Calcium oxalate kidney stones, the most prevalent type of kidney stones, undergo a multi-step process of crystal nucleation, growth, aggregation, and secondary transition. The secondary transition has been rather overlooked, and thus, the effects on the disease and the underlying mechanism remain unclear. Here, we show, by periodic micro-CT images of human kidney stones in an ex vivo incubation experiment, that the growth of porous aggregates of calcium oxalate dihydrate (COD) crystals triggers the hardening of the kidney stones that causes difficulty in lithotripsy of kidney stone disease in the secondary transition. This hardening was caused by the internal nucleation and growth of precise calcium oxalate monohydrate (COM) crystals from isolated urine in which the calcium oxalate concentrations decreased by the growth of COD in closed grain boundaries of COD aggregate kidney stones. Reducing the calcium oxalate concentrations in urine is regarded as a typical approach for avoiding the recurrence. However, our results revealed that the decrease of the concentrations in closed microenvironments conversely promotes the transition of the COD aggregates into hard COM aggregates. We anticipate that the suppression of the secondary transition has the potential to manage the deterioration of kidney stone disease.
Urolithiasis. 2024 Apr 02*** epublish ***
Uta Michibata, Mihoko Maruyama, Yutaro Tanaka, Masashi Yoshimura, Hiroshi Y Yoshikawa, Kazufumi Takano, Yoshihiro Furukawa, Koichi Momma, Rie Tajiri, Kazumi Taguchi, Shuzo Hamamoto, Atsushi Okada, Kenjiro Kohri, Takahiro Yasui, Shigeyoshi Usami, Masayuki Imanishi, Yusuke Mori
Graduate School of Engineering, Osaka University, 2-1, Yamadaoka, Suita, 565-0871, Japan., Graduate School of Engineering, Osaka University, 2-1, Yamadaoka, Suita, 565-0871, Japan. ., Institute of Laser Engineering, Osaka University, 2-6, Yamadaoka, Suita City, 565-0871, Osaka, Japan., Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, 1-5, Hangi-cho, Shimogamo, Sakyo-ku, Kyoto, 606-8522, Japan., Department of Earth Science, Tohoku University, 6-3 Aza-Aoba, Aramaki, Aoba-ku, Sendai, 980-8578, Japan., National Museum of Nature and Science, 4-1-1 Amakubo, Tsukuba, 305-0005, Japan., Tajiri Thin Section Laboratory, 3-1-11 Sannose, Higashiosaka, 577-0849, Osaka, Japan., Department of Nephro-urology, Graduate School of Medical Sciences, Nagoya City University, 1-Kawasumi, Mizuho- cho, Mizuho-Ku, Nagoya, 467-8601, Japan.