Role of renal epithelial cells in the initiation of calcium oxalate stones

SR Khan - Nephron Experimental Nephrology, 2004 - karger.com
SR Khan
Nephron Experimental Nephrology, 2004karger.com
Normal urinary environment is inhibitory to crystallization. Occasional crystals are
internalized by the renal epithelial cells and sequestered to lysosomes or externalized into
the interstitium to be handled by the inflammatory cells. Elevated levels of oxalate and
calcium oxalate crystals, however, provoke renal cells to increase the synthesis of
osteopontin, bikunin, heparan sulfate proteoglycan, monocyte chemoattractant protein-1,
and prostaglandin E 2, which are known mediators of the inflammatory processes and …
Abstract
Normal urinary environment is inhibitory to crystallization. Occasional crystals are internalized by the renal epithelial cells and sequestered to lysosomes or externalized into the interstitium to be handled by the inflammatory cells. Elevated levels of oxalate and calcium oxalate crystals, however, provoke renal cells to increase the synthesis of osteopontin, bikunin, heparan sulfate proteoglycan, monocyte chemoattractant protein-1, and prostaglandin E 2, which are known mediators of the inflammatory processes and extracellular matrix production. Osteopontin and bikunin are also modulators of crystallization. Exposed renal epithelial cells are often injured and go through apoptosis and/or necrosis initiating a cascade of events leading to further crystallization, crystal retention and development of stone nidi. Reactive oxygen species are produced during the interactions between the oxalate/crystals and renal cells and are responsible for the various cellular responses. Calcium oxalate crystal deposition in the rat kidneys also activates the renin-angiotensin system. Both oxalate and calcium oxalate crystals selectively activate p38 mitogen-activated protein kinase in the exposed tubular cells. Extracellular environment changes from one that inhibits crystal nucleation, growth, aggregation and retention to that, which promotes these processes.
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