Human kidney stones: a natural record of universal biomineralization

Abstract

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. Data from an emerging field, GeoBioMed, show that human kidney stone formation is controlled by the same fundamental sequence of processes that governs phosphate, carbonate and silicate deposition in other natural and engineered environments on Earth, which are known as universal biomineralization and diagenetic phase transitions. Human kidney stones classified as ‘apatite’, ‘COD’ (calcium oxalate dihydrate), ‘COM’ (calcium oxalate monohydrate), or simply ‘CaOx’ (calcium oxalate) are actually composed of multiple mineralogical components (none is 100% purely one mineral) that comprise the continuum of diagenetic phase transitions from which they formed, which include amorphous calcium phosphate (ACP), hydroxyapatite (HAP), COD and COM. ACP and HAP spherules grow, cluster and coalesce to form euhedral COD crystals with planar concentric zoning and sector zones, indicating disequilibrium precipitation from supersaturated urine. ACP, HAP, COD and COM nanolayering and cross-cutting crystalline relationships (for example, dissolution voids, fracturing and faulting) record a complete stratigraphic record and paragenetic sequence that is analogous to natural and engineered biomineralization and diagenetic phase transition systems, the only difference being time and scale. At least 50% of the total volume of whole and fragmented kidney stones has naturally undergone repeated events of in vivo dissolution and recrystallization. This approach has revealed multiple testing targets for the development of new clinical therapies, which includes growth of kidney stones within GeoBioCell microfluidic testbeds during control of key parameters, such as gradients and fluctuations in urine solution chemistry, changing flow, protein and small-molecule concentrations, and microbiome composition. Data from an emerging field, GeoBioMed, show that human kidney stone formation is controlled by the same fundamental sequence of processes that governs phosphate, carbonate and silicate deposition in other natural and engineered environments on Earth, which are known as universal biomineralization and diagenetic phase transitions. Human kidney stones classified as ‘apatite’, ‘COD’ (calcium oxalate dihydrate), ‘COM’ (calcium oxalate monohydrate), or simply ‘CaOx’ (calcium oxalate) are actually composed of multiple mineralogical components (none is 100% purely one mineral) that comprise the continuum of diagenetic phase transitions from which they formed, which include amorphous calcium phosphate (ACP), hydroxyapatite (HAP), COD and COM. ACP and HAP spherules grow, cluster and coalesce to form euhedral COD crystals with planar concentric zoning and sector zones, indicating disequilibrium precipitation from supersaturated urine. ACP, HAP, COD and COM nanolayering and cross-cutting crystalline relationships (for example, dissolution voids, fracturing and faulting) record a complete stratigraphic record and paragenetic sequence that is analogous to natural and engineered biomineralization and diagenetic phase transition systems, the only difference being time and scale. At least 50% of the total volume of whole and fragmented kidney stones has naturally undergone repeated events of in vivo dissolution and recrystallization. This approach has revealed multiple testing targets for the development of new clinical therapies, which includes growth of kidney stones within GeoBioCell microfluidic testbeds during control of key parameters, such as gradients and fluctuations in urine solution chemistry, changing flow, protein and small-molecule concentrations, and microbiome composition.