A hypothesis of calcium stone formation: an interpretation of stone research during the past decades

An interpretation of previous and recent observation on calcium salt crystallization and calcium stone formation provide the basis for formulation of a hypothetical series of events leading to calcium oxalate (CaOx) stone formation in the urinary tract. The various steps comprise a primary precipitation of calcium phosphate (CaP) at high nephron levels, establishment of large intratubular and/or interstitial (sub-epithelial) aggregates of CaP. These crystal masses subsequently might be dissolved during periods with low urine pH. On the denuded surface of subepithelial or intratubularly trapped CaP, release of calcium ions can result in very high ion-activity products of CaOx, particularly during simultaneous periods with peaks of CaOx supersaturation. Crystals of CaOx may result from nucleation in the macromolecular environment surrounding the apatite crystal phase. In the presence of low pH, low citrate and high ion-strength of urine, formation of large CaOx crystal masses can be accomplished by self-aggregation of Tamm-Horsfall mucoprotein. Following dislodgment of the initially fixed CaOx stone embryo, the further development into to clinically relevant stone is accomplished by CaOx crystal growth and CaOx crystal aggregation of the retained stone material. The latter process is modified by a number of inhibitors and promoters present in urine. The retention of the stone is a consequence of anatomical as well as hydrodynamic factors.