Mager R, Neisius A
Klinik und Poliklinik für Urologie und Kinderurologie, Universitätsmedizin Mainz, Langenbeckstr. 1, 55131, Mainz, Deutschland.
Abteilung für Urologie und Kinderurologie, Krankenhaus der Barmherzigen Brüder Trier, Nordallee 1, 54292, Trier, Deutschland.
Urologe A. 2019 Nov;58(11):1272-1280. doi: 10.1007/s00120-019-1017-z.
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.
肾结石形成的过程很复杂，目前仍未完全了解。过饱和和结晶是尿酸、黄嘌呤和胱氨酸结石发病机制的主要驱动因素，但这种物理化学概念无法充分解释以钙为基础的肾结石的形成，而以钙为基础的肾结石占肾结石的大多数。当代关于以钙为基础的肾结石发病机制的概念集中在兰德尔斑或肾乳头管栓子上与病灶相关的以钙为基础的肾结石形成。兰德尔斑起源于肾乳头间质钙过饱和、血管和间质炎症过程以及亨氏袢细升支基底膜上钙化纳米颗粒的矿物质沉积之间的相互作用；然而，肾乳头管栓子被认为是由集合管壁上的矿物质沉积引起的。聚集和过度生长受基质蛋白与钙过饱和尿液的相互作用、肾盂尿液中结石形成促进剂和抑制剂之间的失衡影响。目前的研究通过揭示对肾单位和肾乳头生理学的新见解、分析肾髓质中的血管、炎症和钙化过程、检查蛋白质组、微生物组、尿液中结石形成的促进剂和抑制剂以及进行首次全基因组关联研究，阐明了许多促成结石形成的因素；然而，未来还需要更多研究来填补知识空白，并有望获得超越当前知识水平的新型预防、治疗和预防后处理工具。
