Effects of Human Urine on Aggregation of Calcium Oxalate Crystals

Springmann, Kurt E.; Drach, George W.; Gottung, Beth Ellen.; Randolph, Alan D.

doi:10.1016/s0022-5347(17)45520-0

Cited by 21 publications

(4 citation statements)

References 16 publications

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“…For the COM system we have therefore developed a physico-chemical model that gives direct insight into the mechawe may conclude that in a typical urine, with a ӷ 1 (22), it is the oxalate concentration that determines the rate of nism by which crystals aggregate during precipitation from solution; further work, with different systems, is required to aggregation.…”

Section: Discussionmentioning

confidence: 99%

Aggregation During Precipitation from Solution. A Pore Diffusion–Reaction Model for Calcium Oxalate Monohydrate

Hounslow

Bramley

Paterson

1998

Journal of Colloid and Interface Science

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Section: Discussionmentioning

confidence: 99%

Aggregation During Precipitation from Solution. A Pore Diffusion–Reaction Model for Calcium Oxalate Monohydrate

Hounslow

Bramley

Paterson

1998

Journal of Colloid and Interface Science

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“…In the case of kidney stones, interactions between urinary constituents and CaOx crystals may influence one or more critical processes in stone pathogenesis, including crystal nucleation, growth, aggregation, and attachment of crystals and/or aggregates to epithelial surfaces of the kidney [30] . A variety of urinary constituents have emerged as possible inhibitors of crystal aggregation and cell attachment, particularly anionic proteins and glycosaminoglycans [31–34] . Yet urinary macromolecules also are reported to promote COM aggregation and/or attachment to epithelial cells in some studies [35–37] .…”

Section: 0 Introductionmentioning

confidence: 99%

The role of macromolecules in the formation of kidney stones

et al. 2016

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The formation of crystal aggregates, one of the critical processes in kidney stone pathogenesis, involves interactions between crystals (predominantly calcium oxalate monohydrate, COM) and urinary constituents (e.g. proteins), which serve as an adhesive “glue” between crystals in stones. To develop a better understanding of the protein-crystal interactions that lead to crystal aggregation, we have measured the effect of model proteins on bulk COM crystal properties as well as their adsorption on crystal surfaces using three synthetic polyanions: poly(aspartic acid) (polyD), poly(glutamic acid) (polyE), and poly(acrylic acid) (polyAA). These anionic macromolecules reduced the amount of COM crystal aggregation in bulk solution to an extent similar to that observed for mixture of proteins from normal urine, with little difference between the polymers. In contrast, the polymers exhibited differences in measures of COM crystal growth. Polycations such as poly(arginine) (polyR) and poly(lysine) (polyK) reduced aggregation weakly and exerted negligible effects on crystal growth. All polyions were found to associate with COM crystal surfaces, as evidenced by changes in the zeta potential of COM crystals in electrophoretic mobility measurements. On the other hand, COM aggregation and possibly growth can be promoted by many binary mixtures of polycations and polyanions, which appeared to be mediated by polymer aggregate formation rather than loss of crystal charge stabilization. Similarly, crystal aggregation promotion behavior can be driven by forming aggregates of weakly charged polyanions, like Tamm-Horsfall Protein, suggesting that polymer (protein) aggregation may play a critical role in stone formation. Sensitivity of polyanion–COM crystal surface interactions to the chemical composition of polymer side groups were demonstrated by large differences in crystal aggregation behavior between polyD and polyE, which correlated with atomic force microscopy (AFM) measurements of growth inhibition on various COM surfaces and chemical force microscopy (CFM) measurements of unbinding forces between COM crystal surfaces and AFM tips decorated with either carboxylate or amidinium moieties (mimicking polyanion and polyR side chains, respectively). The lack of strong interaction for polyE at the COM (100) surface compared to polyD appeared to be the critical difference. Finally, the simultaneous presence of polyanions and polycations appeared to alter the ability of polycations to mediate unbinding forces in CFM and promote crystal growth. In summary, polyanions strongly associated with COM surfaces and influenced crystallization, while polycations did not, though important differences were observed based on the physicochemical properties of polyanions. Observations suggest that COM aggregation with both polyanion–polycation mixtures and weakly charged polyanions is promoted by polymer aggregate formation, which plays a critical role in bridging crystal surfaces.

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“…It also has been suggested that COM mineralization may occur on Randall's plaques, which are subepithelial hydroxyapatite deposits (8). However, certain urinary molecules are thought by others to suppress crystal aggregation and cell attachment, presumably because of adsorption on COM crystal faces (9)(10)(11)(12)(13)(14). Unfortunately, little is known of the actual strength of adhesion between calcium oxalate surfaces and functional groups on small molecules or on side chains of urinary proteins.…”

mentioning

confidence: 99%

Adhesion at calcium oxalate crystal surfaces and the effect of urinary constituents

Sheng

Jung

Wesson

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

190

160

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Kidney stones, aggregates of microcrystals, most commonly contain calcium oxalate monohydrate (COM) as the primary constituent. The aggregation of COM microcrystals and their attachment to epithelial cells are thought to involve adhesion at COM crystal surfaces, mediated by anionic molecules or urinary macromolecules. Identification of the most important functional group-crystal face adhesive combinations is crucial to understanding the stability of COM aggregates and the strength of their attachments to epithelial cell surfaces under flow in the renal tubules of the kidney. Here, we describe direct measurements of adhesion forces, by atomic force microscopy, between various functional groups and select faces of COM crystals immersed in aqueous media. Tip-immobilized carboxylate and amidinium groups displayed the largest adhesion forces, and the adhesive strength of the COM crystal faces decreased in the order (100) > (121 ) > (010), demonstrating that adhesion is sensitive to the structure and composition of crystal faces. The influence of citrate and certain urinary proteins on adhesion was examined, and it was curious that osteopontin, a suspected regulator of stone formation, increased the adhesion force between a carboxylate tip and the (100) crystal face. This behavior was unique among the various combinations of additives and COM crystal faces examined here. Collectively, the force measurements demonstrate that adhesion of functional groups and binding of soluble additives, including urinary macromolecules, to COM crystal surfaces are highly specific in nature, suggesting a path toward a better understanding of kidney stone disease and the eventual design of therapeutic agents.

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Effects of Human Urine on Aggregation of Calcium Oxalate Crystals

Cited by 21 publications

References 16 publications

Aggregation During Precipitation from Solution. A Pore Diffusion–Reaction Model for Calcium Oxalate Monohydrate

Aggregation During Precipitation from Solution. A Pore Diffusion–Reaction Model for Calcium Oxalate Monohydrate

The role of macromolecules in the formation of kidney stones

Adhesion at calcium oxalate crystal surfaces and the effect of urinary constituents

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