Human kidney stones: a natural record of universal biomineralization

GeoBioMed — a new transdisciplinary approach that integrates the fields of geology, biology and medicine — reveals that kidney stones composed of calcium-rich minerals precipitate from a continuum of repeated events of crystallization, dissolution and recrystallization that result from the same fundamental natural processes that have governed billions of years of biomineralization on Earth. This contextual change in our understanding of renal stone formation opens fundamentally new avenues of human kidney stone investigation that include analyses of crystalline structure and stratigraphy, diagenetic phase transitions, and paragenetic sequences across broad length scales from hundreds of nanometres to centimetres (five Powers of 10). This paradigm shift has also enabled the development of a new kidney stone classification scheme according to thermodynamic energetics and crystalline architecture. Evidence suggests that ≥50% of the total volume of individual stones have undergone repeated in vivo dissolution and recrystallization. Amorphous calcium phosphate and hydroxyapatite spherules coalesce to form planar concentric zoning and sector zones that indicate disequilibrium precipitation. In addition, calcium oxalate dihydrate and calcium oxalate monohydrate crystal aggregates exhibit high-frequency organic-matter-rich and mineral-rich nanolayering that is orders of magnitude higher than layering observed in analogous coral reef, Roman aqueduct, cave, deep subsurface and hot-spring deposits. This higher frequency nanolayering represents the unique microenvironment of the kidney in which potent crystallization promoters and inhibitors are working in opposition. These GeoBioMed insights identify previously unexplored strategies for development and testing of new clinical therapies for the prevention and treatment of kidney stones. The formation of kidney stones is governed by the same principles as other stone systems. These ‘diagenetic phase transitions’ that create human kidney stones reflect the environment within the kidney during stone formation and could, therefore, improve understanding of urolithiasis and enable future treatment development. In this wide-ranging and unique Review, the authors explain how kidney stone formation parallels that of other stone systems such as stony corals, travertine in Roman aqueducts, stalactites and agates, and describe how the new field of GeoBioMed could be harnessed to improve patient care.