Autosomal dominant polycystic kidney disease (ADPKD) shows heterogeneous disease onset and progression in patients, demanding preclinical models that capture the full natural history of the condition. Presented at the 8th CKD Drug Development Summit in Boston (2026), this poster from our nephrology team presents comprehensive longitudinal characterization of an adult-onset ADPKD mouse model induced by Pkd1 knockout at postnatal day 40 (P40). 

With an in-life phase of approximately 28 weeks, this model enables non-invasive monitoring of progressive kidney enlargement by ultrasound, renal dysfunction via blood urea nitrogen (BUN), and cystic disease progression by histopathology. Compared with established P10 and P18 induction models, the P40 model provides a substantially extended therapeutic window, making it well suited for disease prevention studies, biomarker identification, and long-duration efficacy assessment of novel ADPKD therapeutics.

Autosomal dominant polycystic kidney disease (ADPKD) shows heterogeneous disease onset and progression in patients, necessitating preclinical models capturing this variability. While early postnatal Pkd1 inactivation models (PND10 and PND18) are widely used for efficacy studies due to rapid phenotype induction, adult-onset models with a more progressive disease course provide a complementary platform for biomarker identification and extended therapeutic evaluation before the onset of significant kidney function decline. 

Pkd1 knockout was induced at PND40 (P40) in the Cre;Pkd1lox,lox mouse model. PKD progression was assessed at baseline (PND49), early (PND84), intermediate (PND119), late (PND146), and terminal (PND180) timepoints via kidney volume by ultrasound, blood urea nitrogen (BUN), and H&E histopathology. 

Progressive renal enlargement was confirmed by longitudinal ultrasound, with strong correlation between kidney volume and kidney weight/body weight (R²=0.8551). BUN was consistently elevated in tamoxifen-induced Pkd1 cKO mice versus uninduced littermate controls, with BUN correlating with kidney weight/body weight (R²=0.7603). Histological analysis demonstrated progressive cyst formation from baseline through terminal stages, with proximal tubule involvement predominating in the P40 model. 

The P40 ADPKD mouse model provides an extended in vivo phase of approximately 28 weeks, suitable for disease prevention studies, biomarker identification, longitudinal efficacy assessment, and evaluation of adverse effects. The InnoSer ADPKD platform — spanning P10, P18, and P40 induction variants — models the heterogeneous ADPKD patient population across different disease stages.