The prevalence of kidney stones is increasing and its recurrence rate within the first 5 years is over 50%. No treatments that prevent the occurrence/recurrence of stones have reached the clinic. Here, we show that AIM (also called CD5L) suppresses stone development and improves stone-associated physical damages. The N-terminal domain of AIM associates with calcium oxalate crystals via charge-based interaction to impede the development of stones, whereas the 2nd and C-terminal domains capture the inflammatory DAMPs to promote their phagocytic removal. Accordingly, when stones were induced by glyoxylate in mice, recombinant AIM (rAIM) injection dramatically reduced stone development. Expression of injury molecules and inflammatory cytokines in the kidney and overall renal dysfunction were abrogated by rAIM. Among various negatively charged substances, rAIM was most effective in stone prevention due to its high binding affinity to crystals. Furthermore, only AIM was effective in improving the physical complaints including bodyweight-loss through its DAMPs removal effect. We also found that tubular KIM-1 may remove developed stones. Our results could be the basis for the development of a comprehensive therapy against kidney stone disease.
Communications biology. 2022 Aug 03*** epublish ***
Kyohei Matsuura, Natsumi Maehara, Aika Hirota, Ayaka Eguchi, Keisuke Yasuda, Kaori Taniguchi, Akemi Nishijima, Nobuyuki Matsuhashi, Yoshiyuki Shiga, Rumi Ishii, Yasuhiro Iguchi, Kazunari Tanabe, Satoko Arai, Toru Miyazaki
Laboratory of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan., Department of Gastroenterology, NTT Medical Center Tokyo, Tokyo, 141-8625, Japan., Department of Urology, Robotic Surgical Center, NTT Medical Center Tokyo, Tokyo, 141-8625, Japan., Department of Urology, Tokyo Women's Medical University, Tokyo, 162-8666, Japan., Medical corporation JISEIKAI, Tokyo, 132-0033, Japan., Laboratory of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan. .