Development of prophylaxis by the elucidation of the pathogenesis in the initial urinary stone formation

• Project/Area Number: 23592375
• 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, 医学(系)研究科(研究院), 講師 (40326153)
• Co-Investigator(Kenkyū-buntansha): HAMAMOTO Shuzo 名古屋市立大学, 大学院医学研究科, 研究員 (80551267) ; OKADA Atsushi 名古屋市立大学, 大学院医学研究科, 講師 (70444966) ; KEIICHI Tozawa 名古屋市立大学, 大学院医学研究科, 准教授 (40264733) ; KOHRI Kenjiro 名古屋市立大学, 大学院医学研究科, 教授 (30122047)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 尿路結石 / 酸化ストレス / ミトコンドリア / 一塩基多型 / 肥満 / メタボリックシンドローム

Research Abstract

(1) Renal tubular cell injury induced by oxidative stress via mitochondrial collapse is said to be the initial step of urinary stone formation. We elucidated that mitochondrial permeability transition pore opening, which is blocked by cyclosporine A, is associated with mitochondrial collapse, oxidative stress, and activation of apoptotic pathway in the initial steps of renal calcium crystallization. New medicines for urolithiasis prevention are expected to target this mechanism. (2) The mechanism of urinary stone formation in the obesity and metabolic syndrome environment involves the progression of an inflammation and immunoresponse, including oxidative stress and adhesion reactions in renal tissues. (3) Genome-wide association studies show that 5q35.3, 7p14.3, and 13q14.1 in Japanese are associated with urolithiasis. Thus, SNP analysis would aid in the prediction of urolithiasis risk and recurrence.

Research Products

• [Journal Article] Novel effect of the inhibitor of mitochondrial cyclophilin D activation, N-methyl-4-isoleucine cyclosporin, on renal calcium crystallization (2014)
  • Author(s): Niimi K, Yasui T, Okada A, Hirose Y, Kubota Y, Umemoto Y, Kawai N, Tozawa K, Kohri K
  • Journal Title: Int J Urol Volume: ― Issue: 7 Pages: 707-13
  • DOI: 10.1111/iju.12425
  • Peer Reviewed
• [Journal Article] A Paracrine Mechanism Involving Renal Tubular Cells, Adipocytes, and Macrophages Promotes Kidney Stone Formation in a Simulated Metabolic Syndrome Environment. (2014)
  • Author(s): Li Zuo, Okada Atsushi, Yasui Takahiro, Taguchi Kazumi, Ito Yasuhiko, Hirose Yasuhiko, Fujii Yasuhiro, Niimi Kazuhiro, Hamamoto Shuzo, Ando Ryosuke, Itoh Yasunori, Zuo Jiangang, Tozawa Keiichi, Kohri Kenjiro
  • Journal Title: The Journal of Urology Volume: 191 Issue: 6 Pages: 1906-1912
  • DOI: 10.1016/j.juro.2014.01.013
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Increased crystal-cell interaction in vitro under co-culture of renal tubular cells and adipocytes by in vitro co-culture paracrine systems simulating metabolic syndrome. (2014)
  • Author(s): Ichikawa J, Okada A, Taguchi K, Fujii Y, Zuo L, Niimi K, Hamamoto S, Kubota Y, Umemoto Y, Itoh Y, Yasui T, Kawai N, Tozawa K, Kohri K.
  • Journal Title: Urolithiasis. Volume: 42 Issue: 1 Pages: 17-28
  • DOI: 10.1007/s00240-013-0612-5
  • Peer Reviewed
• [Journal Article] A replication study for three nephrolithiasis loci at 5q35.3, 7p14.3 and 13q14.1 in the Japanese population (2013)
  • Author(s): Yasui T, Okada A, Urabe Y, Usami M, Mizuno K, Kubota Y, Tozawa K, Sasaki S, Higashi Y, Sato Y, Kubo M, Nakamura Y, Matsuda K, Kohri K
  • Journal Title: J Hum Genet Volume: 58 Issue: 9 Pages: 588-93
  • DOI: 10.1038/jhg.2013.59
  • NAID: 10031195294
  • Peer Reviewed
• [Journal Article] The association between the incidence of urolithiasis and nutrition based on Japanese National Health and Nutrition Surveys (2013)
  • Author(s): Yasui T, Okada A, Hamamoto S, Hirose M, Ando R, Kubota Y, Tozawa K, Hayashi Y, Gao B, Suzuki S, Kohri K
  • Journal Title: Urolithiasis Volume: 41 Issue: 3 Pages: 217-24
  • DOI: 10.1007/s00240-013-0567-6
  • Peer Reviewed
• [Journal Article] Effect of Adiponectin on Kidney Crystal Formation in Metabolic Syndrome Model Mice via Inhibition of Inflammation and Apoptosis (2013)
  • Author(s): Fujii Y, Okada A, Yasui T, Niimi K,Hamamoto S, Hirose M, Kubota Y, Tozawa K, Hayashi Y, Kohri K.
  • Journal Title: PLoS One Volume: 8 Issue: 4 Pages: e61343-e61343
  • DOI: 10.1371/journal.pone.0061343
  • Peer Reviewed
• [Journal Article] Kidney stone formation is positively associated with conventional risk factors for coronary heart disease in Japanese men. (2013)
  • Author(s): Ando R, Nagaya T, Suzuki S, Takahashi H, Kawai M, Okada A, Yasui T, Kubota Y, Umemoto Y, Tozawa K, Kohri K.
  • Journal Title: Journal of urology Volume: 189 Issue: 4 Pages: 1340-1346
  • DOI: 10.1016/j.juro.2012.11.045
  • Peer Reviewed
• [Journal Article] Biomolecular mechanism of urinary stone formation involving osteopontin (2012)
  • Author(s): Kohri K
  • Journal Title: Urol Res Volume: 40 Issue: 6 Pages: 623-637
  • DOI: 10.1007/s00240-012-0514-y
  • Peer Reviewed
• [Journal Article] Pioglitazone, a peroxisome proliferator activated receptor γ agonist, decreases renal crystal deposition, oxidative stress and inflammation in hyperoxaluric rats (2012)
  • Author(s): Taguchi K
  • Journal Title: J Urol Volume: 188 Issue: 3 Pages: 1002-1011
  • DOI: 10.1016/j.juro.2012.04.103
  • Peer Reviewed
• [Journal Article] Mitocondrial permeability transition pore opening induces the initial process of renal calcium crystallization (2012)
  • Author(s): Niimi Kazuhiro, Yasui Takahiro, Hirose Masahito, Hamamoto Shuzo, Itoh Yasunori, Okada Atsushi, Kubota Yasue, Kojima Yoshiyuki, Tozawa Keiichi, Sasaki Shoichi, Hayashi Yutaro, Kohri Kenjiro
  • Journal Title: Free Radical Biology & Medicine Volume: 52 Issue: 7 Pages: 1207-1217
  • DOI: 10.1016/j.freeradbiomed.2012.01.005
  • Peer Reviewed
• [Journal Article] Role of osteopontin in early phase of renal crystal formation: immunohistochemical and microstructural comparisons with osteopontin knock-out mice (2012)
  • Author(s): Hirose M, Tozawa K, Okada A, Hamamoto S, Higashibata Y, Gao B, Hayashi Y, Shimizu H, Kubota Y, Yasui T, Kohri K
  • Journal Title: Urol Res. Volume: 40 Issue: 2 Pages: 121-9
  • DOI: 10.1007/s00240-011-0400-z
  • Peer Reviewed
• [Journal Article] 尿路結石症の遺伝子多型 (2012)
  • Author(s): 安井孝周 他
  • Journal Title: 臨床医学 Volume: 56 Pages: 303-308
• [Journal Article] Crucial role of the cryptic epitope SLAYGLR within osteopontinin renal crystal formation of mice (2011)
  • Author(s): Hamamoto S, Yasui T, Okada A, Hirose M, Matsui Y, Kon S, Sakai F, Kojima Y, Hayashi Y, Tozawa K, Uede T, Ko- hri K
  • Journal Title: J Bone Miner Res Volume: 26 Issue: 12 Pages: 2967-77
  • DOI: 10.1002/jbmr.495
  • Peer Reviewed
• [Journal Article] Colony-Stimulating factor-1 signaling suppresses renal crystal formation
  • Author(s): Taguchi K, Okada A, Kitamura H, Yasui T, Naiki T, Hamamoto S, Ando R, Mizuno K, Kawai N, Tozawa K, Asano K, Tanaka M, Miyoshi I, Kohri K
  • Journal Title: J Am Soc Nephrol Volume: (PMID:24578130)(Epub ahead of print)
  • Peer Reviewed
• [Presentation] Management of stone disease in the 21st century (2013)
  • Author(s): Takahiro Yasui
  • Organizer: The 8th American Urological Association and the Japanese Urological Association International Affiliate Society Meeting
  • Place of Presentation: San Diego, California, USA
  • Year and Date: 2013-05-05
• [Presentation] Association of the loci 5q35.3, 7p14.3 and 13q14.1 with urolithiasis in the Japanesse population (2013)
  • Author(s): Takahiro Yasui, Atsushi Okada, Masayuki Usami, Yasuhiko Ito, Kazumi Taguchi, Yasuhiro Fujii, Kazuhiro Niimi, Shuzo Hamamoto, Ryosuke Ando, Masahito Hitrose, Yasunori Itoh, Keiichi Tozawa, Yoshikazu Higashi, Yoshikazu Sato, Koichi Matsuda, Kenjiro Kohri
  • Organizer: 2nd Meeting of the EAU Section of Urolithiasis (EULIS)
  • Place of Presentation: Copenhagen, Denmark
• [Presentation] 尿路結石のゲノムワイド解析による再発リスク診断法の確立 (2013)
  • Author(s): 安井孝周、岡田淳志、新美和寛、田口和己、戸澤啓一、郡健二郎
  • Organizer: 第56回日本腎臓学会学術総会
  • Place of Presentation: 東京
• [Presentation] Association between nephrolithiasis incidence and nutrition, based on data from Japanese national surveys (2013)
  • Author(s): Takahiro Yasui, Atsushi Okada, Li Zuo, Yasuhiko Hirose, Kazumi Taguchi, Takahiro Kobayashi, Masahito Hirose, Ryosuke Ando, Shoichi Sasaki, Kenjiro Kohri
  • Organizer: 2013 (108th) Annual Meeting of American Urological Association
  • Place of Presentation: San Diego, California, USA
• [Presentation] Association of the loci 5q35.3, 7q14.3, and 13.q14.1 with urolithiasis : A case-control study in the Japanese population, involving genome-wide association study (2013)
  • Author(s): Takahiro Yasui, Atsushi Okada, Masayuki Usami, Shuzo Hamamoto, Ryosuke Ando, Yasunori Itoh, Shoichi Sasaki, Keiichi Tozawa, Yoshihito Higashi, Yoshikazu Sato, Kenjiro Kohri
  • Organizer: 2013 (108th) Annual Meeting of American Urological Association
  • Place of Presentation: San Diego, California, USA
• [Presentation] 尿路結石症のリスクファクターと再発予防-薬物療法の未来と再発予防 (2013)
  • Author(s): 安井孝周、新美和寛、浜本周造、岡田淳志、戸澤啓一、郡健二郎
  • Organizer: 第101回日本泌尿器科学会総会
  • Place of Presentation: 札幌市
• [Presentation] ゲノムワイド関連解析による尿路結石の新規遺伝子領域の同定と発症リスク診断法への応用 (2013)
  • Author(s): 安井孝周、岡田淳志、宇佐美雅之、伊藤恭典、戸澤啓一、東義一、佐藤嘉一、郡健二郎
  • Organizer: 第101回日本泌尿器科学会総会
  • Place of Presentation: 札幌市
• [Presentation] Association of the loci 5q35.3, 7q14.3, and 13.q14.1 with urolithiasis: A case-control study in the Japanese population, involving genome-wide association study (2013)
  • Author(s): Takahiro Yasui, Atsushi Okada, Masayuki Usami, Shuzo Hamamoto, Ryosuke Ando, Yasunori Itoh, Shoichi Sasaki, Keiichi Tozawa, Yoshihito Higashi, Yoshikazu Sato, Kenjiro Kohri
  • Organizer: 2013 (108th) Annual Meeting of American Urological Association
  • Place of Presentation: San Diego Convention Center( San Diego, USA)
• [Presentation] Management of stone disease in the 21st century (2013)
  • Author(s): Takahiro Yasui
  • Organizer: 2013 (108th) Annual Meeting of American Urological Association
  • Place of Presentation: San Diego Convention Center( San Diego, USA)
  • Invited
• [Presentation] Elucidation of metabolic syndrome-related paracrine system by co-culturing renal tubular epithelial cells and adipocytes (2013)
  • Author(s): Yasuhiro Fujii, Atsushi Okada, Kazumi Taguchi, Kazuhiro Niimi, Shuzo Hamamoto, Masahito Hirose, Takahiro Yasui, Kenjiro Kohri
  • Organizer: 2013 (108th) Annual Meeting of American Urological Association
  • Place of Presentation: San Diego Convention Center( San Diego, USA)
• [Presentation] Association between nephrolithiasis incidence and nutrition based on data from a Japanese national survey (2012)
  • Author(s): Takahiro Yasui, Atsushi Okada, Kazuhiro Niimi, Shuzo Hamamoto, Takahiro Kobayashi, Masahito Hirose, Yasunori Itoh, Keiichi Tozawa, Masanori Iguchi, Kenjiro Kohri
  • Organizer: 32nd Congress of the Societe Internationale d'Urologie
  • Place of Presentation: Fukuoka, Japan
• [Presentation] Bisphosphonate prevents urolithiasis in men with osteoporosis by reducing the urinary ion activity product of calcium stone (2012)
  • Author(s): Takahiro Yasui, Atsushi Okada, Kazumi Taguchi, Yasuhiko Hirose, Yasuhiro Fujii, Kazuhiro Niimi, Masayuki Usami, Ryosuke Ando, Shuzo Hamamoto, Takahiro Kobayashi, Masahito Hirose, Yasue Kubota, Yoshiyuki Kojima, Yasunori Itoh, Shoichi Sasaki, Keiichi Tozawa, Kenjiro Kohri
  • Organizer: 2012 (107th) Annual Meeting of American Urological Association
  • Place of Presentation: Atlanta, Georgia, US
• [Presentation] 疫学から見えてくる尿路結石症の本態. (2012)
  • Author(s): 安井孝周
  • Organizer: 第100回日本泌尿器科学会総会
  • Place of Presentation: 横浜市
• [Presentation] 診療に活用できる尿路結石症の疫学 (2011)
  • Author(s): 安井孝周、安藤亮介、岡田淳志、戸澤啓一、郡健二郎
  • Organizer: 第61回日本泌尿器科学会中部総会
  • Place of Presentation: 京都市
• [Presentation] Bisphosphonate prevents urolithiasis in men with osteoporosis (2011)
  • Author(s): Takahiro Yasui, Atsushi Okada, Jun Ichikawa, Kazumi Taguchi, Yasuhiko Hirose, Yasuhiro Fujii, Kauhiro Niimi, Masayuki Usami, Ryosuke Ando, Shuzo Hamamoto, Takahiro Kobayashi, Masahito Hirose, Yasunori Itoh, Keiichi Tozawa, Kenjiro Kohri
  • Organizer: 1st Meeting of the EAU Section of Urolithiasis (EULIS)
  • Place of Presentation: London, United Kingdom
• [Presentation] Alendronate prevent the recurrence of urolithiasis by reducing urinary ion activity product of calcium stone (2011)
  • Author(s): Takahiro Yasui, Atsushi Okada, Kazumi Taguchi, Yasuhiko Hirose, Yasuhiro Fujii, Kauhiro Niimi, Masayuki Usami, Shuzo Hamamoto, Takahiro Kobayashi, Masahito Hirose, Yasunori Itoh, Keiichi Tozawa, Yutaro Hayashi, Kenjiro Kohri
  • Organizer: 2011 (106th) Annual Meeting of American Urological Association
  • Place of Presentation: Washington, D.C., USA
• [Presentation] Association between urolithiasis and food intake based on data from a Japanese national survey (2011)
  • Author(s): Takahiro Yasui, Atsushi Okada, Kazumi Taguchi, Yasuhiko Hirose, Yasuhiro Fujii, Kazuhiro Niimi, Masayuki Usami, Ryosuke Ando, Shuzo Hamamoto, Takahiro Kobayashi, Masahito Hirose, Yasunori Itoh, Keiichi Tozawa, and Kenjiro Kohri
  • Organizer: 2011 (106th) Annual Meeting of American Urological Association
  • Place of Presentation: Washington, D.C., USA
• [Presentation] Regional variations and characteristics of urolithiasis in Japan determined from a national survey (2011)
  • Author(s): Takahiro Yasui, Atsushi Okada, Kazumi Taguchi, Yasuhiro Fujii, Kauhiro Niimi, Masayuki Usami, Shuzo Hamamoto, Takahiro Kobayashi, Masahito Hirose, Yasunori Itoh, Keiichi Tozawa, Kenjiro Kohri
  • Organizer: 26th Annual EAU (European Association of Urology) Congress
  • Place of Presentation: Vienna, Austria
• [Presentation] Association between urolithiasis and food intake based on data from a Japanese national survey (2011)
  • Author(s): Takahiro Yasui et al.
  • Organizer: 2011 Annual Meeting of American Urological Association
  • Place of Presentation: Washington,D.C.
• [Book] 尿路結石症,ベッドサイド泌尿器科学(改訂第4版) (2013)
  • Author(s): 安井孝周,郡健二郎(監修:吉田修,編集:岡田裕作, et al.)
  • Publisher: 南江堂
• [Book] 尿路結石の疫学・診断・治療,日本泌尿器科学会2012年卒後教育プログラムテキスト (2012)
  • Author(s): 安井孝周(編集:日本泌尿器科学会)
  • Publisher: 日本泌尿器科学会