Recent reports suggest that kidney stone disease prevalence is increasing. Despite significant treatment advances, the inciting factor and sequence of events leading to kidney stone formation remain elusive; however, recent efforts to understand the pathogenesis of nephrolithiasis have led to a delineation of the human surgical anatomy, histopathology, and metabolic factors in a variety of kidney stone formers. This article reviews the fundamental concepts of calculus formation, and the leading theories of stone pathogenesis, focusing on recent data from human papillary and renal cortical biopsies in stone formers that provide evidence for the role of Randall's plaque in kidney stone disease pathogenesis. These data suggest there are individual stone-forming phenotypes with unique surgical anatomy, histology, and metabolic profiles.
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