyping is as being an important issue, and in vivo imaging allows for longitudinal studies. Therefore, micro-CT appears to be a suitable method for phenotyping the kidney anatomy.…”

“…9,14 Another study compared the efficacy of contrast-enhanced micro-CT and MRI in animal models. The authors concluded that, in addition to the advantages of not exposing the animal to ionizing radiation, MRI provides a more complete assessment.…”

Utilizing magnetization transfer imaging to investigate tissue remodeling in a murine model of autosomal dominant polycystic kidney disease

“…Imaging modalities such as ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI) are used to monitor disease progression (8). Clinical studies utilize total kidney volume (TKV) measured by MRI as an image-based biomarker to follow the progression of ADPKD since larger TKVs have been shown to correlate with worse prognosis in ADPKD in both human (9), and murine studies (10). However, there are challenges with using TKV as a marker of disease progression.…”