Chronic kidney disease: a rodent model with cardio metabolic risk factors
Embargo Date
2027-09-25
OA Version
Citation
Abstract
Chronic kidney disease is highly prevalent, with comorbidities affecting 1 in 5 individuals in the United States. However, chronic kidney disease rarely occurs in isolation, it is accompanied by several comorbidities, such as, hypertension, diabetes, dyslipidemia, and hypercholesteremia. These comorbidities can further augment the progression of chronic kidney disease. The current animal models examine different etiologies of chronic kidney disease. There is a dearth of models where chronic kidney disease is examined in combination of cardiometabolic risk factors. We set out to generate an animal model of chronic kidney disease with cardiometabolic risk factor characterized by obesity, hyperinsulinemia, hyperglycemia, and insulin resistance. In this study we examined a group of wild type C57BL/6J mice that were randomized into four groups. Mice on Normal diet [normal renal function]; Adenine diet [chronic kidney disease alone]; High fat diet 60% kilocalories from fat [a model of obesity, hyperinsulinemia, and insulin resistance]; high-fat plus adenine diet [model of chronic kidney disease along with other cardiometabolic risk factor]. A longitudinal study of GFR using a dye excretion method was conducted. Kidneys were examined for histological changes. Our results showed that mice on adenine diet had profound loss of GFR and tubular interstitial fibrosis and tubular atrophy. Mice on high fat diet showed 12 to 13% reduction in GFR and 10 to 12% increase in interstitial fibrosis and tubular atrophy on histology. However, mice on high fat plus adenine diets showed a 43% reduction in GFR compared to baseline and with a near threefold increase in interstitial fibrosis and tubular atrophy. In conclusion, this study, for the first time documented that the addition of a high fat diet plus an adenine diet results in a validated model of chronic kidney disease with cardiometabolic risk factors.
Description
2024