The kidneys of autosomal dominant polycystic kidney disease (ADPKD) patients progressively enlarge due to the formation and expansion of fluid-filled cysts. However, currently there is no available therapy for ADPKD patients that targets the growth of cysts, representing a potential target for therapeutic intervention. Well-designed preclinical studies are the key to accelerating the development of safe and efficacious ADPKD treatment.  

Therefore, in addition to translational, longitudinal readouts such as kidney volume and glomerular filtration rate (GFR; click here for a review of GFR applied in preclinical research), experts at InnoSer strongly recommend the inclusion of end-point assessments of renal health such as histopathology when evaluating the efficacy and safety of your candidate compounds.  

Histopathological evaluation of isolated kidneys allows you to evaluate your candidate compound’s effect on cyst growth. At InnoSer, this is evaluated by measuring the cystic index, which shows how much percentage of the kidney is occupied by fluid-filled cysts (Figure 1).  

InnoSer offers a uniquely engineered inducible, kidney-specific Cre(lox,lox)–Pkd1 knock-out mouse model that faithfully mimics the pathophysiology of the human ADPKD disease (click here for a review of this model). In line, our nephrology study director, Laura Blockken, has recently co-authored a paper, whereby the authors have evaluated a selective allosteric AMPK activator in our ADPKD model (Dagorn et al., 2023). In this study, Dagorn and colleagues report that the test compound improved cystic index in the ADPKD mouse model, which was correlated to measures of cell proliferation, fibrosis, and to a lesser degree with macrophage infiltration.

FIGURE 1. Cystic index enables the end-stage efficacy assessment of your test compound on renal health. (A) Cystic index in the P10 model is significantly lower in the Everolimus and test compound A groups compared to the vehicle control group (mean ± SEM; one-way ANOVA). (B) Cystic Index in the P18 model is significantly lower in the Tolvaptan and test compound B groups compared to the vehicle control group (mean ± SEM; one-way ANOVA). Read more about the difference between the P10 and P18 models here.