Elucidation of the pathology of mitochondrial injury during urinary calculi formation and development of prevention.

• Project/Area Number: 15K10627
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Nagoya City University
• Principal Investigator: YASUI TAKAHIRO 名古屋市立大学, 大学院医学研究科, 教授 (40326153)
• Co-Investigator(Kenkyū-buntansha): 田口 和己 名古屋市立大学, 医学(系)研究科(研究院), 研究員 (00595184) ; 郡 健二郎 名古屋市立大学, その他部局等, 学長 (30122047) ; 安藤 亮介 名古屋市立大学, 医学(系)研究科(研究院), その他 (30381867) ; 戸澤 啓一 名古屋市立大学, 大学院医学研究科, 教授 (40264733) ; 岡田 淳志 名古屋市立大学, 大学院医学研究科, 講師 (70444966) ; 濱本 周造 名古屋市立大学, 大学院医学研究科, 講師 (80551267)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 尿路結石 / 酸化ストレス / ミトコンドリア / マクロファージ / ゲノムワイド関連解析

Outline of Final Research Achievements

(1) Development of medicine and biomarkers focusing on the mitochondrial injury of renal tubule cells.:The oxalic acid precursor was administered to the knockout mouse of Cyclophilin D (cypD), and the formation of stone and the molecular mechanism were elucidated. Compared to in wild-type, mitochondrial injury and stone formation were small in CypD knockout mice.
(2) Identification of new related genes and development of risk diagnosis method.:We tried to establish a diagnosis method of onset risk from the gene region identified by comprehensive human genome-wide association analysis. The related genes were examined using a multiplex analysis system. M1 macrophage-related substances decreased in healthy subjects and M2 macrophage-related substances decreased in stone patients.

Research Products

• [Journal Article] Kidney stone formers have more renal parenchymal crystals than non-stone formers, particularly in the papilla region. (2018)
  • Author(s): Okada A, Hamamoto S, Taguchi K, Unno R, Sugino T, Ando R, Mizuno K, Tozawa K, Kohri K, Yasui T.
  • Journal Title: BMC Urol. Volume: 18 Issue: 1 Pages: 19-19
  • DOI: 10.1186/s12894-018-0331-x
  • Peer Reviewed / Open Access
• [Journal Article] Genetic differences in C57BL/6 mouse substrains affect kidney crystal deposition. (2018)
  • Author(s): Usami M, Okada A, Taguchi K, Hamamoto S, Kohri K, Yasui T.
  • Journal Title: Urolithiasis Volume: 印刷中 Issue: 6 Pages: 515-522
  • DOI: 10.1007/s00240-018-1040-3
  • Peer Reviewed
• [Journal Article] Potassium-sodium citrate prevents the development of renal microcalculi into symptomatic stones in calcium stone-forming patients. (2017)
  • Author(s): Unno Rei, Taguchi Kazumi, Okada Atsushi, Ando Ryosuke, Hamamoto Shuzo, Kubota Yasue, Zuo Li, Tozawa Keiichi, Kohri Kenjiro, Yasui Takahiro
  • Journal Title: International Journal of Urology Volume: 24 Issue: 1 Pages: 75-81
  • DOI: 10.1111/iju.13242
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Pathophysiology-based treatment of urolithiasis. (2017)
  • Author(s): Yasui T, Okada A, Hamamoto S, Ando R, Taguchi K, Tozawa K, Kohri K.
  • Journal Title: Int J Urol Volume: 24 Issue: 1 Pages: 32-38
  • DOI: 10.1111/iju.13187
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Genetic Risk Factors for Idiopathic Urolithiasis: A Systematic Review of the Literature and Causal Network Analysis. (2017)
  • Author(s): Taguchi Kazumi, Yasui Takahiro, Milliner Schmautz Dawn, Hoppe Bernd, Chi Thomas
  • Journal Title: EUROPEAN UROLOGY FOCUS Volume: 3 Issue: 1 Pages: 71-81
  • DOI: 10.1016/j.euf.2017.04.010
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Genome-wide gene expression profiling of Randall's plaques in calcium oxalate stone formers (2017)
  • Author(s): Taguchi K, Hamamoto S, Okada A, Unno R, Kamisawa H, Naiki T, Ando R, Mizuno K, Kawai N, Tozawa K, Kohri K, Yasui T
  • Journal Title: J Am Soc Nephrol Volume: 28 Issue: 1 Pages: 333-347
  • DOI: 10.1681/asn.2015111271
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] M1/M2-macrophage phenotypes regulate renal calcium oxalate crystal development (2017)
  • Author(s): 70.Taguchi Kazumi, Okada Atsushi, Hamamoto Shuzo, Unno Rei, Moritoki Yoshinobu, Ando Ryosuke, Mizuno Kentaro, Tozawa Keiichi, Kohri Kenjiro, Yasui Takaihro
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 35167-35167
  • DOI: 10.1038/srep35167
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Differential Roles of Peroxisome Proliferator-Activated Receptor-α and Receptor-γ on Renal Crystal Formation in Hyperoxaluric Rodents (2016)
  • Author(s): Taguchi K, Okada A, Hamamoto S, Unno R, Kobayashi T, Ando R, Tozawa K, Gao B, Kohri K, Yasui T
  • Journal Title: PPAR Res Volume: 2016 Pages: 9605890-9605890
  • DOI: 10.1155/2016/9605890
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Do teas rich in antioxidants reduce the physicochemical and peroxidative risk factors for calcium oxalate nephrolithiasis in humans? Pilot studies with Rooibos herbal tea and Japanese green tea. Urolithiasis. (2016)
  • Author(s): Rodgers A, Mokoena M, Durbach I, Lazarus J, de Jager S, Ackermann H, Breytenbach I, Okada A, Usami M, Hirose Y, Ando R, Yasui T, Kohri K
  • Journal Title: Urolithiasis Volume: Epub Issue: 4 Pages: 299-310
  • DOI: 10.1007/s00240-015-0855-4
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Proinflammatory and Metabolic Changes Facilitate Renal Crystal Deposition in an Obese Mouse Model of Metabolic Syndrome. (2015)
  • Author(s): Taguchi K, Okada A, Hamamoto S, Iwatsuki S, Naiki T, Ando R, Mizuno K, Tozawa K, Kohri K, Yasui T.
  • Journal Title: J Urol. Volume: 194 Issue: 6 Pages: 1787-96
  • DOI: 10.1016/j.juro.2015.07.083
  • Peer Reviewed / Open Access
• [Presentation] Japanese topics for stone management -epidemiology, endoscopic surgery, and prevention- (2018)
  • Author(s): Takahiro Yasui
  • Organizer: JUA_AUA Joint Symposium（第105回日本泌尿器科学会総会）
  • Int'l Joint Research / Invited
• [Presentation] Management for renal stone disease -epidemiology, endoscopic surgery, and prevention- (2018)
  • Author(s): Takahiro Yasui
  • Organizer: 16th Urological Association of Asia Congress 2018
  • Int'l Joint Research / Invited
• [Presentation] 尿路結石全国疫学調査からわかること (2017)
  • Author(s): 安井孝周
  • Organizer: 第67回日本泌尿器科学会中部総会
  • Invited
• [Presentation] Guidelines for stone management: what we have and what we need? (2017)
  • Author(s): Takahiro Yasui
  • Organizer: 15th Urological Association of Asia Congress 2017
  • Int'l Joint Research / Invited
• [Presentation] Role of mitochondrial permeability transition in kidney stone formation (2016)
  • Author(s): Ito Yasuhiko, Sugino Teruaki, Niimi Kazuhiro, Hirose Masahito, Itoh Yasunori, Okada Atsushi, Kohri Kenjiro, Yasui Takahiro
  • Organizer: 13th International Symposium on Urolithiasis
  • Place of Presentation: 幕張メッセ(千葉県千葉市)
  • Year and Date: 2016-07-19
  • Int'l Joint Research
• [Presentation] Preventive effect of citrate against recurrent calcium stones detected as microcalculi on computed tomography. (2016)
  • Author(s): Unno Rei, Okada Atsushi, Taguchi Kazumi, Hamamoto Shuzo, Ando Ryosuke, Tozawa Keiichi, Kohri Kenjiro, Yasui Takahiro
  • Organizer: American Urological Association Annual Meeting
  • Place of Presentation: San Diego（USA）
  • Year and Date: 2016-05-06
  • Int'l Joint Research
• [Presentation] 過去の疫学調査の総括 (2016)
  • Author(s): 安井孝周、井口 正典、郡 健二郎
  • Organizer: 日本尿路結石症学会第26回学術集会
  • Place of Presentation: 幕張メッセ(千葉県千葉市)
  • Invited
• [Presentation] 尿路結石に対する新規治療法の開発をめざして (2015)
  • Author(s): 安井孝周
  • Organizer: 第270回日本泌尿器科学会東海地方会
  • Place of Presentation: KDX桜通ビル(名古屋市)
  • Year and Date: 2015-12-13
  • Invited
• [Presentation] Alendronate has a preventive effect for urolithiasis recurrence in men and postmenopausal women with osteoporosis (2015)
  • Author(s): Takahiro Yasui, Atsushi Okada, Kazumi Taguchi, Masayuki Usami, Yasuhiro Fujii, Kazuhiro Niimi, Shuzo Hamamoto, Masahito Hirose, Ryosuke Ando, Yasunori Itoh, Keiichi, Tozawa, Yutaro Hayashi, Kenjiro Kohri,
  • Organizer: 2015 (110th) Annual Meeting of American Urological Association
  • Place of Presentation: ニューオリンズ・アメリカ合衆国
  • Year and Date: 2015-05-15
  • Int'l Joint Research
• [Presentation] N-methyl-4-isoleucine cyclosporine, an inhibitor of mitochondrial cyclophilin D activation, prevents kidney stone formation by alleviating oxidative stress in renal tubular cells (2015)
  • Author(s): Takahiro Yasui, Kazuhiro Niimi, Atsushi Okada, Kazumi Taguchi, Yasuhiro Fujii, Yasuhiko Hirose, Yasuhiko Ito, Shuzo Hamamoto, Masahito Hirose, Keiichi Tozawa, Shoichi Sasaki, Yutaro Hayashi, Kenjiro Kohri
  • Organizer: 2015 (110th) Annual Meeting of American Urological Association
  • Place of Presentation: ニューオリンズ・アメリカ合衆国
  • Year and Date: 2015-05-15
  • Int'l Joint Research
• [Presentation] Genetic diagnosis trial by single nucleotide polymorphism analysis from a case-control study, using three novel loci associated with susceptibility to urolithiasis from a genome-wide association study (GWAS) (2015)
  • Author(s): Takahiro Yasui, Atsushi Okada, Masayuki Usami, Shuzo Hamamoto, Ryosuke Ando, Yasunori Itoh, Keiichi Tozawa, Shoichi Sasaki, Yutaro Hayashi, Nagoya, Japan, Yoshikazu Sato, Yoshihito Higashi, Kenjiro Kohri
  • Organizer: 2015 (110th) Annual Meeting of American Urological Association
  • Place of Presentation: ニューオリンズ・アメリカ合衆国
  • Year and Date: 2015-05-15
  • Int'l Joint Research
• [Presentation] 尿路結石の分子機構の解明と溶解療法に向けた治療戦略 (2015)
  • Author(s): 安井孝周
  • Organizer: 第103回日本泌尿器科学会総会
  • Place of Presentation: 石川県立音楽堂、ANAクラウンプラザホテル金沢他(金沢市)
  • Year and Date: 2015-04-18
  • Invited
• [Presentation] 尿路結石の疫学 (2015)
  • Author(s): 安井孝周
  • Organizer: 第103回日本泌尿器科学会総会
  • Place of Presentation: 石川県立音楽堂、ANAクラウンプラザホテル金沢他(金沢市)
  • Year and Date: 2015-04-18
  • Invited
• [Book] EBM泌尿器疾患の治療2015-2016 (2015)
  • Author(s): 安井孝周
  • Total Pages: 616
  • Publisher: 中外医学社