Mimicking the initial development of calcium urolithiasis by screening calcium oxalate and calcium phosphate phases in various urinelike solutions, time points, and pH values at 37 °c

Crystalluria may not always lead to urolithiasis. To understand how crystals of <4 μm size were retained in the beginning for the formation of a clinically symptomatic stone, we had devised a screening experiment of calcium oxalate and phosphate phases systematically in various urinelike solutions at t = 30 s and 30 min and pH = 6, 7, and 8 at 37 °C. Five key lessons were learned: (1) A simple direct association between hypercalciuria and calcium oxalate dihydrate stones in the literature might have only told part of the story until the conditions that produce calcium oxalate dihydrate in vivo are better understood. (2) Magnesium ions could minimize the formation of calcium oxalate dihydrate crystals and induce and stabilize the formation of dicalcium phosphate dihydrate or brushite. (3) A new role of citrate in inhibiting the formation of dicalcium phosphate dihydrate was discovered. (4) The fast-growing amorphous calcium phosphate due to a slight pH imbalance and variation was thought to serve as a "glue" initially to randomly consolidate preformed, platelike 4-10 μm sized calcium oxalate monohydrate and dicalcium phosphate dihydrate crystallites. This initial development of aggregation would become the kernel of the urinary stone. (5) The physiological importance of the calcium phosphate phase rather than calcium oxalate deserves more attention, since dicalcium phosphate dihydrate and amorphous calcium phosphate could easily grow into large clusters of about 50 μm within a short period of time.