Session: MP05: Stone Disease: Basic Research & Pathophysiology
MP05-07: Validating the theory of phase transition from calcium oxalate dihydrate to monohydrate in the stone formation: the first artificial in vivo experiment
Introduction: We have previously reported that the phase transition phenomenon of calcium oxalate (CaOx) makes urinary stones harder. Knowing phase transition velocity helps estimate the change of the patient's stone hardness over time. It affects the decision-making of the fragmentation treatment methods. However, the mechanism of the phase transition has not been clarified. Therefore, we stimulated the phase transition of CaOx dihydrate (COD) stone to CaOx monohydrate (COM), and observed the time course of the internal and surface structure. Methods: A urinary stone mainly composed of COD, in which the phase transition has not progressed much, was stored in a vial containing CaOx supersaturated solution at 37oC with gentle shaking. We picked up the stone from the solution every week and observed the phase transition process from COD to COM. X-ray micro-CT and scanning electron microscopy were introduced. After completing the phase transition observation, a thin section of the stone was prepared. Then, the phase identification was performed in more detail using polarizing microscopy and Raman microscopy. Results: The dissolution of the COD crystal surface and nucleation of COM crystals co-occurred. The inside of the COD stone underwent a phase transition to COM. After the transition, we found typical mosaic and concentric structures of COM (Figure 1). The extent of the transition from COD to COM strongly depended on the area. An area where crystal defects, cracks, and crystal boundaries exist, transited fast (~10 µm/h); a few millimeter size COD crystals almost turned into COM structures in only two weeks. The transition ratio was faster than that in the human body. Conclusions: We have succeeded in the world's first artificial urinary stone phase transition experiment. Once the phase transition starts, rapid progress possibly occurs. Further, transformation velocity strongly depends on COD crystal structure and aggregation state. Our observation showed experimental phase transition of a natural urinary stone is faster than that in the human body, and indicated a potential mechanism enabled to slow down the phase transition of crystals in vivo, which could be useful to prevent stone formation. SOURCE OF Funding: JSPS KAKENHI Grant Numbers (JP19K22965, JP20K21658, JP22H00302, JP22H01971)
