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.