(288a) Elucidating Growth Mechanisms of Calcium Oxalate Dihydrate: Insights into Modifier-Crystal Interactions

Renal calculi, also known as kidney stones, are precipitates of inorganic and organic constituents formed either in the kidneys, urethra, or bladder in the human body. The most common inorganic constituent is calcium oxalate crystals, which account for approximately 80% of all human stones.¹ Calcium oxalate has three solvates: monohydrate – the most prominent; dihydrate – crystallized in the presence of various modifiers; and trihydrate.^1-3 Studies in literature have focused on the most thermodynamically stable form, calcium oxalate monohydrate (COM), to report nucleation and growth under the influence of various modifiers, such as (macro)molecules and salts.^4-6 Relatively few studies have focused on the conditions leading to calcium oxalate dihydrate (COD) formation. In this presentation, we will highlight our studies identifying a library of diverse modifiers using a combination of state-of-the-art techniques for probing crystallization at both macroscopic and microscopic length scales. Our findings reveal a series of modifiers that are capable of tailoring the size and morphology of COD crystals. Many of these modifiers are also effective inhibitors, which was confirmed by in situ atomic force microscopy (AFM) measurements to probe detailed surface nucleation and growth mechanisms in the absence and presence of modifiers. These studies are the first to examine COD surface growth in real time wherein we uncover a mechanism of layer nucleation and spreading that deviate from those observed in COM crystallization. These same methods have been used to assess the kinetics of growth and dissolution where the cooperative effects of organic modifiers and salts are assessed under different conditions (e.g., supersaturation, temperature, etc.). Our collective results have uncovered new insights into COD growth and identified effective routes to suppress crystal formation, which may potentially guide the design of new therapies to combat pathological crystallization.

References:

1. Wesson, J. A.; Ward, M. D., Pathological biomineralization of kidney stones. Elements 2007,3 (6), 415-421.
2. Sterling C, Crystal structure analysis of weddellite, CaC₂O₄(2 + x)H₂O. Acta Crystallographica 1965, 18: 917-921
3. Deganello S; Kampf AR; Moore PB, The crystal structure of calcium oxalate trihydrate: Ca(H₂O)₃(C₂O₄). American Mineralogist 1981, 66: 859-865
4. Alamani, B. G., Rimer, J. D., Molecular modifiers of kidney stones. Curr Opin Nephrol Hy 2017.
5. Olafson, K. N.; Li, R.; Alamani, B. G.; Rimer, J. D., Engineering Crystal Modifiers: Bridging Classical and Nonclassical Crystallization. Chemistry of Materials 2016,28 (23), 8453-8465.
6. Chung, J.; Granja, I.; Taylor, M. G.; Mpourmpakis, G.; Asplin, J. R.; Rimer, J. D., Molecular modifiers reveal a mechanism of pathological crystal growth inhibition. Nature 2016,536 (7617), 446-450.