Establishment of a novel biomarker for renal calculi

• Project/Area Number: 18K09143
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Nagoya City University
• Principal Investigator: Hamamoto Shuzo 名古屋市立大学, 医薬学総合研究院(医学), 講師 (80551267)
• Co-Investigator(Kenkyū-buntansha): 郡 健二郎 名古屋市立大学, その他部局等, 学長 (30122047) ; 安井 孝周 名古屋市立大学, 医薬学総合研究院(医学), 教授 (40326153) ; 戸澤 啓一 名古屋市立大学, 医薬学総合研究院(医学), 教授 (40264733) ; 岡田 淳志 名古屋市立大学, 医薬学総合研究院(医学), 准教授 (70444966) ; 田口 和己 名古屋市立大学, 医薬学総合研究院(医学), 講師 (00595184) ; 海野 怜 名古屋市立大学, 医薬学総合研究院(医学), 研究員 (40755683)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2018: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 腎結石 / オステオポンチン / Randall's plaque / Osteopontin / 尿路結石 / バイオマーカー

Outline of Final Research Achievements

Osteopontin plays a crucial role in the formation of renal calcium crystals, which are primarily induced by renal tubular cell injury, especially mitochondrial damage. In this study, we analyze the effect of the cryptic OPN epitope generated by thrombin cleavage and by polymeraization on renal crystal formation. We found that a specific anti-OPN antibody contributes to the remarkable inhibition of early stage of renal crystal formation and that thrombin-cleaved OPN contributes to promote the renal crystal formation. As regard to OPN polymerization, the amount of polymerized OPN in the urine of stone formers were higher than that of the healthy human. We speculated that polymerized OPN could be the marker of kidney stone formation.

Academic Significance and Societal Importance of the Research Achievements

私たちは、結石内にわずか数％しか含まれていない有機物質が腎結石形成に重要な作用をしているものと考え、腎結石の形成機序を分子レベルで解明することに世界に先駆けて成功した。今後これまでの成果を発展させたヒトへの臨床応用に向けたトランスレーショナルリサーチが必須と考えるが、結石の予防治療の効果判定のためのバイオマーカーがない。本研究において、切断型OPNや重合OPNが腎結石形成におけるバイオマーカーとなることが初めて示された。このことにより、今後再発性結石患者に対する予防治療を目指したトランスレーショナルリサーチが可能になると確信している。

Research Products

• [Journal Article] Taguchi KaRobot-assisted fluoroscopy-guided renal puncture for endoscopic combined intrarenal surgery: a pilot single-centre clinical trialzumi, Hamamoto Shuzo, Kato Taiki, Iwatsuki Shoichiro, Etani Toshiki, Okada Atsushi, Yasui Takahiro (2021)
  • Author(s): Taguchi K, Hamamoto S, Kato T, Iwatsuki S, Etani T, Okada A, Yasui T
  • Journal Title: BJU International Volume: 127 Issue: 3 Pages: 307-310
  • DOI: 10.1111/bju.15291
  • Peer Reviewed / Open Access
• [Journal Article] LigaSure versus the standard technique (Hem-o-lok clips) for robot-assisted radical prostatectomy: a propensity score-matched study (2021)
  • Author(s): Hamamoto S,AbdelRazek M, Naiki T, Taguchi K,Etani T, Iwatsuki S,Ando R,Okada A,Kawai N, Yasui T
  • Journal Title: J Robot Surg Volume: - Issue: 6 Pages: 869-875
  • DOI: 10.1007/s11701-020-01180-6
  • Peer Reviewed
• [Journal Article] One- versus two-surgeon active stone retrieval procedures for flexible ureteroscopy:An off-site simulator comparative study (2021)
  • Author(s): Okada S, Hamamoto S, Inoue T, Minagawa S, Morikawa H, Matsuda T, Miura H
  • Journal Title: Int J Urol Volume: - Issue: 6 Pages: 665-671
  • DOI: 10.1111/iju.14534
  • Peer Reviewed
• [Journal Article] Comparison of real-time virtual sonography navigation versus BioJet navigation on magnetic resonance imaging guided prostate needle biopsy: a single institutional analysis (2020)
  • Author(s): Takashi Nagai, Taku Naiki, Shuzo Hamamoto, Toshiki Etani, Aya Naiki-Ito, Motoo Nakagawa, Keitaro Iida, Shoichiro Iwatsuki, Kazumi Taguchi, Tetsuji Maruyama, Noriyasu Kawai, Satoru Takahashi, Takahiro Yasui
  • Journal Title: Journal of Endourology Volume: オンライン Issue: 7 Pages: 739-745
  • DOI: 10.1089/end.2020.0042
  • Peer Reviewed
• [Journal Article] Low bone mineral density is a potential risk factor for symptom onset and related with hypocitraturia in urolithiasis patients: a single-center retrospective cohort study (2020)
  • Author(s): Taguchi K, Hamamoto S, Okada A, Tanaka Y, Sugino T, Unno R, Kato T, Ando R, Tozawa K, Yasui T
  • Journal Title: BMC Urology Volume: 20 Issue: 1 Pages: 174-174
  • DOI: 10.1186/s12894-020-00749-5
  • Peer Reviewed / Open Access
• [Journal Article] A novel flexible ureteroscope with omnidirectional bending tip using joystick-type control unit (URF-Y0016): initial validation study in bench models (2020)
  • Author(s): Tambo Mitsuhiro, Inoue Takaaki, Miura Hiroyasu, Matsuzaki Junichi, Nutahara Kikuo, Hamamoto Shuzo, Okada Shinsuke, Fukuhara Hiroshi, Fujisawa Masato
  • Journal Title: Journal of Endourology Volume: E-pub Issue: 6 Pages: 676-681
  • DOI: 10.1089/end.2019.0895
  • Peer Reviewed
• [Journal Article] Evaluation of flexible ureteroscope with an omni-directional bending tip, using a JOYSTICK unit (URF-Y0016): an ex-vivo study (2020)
  • Author(s): Inoue Takaaki, Okada Shinsuke, Hamamoto Shuzo, Miura Hiroyasu, Matsuzaki Junichi, Tambo Mitsuhiro, Fukuhara Hiroshi, Fujisawa Masato, Matsuda Tadashi, Nutahara Kikuo
  • Journal Title: World Journal of Urology Volume: E-pub Issue: 1 Pages: 209-215
  • DOI: 10.1007/s00345-020-03151-w
  • Peer Reviewed
• [Journal Article] Editorial comment from Dr Hamamoto to endurological treatment trend of upper urinary urolithiasis in japan from the japanese diagnosis procedure combination database (2019)
  • Author(s): Hamamoto Shuzo
  • Journal Title: International Journal of Urology Volume: 26 Issue: 10 Pages: 1009-1009
  • DOI: 10.1111/iju.14080
  • Peer Reviewed
• [Journal Article] Robot-assisted fluoroscopy- vs ultrasound-guided renal access for nephrolithotomy: A phantom model bench-top study (2019)
  • Author(s): Taguchi Kazumi, Hamamoto Shuzo, Okada Atsushi, Tanaka Yutaro, Sugino Teruaki, Unno Rei, Kato Taiki, Ando Ryosuke, Tan Yung-Khan, Yasui Takahiro
  • Journal Title: Journal of Endourology Volume: E-pub Issue: 12 Pages: 987-994
  • DOI: 10.1089/end.2019.0432
  • Peer Reviewed
• [Journal Article] Brown adipocytes and β3-stimulant-induced brown-like adipocytes contribute to the prevention of renal crystal formation (2019)
  • Author(s): Sugino Teruaki, Okada Atsushi, Taguchi Kazumi, Unno Rei, Hamamoto Shuzo, Ando Ryosuke, Mogami Tohru, Kohri Kenjiro, Yamashita Hitoshi, Yasui Takahiro
  • Journal Title: American Journal of Physiology. Renal Physiology Volume: 316 Issue: 6 Pages: 1282-1282
  • DOI: 10.1152/ajprenal.00523.2018
  • Peer Reviewed
• [Journal Article] Deregulated MTOR (mechanistic target of rapamycin kinase) is responsible for autophagy defects exacerbating kidney stone development (2019)
  • Author(s): Unno Rei, Kawabata Tsuyoshi, Taguchi Kazumi, Sugino Teruaki, Hamamoto Shuzo, Ando Ryosuke, Okada Atsushi, Kohri Kenjiro, Yoshimori Tamotsu, Yasui Takahiro
  • Journal Title: Autophagy Volume: E-pub Issue: 4 Pages: 709-723
  • DOI: 10.1080/15548627.2019.1635382
  • Peer Reviewed / Open Access
• [Journal Article] Active phagocytosis and diachronic processing of calcium oxalate monohydrate crystals in an in vitro macrophage model (2019)
  • Author(s): Okada Atsushi, Aoki Hiromasa, Onozato Daichi, Kato Taiki, Hashita Tadahiro, Takase Hiroshi, Sugino Teruaki, Unno Rei, Taguchi Kazumi, Hamamoto Shuzo, Ando Ryosuke, Mizuno Kentaro, Tozawa Keiichi, Matsunaga Tamihide, Kohri Kenjiro, Yasui Takahiro
  • Journal Title: Kidney and Blood Pressure Research Volume: 44 Issue: 5 Pages: 1014-1014
  • DOI: 10.1159/000501965
  • Peer Reviewed / Open Access
• [Journal Article] Testicular teratoma demanded in-depth pathological exploration to rule out malignancy: A pediatric case report (2019)
  • Author(s): Moritoki Yoshinobu, Mizuno Kentaro, Kato Taiki, Hamamoto Shuzo, Hattori Hideo, Ito Yasuhiko, Saitoh Shinji, Yasui Takahiro, Hayashi Yutaro
  • Journal Title: IJU Case Reports Volume: 2 Issue: 3 Pages: 115-115
  • DOI: 10.1002/iju5.12050
  • Peer Reviewed
• [Journal Article] Effectiveness of ureteroscope-assisted renal puncture for endoscopic combined intrarenal surgery (2019)
  • Author(s): Sugino Teruaki, Hamamoto Shuzo, Unno Rei, Taguchi Kazumi, Okada Atsushi, Yasui Takahiro
  • Journal Title: International Journal of Urology Volume: 26 Issue: 3 Pages: 424-424
  • DOI: 10.1111/iju.13865
• [Journal Article] Complete surgical removal of multiple tumor lesions in malignant pheochromocytomas produces a good prognosis (2019)
  • Author(s): Nozaki Satoshi, Naiki Taku, Moritoki Yoshinobu, Hamamoto Shuzo, Etani Toshiki, Iida Keitaro, Unno Rei, Okada Atsushi, Kawai Noriyasu, Yasui Takahiro
  • Journal Title: IJU Case Reports Volume: 2 Issue: 3 Pages: 146-146
  • DOI: 10.1002/iju5.12065
• [Journal Article] Identification of new urinary risk markers for urinary stones using a logistic model and multinomial logit model (2019)
  • Author(s): Okada Atsushi、Ando Ryosuke、Taguchi Kazumi、Hamamoto Shuzo、Unno Rei、Sugino Teruaki、Tanaka Yutaro、Mizuno Kentaro、Tozawa Keiichi、Kohri Kenjiro、Yasui Takahiro
  • Journal Title: Clinical and Experimental Nephrology Volume: 23 Issue: 5 Pages: 710-716
  • DOI: 10.1007/s10157-019-01693-x
  • Peer Reviewed
• [Journal Article] Impact of ureteric stent removal by string on patient's quality of life and on complications at post-ureteroscopy for urolithiasis: a controlled trial (2018)
  • Author(s): Inoue Takaaki、Okada Shinsuke、Hamamoto Shuzo、Yoshida Takashi、Murota Takashi、Matsuda Tadashi、On behalf of the SMART Study Group
  • Journal Title: BJU International Volume: Epub Issue: 2 Pages: 314-314
  • DOI: 10.1111/bju.14622
  • Peer Reviewed
• [Journal Article] A kit ligand, stem cell factor as a possible mediator inducing overactive bladder. (2018)
  • Author(s): Kubota Yasue, Hamakawa Takashi, Osaga Satoshi, Okada Atsushi, Hamamoto Shuzo, Kawai Noriyasu, Kohri Kenjiro, Yasui Takahiro
  • Journal Title: Neurourology and Urodynamics Volume: 37 Issue: 4 Pages: 1258-1265
  • DOI: 10.1002/nau.23449
  • Peer Reviewed
• [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] Current trends and pitfalls in endoscopic treatment of urolithiasis (2017)
  • Author(s): Inoue Takaaki、Okada Shinsuke、Hamamoto Shuzo、Yoshida Takashi、Matsuda Tadashi
  • Journal Title: Int J Urol Volume: 25 Issue: 2 Pages: 121-133
  • DOI: 10.1111/iju.13491
  • Peer Reviewed
• [Presentation] Retzius sparing RARPによる尿失禁ゼロを目指した取り組み (2021)
  • Author(s): 濵本 周造、岩月 正一郎、惠谷 俊紀、田口 和己、内木 拓、岡田 淳志、河合 憲康、安井 孝周
  • Organizer: 第33回日本内視鏡外学会
  • Invited
• [Presentation] 「尿路結石・前立腺肥大症治療の進歩」：ECIRSスピードラーニング (2021)
  • Author(s): 濵本 周造
  • Organizer: 第50回泌尿器科紀の国フォーラム
  • Invited
• [Presentation] 尿管内視鏡所見から考える経尿道的尿管砕石術における適切な治療介入時期の解析 (2020)
  • Author(s): 濵本 周造、岡田 真介、井上 貴昭、田口 和己、安藤 亮介、岡田 淳志、三浦 浩康、松田 公志、安井 孝周
  • Organizer: 第108回日本泌尿器科学会総会
• [Presentation] The importance of hands-on training for flexible ureteroscope (fURS): Appropriate training as examined based on questionnaires (2020)
  • Author(s): Hamamoto Shuzo, Okada Shinsuke, Inoue Takaaki, Okada Tomoki, Chaya Ryosuke, Kawase Kengo, Taguchi Kazumi, Okada Atsushi, Miura Hiroyasu, Matsuda Tadashi, Yasui Takahiro
  • Organizer: American Urological Association Annual Meeting 2020
  • Int'l Joint Research
• [Presentation] Prospective evaluation of endoscopic findings and analyses of the risk factors for ureteral changes during URSL (2020)
  • Author(s): Hamamoto Shuzo, Okada Shinsuke, Inoue Takaaki, Okada Tomoki, Chaya Ryosuke, Kawase Kengo, Taguchi Kazumi, Okada Atsushi, Miura Hiroyasu, Matsuda Tadashi, Yasui Takahiro
  • Organizer: American Urological Association Annual Meeting 2020
  • Int'l Joint Research
• [Presentation] Retzius腔温存ロボット支援腹腔鏡下前立腺全摘術（Retzius spearing RARP）における神経温存の工夫 (2019)
  • Author(s): 濵本 周造、岡田 淳志、安井 孝周
  • Organizer: 第32回日本内視鏡外科学会総会
• [Presentation] 新・異物付着防止型ステントTriaTMの可能性 (2019)
  • Author(s): 濵本 周造
  • Organizer: 第33回日本泌尿器内視鏡学会総会
• [Presentation] ECIRSの術式標準化：PNL術者の役割 (2019)
  • Author(s): 濵本 周造、田口 和己、岡田 淳志、安井 孝周
  • Organizer: 第33回日本泌尿器内視鏡学会総会
• [Presentation] 同一術者によるConventional RARPとRetzius spearing RARPの治療成績の比較 (2019)
  • Author(s): 濵本 周造、岡田 淳志、岩月 正一郎、惠谷 俊紀、田口 和己、内木 拓、安藤 亮介、河合 憲康、戸澤 啓一、安井 孝周
  • Organizer: 第33回日本泌尿器内視鏡学会総会
• [Presentation] Retzius sparing RARPは患者よし? (2019)
  • Author(s): 濵本 周造、内木 拓、安藤 亮介、岡田 淳志、河合 憲康、安井 孝周
  • Organizer: 第33回日本泌尿器内視鏡学会総会
• [Presentation] How to approach this situation? (2019)
  • Author(s): Hamamoto Shuzo
  • Organizer: American Urological Association Annual Meeting 2019
  • Int'l Joint Research / Invited
• [Presentation] ECIRSのコツとpitfall (2019)
  • Author(s): 濵本 周造、田口 和己、岡田 淳志、安井 孝周
  • Organizer: 第107回日本泌尿器科学会総会
• [Presentation] Medical and dietary stone prevention. (2019)
  • Author(s): Hamamoto Shuzo
  • Organizer: Advancements in Urology 2019
  • Invited
• [Presentation] Impact of preoperative ureteral stenting on ureteroscopic findings: A propensity score matching analysis. (2019)
  • Author(s): Hamamoto Shuzo, Sugino Teruaki, Hasebe Kenichi, Isogai Masahiko, Taguchi Kazumi, Ando Ryosuke, Inoue Takaaki, Okada Shinsuke, Okada Atsushi, Matasuda Tadashi, Yasui Takahiro
  • Organizer: 34th Anuual EAU Congress
• [Presentation] Prospective evaluation and classification of ureterosocopic findings of impacted calculi. (2019)
  • Author(s): Hamamoto Shuzo, Sugino Teruaki, Taguchi Kazumi, Ando Ryosuke, Inoue Takaaki, Okada Shinsuke, Okada Atsushi, Matsuda Tadashi, Yasui Takahiro
  • Organizer: 34th Anuual EAU Congress
• [Presentation] 進化を続けるPNL/ECIRS～軌跡をたどり、今後の可能性を考える～ (2018)
  • Author(s): 濵本 周造
  • Organizer: 第106回日本泌尿器科学会総会
  • Invited
• [Presentation] どのような患者に再発予防が必要か？ (2018)
  • Author(s): 濵本 周造、田口 和己、岡田 淳志、安井 孝周
  • Organizer: 第106回日本泌尿器科学会総会
  • Invited
• [Presentation] Establishment of treatment strategies for impacted calculi by analyzing the ureteroscopic findings. (2018)
  • Author(s): Hamamoto Shuzo, Unno Rei, Taguchi Kazumi, Ando Ryosuke, Okada Shinsuke, Inoue Takaaki, Okada Atsushi, Tozawa Keiichi, Miura Hiroyasu, Matsuda Tadashi, Yasui Takahiro
  • Organizer: American Urological Association Annual Meeting 2018
• [Presentation] 難治性尿路結石に対する治療戦略 (2018)
  • Author(s): 濵本 周造
  • Organizer: 第19回Osaka Practical Conference of Urological Oncology(OPCUO)
  • Invited