#5842 ULTRASOUND AND 3D IMAGING CHARACTERISATION OF A RAT MODEL OF POLYCYSTIC KIDNEY DISEASE

Abstract Background and Aims Polycystic kidney disease (PKD) is a congenital fibrocystic disorder where cysts are primarily forming within the kidneys causing enlargement, loss of function resulting in chronic for which there no curative treatment. Consequently, PKD classified as medical condition with high unmet therapeutic need. Animal models improved clinical translatability can optimally inform about potential efficacy novel drug candidates PKD. The polycystic (PCK) rat an established genetic model natural history renal histologic abnormalities that resemble human disease. Gubra has PCK breeding program to enable fast turnaround time preclinical discovery studies In this study, we have characterised progression aid designing future pharmacological intervention studies. Method Male (PCK/CrljCrl-Pkhd1pck/Crl) control (CRL:CD(SD)) rats (Charles River) were randomised into groups based on body weight at age 10 weeks. At 17 25 weeks, underwent ultrasound assessment volume, urine collection quantification albuminuria, plasma sampling analysis urea creatinine levels. termination, whole harvested total cyst number volume analysed using quantitative 3D light sheet imaging. Results Compared age-matched rats, displayed marked albuminuria was significantly increased week age. Whereas progressively both points, 25. Ultrasound measurements revealed progressive compared rats. Light imaging enabled whole-kidney counting wells closely correlated results. Conclusion displays histological hallmarks PKD, characterized by age-dependent increases biomarkers injury, hypertrophy formation. vivo ex highly instrumental detailed rat. histopathological markers may serve key endpoints effects translational