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Kidney Week

Abstract: SA-PO786

Ultrasound and 3D Imaging Characterisation of a Rat Model of Polycystic Kidney Disease

Session Information

Category: Genetic Diseases of the Kidneys

  • 1201 Genetic Diseases of the Kidneys: Cystic

Authors

  • Ougaard, Maria Katarina, Gubra, Hoersholm, Denmark
  • Porsgaard, Trine, Gubra, Hoersholm, Denmark
  • Sembach, Frederikke Emilie, Gubra, Hoersholm, Denmark
  • Thisted, Louise, Gubra, Hoersholm, Denmark
  • Skytte, Jacob Lercke, Gubra, Hoersholm, Denmark
  • Perens, Johanna, Gubra, Hoersholm, Denmark
  • Christensen, Michael, Gubra, Hoersholm, Denmark
Background

Polycystic kidney disease (PKD) is a congenital fibrocystic disorder for which there is no curative treatment. Consequently, PKD is classified as a medical condition with high unmet therapeutic need. Animal models with improved clinical translatability can optimally inform about potential efficacy of novel drug candidates for PKD. The polycystic kidney (PCK) rat is an established genetic model of PKD with natural history and renal histologic abnormalities that resemble the human disease. Gubra has established a PCK rat breeding program to enable fast turnaround time of preclinical drug discovery within PKD. In this study, we have characterised disease progression in the PCK rat to aid in designing future pharmacological intervention studies.

Methods

Male PCK (PCK/CrljCrl-Pkhd1pck/Crl) and control (CRL:CD(SD)) rats were randomised into study groups based on body weight (10 weeks). At the age of 17 and 25 weeks, rats underwent ultrasound assessment of kidney volume, urine collection for quantification of albuminuria, and plasma sampling for urea and creatinine analysis. At termination, kidneys were collected and total kidney volume, cyst number and volume were analysed using quantitative 3D imaging.

Results

Compared to age-matched control rats, PCK rats displayed marked albuminuria at 25 weeks of age. Plasma urea was progressively increased at both 17 and 25 weeks, while plasma creatinine was only increased at week 25. In vivo ultrasound measurements revealed that total kidney volume progressively increased (25 wks.: 4909 mm3) compared to control rats (2174 mm3). 3D light sheet imaging enabled whole-kidney counting of cysts and quantification of cyst volume (control: 10.9 mm3 vs 25 wks.: 413.5 mm3) as well as the total kidney volume that correlated to kidney ultrasound results.

Conclusion

The PCK rat displays hallmarks of PKD, characterized by age-dependent progressive increase in biomarkers of kidney injury, kidney hypertrophy and cyst formation. In vivo ultrasound and ex vivo quantitative whole-kidney 3D light sheet imaging is highly instrumental for detailed assessment of progressive kidney disease in the PCK rat. Accordingly, these imaging modalities are instrumental as key endpoints for assessment of potential therapeutic effects of preclinical drug candidates in the PCK rat model.

Funding

  • Commercial Support – Gubra