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Query: UMLS:C0392525 (nephrolithiasis)
 2,669 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During about ten years, nephrocalcin was considered the main calcium oxalate crystal growth inhibitor. Today, it appears only a urinary protein inhibitor among other ones such as non polymerized Tamm-Horsfall protein, uropontin or crystal matrix protein (CMP), a protein derived from prothrombin. All these molecules are able to inhibit either crystal growth or aggregation of calcium oxalate in urine. Another protein, named renal lithostathine, was also reported to be a potent inhibitor of secondary nucleation and growth of calcium carbonate crystals. A new urinary inhibitor of calcium oxalate formation was isolated from the urine of healthy subjects using chromatographic procedures. It is a macromolecule with a molecular weight (MW) of approximately 35 kDa as estimated by polyacrylamide gel electrophoresis. Its carbohydrate content represents an average of 8.5% of its MW. Glutamic and aspartic acids represent 24% of total amino acids. This protein is called Uronic-Acid-rich Protein (UAP) because of its uronic acid content. The same protein isolated from the urine of stone formers showed less inhibitory activity than that purified from the urine of healthy subjects. Structural modifications may explain this diminution of its inhibitory activity. This protein was also purified from rat urine using same procedures. Human and rat UAP exhibit similar biochemical characteristics and strongly inhibit calcium oxalate crystallization in vitro. Partial amino acid sequence analysis showed a homology with inter-alpha-trypsin inhibitor (ITI), confirmed by the immunological results on Western blot. Nevertheless, various chemical and enzymic treatments revealed that UAP and ITI are not identical molecules. Consequently, urine contains several macromolecular substances belonging to ITI superfamily which are involved in the inhibition of calcium oxalate crystallization. UAP takes place among the most efficient macromolecular substances known as inhibitors in calcium oxalate nephrolithiasis.
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PMID:[Uronic-acid-rich protein: a new glycoprotein inhibiting the crystallization of calcium oxalate in vitro]. 906 64

Calcific kidney stones in both humans and mildly hyperoxaluric rats are located on renal papillary surfaces and consist of an organic matrix and crystals of calcium oxalate and/or calcium phosphate. The matrix is intimately associated with the crystals and contains substances that can promote as well as inhibit calcification. Osteopontin, Tamm-Horsfall protein, bikunin, and prothrombin fragment 1 have been identified in matrices of both human and rat stones. Hyperoxaluria can provoke calcium oxalate nephrolithiasis in both humans and rats. Kidney-stone-forming rats are hypomagnesuric and hypocitraturic during nephrolithiasis. Human stone formers may have the same disorders. Males of both species are prone to develop calcium oxalate nephrolithiasis, whereas females tend to form calcium phosphate stones. Oxalate metabolism is considered to be almost identical between rats and humans. Thus, there are many similarities between experimental nephrolithiasis induced in rats and human kidney-stone formation, and a rat model of calcium oxalate nephrolithiasis can be used to investigate the mechanisms involved in human kidney stone formation.
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PMID:Animal models of kidney stone formation: an analysis. 928 52

Crystal polymorphism is exhibited by calcium oxalates in nephrolithiasis, and we have proposed that a shift in the preferred crystalline form of calcium oxalate (CaOx) from monohydrate (COM) to dihydrate (COD) induced by urinary macromolecules reduces crystal attachment to epithelial cell surfaces, thus potentially inhibiting a critical step in the genesis of kidney stones. We have tested the validity of this hypothesis by studying both the binding of monohydrate and dihydrate crystals to renal tubule cells and the effect of macromolecular urinary solutes on crystal structure. Renal tubule cells grown in culture bound 50% more CaOx monohydrate than dihydrate crystals of comparable size. The effects of macromolecules on the spontaneous nucleation of CaOx were examined in HEPES-buffered saline solutions containing Ca2+ and C2O4(2-) at physiologic concentrations and supersaturation. Many naturally occurring macromolecules known to be inhibitors of crystallization, specifically osteopontin, nephrocalcin and urinary prothrombin fragment 1, were found to favor the formation of calcium oxalate dihydrate in this in vitro system, while other polymers did not affect CaOx crystal structure. Thus, the natural defense against nephrolithiasis may include impeding crystal attachment by an effect of macromolecular inhibitors on the preferred CaOx crystal structure that forms in urine.
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PMID:Control of calcium oxalate crystal structure and cell adherence by urinary macromolecules. 955 3

In the past two decades an increasing number of nephrolithiasis-related urinary proteins have been identified. This paper focuses on two of them, namely prothrombin fragment 1 and bikunin, members of the prothrombin and inter-alpha-trypsin inhibitor families of proteins, respectively. Besides their role as inhibitors of crystallization, these proteins are also involved in inflammation-mediated tissue repair. This is the basis for the concept that the response of renal tissue to injury might play an important role in the aetiology of kidney stones.
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PMID:Changing concepts in the aetiology of renal stones. 1114 22

Urine contains compounds that modulate the nucleation, growth and aggregation of crystals as well as their attachment to renal epithelial cells. These compounds may function to protect the kidneys against: 1, the possibility of crystallization in tubular fluid and urine, which are generally metastable with respect to calcium salts, 2, crystal retention within the kidneys thereby preventing stone formation and 3, possibly against plaque formation at the nephron basement membrane. Since oxalate is the most common stone type, the effect of various modulators on calcium oxalate (CaOx) crystallization has been examined in greater details. Most of the inhibitory activity resides in macromolecules such as glycoproteins and glycosaminoglycans while nucleation promotion activity is most likely sustained by membrane lipids. Nephrocalcin, Tamm-Horsfall protein, osteopontin, urinary prothrombin fragment 1, and bikunin are the most studied inhibitory proteins while chondroitin sulfate (CS), heparan sulfate (HS) and hyaluronic acid (HA) are the best studied glycosaminoglycans. Crystallization modulating macromolecules discussed here are also prominent in cell injury, inflammation and recovery. Renal epithelial cells on exposure to oxalate and CaOx crystals produce some of the inflammatory molecules such as monocyte chemoattractant protein-1 (MCP-1) with no apparent role in crystal formation. In addition, macrophages surround the CaOx crystals present in the renal interstitium. These observations indicate a close relationship between inflammation and nephrolithiasis.
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PMID:Modulators of urinary stone formation. 1497 59

We have investigated urine protein inhibitors of calcium oxalate crystallization to determine whether variations in these proteins are associated with kidney stone disease and whether protein measurements improve the identification of stone formers compared with conventional risk factors (RF). Using Western blotting, we studied variations in the electrophoretic mobility patterns and relative abundances of crystallization-inhibitory proteins in urine from 50 stone-forming (SF) and 50 non-stone-forming (NS) first-degree relatives of calcium SF patients, matched by gender and age. Standard urine chemistry stone risk measurements were also made. Multivariate discriminant analysis was used to test the association of these proteins with nephrolithiasis. Differences in form and abundance of several urine proteins including inter-alpha-trypsin inhibitor (ITI), prothrombin fragment 1 (PF1), CD59, and calgranulin B (calB) were found to be associated with stone formation. By multivariate discriminant analysis, measurements of forms of PF1, ITI, and calB in men and ITI and CD59 in women, classified 84% of men and 76% of women correctly by stone status. In contrast, standard urine chemistry RF identified only 70% of men correctly and failed to distinguish female SF from NS. Thus a small subset of protein measurements distinguished SF from NS far better than conventional RF in a population of relatives of calcium SF, illustrating the significant association of these proteins with stone disease. Variations in these proteins may serve as markers of stone disease activity or vulnerability to recurrence and may provide new insights into mechanisms of stone formation.
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PMID:Urine protein markers distinguish stone-forming from non-stone-forming relatives of calcium stone formers. 1662 76

Urinary stone disease is an ailment that has afflicted human kind for many centuries. Nephrolithiasis is a significant clinical problem in everyday practice with a subsequent burden for the health system. Nephrolithiasis remains a chronic disease and our fundamental understanding of the pathogenesis of stones as well as their prevention and cure still remains rudimentary. Regardless of the fact that supersaturation of stone-forming salts in urine is essential, abundance of these salts by itself will not always result in stone formation. The pathogenesis of calcium oxalate stone formation is a multistep process and essentially includes nucleation, crystal growth, crystal aggregation, and crystal retention. Various substances in the body have an effect on one or more of the above stone-forming processes, thereby influencing a person's ability to promote or prevent stone formation. Promoters facilitate the stone formation while inhibitors prevent it. Besides low urine volume and low urine pH, high calcium, sodium, oxalate and urate are also known to promote calcium oxalate stone formation. Many inorganic (citrate, magnesium) and organic substances (nephrocalcin, urinary prothrombin fragment-1, osteopontin) are known to inhibit stone formation. This review presents a comprehensive account of the mechanism of renal stone formation and the role of inhibitors/promoters in calcium oxalate crystallisation.
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PMID:Nephrolithiasis: molecular mechanism of renal stone formation and the critical role played by modulators. 2415 93