Construction of Chronic Kidney Disease Mouse Model Induced by Diets With Different Adenine Content

ABSTRACT Chronic kidney disease (CKD) is projected to become the fifth most prevalent chronic disease globally. Establishing a reliable animal model is essential for advancing prevention and treatment strategies. In this study, we compared CKD mice induced by four adenine‐containing diets: 0.2% or 0.25% adenine in conventional or purified feed. All diets significantly elevated serum urea nitrogen and creatinine levels, causing renal damage, and disrupted gut microbiota and metabolic function. Notably, the group receiving the 0.2% adenine purified diet displayed the most severe renal lesions and uniquely developed hyperphosphatemia and hypercalcemia, which are hallmarks of mineral bone disorder and indicate an increased cardiovascular risk in advanced CKD. Gut microbiota alterations included a reduction in Akkermansia ( p < 0.01), and enriched Lactobacillus ( p < 0.05). Metabolic pathway analysis revealed significant upregulation of phenylalanine, tyrosine, and tryptophan biosynthesis ( p < 0.01) in the 0.2% purified diet group which linked to uremic toxin production. Overall, the 0.2% adenine purified diet induces a comprehensive, reproducible, and clinically relevant CKD model, ideal for studying pathophysiological mechanisms and evaluating therapeutic interventions.