Histological aspects of the “fixed-particle” model of stone formation: animal studies

Abstract

Crystallization by itself is not harmful as long as the crystals are not retained in the kidneys and are allowed to pass freely down the renal tubules to be excreted in the urine. A number of theories have been proposed, and studies performed, to determine the mechanisms involved in crystal retention within the kidneys. It has been suggested that urinary transit through the nephron is too fast for crystals to grow large enough to be retained. Thus free particle mechanism alone cannot lead to stone formation, there must be a mechanism for crystal fixation within the kidneys. Animal model studies suggest that crystal retention is possible through both the free and fixed particle mechanisms. Crystal cell interaction leads to pathological changes which promote crystal attachment to either epithelial cells or their basement membrane. Alternatively, crystals aggregate and produce large enough particles to block the tubules particularly at sites where urinary flow is affected because of changes in the luminal diameter of the tubule. Crystal deposits plugging the openings of the ducts of Bellini may be the result of such a phenomenon. Intra-tubular crystals translocating to renal interstitium may produce osteogenic changes in the epithelial or endothelial cells resulting in the formation of the Randall’s plaques. Thus, fixation appears to be either through the formation of Randall’s plugs, crystal plugs clogging the openings of the ducts of Bellini or sub-epithelial crystal deposits, the Randall’s plaques.

Current insights into the mechanisms and management of infection stones

“…Thus, the binding of ammonium ions to sulfated glycosamino glycans has been suggested to diminish their hydrophilicity, resulting in a potential increase in the amount of crystals, bacteria, and macromolecules that adhere to the urothelium 117 . According to the fixed particle model of stone formation 9,72,118 , which suggests that the attachment of crystals to the epithelial lining is necessary for stone formation, the adherence of crystals to the urothelium would permit sufficient time for these crystals to grow. Thus, the formation of larger aggregates would be highly likely under these conditions 118 .…”

“…According to the fixed particle model of stone formation 9,72,118 , which suggests that the attachment of crystals to the epithelial lining is necessary for stone formation, the adherence of crystals to the urothelium would permit sufficient time for these crystals to grow. Thus, the formation of larger aggregates would be highly likely under these conditions 118 . Bacterial adhesion also seems to be influenced by damage to the glycosaminoglycan layer by enabling bacterial colonization in the urothelium 119 , which might have a role in infection stone formation by providing the necessary conditions to promote biofilm formation ( fig.…”

High frequency and wide range of human kidney papillary crystalline plugs

“…Whether this process allows elimination of large plugs in urine through collecting ducts remains to be confirmed. Interestingly, animal models of kidneys stones and nephrocalcinosis were characterized by calcium phosphate plugs in kidney tubules and crystal translocation to the interstitium, highlighting that calcium phosphate deposits can, in some conditions, cross the epithelium [22,23]. Long-term experimental animal models of intratubular calcium phosphate precipitation could be of help to analyse whether calcium phosphate tubular plugs are able to promote collecting duct deformation and at last their rupture.…”

Inflammation and injury: what role do they play in the development of Randall’s plaques and formation of calcium oxalate kidney stones?

“…Obviously, plug formation is a result of crystal retention within the terminal collecting ducts. Results of animal model and tissue culture studies clearly show that crystals can be retained by either attachment to the epithelial surface or aggregation during excessive supersaturation [33][34][35]. Crystal nucleation, and aggregation can be supported by the membranous products of renal tubular injury [36][37][38].…”