Exploring the Role of Matrix Proteins from Human Calcium Oxalate Stones in Nephrolithiasis

Abstract

Kidney stone formation is a complex process involving multiple factors. Under physiological conditions urinary supersaturation with calcium oxalate (CaOx) is never high enough to result in homogenous nucleation; a promoter is likely to contribute to the precipitation of this salt. Modulators of urolithiasis are suggested to direct the course of crystallization, although their precise role has not been defined. Kidney stones invariably comprise a combination of inorganic crystals and organic macromolecules consisting principally of proteins. Many proteins occur in stones, but their role in urolithiasis remains unknown. Calculi contain some proteins normally present in urine, in addition to others arising from injury inflicted by the stones themselves. This makes it impossible to discriminate between the proteins that bind to the stone as it grows but play no role in its development and those that may be involved in regulating the formation of stone crystals. Pure promoters of urolithiasis are rare but some substances can act as promoters at particular stages of crystal formation and as inhibitors at other stages, e.g. glycosaminoglycans promote crystal nucleation but inhibit crystal aggregation and growth. Tamm-Horsfall glycoprotein (THP) depending on its stage of aggregation may act as a promoter or an inhibitor of crystal formation. There are several hypotheses regarding kidney stone formation. According to one hypothesis, it is related to intratubular crystal nucleation, growth, and aggregation while other hypothesis explains that the locale of crystal deposition is at a renal interstitium near or at the tip of renal papillae. The increasing number of patients suffering from urolithiasis represents one of the major challenges which nephrologists face worldwide today.