The search trial of phosphorus sensing system or sensing molecule for phosphorus overload in chronic kidney dysfunction

• Project/Area Number: 23591222
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Wakayama Medical University
• Principal Investigator: SHIGEMATSU Takashi 和歌山県立医科大学, 医学部, 教授 (30187348)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: リン / FGF-23 / 骨 / リン吸着剤 / 血管石灰化 / リン感受性 / ビタミンD / 慢性腎臓病 / 高リン血症 / FGF-3

Research Abstract

Phosphorus is essential, but its excess shows the toxicity. This study is fundamental researches aiming at phosphorus toxicity conquest.
Firstly, I have estimated vascular calcification as the phosphorus toxicity in clinical study with hemodialysis patients. Secondary, I have tried to establish the phosphorus induced vascular calcification model in vitro to know the detail mechanism of vascular disorder by phosphorus. We have succeeded ex vivo vascular medial calcification model by the aortic tissue culture under high phosphorus condition 3.8mM for ten days. Next, I have made a research the phosphorus sensing system and/or phosphorus induced molecules. Fibroblast growth factor 23 (FGF23) derived from a bone has been explicated to play key role in phosphorus toxicity-induced vascular dysfunction. I am progressing the research to know the detail phosphorus sensing mechanism by FGF23 production and by the vascular medial calcification.

Research Products

• [Journal Article] Alendronate as an effective treatment for bone loss and vascular calcification in kidney transplant recipients. (2014)
  • Author(s): Okamoto M, Yamanaka S, Yoshimoto W, Shigematsu T.
  • Journal Title: J Transplant. Volume: 00 Pages: 269613-269613
  • DOI: 10.1155/2014/269613
  • Peer Reviewed
• [Journal Article] A higher serum alkaline phosphatase is associated with the incidence of hip fracture and mortality among patients receiving hemodialysis in Japan (2014)
  • Author(s): Maruyama Y, Taniguchi M, Kazama JJ, Yokoyama K, Hosoya T, Yokoo T, Shigematsu T, Iseki K, Tsubakihara Y
  • Journal Title: Nephrol Dial Transplant Volume: (In press)
  • Peer Reviewed
• [Journal Article] A higher serum alkaline phosphatase is associated with the incidence of hip fracture and mortality among patients receiving hemodialysis in Japan. (2014)
  • Author(s): Maruyama Y, Taniguchi M, Kazama JJ, Yokoyama K, Hosoya T, Yokoo T,Shigematsu T, Iseki K, Tsubakihara Y.
  • Journal Title: Nephrol Dial Transplant. Volume: 00
  • Peer Reviewed
• [Journal Article] Committee of Renal Data Registry of the Japanese Society for Dialysis Therapy.:Serum phosphate and calcium should be primarily and consistently controlled in prevalent hemodialysis patients (2013)
  • Author(s): Taniguchi M, Fukagawa M, Fujii N, Hamano T, Shoji T, Yokoyama K, Nakai S, Shigematsu T, Iseki K, Tsubakihara Y
  • Journal Title: Ther Apher Dial Volume: 17 Pages: 221-228
  • Peer Reviewed
• [Journal Article] Serum phosphate and calcium should be primarily and consistently controlled in prevalent hemodialysis patients. (2013)
  • Author(s): Taniguchi M, Fukagawa M, Fujii N, Hamano T, Shoji T, Yokoyama K, Nakai S,Shigematsu T, Iseki K, Tsubakihara Y
  • Journal Title: Ther Apher Dial. Volume: 17 Issue: 2 Pages: 221-8
  • DOI: 10.1111/1744-9987.12030
  • Peer Reviewed
• [Journal Article] Clinical practice guideline for the management of chronic kidney disease-mineral and bone disorder. (2013)
  • Author(s): Fukagawa M, Yokoyama K, Koiwa F, Taniguchi M, Shoji T, Kazama JJ, Komaba H, Ando R, Kakuta T, Fujii H, Nakayama M, Shibagaki Y, Fukumoto S, Fujii N, Hattori M, Ashida A, Iseki K, Shigematsu T, Tsukamoto Y, Tsubakihara Y, Tomo T, Hirakata H, Akizawa T
  • Journal Title: Ther Apher Dial. Volume: 17 Issue: 3 Pages: 247-88
  • DOI: 10.1111/1744-9987.12058
  • Peer Reviewed
• [Journal Article] The management of hyperphosphatemia by lanthanum carbonate in chronic kidney disease patients (2012)
  • Author(s): Shigematsu T, Nakashima Y, Ohya M, Tatsuta K, Koreeda D, Yoshimoto W, Yamanaka S, Sakaguchi T, Hanba Y, Mima T, Negi S
  • Journal Title: Int J Nephrol Renovasc Dis Volume: 5 Pages: 81-89
  • Peer Reviewed
• [Journal Article] Influence of renin-angiotensin system on serum parathyroid hormone levels in uremic patients (2012)
  • Author(s): Koiwa F, Komukai D, Hirose M, Yoshimura A, Ando R, Sakaguchi T, Komatsu Y, Shinoda T, Inaguma D, Joki N, Nishida H, Ikeda M, Shigematsu T
  • Journal Title: Clin Exp Nephrol Volume: 16 Pages: 130-1355
  • NAID: 10030343171
  • Peer Reviewed
• [Journal Article] Combined therapy with lanthanum carbonate and calcium carbonate for hyperphosphatemia decreases serum FGF-23 level independently of calcium and PTH (COLC Study) (2012)
  • Author(s): Shigematsu T, Negi S; COLC Research Group
  • Journal Title: Nephrol Dial Transplant Volume: 27 Pages: 1050-1054
  • Peer Reviewed
• [Journal Article] Combined therapy with lanthanum carbonate and calcium carbonate for hyperphosphatemia decreases serum FGF-23 level independently of calcium and PTH(COLC Study). (2012)
  • Author(s): Shigematsu T,Negi S,and the COLC Research Group
  • Journal Title: Nephrol Dial Transplant Volume: 27 Pages: 1050-1054
  • Peer Reviewed
• [Journal Article] Combined therapy with lanthanum carbonate and calcium carbonate for hyperphosphatemia decreases serum FGF-23 level independently of calcium and PTH (COLC Study). (2012)
  • Author(s): Shigematsu T, Negi S; COLC Research Group.
  • Journal Title: Nephrol Dial Transplant. Volume: 27 Pages: 1050-1054
  • Peer Reviewed
• [Journal Article] Vascular calcification estimated by aortic calcification area index is a significant predictive parameter of cardiovascular mortality in hemodialysis patients (2011)
  • Author(s): Ohya M, Otani H, Kimura K, Saika Y, Fujii R, Yukawa S, Shigematsu T
  • Journal Title: Clin Exp Nephrol Volume: 15 Pages: 877-83
  • NAID: 10030341794
  • Peer Reviewed
• [Journal Article] Comparison between whole and intact parathyroid hormone assays (2011)
  • Author(s): Taniguchi M, Tanaka M, Hamano T, Nakanishi S, Fujii H, Kato H, Koiwa F, Ando R, Kimata N, Akiba T, Kono T, Yokoyama K, Shigematsu T, Kakuta T, Kazama JJ, Tominaga Y, Fukagawa M
  • Journal Title: Ther Apher Dial Volume: 15 Suppl 1 Pages: 42-49
  • Peer Reviewed
• [Journal Article] Effect of lanthanum carbonate treatment on bone in Japanese dialysis patients with hyperphosphatemia (2011)
  • Author(s): Shigematsu T, Tokumoto A, Nakaoka A, Arisaka H
  • Journal Title: Ther Apher Dial Volume: 15 Pages: 176-184
  • Peer Reviewed
• [Journal Article] Vascular calcification estimated by aortic calcification area index is a significant predictive parameter of cardiovascular mortality in hemodialysis patients. (2011)
  • Author(s): Ohya M, Otani H, Kimura K, Saika Y, Fujii R, Yukawa S, Shigematsu T.
  • Journal Title: Clin Exp Nephrol. Volume: 15 Pages: 877-883
  • NAID: 10030341794
  • Peer Reviewed
• [Journal Article] Effect of lanthanum carbonate treatment on bone in Japanese dialysis patients with hyperphosphatemia. (2011)
  • Author(s): Shigematsu T, Tokumoto A, Nakaoka A, Arisaka H.
  • Journal Title: Ther Apher Dial. Volume: 11 Pages: 176-184
  • Peer Reviewed
• [Presentation] CKD-MBDとマグネシウム (2014)
  • Author(s): 大矢昌樹、重松 隆
  • Organizer: 第59回日本透析医学会学術集会・総会
  • Place of Presentation: 神戸
• [Presentation] 今後のCKD-MBD療法を考える (2014)
  • Author(s): 重松 隆
  • Organizer: 第59回日本透析医学会学術集会・総会
  • Place of Presentation: 神戸
  • Invited
• [Presentation] 高リン血症を呈する保存期慢性腎不全患者に対する炭酸ランタンの二重盲検プラセボ対象のリン低下効果の検討 (2013)
  • Author(s): 重松隆・根木茂雄
  • Organizer: 第56回日本腎臓学会学術総会
  • Place of Presentation: 東京
• [Presentation] CKD患者におけるCKD-MBD管理 (2013)
  • Author(s): 重松隆
  • Organizer: 第56回日本腎臓学会学術総会
  • Place of Presentation: 東京
• [Presentation] 慢性血液透析患者における血中ALP値と生命予後の検討 (2013)
  • Author(s): 丸山之雄・横山啓太郎・重松隆・谷口正智・風間順一郎・細谷龍男
  • Organizer: 第58回日本透析医学会学術集会・総会
  • Place of Presentation: 福岡
• [Presentation] 透析患者のCKD-MBD管理 (2013)
  • Author(s): 重松隆
  • Organizer: 第58回日本透析医学会学術集会・総会ランチョンセミナー41
  • Place of Presentation: 福岡
• [Presentation] CKDにおけるCKD-MBD治療 (2013)
  • Author(s): 重松 隆
  • Organizer: 第56回日本腎臓学会総会
  • Place of Presentation: 東京
  • Invited
• [Presentation] The CKD-MBD (2013)
  • Author(s): 重松 隆
  • Organizer: 第43回日本腎臓学会西部学術大会
  • Place of Presentation: 松山
  • Invited
• [Presentation] 高リン血症治療の過去・現在・未来 (2013)
  • Author(s): 重松 隆
  • Organizer: 第43回日本腎臓学会東部学術大会
  • Place of Presentation: 東京
  • Invited
• [Presentation] 血管石灰化の進行を抑制するための望ましい透析液ca濃度に関する検討 (2012)
  • Author(s): 伊達敏行・山本忠司、前田兼徳・重松隆
  • Organizer: 第57回(社)日本透析医学会学術集会・総会
  • Place of Presentation: 札幌
• [Presentation] 透析導入時の活性型ビタミンD、炭酸Caがミネラル代謝に及ぼす影響 (2012)
  • Author(s): 小岩文彦・高安真美子・吉村吾志夫・坂口俊文・安藤亮一・山家敏彦・篠田俊雄・常喜信彦・渡邊尚・稲熊大城・重松隆
  • Organizer: 第57回(社)日本透析医学会学術集会・総会
  • Place of Presentation: 札幌
• [Presentation] Combined therapy with lanthanum carbonate and calcium carbonate for hyperphosphatemia decreases serum FGF-23 level independently of calcium and PTH (2011)
  • Author(s): Negi S, Shigematsu T, the Japan COLC Study Group
  • Organizer: 7th International Congress on Uremia Research and Toxicity
  • Place of Presentation: Nagoya
• [Presentation] The evaluation of affecting factors for phosphate removal during hemodialysis session using direct measurement of dialysate phosphate (2011)
  • Author(s): Shigematsu T, Ueki H, Arima M, Kodama N, Goto T, Kodama T, Maeda A, Negi S, Mima T, Sakaguchi T
  • Organizer: 7th International Congress on Uremia Research and Toxicity
  • Place of Presentation: Nagoya
• [Presentation] The evaluation of affecting factors for phosphate removal during hemodialysis session using direct measurement of dialysate phosphate. (2011)
  • Author(s): Takashi Shigematsu,Hayato Ueki,Miki Arima,Naoya Kodama,Tetsuya Goto,Toshihiro Kodama,Akifumi Maeda,Shigeo Negi,Tooru Mima,Toshifumi Sakaguchi
  • Organizer: 7th International Congress on Uremia Research and Toxicity.
  • Place of Presentation: Nagoya, Japan
• [Presentation] Combined therapy with lanthanum carbonate and calcium carbonate for hyperphosphatemia decreases serum FGF-23 level independently of calcium and PTH. (2011)
  • Author(s): Shigeo Negi,Takashi Shigematsu,the Japan COLC Study Group
  • Organizer: 7th International Congress on Uremia Research and Toxicity.
  • Place of Presentation: Nagoya, Japan
• [Presentation] CKD-MBD as the risk factors of incident cardiovascular disease (CVD) and fatality after CVD in a nationwide registry of Japanese hemodialysis patients. (2011)
  • Author(s): Tetsuo Shoji, Seiji Marubayashi, Takashi Shigematsu, Kunitoshi Iseki, Yoshiharu Tsubakihara
  • Organizer: 44th American Society of Nephrology Renal Week
  • Place of Presentation: Philadelphia, USA
• [Presentation] シンポジウム12「CKD-MBD発症機序から考える治療戦略総論 - 二次性副甲状腺機能亢進症を中心に」 (2011)
  • Author(s): 重松隆・佐治文恵・根木茂雄
  • Organizer: 第99回日本泌尿器科学会総会(招待講演)
  • Place of Presentation: 名古屋市
• [Presentation] シンポジウム「CKDにおけるミネラル代謝異常 最新情報」 (2011)
  • Author(s): 重松隆
  • Organizer: 第56回（社）日本透析医学会学術集会・総会(招待講演)
  • Place of Presentation: 横浜市
• [Presentation] 「CKD患者における副甲状腺コントロール」 (2011)
  • Author(s): 重松隆
  • Organizer: 第56回（社）日本透析医学会学術集会・総会(招待講演)
  • Place of Presentation: 横浜市
• [Presentation] シンポジウム2「血管石灰化の成因に対する基礎的、臨床的検討」 (2011)
  • Author(s): 大矢昌樹・根木茂雄・重松隆
  • Organizer: 第17回日本腹膜透析医学会学術集会・総会(招待講演)
  • Place of Presentation: さいたま市
• [Presentation] 「慢性腎臓病患者における副甲状腺機能異常の成り立ちから考える治療」 (2011)
  • Author(s): 重松隆
  • Organizer: 第13回日本骨粗鬆症学会 骨ドック・健診分科会(招待講演)
  • Place of Presentation: 神戸市
• [Book] 血液透析患者における大動脈瘤石灰化と骨密度の関連厚生労働科学研究費補助金難治性疾患克服研究事業Calciphylaxisの診断・治療に関わる調査・研究平成22年度−23年度総合研究報告書 (2012)
  • Author(s): 重松隆・大矢昌樹
• [Book] 血液透析患者における大動脈瘤石灰化と骨密度の関連厚生労働科学研究費補助金難治性疾患克服研究事業カルシフィラキシスの診断・治療に関わる調査・研究平成23年度総括・分担研究報告書 (2012)
  • Author(s): 重松隆・大矢昌樹
• [Remarks] 和歌山県立以下大学附属病院腎臓内科
  • URL: http://www.wakayama-med.ac.jp/hospital/shinryo/blood-cleansing/index.html
• [Remarks] 和歌山県立医科大学腎臓内科学講座
  • URL: http://www.wakayama-med.ac.jp/med/nephrology/contents/Professor.html
• [Remarks] 日本腎循環器病研究会
  • URL: http://jjbkk.kenkyuukai.jp/special/?id=11024
• [Remarks] 和歌山透析研究会
  • URL: http://wakayama-rrt.kenkyuukai.jp/event/event_detail.asp?id=9953
• [Remarks] 和歌山県立医科大学 医学部各教室一覧 腎臓内科学講座
  • URL: http://www.wakayama-med.ac.jp/dept/igakubu/160601/index.html
• [Remarks] 和歌山県立医科大学 腎臓内科学
  • URL: http://www.wakayama-med.ac.jp/med/nephrology/index.html