The precipitation of struvite (MgNH₄PO₄ · 6H₂O), described in Eq. 5.2, requires dissolved ions of magnesium (Mg²⁺), ammonium (NH₄ ⁺) and phosphate (PO₄ ³⁻). Sterile urine contains dissolved Mg²⁺ and PO₄ ³⁻, and sufficient concentrations of NH₄ ⁺ can be produced by bacterial ureolysis (according to Eq. 5.1). For precipitation to occur, the ion activity product (IAP) must be greater than the ion activity product at equilibrium in a solution with struvite (K_sp). The activity of a species is an effective concentration, which takes into account interactions with other species. Thus, in urine where other ions are present, they will interact with each other and change the “effective concentration” of neighboring ions. Because activity is based on a ratio comparing concentration to the pure species concentration, it is dimensionless by convention. In very dilute solutions, activity is well-approximated by concentration. If the IAP is greater than the K_sp, the saturation index (Eq. 5.3) is positive and the solution is called supersaturated. For struvite at body temperature, the K_sp value is approximately 10⁻¹³ [13]. Supersaturation implies that precipitation is possible, but we must consider that slow rates of precipitation or molecules that inhibit precipitation (e.g., proteins or polysaccharides that either block surfaces or sequester ions from solution) can allow a solution to remain supersaturated on practical time scales without precipitation. In other words, supersaturation is necessary for precipitation, but does not guarantee that it will occur.

The mechanism of struvite stone formation starts with nucleation and proceeds via layer-by-layer crystal growth along with the aggregation of crystals. The precise mechanisms of nucleation and growth are controlled by the saturation index, impurities, and surface structures. For a detailed description of crystal growth and nucleation, the interested reader is referred to De Yoreo and Vekilov [14]. Conceptually, it is important to keep in mind that, very likely, all nucleation in the urinary tract occurs on pre-existing surfaces (i.e., heterogeneous nucleation) rather than in solution (i.e., homogeneous nucleation). In other words, nearly all crystals will be associated with surfaces, but these surfaces could be from suspended particles in the bulk fluid (e.g., bacteria, proteins, dead human cells, etc.), and not only the surface of the ureter, catheter, etc.

Biofilms can promote the aggregation of small crystals to form larger stones. For this reason, infection stones are known to grow exceptionally fast compared to metabolic stones [15]. Furthermore, the shape and properties of struvite stones are influenced by the organic molecules that are incorporated within the stones, such as polysaccharides, mucoproteins, and glycosaminoglycans [16]. Treatment methods aimed at breaking up or dissolving infection stones must therefore consider the biomolecules integrated within the stones.

Mineral precipitation and biofilm formation are governed by micro- and nano-scale processes that are difficult to observe in vivo. Until recently, our knowledge of stone formation and treatment has relied primarily on clinical observations such as treatment efficacy and patient history. But in order to understand the underlying processes, clinical-based hypotheses must be tested in controlled experiments. Laboratory (in vitro) systems and computer (in silico) simulations offer advantages for studying stone formation. Noninvasive clinical observations are generally limited to urine analysis and ultrasound, MRI or CT imaging which do not have the spatial and temporal resolution required to study microbe-induced stone formation in detail. Furthermore, ethical issues prevent many types of controlled in vivo experiments (e.g., varying pH, the addition of non-clinically-approved compounds or the use of destructive imaging techniques).