Gavage versus dietary adenine administration is more effective for the female mouse model of chronic kidney disease

The high incidence of chronic kidney disease (CKD) requires the refinement of animal models for its study. Adenine-induced CKD model has emerged as a non-invasive model that can replicate human CKD. Historically, most studies employ adenine through the diet. However, the lack of details regarding the preparation makes reproducibility difficult. This study aimed to identify the best approach to induce CKD through adenine administration in C-57BL/6J female mice: oral gavage or via their standard pelleted diet. After 4 weeks of both routes of adenine administration, plasma creatinine and urea levels were increased, while both parameters in urine were decreased, the pellet group showing increased plasma creatinine levels compared with the gavage group and urea levels showing the opposite trend. Both adenine administration routes demonstrated histological changes in the kidney tissues, particularly tubular dilation and necrotic debris. Gavage adenine-induced CKD showed greater tubular dilation compared to the pelleted administration. Adenine treatment increased water intake and urine output, with no differences between administration routes. Finally, a significant decrease in body weight loss and food intake was observed in the pelleted administration compared to the oral gavage administration. Our results suggest that the oral gavage model is less aggressive, with a more linear progression in kidney lesioning, thus providing an even greater opportunity for veterinary oversight and intervention when needed. Therefore, administering adenine by oral gavage is more suitable to induce a stable and reproducible model of CKD in C-57BL/6J female mice.