Animal models for calcium oxalate kidney stone research

Calcium oxalate (CaOx) stones are the most prevalent form of nephrolithiasis and are characterized by a substantial risk of recurrence. Their pathogenesis arises through distinct etiological pathways, including idiopathic metabolic susceptibility, monogenic disorders such as primary hyperoxaluria, enteric hyperoxaluria, and toxicant-associated injury, and is shaped by two primary papillary mechanisms: Randall’s plaque formation and ductal plugging. A central translational limitation is that most experimental systems, particularly chemically induced rodent models, rely on acute hyperoxaluria. These models capture crystal nucleation, aggregation, and deposition but do not adequately recapitulate the decades-long natural history of idiopathic CaOx stone disease in humans or the gradual formation of Randall’s plaques. This review systematically evaluates CaOx stone models in mice, rats, Drosophila, pigs, dogs, and cats, with an emphasis on induction methods, analytical endpoints, strengths, limitations, and applications in mechanistic research, drug discovery, and surgical instrument evaluation. Particular attention is given to plaque-related models such as Abcc6 deficiency, etiologically aligned models of primary and enteric hyperoxaluria, and naturally occurring disease in companion animals. Finally, this review proposes a stepwise framework for selecting CaOx stone animal models according to research objectives, etiological relevances, pathological mechanisms, and translational applications.