On the Composition and Structure of Human Kidney Stone Nano-layers at Atomic Scale

Human kidney stones (nephrolithiasis) are hard crystalline deposits primarily composed of five mineral types: calcium oxalate, calcium phosphate, uric acid, struvite, and cystine. This urological disorder is common globally and can lead to renal failure, affecting 12% of the world population with a recurrence rate of 50-70%. Currently there is no effective treatment to cure and/or prevent formation of kidney stones due to a complex formation processes and the presumed thermodynamic stability of the crystalline product. However, Sivaguru et al. (2018) reported, through geobiological approaches and high-resolution microscopy of Ca-oxalate stones from six Mayo Clinic patients, that extensive and repeated dissolution occurs throughout the growth history of each stone and opened the door to novel strategies targeting in vivo dissolution treatments. To better understand the mechanisms driving kidney stone dissolution and the development of new clinical treatments, we have adopted a geo-materials approach to analyze the structure and composition, at the atomic scale, of human kidney stones. Based on our, as earth scientists, extensive understanding of formation and dissolution of minerals in the geosphere, transformative insights can be gleaned to mineral formation in the human body as well. Our translational approach utilizes Atom Probe Tomography (APT), a material analysis technique offering both 3D imaging and chemical composition measurements at the atomic scale (around 0.1-0.3nm resolution in depth and 0.3-0.5nm laterally) as well as visualization through Transmission Electron Microscopy (TEM), to further characterize the crystalline nature of the material. The combination of these techniques provides a novel data set to further understand the complex and repeated growth and dissolution of human kidney stones and provides a new path for future development of in vivo solutions to address this increasing urological health disorder. Geo-materials approaches developed here can further be used to address a wide variety of other adverse heath affects concerning mineralized components of the human body and highlight the benefits of cross-disciplinary approaches to bio-medical research.