Pathogenesis of calcium oxalate urinary stone disease: species comparison of humans, dogs, and cats

Idiopathic calcium oxalate nephrolithiasis is a highly recurrent disease that is increasing in prevalence. Decades of research have not identified effective methods to consistently prevent the formation of nephroliths or induce medical dissolution. Idiopathic calcium oxalate nephroliths form in association with renal papillary subepithelial calcium phosphate deposits called Randall’s plaques (RPs). Rodent models are commonly used to experimentally induce calcium oxalate crystal and stone formation, but a rodent model that conclusively forms RPs has not been identified. Both dogs and cats form calcium oxalate uroliths that can be recurrent, but the etiopathologic mechanisms of stone formation, especially renal pathologic findings, are a relatively unexploited area of study. A large animal model that shares a similar environment to humans, along with a shorter lifespan and thus shorter time to recurrence, might provide an excellent means to study preventative and therapeutic measures, along with enhancing the concepts of the one health initiative. This review article summarizes and compares important known features of idiopathic calcium oxalate stone disease in humans, dogs, and cats, and emphasizes important knowledge gaps and areas for future study in the quest to discover a naturally occurring animal model of idiopathic calcium oxalate stone disease.