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Abstract: FR-PO746

Kidney and Cystic Volume Imaging for Disease Presentation and Progression in the Cat ADPKD Large Animal Model

Session Information

Category: Genetic Diseases of the Kidneys

  • 1001 Genetic Diseases of the Kidneys: Cystic

Authors

  • Lyons, Leslie A., College of Veterinary Medicine, University of Missouri, Columbia, Missouri, United States
  • Shumway, Kate, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, United States
  • Matheson, Jodi Suzanne, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, United States
  • Edwards, Marie E., Mayo Clinic, Rochester, Minnesota, United States
  • Kline, Timothy L., Mayo Clinic, Rochester, Minnesota, United States
  • Yu, Yoshihiko, Nippon Veterinary and Life Science University, Musashinoshi, Tokyo, Japan
Background

Persian cats have a variant in polycystin – 1 (PKD1) causing autosomal dominant polycystic kidney disease (ADPKD). The variant (c.10063C>A) causes a protein truncation (p.C3284X) and is the only known variant in cats. As in humans, the variant is lethal in utero when in the homozygous state. Affected cats can have a wide range of progression and severity of disease. However, cats are an overlooked biomedical model and have not been used to test therapeutics and diets that may support human clinical trials. To reinvigorate the cat as a large animal model for ADPKD, the efficacy of imaging modalities in cats was demonstrated and supported robust estimates of kidney and fractional cystic volumes.

Methods

Three imaging modalities, ultrasound, computed tomography (CT), and magnetic resonance imaging, were used to examine variation in disease presentation and disease progression in 11 felines with ADPKD. Imaging was compared to well-known biomarkers for chronic kidney disease and glomerular filtration rate. Total kidney volume, total cystic volume, and fractional cystic volume (FCV) were determined for the first time in ADPKD cats. A few cats had follow-up examinations to evaluate progression.

Results

The size of the cat’s kidney supported the determination of FCV measurements. CT was a rapid and efficient modality for evaluating therapeutic effects that cause alterations in kidney volume and/or FCV. Biomarkers, including glomerular filtration rate and creatinine, were not good indicators of kidney function. The wide variation in cystic presentation suggested genetic modifiers likely influence disease progression in cats. All imaging modalities had comparable resolutions to those acquired for humans, and software used for kidney and cystic volume estimates in humans can be used in cats.

Conclusion

Veterinary-based imaging protocols are as robust and efficient for evaluating ADPKD in cats as in humans. Cats can be identified as fast and slow progressors, thus, could assist with modifier discovery. Software to measure kidney and cystic volume in human ADPKD kidney studies is applicable and efficient in cats. The longer life span, similar genetics, disease presentation and progression, and the large kidney size suggest cats as an efficient biomedical model for evaluation of ADPKD therapeutics.

Funding

  • NIDDK Support