Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020500 (hyperoxaluria)
 912 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Inter-alpha-inhibitor and other bikunin-containing proteins are synthesized in relatively large quantities by the liver. These proteins function as Kunitz-type serine protease inhibitors and appear capable of inhibiting calcium oxalate (CaOx) crystallization in vitro. Preliminary studies have shown that renal tubular epithelial cells synthesize bikunin in response to CaOx challenge. To examine this response in vivo, a sensitive reverse transcription-quantitative competitive template-PCR was developed to detect and quantify poly(A)+ -tailed bikunin mRNA expression in kidney tissue from normal rats and rats developing CaOx nephrolithiasis after challenge with ethylene glycol. Bikunin mRNA expression in rat liver tissue was assessed as a positive control. The expression of bikunin mRNA in liver did not differ significantly between normal control rats and experimental rats with induced hyperoxaluria and renal CaOx crystallization. In contrast, there were significant temporal increases in the levels of bikunin mRNA expression in rat kidneys during CaOx nephrolithiasis after challenge with ethylene glycol. Urinary excretion of bikunin-containing proteins seemed to increase concomitantly. These findings indicate an association between the induction of hyperoxaluria/CaOx nephrolithiasis and the expression of the bikunin gene in rat kidneys.
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PMID:Temporal changes in mRNA expression for bikunin in the kidneys of rats during calcium oxalate nephrolithiasis. 1023 84

Nephrolithiasis is a result of formation and retention of crystals within the kidneys. The driving force behind crystal formation is urinary supersaturation with respect to the stone-forming salts, which means that crystals form when the concentrations of participating ions are higher than the thermodynamic solubility for that salt. Levels of supersaturation are kept low and under control by proper functioning of a variety of cells including those that line the renal tubules. It is our hypothesis that crystal deposition, i.e., formation and retention in the kidneys, is a result of impaired cellular function, which may be intrinsic and inherent or triggered by external stimuli and challenges. Cellular impairment or dysfunction affects the supersaturation, by influencing the excretion of participating ions such as calcium, oxalate and citrate and causing hypercalciuria, hyperoxaluria or hypocitraturia. The production and excretion of macromolecular promoters and inhibitors of crystallization is also dependent upon proper functioning of the renal epithelial cells. Insufficient or ineffective crystallization modulators such as osteopontin, Tamm-Horsfall protein, bikunin, etc. are most likely produced by the impaired cells.
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PMID:Genetic basis of renal cellular dysfunction and the formation of kidney stones. 1951 3

Experimental animal model studies suggest that calcium oxalate (CaOx) crystal deposition in the kidneys is associated with the development of oxidative stress, epithelial injury and inflammation. There is increased production of inflammatory molecules including osteopontin (OPN), monocyte chemoattractant protein-1 (MCP-1) and various subunits of inter-alpha-inhibitor such as bikunin. What does the increased production of such molecules suggest? Is it a cause or consequence of crystal deposition? We hypothesized that over-expression and increased production of MCP-1 is a result of the interaction between renal epithelial cells and CaOx crystals after their deposition in the renal tubules. We induced hyperoxaluria in MCP-1 null as well as wild type mice and examined pathological changes in their kidneys and urine. Both wild type and MCP-1 null male mice became hyperoxaluric and demonstrated CaOx crystalluria. Neither of them developed crystal deposits in their kidneys. Both showed some morphological changes in their renal proximal tubules. Significant pathological changes such as cell death and increased urinary excretion of LDH were not seen. Results suggest that at least in mice (1) Increase in oxalate and decrease in citrate excretion can lead to CaOx crystalluria but not CaOx nephrolithiasis; (2) MCP-1 does not play a role in crystal retention within the kidneys; (3) Expression of OPN and MCP-1 is not increased in the kidneys in the absence of crystal deposition; (4) Crystal deposition is necessary for significant pathological changes and movement of monocytes and macrophages into the interstitium.
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PMID:Experimentally induced hyperoxaluria in MCP-1 null mice. 2116 47