The Zucker Diabetic Fatty Rat as a Model for Vascular Changes in Diabetic Kidney Disease: Characterising...

Background/Objectives: Diabetic kidney disease (DKD) is a significant concern for global healthcare, particularly in individuals with diabetes. The Zucker rat strain is a commonly used model of type 2 diabetes, despite awareness that this animal can develop hydronephrosis. In this study, we present novel imaging data evaluating the accuracy of this animal model in replicating the vascular aspects of human DKD while examining the impact of hydronephrosis on its validity as a disease model. Methods: This study reused data from a population of male Zucker Diabetic Fatty (ZDF; n = 22) rats and Zucker Lean (ZL) rats (n = 22) aged 12 to approximately 40 weeks. Vascular casting was performed to enable visualisation of the renal vasculature. Anatomical regional volumes and vascular density data were obtained from μCT scans using image thresholding and manual analysis. The effects of hydronephrosis were evaluated using renal functional parameters and histological examination. Results: A significantly lower cortical vascular density, as well as lower total renal vascular density, was seen in ZDF rats compared to ZL rats, independent of age. We identified that hydronephrosis affected 92% of ZDF rats and 69% of ZL rats. Hydronephrosis cavity size was significantly correlated with the degree of hyperglycaemia and rate of diuresis but had no other detected impact on renal function, vascularity, or tissue histological architecture. Conclusions: These findings support using the Zucker rat strain as a model for vascular changes in DKD. Despite identifying severe hydronephrosis in this population, it had minimal quantifiable impact on renal function or diabetes modelling.