Kidney stone matrix proteins: Role in stone formation

Abstract

Stone formation is induced by an increased level of urine crystallization promoters and reduced levels of its inhibitors. Crystallization inhibitors include citrate, magnesium, zinc, and organic compounds such as glycosaminoglycans. In the urine, there are various proteins, such as uromodulin (Tamm-Horsfall protein), calgranulin, osteopontin, bikunin, and nephrocalcin, that are present in the stone matrix. The presence of several carboxyl groups in these macromolecules reduces calcium oxalate monohydrate crystal adhesion to the urinary epithelium and could potentially protect against lithiasis. Proteins are the most abundant component of kidney stone matrix, and their presence may reflect the process of stone formation. Many recent studies have explored the proteomics of urinary stones. Among the stone matrix proteins, the most frequently identified were uromodulin, S100 proteins (calgranulins A and B), osteopontin, and several other proteins typically engaged in inflammation and immune response. The normal level and structure of these macromolecules may constitute protection against calcium salt formation. Paradoxically, most of them may act as both promoters and inhibitors depending on circumstances. Many of these proteins have other functions in modulating oxidative stress, immune function, and inflammation that could also influence stone formation. Yet, the role of these kidney stone matrix proteins needs to be established through more studies comparing urinary stone proteomics between stone formers and non-stone formers.

Keywords: Calgranulin; Kidney stone; Matrix proteins; Proteomics; Stone formation; Uromodulin.