Establishment of the new concept, 'spontaneous elimination of kidney stones' and application to development of the dissolution therapy

• Project/Area Number: 25670685
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: Nagoya City University
• Principal Investigator: OKADA ATSUSHI 名古屋市立大学, 医学(系)研究科(研究院), 講師 (70444966)
• Co-Investigator(Kenkyū-buntansha): KOHRI Kenjiro 名古屋市立大学, 学長 (30122047) ; YASUI Takahiro 名古屋市立大学, 大学院医学研究科, 教授 (40326153) ; HIROSE Masahito 名古屋市立大学, 大学院医学研究科, 研究員 (70529172) ; HAMAMOTO Shuzo 名古屋市立大学, 大学院医学研究科, 助教 (80551267) ; Niimi Kazuhiro 名古屋市立大学, 大学院医学研究科, 研究員 (70551274) ; Hirose Yasuhiko 名古屋市立大学, 大学院医学研究科, 研究員 (60381894)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 尿路結石 / マクロファージ / op/op / Randall's plaque / M2マクロファージ / 結晶貪食 / ゲノムワイド解析 / マイクロアレイ

Outline of Final Research Achievements

We discovered the new phenomenon, "spontaneous elimination of kidney stones " ahead of the world. Furthermore, We proved that the crystal phagocytosis by the anti-inflammatory macrophages (M2-typed Mφs) affected this phenomenon. Based on these results, this study analyzed M2-typed Mφs deficient mice and the genome-wide expression using the human renal papilla tissue for development of the dissolution therapy of the kidney stones.
There was significantly increased number of stones in the M2-typed Mφ deficient mice, and decreased expression of genes related with immunity, inflammation was recognized in comparison with the wild-type mice in the stone formative period. In addition, We recognized decreased expression of the M2-typed Mφ-related gene clusters in the Randall's plaques which is the original part of kidney stones at the human renal papilla tissues.

Research Products

• [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
• [Journal Article] Endoscopic combined intrarenal surgery for large calculi: Simultaneous use of flexible ureteroscopy and mini-percutaneous nephrolithotomy overcomes the disadvantageous of percutaneous nephrolithotomy monotherapy. (2014)
  • Author(s): Hamamoto Shuzo, Yasui Takahiro, Okada Atsushi, Taguchi Kazumi, Kawai Noriyasu, Ando Ryosuke, Mizuno Kentaro, Kubota Yasue, Kamiya Hiroyuki, Tozawa Keiichi, Kohri Kenjiro
  • Journal Title: Journal of Endourology Volume: 28 Issue: 1 Pages: 28-33
  • DOI: 10.1089/end.2013.0361
  • Peer Reviewed / Open Access
• [Journal Article] Impact of prostate weight on perioperative outcomes of robot-assisted laparoscopic prostatectomy with a posterior approach to the seminal vesicle. (2014)
  • Author(s): Yasui Takahiro, Tozawa Keiichi, Kurokawa Satoshi, Okada Atsushi, Mizuno Kentaro, Umemoto Yukihiro, Kawai Noriyasu, Sasaki Shoichi, Hayashi Yutaro, Kojima Yoshiyuki, Kohri Kenjiro
  • Journal Title: Bio Med Central Urology Volume: 14 Issue: 1 Pages: 6-6
  • DOI: 10.1186/1471-2490-14-6
  • Peer Reviewed
• [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] Laparoendoscopic Single-Site Partial Nephrectomy Without Hilar Clamping Using a Microwave Tissue Coagulator. (2014)
  • Author(s): Kawai Noriyasu, Ando Ryosuke, Tozawa Keiichi, Kohri Kenjiro
  • Journal Title: Journal of Endourology Volume: 28(2) Issue: 2 Pages: 184-190
  • DOI: 10.1089/end.2013.0135
  • Peer Reviewed
• [Journal Article] Long-term follow-up of nephrotoxicity in rats administered both melamine and cyanuric acid. (2014)
  • Author(s): Yasui T, Kobayashi T, Okada A, Hamamoto S, Hirose M, Mizuno K, Kubota Y, Umemoto Y, Kawai N, Tozawa K, Gao B, Kohri K.
  • Journal Title: BMC Res Notes. Volume: 7 Issue: 1 Pages: 87-87
  • DOI: 10.1186/1756-0500-7-87
  • Peer Reviewed / Open Access
• [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] 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] Gemcitabine and docetaxel, an effective second-line chemotherapy for lung metastasis of urothelial carcinoma. (2014)
  • Author(s): Naiki Taku, Kawai Noriyasu, Hashimoto Yoshihiro, Okamura Takehiko, Ando Ryosuke, Yasui Takahiro, Okada Atsushi, Etani Toshiki, Tozawa Keiichi, Kohri Kenjiro
  • Journal Title: International Journal of Clinical Oncology Volume: 19 Issue: 3 Pages: 516-522
  • DOI: 10.1007/s10147-013-0574-1
  • Peer Reviewed
• [Journal Article] Developments in the technique of endoscopic combined intrarenal surgery in the prone split-leg position. (2014)
  • Author(s): Shuzo Hamamoto, Takahiro Yasui, Atsushi Okada, Mitsuru Takeuchi, Kazumi Taguchi, Yuta Shibamoto, Yutaka Iwase, Noriyasu Kawai, Keiichi Tozawa, Kohri Kenjiro
  • Journal Title: Urology Volume: 84 Issue: 3 Pages: 565-570
  • DOI: 10.1016/j.urology.2014.04.020
  • Peer Reviewed / Open Access
• [Journal Article] Pitfalls of robot-assisted radical prostatectomy: A comparison of positive surgical margins between robotic and laparoscopic surgery. (2014)
  • Author(s): Tozawa Keiichi, Yasui Takahiro, Umemoto Yukihiro, Mizuno Kentaro, Okada Atsushi, Kawai Noriyasu, Takahashi Satoru, Kohri Kenjiro
  • Journal Title: International Journal of Urology Volume: 21 Issue: 10 Pages: 976-979
  • DOI: 10.1111/iju.12492
  • Peer Reviewed
• [Journal Article] Efficacy of retroperitoneal laparoscopic ureterolithotomy for the treatment of large proximal ureteric stones and its impact on renal function. (2013)
  • Author(s): Yasui T, Okada A, Hamamoto S, Taguchi K, Ando R, Mizuno K, Itoh Y, Tozawa K, Hayashi Y, Kohri K.
  • Journal Title: Springerplus. Volume: 2 Issue: 1 Pages: 600-600
  • DOI: 10.1186/2193-1801-2-600
  • Peer Reviewed
• [Journal Article] Impact of official technical training for urologists on the efficacy of shock wave lithotripsy. (2013)
  • Author(s): Okada A, Yasui T, Taguchi K, Niimi K, Hirose Y, Hamamoto S, Ando R, Kubota Y, Umemoto Y, Tozawa K, Sasaki S, Hayashi Y, Kohri K.
  • Journal Title: Urolithiasis. Volume: 41 Issue: 6 Pages: 287-492
  • DOI: 10.1007/s00240-013-0586-3
  • Peer Reviewed
• [Journal Article] Oxygen nano-bubble water reduces calcium oxalate deposits and tubular cell injury in ethylene glycol-treated rat kidney. (2013)
  • Author(s): Hirose Y, Yasui T, Taguchi K, Fujii Y, Niimi K, Hamamoto S, Okada A, Kubota Y, Kawai N, Itoh Y, Tozawa K, Sasaki S, Kohri K.
  • Journal Title: Urolithiasis. Volume: 41 Issue: 4 Pages: 279-294
  • DOI: 10.1007/s00240-013-0576-5
  • 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] 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
• [Presentation] Hypercalciuria and migration of inflammatory macrophages play key roles for kidney stone formation in metabolic syndrome. (2015)
  • Author(s): Taguchi Kazumi, Unno Rei, Fujii Yasuhiro, Hamamoto Shuzo, Ando Ryosuke, Okada Atsushi, Yasui Takahiro, Fujita Keiji, Tozawa Keiichi, Hayashi Yutaro, Kohri Kenjiro
  • Organizer: American Urological Association Annual Meeting 2015
  • Place of Presentation: New Orleans（USA）
  • Year and Date: 2015-05-15
  • Int'l Joint Research
• [Presentation] The role of renal tubular cell injury in the earlyperiod of renal crystal formation identified from the cell injury-inhibiting effect of green tea. (2015)
  • Author(s): Hirose Masahito, Banno Rika, Kanemoto Kazuhiro, Okada Atsushi, Yasui Takahiro, Sakakura Takeshi, Tozawa Keiichi, Kohri Kenjiro
  • Organizer: American Urological Association Annual Meeting 2015
  • Place of Presentation: New Orleans（USA）
  • Year and Date: 2015-05-15
  • Int'l Joint Research
• [Presentation] Gene expression profile of Randall's plaque in idiopathic CaOx stone formers suggests dysregulation of Mφ-related genes. (2015)
  • Author(s): Taguchi Kazumi, Unno Rei, Fujii Yasuhiro, Naiki Taku, Hamamoto Shuzo, Ando Ryosuke, Kanemoto Kazuhiro, Okada Atsushi, Yasui Takahiro, Tozawa Keiichi, Hayashi Yutaro, Kohri Kenjiro
  • Organizer: American Urological Association Annual Meeting 2015
  • Place of Presentation: New Orleans（USA）
  • Year and Date: 2015-05-15
  • Int'l Joint Research
• [Presentation] シュウ酸カルシウム結石患者に特異的な新規尿中因子IL-4の同定 (2015)
  • Author(s): 岡田 淳志、安井 孝周、田口 和己、海野 怜、藤井 泰普、濵本 周造、広瀬 真仁、戸澤 啓一、郡 健二郎
  • 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(石川県金沢市)
  • Year and Date: 2015-04-18
• [Presentation] 尿路結石の分子機構の解明と溶解療法に向けた研究戦略 (2015)
  • Author(s): 安井 孝周、田口 和己、濵本 周造、岡田 淳志、戸澤 啓一、郡 健二郎
  • 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(石川県金沢市)
  • Year and Date: 2015-04-18
  • Invited
• [Presentation] マクロファージによる尿路結石防御メカニズムの解明と溶解療法への臨床応用 (2015)
  • Author(s): 田口 和己、海野 怜、安藤 亮介、岡田 淳志、戸澤 啓一、安井 孝周、郡 健二郎
  • 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(石川県金沢市)
  • Year and Date: 2015-04-18
  • Invited
• [Presentation] シュウ酸カルシウム結石の発生母地「Randall’s Plaque」の制御因子同定による尿路結石分子標的治療の開発 (2015)
  • Author(s): 田口 和己、海野 怜、濵本 周造、安藤 亮介、金本 一洋、岡田 淳志、安井 孝周、藤田 圭治、戸澤 啓一、郡 健二郎
  • 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(石川県金沢市)
  • Year and Date: 2015-04-18
• [Presentation] A paracrine mechanism promotes kidney stone formation in a simulated metabolic syndrome environment using in vitro and in vivo studies. (2014)
  • Author(s): Okada Atsushi, Yasui Takahiro, Zou Li, Unno Rei, Fujii Yasuhiro, Taguchi Kazumi, Hamamoto Shuzo, Ando Ryosuke, Itoh Yasunori, Tozawa Keiichi, Sasaki Shoichi, Rodgers Allen, Kohri Kenjiro
  • Organizer: 2nd of Experts in Stone Disease (ESD)
  • Place of Presentation: Cape Town（South Africa）
  • Year and Date: 2014-12-10 – 2014-12-13
• [Presentation] ロボット支援腹腔鏡手術創の疼痛・満足度に関わる因子 (2014)
  • Author(s): 岡田 淳志、黒川 覚史、水野 健太郎、安井 孝周、梅本 幸裕、河合 憲康、戸澤 啓一、佐々木 昌一、林 祐太郎、郡 健二郎
  • Organizer: 第28回日本泌尿器内視鏡学会
  • Place of Presentation: ヒルトン福岡シーホーク（福岡県福岡市）
  • Year and Date: 2014-11-26 – 2014-11-28
• [Presentation] Possible new urine markers for calcium oxalate “stone formers”: macrophage-related cytokines/chemokines detected by multiplex analysis. (2014)
  • Author(s): Okada Atsushi, Yasui Takahiro, Taguchi Kazumi, Fujii Yasuhiro, Niimi Kazuhiro, Hamamoto Shuzo, Hirose Masahito, Ando Ryosuke, Kubota Yasue, Itoh Yasunori, Tozawa Keiichi, Kohri Kenjiro
  • Organizer: American Urological Association Annual Meeting 2014
  • Place of Presentation: Orlando（USA）
  • Year and Date: 2014-05-16 – 2014-05-21
• [Presentation] マルチプレックス解析を用いた尿路結石患者に特異的な尿中マクロファージ関連因子の同定 (2014)
  • Author(s): 岡田 淳志、田口 和己、藤井 泰普、新美 和寛、濵本 周造、安井 孝周、広瀬 真仁、戸澤 啓一、郡 健二郎
  • Organizer: 第102回日本泌尿器科学会総会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Year and Date: 2014-04-24 – 2014-04-27
• [Presentation] 2.尿路結石の再発予防（2）薬物療法。 (2014)
  • Author(s): 岡田 淳志
  • Organizer: 第102回日本泌尿器科学会総会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Year and Date: 2014-04-24 – 2014-04-27
  • Invited
• [Presentation] Effect of an ultrasonic targeting method for kidney and proximal ureter stones on the success rate of shock wave lithotripsy. (2013)
  • Author(s): Okada Atsushi, Taguchi Kazumi, Ando Ryosuke, Umemoto Yukihiro, Itoh Yasunori, Yasui Takahiro, Sasaki Shoichi, Kohri Kenjiro
  • Organizer: American Urological Association Annual Meeting 2013
  • Place of Presentation: San Diego Convention Center( San Diego, USA)
• [Presentation] 尿路結石の成因からみた予防法 (2013)
  • Author(s): 岡田 淳志、郡 健二郎
  • Organizer: 第101回日本泌尿器科学会総会
  • Place of Presentation: さっぽろ芸術文化の館（札幌）
  • Invited
• [Presentation] 腎結石の溶解療法の開発に向けたマクロファージによるシュウ酸カルシウム結晶の貪食機序の解明 (2013)
  • Author(s): 岡田 淳志、安井 孝周、田口 和己、藤井 泰普、濵本 周造、伊藤 恭典、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: さっぽろ芸術文化の館（札幌）
• [Presentation] R2-U1結石に対するESWL成功率における超音波照準の有用性 (2013)
  • Author(s): 岡田 淳志、飯田 啓太郎、田口 和己、藤井 泰普、岩月 正一郎、内木 拓、井村 誠、神沢 英幸、広瀬 真仁、梅本 幸裕、河合 憲康、佐々木 昌一、郡 健二郎
  • Organizer: 第101回日本泌尿器科学会総会
  • Place of Presentation: さっぽろ芸術文化の館（札幌）