Crystal Retention in Renal Stone Disease

Abstract

The mechanisms that are involved in renal stone disease are not entirely clear. In this article, the various concepts that have been proposed during the past century are reviewed briefly and integrated into current insights. Much attention is dedicated to hyaluronan (HA), an extremely large glycosaminoglycan that may play a central role in renal stone disease. The precipitation of poorly soluble calcium salts (crystal formation) in the kidney is the inevitable consequence of producing concentrated urine. HA is a major constituent of the extracellular matrix in the renal medullary interstitium and the pericellular matrix of mitogen/stress-activated renal tubular cells. HA is an excellent crystal-binding molecule because of its size, negative ionic charge, and ability to form hydrated gel-like matrices. Crystal binding to HA leads to crystal retention in the renal tubules (nephrocalcinosis) and to the formation of calcified plaques in the renal interstitium (Randall's plaques). It remains to be determined whether one or both forms of renal crystal retention are involved in the development of kidney stones (nephrolithiasis).

Oxalate in renal stone disease: the terminal metabolite that just won't go away

“…92 The exposure of renal epithelial cells to oxalate causes oxidative damage, mitochondrial damage, activation of second messenger path ways (such as those mediated by p38 MAP kinase and phospholipase A), inflammatory response signaling, changes in the expression of putative modulators of crystallization (such as osteopontin, bikunin and Tamm-Horsfall protein), and changes in the glycocalyx. [93][94][95][96][97][98][99][100][101][102][103][104] The effects of oxalate on renal epithelial cells have been extensively discussed by Jonassen et al 105 Although some of these effects are directly due to oxalate, others are secondary to oxalate induced oxidative damage or inflammatory responses. 96,106 The changes effected by oxalate could promote nephrolithiasis by providing debris for crystal nucleation, making the apical plasma membrane more adhesive to crystals, or altering the availability of crystallizationinhibiting proteins.…”

Elucidation of the Mechanism of Crystal-Cell Interaction Using Fibronectin-Overexpressing Madin-Darby Canine Kidney Cells

“…Verkoelen [15] identified crystal-binding molecules such as hyaluronan, osteopontin, and CD44. The mechanisms of crystal-cell interaction are thought to be very complex, and many processes are unexplored.…”

Hyaluronan and Stone Disease

“…We hypothesized from these results that the risk for crystal retention in the human nephron is increased when tubular cells express hyaluronan at their apical cell membrane [4,8,22]. The next step was to investigate this hypothesis in vivo, looking at crystal retention in cases of renal tubular injury and hyaluronan expression.…”

“…Luminal hyaluronan is found during nephrogenesis and during tubular regeneration in epithelial repair. It is thought to play a key role in (re)establishment of the epithelial barrier integrity and restoration of renal function, but as a negative side-effect it turns a non-crystal binding epithelium into a crystal-binding one due to its crystal binding properties [3,6,8,18,21,22,[32][33][34].…”