[Current concepts on the pathogenesis of urinary stones]

The process of kidney stone formation is complex and still not completely understood. Supersaturation and crystallization are the main drivers for the etiopathogenesis of uric acid, xanthine and cystine stones but this physicochemical concept fails to adequately explain the formation of calcium-based nephrolithiasis, which represents the majority of kidney stones. Contemporary concepts of the pathogenesis of calcium-based nephrolithiasis focus on a nidus-associated stone formation of calcium-based nephrolithiasis on Randall's plaques or on plugs of Bellini's duct. Randall's plaques originate from the interaction of interstitial calcium supersaturation in the renal papilla, vascular and interstitial inflammatory processes and mineral deposits of calcifying nanoparticles on the basal membrane of the thin ascending branch of the loop of Henle; however, plugs of Bellini's duct are assumed to be caused by mineral deposits on the wall of the collecting ducts. Aggregation and overgrowth are influenced by the interaction of matrix proteins with calcium supersaturated urine, by an imbalance between promoters and inhibitors of stone formation in the calyceal urine. Current research has elucidated many factors contributing to stone formation by revealing novel insights into the physiology of nephron and papilla, by analyzing vascular, inflammatory and calcifying processes in the renal medulla, by examining the proteome, the microbiome, promoters and inhibitors of stone formation in the urine and by conducting the first genome-wide association studies; however, more future research is mandatory to fill the gap of knowledge and hopefully, to obtain novel prophylactic, therapeutic and metaphylactic tools beyond the current state of knowledge.