Human kidney stones are composed principally of calcium oxalate (CaOx) and included also Tamm-Horsfall protein, albumin,α and γ-globulins, haemoglobin, neutrophil elastase, transferrin, α1-microglobulin, CD59 protein (protectin), superoxide dismutase, α -antitrypsin, osteopontin, nephrocalcin, b2-microglobulin, α1-acid glycoprotein, apolipoprotein A1, retinolbinding,
protein and renal lithostathine, urinary prothrombin fragment (UPTF), and interα –inhibitor.
Of these, an urinary glycoprotein called urinary prothrombin fragment (UPTF), especially urinary prothrombin fragment 1 (UPTF1) is present in quantities exceeding those of any other protein, indicating that it may play a significant role in CaOx.
Infact the other proteins, like some studies confirmed, occurring in stones because included during crystal nucleation or crystals and developing stones can damage the urothelial lining, causing the release of tissue and blood proteins into the urinary tract.
The assumption that UPTF1 is involved in the stone formation, is supported by the observation that UPTF1 is a potent inhibitor of CaOx crystallization, particularly crystal aggregation.
This property, as well as the protein's presence in calcium stones, its specific location within defined regions of the human nephron, where it is present in stone formers' kidneys in greater quantities than in healthy subjects, and most importantly, its synthesis in the human kidney (UPTF1-RNA was isolated from the kidneys and livers of rats) , suggest that the inhibitory effects on CaOx crystallization exhibited by UPTF1 in vitro may also operate during stone pathogenesis in vivo.
But how does UPTF1 influence the stones’ pathogenesis?
Crystal aggregation is largely influenced by the surface properties of crystals. The binding of proteins, like UPTF1, to crystal surfaces results in a more negative electrostatic potential (or zeta potential), which in turn increases the electrostatic repulsive forces between crystals and decreases their tendency to aggregate.
CaOx crystals exhibit a positive character, due to the presence of calcium ions to the crystal surface while renal cells present a negatively charged surface. Induction of a negative charge on the crystal surface by proteins would reduce crystal adhesion to the renal cell surface by way of electrostatic repulsion.
Also genetics factors may contribute to developing stones. Infact it’s known that black population rarely form stones (incidence <1%) compared with the white population (incidence 12-15%).
Some studies demonstrates that UPTF1 of Blacks has a superior inhibitory activity.
It’s the glycosylation of UPTF1 that causes his activity.
Infact black control sample (health) has the protein significantly more sialylated that white health people.
This demonstrates a possible association between low-percentage sialylation and kidney stone disease and provides a potential diagnostic method for a predisposition to kidney stones that could lead to the implementation of a preventative regimen.
The glycosylation can be O-linked or N-linked, but like a protective factor is best a glycosylation O-linked.