Calcium Human Kidney Stones Naturally Undergo 50% by Volume In Vivo Dissolution during Repeated Events of Diagenetic Alteration

In search of new strategies to prevent, cure and alleviate human kidney stone pathogenesis, recent studies have shown that calcium stones form as a result of repeating natural events of in vivo crystallization, dissolution, recrystallization, fracturing, faulting and microbiome interactions. Basic conceptual and technological approaches from geology, biology and medicine (GeoBioMed) combined with super-resolution autofluorescence microscopy (SRAF) and x-ray microcomputed tomography (micro-CT) have revealed the spatial and temporal history of kidney stone growth (paragenetic sequence). In specific, SRAF excites organic matter entombed within stone crystals and enables the identification and chronological reconstruction of stone formation. These SRAF images indicate that stone recrystallization occurs as multi-scale bulk fabric destructive dissolution that forms irregular voids and crystal molds, later cement precipitation that fills these voids, and Ångstrom-scale mimetic replacement. Importantly, quantification of SRAF and micro-CT images reveal that on average more than 50% of the total volume of calcium stones have undergone repeated naturally occurring in vivo dissolution and recrystallization. This petrography has also identified that 10-100's nm-diameter calcium phosphate and hydroxyapatite spherules coalesce and undergo diagenetic phase transitions to form concentrically well-formed planar (euhedral) and sector zoned calcium oxalate dihydrate (COD) crystals under disequilibrium conditions. Measurements of nanolayered stratigraphy indicates that stone growth rates are lower than those observed in other natural and engineered environments of biomineralization. These analyses have also shown that the frequency of nanolayering in kidney stones is orders-of-magnitude higher than in these other natural environments. Kidney stones are therefore dynamic bioreactors that experience a variety of growth rates and layering frequencies throughout their formational history. These results lay the groundwork for future in vitro and in vivo experimentation to identify previously unexplored targets for clinical therapies, as well better understand a wide variety other forms of biomineralization within the human body.