You have accessJournal of UrologyCME1 May 2022MP05-03 HYPOXIA-INDUCIBLE PROLYL HYDROXYLASE INHIBITOR (ROXADUSTAT) SUPPRESSES KIDNEY STONE FORMATION Kengo Kawase, Shuzo Hamamoto, Tatsuya Hattori, Ryosuke Chaya, Tomoki Okada, Yutaro Tanaka, Takeru Sugino, Rei Unnno, Kazumi Taguchi, Ryosuke Ando, Atsushi Okada, Takahiro Yasui, and Takahiro Yasui Kengo KawaseKengo Kawase More articles by this author , Shuzo HamamotoShuzo Hamamoto More articles by this author , Tatsuya HattoriTatsuya Hattori More articles by this author , Ryosuke ChayaRyosuke Chaya More articles by this author , Tomoki OkadaTomoki Okada More articles by this author , Yutaro TanakaYutaro Tanaka More articles by this author , Takeru SuginoTakeru Sugino More articles by this author , Rei UnnnoRei Unnno More articles by this author , Kazumi TaguchiKazumi Taguchi More articles by this author , Ryosuke AndoRyosuke Ando More articles by this author , Atsushi OkadaAtsushi Okada More articles by this author , Takahiro YasuiTakahiro Yasui More articles by this author , and Takahiro YasuiTakahiro Yasui More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002522.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: In the process of creating a mouse model of kidney stone formation, we discovered that calcium oxalate stones form at the medullary border of the kidney. The anatomy of the medullary border of the kidney is more prone to hypoxia than the other parts of the kidney. In this study, we investigated the effect of a hypoxia-inducible prolyl hydroxylase inhibitor (Roxadustat), which promotes a hypoxic response, on kidney stone formation. METHODS: In vitro: Mouse renal tubular cells were exposed to Roxadustat (0, 25, and 50 μmol/L) for 6 h. Thereafter, calcium oxalate crystals(20 μg/cm2) were added. Inflammation and oxidative stress were determined by quantitative PCR using Ccl2, TNF, Il6, Spp1, and Sod1. Additionally, the extent of crystal adhesion was examined. Next, a negative control group and a group in which siRNA was used to knock down Hif1α was then created and Roxadustat was administered to both groups and the same parameters were studied.In vivo: A PBS-treated group and a Roxadustat-treated group (5 mg, 10 mg/kg/day) were administered to C57BL/6J mice, and 80 mg/kg of glyoxylic acid was administered for 6 days. Stone formation was measured by polarized light microscopy, and Ccl2, Il6, Tnf, Sod1, and Spp1 were examined by PCR. In addition, macrophage infiltration was evaluated by immunostaining for F4/80, a macrophage surface antigen, and PCR for Emr1. RESULTS: In vitro, Ccl2 and Spp1 were significantly suppressed by Roxadustat, and crystal adhesion was decreased as well. In contrast, knockdown of Hif1α increased Ccl2 and Spp1 and significantly increased crystal adhesion. In vivo, Roxadustat significantly suppressed stone formation by inhibiting Ccl2 and Spp1. Additionally, the macrophages infiltration was significantly inhibited. CONCLUSIONS: Roxadustat not only exerted anti-inflammatory effects via HIF1α in renal tubular epithelial cells, but also inhibited the formation of kidney stones by suppressing macrophage infiltration into the kidney. Source of Funding: none © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e68 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kengo Kawase More articles by this author Shuzo Hamamoto More articles by this author Tatsuya Hattori More articles by this author Ryosuke Chaya More articles by this author Tomoki Okada More articles by this author Yutaro Tanaka More articles by this author Takeru Sugino More articles by this author Rei Unnno More articles by this author Kazumi Taguchi More articles by this author Ryosuke Ando More articles by this author Atsushi Okada More articles by this author Takahiro Yasui More articles by this author Takahiro Yasui More articles by this author Expand All Advertisement PDF DownloadLoading ...