Crystal retention in renal stone disease: a crucial role for the glycosaminoglycan hyaluronan?

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).