Animal models for studying calcium oxalate kidney stones

Abstract： Calcium oxalate (CaOx) stones represent the predominant type of kidney stones with high recurrence rate. Its pathogenesis involves multiple etiological pathways (idiopathic metabolic risk, monogenic or primary hyperoxaluria, enteric hyperoxaluria, and toxic exposure), accompanied by two primary papillary mechanisms (Randall's plaques and Randall's plugs). The practical challenge lies in the fact that most experimental models, particularly chemically induced rodent models, rely on acute hyperoxaluria. These models can only reproduce the crystallization process but fail to simulate the natural disease course spanning decades in human idiopathic calcium oxalate stone formation or Randall's plaque development. This paper systematically compares CaOx stone models in mice, rats, drosophila, pigs, dogs, and cats, summarizing their induction methods, detection metrics, advantages and disadvantages, as well as typical applications in mechanism research, drug discovery, and surgical instrument evaluation. It focuses on plaque-related models such as Abcc6 deficiency, clinically relevant etiological models like primary and intestinal hyperoxaluria, and naturally occurring companion animal models. Additionally, this paper proposes for the first time a stepwise selection system for CaOx stone animal models. Keywords: animal model, kidney stone, calcium oxalate, gene knockout, Randall's plaques