Urinary macromolecules and renal lithiasis

Abstract

Summary Intensive investigation into the structure of calcigerous urinary calculi have revealed an inner macrospherular network of concentric fibrous laminations with adherent apatite particles and interdigitating radial striations that surrounds an amorphous matrix containing microspherules and possibly infective organisms. The outer surface encrustation is composed of assorted crystals and laminated microspherules. These constituents are not as organized in other types of urinary stones, though they are present to varying degrees. The connection between structure and pathogenesis of stones may lie with the matrix, the structural base, which is composed mostly of protein but contains some sugar, bound water, calcium and phosphorus. Its antigenic component, matrix substance A, is found abundantly in the urine of stone formers as well as in that of more non-specific renal injuries and infections. Uromucoid, another urinary macromolecule, has not only been shown to be a promotor of crystallization but a structural analogue of matrix as well. Another family of urinary macromolecules, glycosaminoglycans, are repeating disacharides that are present in the urine of normal patients. They are quite ubiquitous and usually found in normal tissues as proteoglycans; that is, groups of glycosaminoglycans are linked to a single protein backbone. While their main function is thought to be structural, providing toughness and flexibility in connective tissues, they also seem to play intrinsic roles in many biological processes such as differentiation, morphogenesis, growth, maturation, aging, normal physiology and pathology. There is laboratory evidence for their action as potent inhibitors of crystal growth and aggregation and possibly nucleation as well. Since most studies so far have not shown any significant difference in the amounts found in the urines of normal and stone forming patients, their clinical significance may very well lie in qualitative differences or the increased presence of other substances in urine (such as sulfate or uric acid) that might enhance their inhibitory powers. Though the etiology of stone formation remains elusive, a deeper understanding of the physical characteristics of the calculus as well as the molecular interactions that contribute to its formation is certain to be highly significant in future clinical practice.