Influence of additives on calcium oxalate crystallization in solution

Undesired deposition of biominerals results in pathological problems. These include crystallization in urinary tract resulting in kidney stone formation [1], crystallization within the joints causing various forms of arthritis [2], plaque formation on teeth resulting in dental calculus [3], and plaque formation within the vascular system causing atherosclerosis [4]. Urinary stone formation is a common urological disorder affecting millions of people each year [5]. Recurrence of stone formation is also very common [6]. Urinary stones may contain a variety of crystals including calcium oxalate, calcium phosphate, uric acid, struvite, and cystine [7]. Calcium oxalate is the primary inorganic component of kidney stones. Human urine is supersaturated with respect to calcium oxalate; however, kidney stones do not form in healthy humans mainly due to the presence of natural inhibitors. Many factors such as the level of supersaturation (concentrations of Ca²⁺ and C₂O₄ ^2- ions), stone-forming promoters (membranes, defective cells, and proteins), and inhibitors (citrate, urinary proteins, etc.) influence the urinary stone formation process [8]. Urinary stones develop in stone-forming humans possibly due to the presence of natural inhibitors in inadequate amounts or due to local conditions (excess of Ca or Ox, pH, presence of molecules that reduces the ability of inhibitory molecules) that reduce the efficiency of the inhibitors. Crystal nucleation, growth, aggregation, and adhesion of crystals to the renal epithelial cells are important processes that finally lead to the formation of urinary stones. Natural inhibitors can impact one or more of these steps toward stone formation. Urinary inhibitors include citrate, magnesium, pyrophosphate, nephrocalcin (NC), Tamm-Horsfall protein (THP), uropontin, crystal matrix protein (F1 prothrombin fragment), lithostathine, inter-alpha-trypsin inhibitor molecule/uronic acid-rich protein (bikunin), albumin, RNA and DNA fragments, glycosaminoglycans (GAGs), and calgranulin [7].