Development of a new prophylactic drug for kidney stones focused on hypoxic stress

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K22981
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0906:Surgery related to the biological and sensory functions and related fields
• Research Institution: Nagoya City University
• Principal Investigator: Kawase Kengo 名古屋市立大学, 医薬学総合研究院(医学), 臨床研究医 (90881772)
• Project Period (FY): 2020-09-11 – 2023-03-31
• Keywords: 尿路結石 / 低酸素 / PHD阻害剤

Outline of Final Research Achievements

In renal tubular cells (M1), calcium oxalate crystals were added to the control and Roxadustat-treated groups, and the amount of crystal adhesion was significantly decreased by Roxadustat treatment, and the expression of Ccl2 and Supp1 was reduced.
Next, the control group and M1 mice with knockdown of Hif1α were treated with Roxadustat, and the same study was conducted.
Finally, we administered roxadustat to a mouse model of stone formation, and found that stone formation was suppressed and the expression of Ccl2, Supp1, Tnfα, and Emr1 was decreased in the roxadustat-treated group.

Free Research Field

尿路結石症

Academic Significance and Societal Importance of the Research Achievements

今回の研究では主にPHD阻害剤であるRoxadustatが腎結石形成に与える影響を検討した。Roxadustatは結石形成の初期段階であるシュウ酸カルシウム結晶の付着による炎症と、それに伴うマクロファージの浸潤を抑制することで結石形成が減少していることが確認できた。Roxadustatはすでに腎性貧血を対象に臨床応用されていることから、人体への投与の安全性は確立されている。そのため、今後結石患者に対しての臨床応用が期待できる。