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Query: UMLS:C0020500 (hyperoxaluria)
 912 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anomalies in the erythrocyte transport of anions and cations have been described in idiopathic calcium oxalate nephrolithiasis and seem to play a pathogenetic role in this disease. In consideration of the hypothesis that the complex array of ion flux cell abnormalities is an epiphenomenon of an anomaly in the composition of cell membranes, this study investigated cell-membrane lipid composition. In idiopathic calcium oxalate renal stone formers, in which ion transport abnormalities were present, and in healthy control subjects, plasma and erythrocyte membrane lipid composition, the erythrocyte oxalate exchange, and Na/K/2Cl cotransport activity were evaluated. Furthermore, in stone formers, the effect of a 30-day fish-oil diet supplementation on plasma lipids, erythrocyte oxalate exchange, oxaluria, and calciuria was investigated. The effect of archidonic acid released by phospholipase A2 on anion-carrier phosphorylation and activity in erythrocytes was evaluated as well. Patients had a lower content of linoleic and higher concentration of archidonic acids in both plasma and erythrocyte membrane phospholipids, and an increased archidonic/linoleic acid ratio. The archidonic acid level correlated with the erythrocyte oxalate exchange and sodium cotransport activity. Fish-oil supplementation lowered calcium and oxalate urine excretion, and normalized the erythrocyte oxalate exchange. Phospholipase A2 increased the erythrocyte anion-carrier protein phosphorylation and the oxalate exchange. This study shows that idiopathic calcium nephrolithiasis in the patient group reported here is characterized by a systemic defect in phospholipid archidonic acid levels that might provide an answer to the link between genetic background, dietary habits, and renal lithiasis.
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PMID:Anomalous phospholipid n-6 polyunsaturated fatty acid composition in idiopathic calcium nephrolithiasis. 872 96

Exposure to oxalate, a constituent of the most common form of kidney stones, generates toxic responses in renal epithelial cells, including altered membrane surface properties and cellular lipids, changes in gene expression, disruption of mitochondrial function, formation of reactive oxygen species and decreased cell viability. Oxalate exposure activates phospholipase A2 (PLA2), which increases two lipid signaling molecules, arachidonic acid and lysophosphatidylcholine (Lyso-PC). PLA2 inhibition blocks, whereas exogenous Lyso-PC or arachidonic acid reproduce many of the effects of oxalate on mitochondrial function, gene expression and cell viability, suggesting that PLA2 activation plays a role in mediating oxalate toxicity. Oxalate exposure also elicits potentially adaptive or protective changes that increase expression of proteins that may prevent crystal formation or attachment. Additional adaptive responses may facilitate removal and replacement of dead or damaged cells. The presence of different inflammatory cells and molecules in the kidneys of rats with hyperoxaluria and in stone patients suggests that inflammatory responses play roles in stone disease. Renal epithelial cells can synthesize a variety of cytokines, chemoattractants and other molecules with the potential to interface with inflammatory cells; moreover, oxalate exposure increases the synthesis of these molecules. The present studies demonstrate that oxalate exposure upregulates cyclooxygenase-2, which catalyzes the rate-limiting step in the synthesis of prostanoids, compounds derived from arachidonic acid that can modify crystal binding and may also influence inflammation. In addition, renal cell oxalate exposure promotes rapid degradation of IkappaBalpha, an endogenous inhibitor of the NF-kappaB transcription factor. A similar response is observed following renal cell exposure to lipopolysaccharide (LPS), a bacterial cell wall component that activates toll-like receptor 4 (TLR4). While TLRs are primarily associated with immune cells, they are also found on many other cell types, including renal epithelial cells, suggesting that TLR signaling could directly impact renal function. Prior exposure of renal epithelial cells to oxalate in vitro produces endotoxin tolerance, i.e. a loss of responsiveness to LPS and conversely, prior exposure to LPS elicits a similar heterologous desensitization to oxalate. Renal cell desensitization to oxalate stimulation may have profound effects on the outcome of renal stone disease by impairing protective responses.
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PMID:Oxalate toxicity in renal cells. 1628 83