Dysfunction of HDL and macrophages in kidney disease-accelerated atherosclerosis and the therapeutic strategy

• Project/Area Number: 24790837
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine
• Research Institution: Niigata University
• Principal Investigator: YAMAMOTO Suguru 新潟大学, 医歯(薬)学総合研究科, 特任助教 (70444156)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 慢性腎臓病 / 動脈硬化 / 心血管病 / HDLコレステロール / マクロファージ / インドキシル硫酸 / 腎臓病 / 尿毒素物質 / 動脈硬化症 / AST-120 / HDL / cholesterol efflux / reactive oxygen species / CKD

Outline of Final Research Achievements

Purpose of the study is to elucidate the mechanism of dysfunction of macrophage and HDL cholesterol in kidney disease-accelerated atherosclerosis. HDL isolated from kidney disease patients induced macrophage inflammation and abnormal lipid metabolism. Indoxyl sulfate also induced macrophage inflammation and abnormal lipid metabolism. Those results indicate that indoxyl sulfate may induce dysfunctions of macrophage and HDL, and the intervention to them will be an attractive therapeutic strategy for kidney disease-accelerated atherosclerosis.

Research Products

• [Journal Article] Use of Renin-Angiotensin system inhibitors is associated with reduction of fracture risk in hemodialysis patients. (2015)
  • Author(s): Yamamoto S, Kido R, Onishi Y, Fukuma S, Akizawa T, Fukagawa M, Kazama JJ, Narita I, Fukuhara S.
  • Journal Title: PLoS One Volume: 10 Issue: 4 Pages: e0122691-e0122691
  • DOI: 10.1371/journal.pone.0122691
  • Peer Reviewed / Open Access
• [Journal Article] Advanced Thymic Cancer Treated with Carboplatin and Paclitaxel in a Patient Undergoing Hemodialysis (2015)
  • Author(s): Miura S, Kagamu H, Sakai T, Nozaki K, Asakawa K, Moro H, Okajima M, Watanabe S, Yamamoto S, Iino N, Goto S, Kazama JJ, Yoshizawa H, Narita I.
  • Journal Title: Internal Medicine Volume: 54 Issue: 1 Pages: 55-58
  • DOI: 10.2169/internalmedicine.54.3484
  • NAID: 130004902998
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed / Open Access
• [Journal Article] Chronic kidney disease induced dysfunction of high density lipoprotein (2014)
  • Author(s): Suguru Yamamoto and Valentina Kon
  • Journal Title: Clin Exp Nephrol Volume: in press Issue: 2 Pages: 251-254
  • DOI: 10.1007/s10157-013-0857-x
  • Peer Reviewed
• [Journal Article] Intact parathyroid hormone and whole parathyroid hormone assay results disagree in hemodialysis patients under cinacalcet hydrochloride therapy. (2014)
  • Author(s): Koda R, Kazama JJ, Matsuo K, Kawamura K, Yamamoto S, Wakasugi M, Takeda T, Narita I.
  • Journal Title: Clin Exp Nephrol Volume: in press
  • Peer Reviewed
• [Journal Article] A hip fracture in a dialysis patient with Abeta2M amyloidosis (2014)
  • Author(s): Kazama JJ, Yamamoto S, Wakasugi M, Narita I
  • Journal Title: Kidney International Volume: 85 Issue: 1 Pages: 214-215
  • DOI: 10.1038/ki.2013.412
  • Peer Reviewed
• [Journal Article] Autophagy: a two-edged sword in diabetes mellitus (2013)
  • Author(s): Suguru Yamamoto, Junichiro J. Kazama, and Masafumi Fukagawa
  • Journal Title: Biochem J Volume: 456 Issue: 3 Pages: e1-e3
  • DOI: 10.1042/bj20131282
  • Peer Reviewed
• [Journal Article] Dysfunctional high-density lipoprotein in patients on chronic hemodialysis. (2012)
  • Author(s): Yamamoto S, Yancey PG, Ikizler TA, Jerome WG, Kaseda R, Cox B, Bian A, Shintani A, Fogo AB, Linton MF, Fazio S, Kon V.
  • Journal Title: J Am Coll Cardiol Volume: 60 Pages: 2372-2379
  • Peer Reviewed
• [Presentation] Continuous Reduction of Protein-bound Uremic Toxins with Improved Oxidative Stress by Oral Charcoal Adsorbent in Maintenance Hemodialysis Patients; An Additional Blood Purification Therapy (2014)
  • Author(s): Suguru Yamamoto, Kentaro Omori, Koji Matsuo, Yoshimitsu Takahashi, Kazuko Kawamura, Minako Wakasugi, Hiroki Maruyama, Hiroshi Watanabe, Toru Maruyama, Junichiro J. Kazama, Ichiei Narita
  • Organizer: Am Soc Nephrol
  • Place of Presentation: Philadelphia convention center, Philadelphia, PA, USA
  • Year and Date: 2014-11-10
• [Presentation] 経口吸着炭薬は維持血液透析患者の 蛋白結合尿毒素物質を減少させる (2014)
  • Author(s): 山本卓、大森健太郎、松尾浩司、 高橋良光、川村和子、 丸山弘樹、渡邊博志、丸山徹、風間順一郎、成田一衛
  • Organizer: 第59回日本透析医学会学術総会・集会
  • Place of Presentation: 神戸国際会議場・神戸国際展示場・神戸ポートピアホテル ワールド記念ホール・クオリティホテル神戸
  • Year and Date: 2014-06-13
• [Presentation] 骨粗鬆症治療の進歩 in CKD-MBD (2014)
  • Author(s): 山本卓、風間順一郎、丸山弘樹、成田一衛
  • Organizer: 第59回日本透析医学会学術総会・集会
  • Place of Presentation: 神戸国際会議場・神戸国際展示場・神戸ポートピアホテル ワールド記念ホール・クオリティホテル神戸
  • Year and Date: 2014-06-13
• [Presentation] Protein-bound uremic toxins were decreased continuously by oral charcoal adsorbent, AST-120, in maintenance hemodialysis patients (2014)
  • Author(s): Suguru Yamamoto, Kentaro Omori, Koji Matsuo, Yoshimitsu Takahashi, Kazuko Kawamura, Minako Wakasugi, Hiroki Maruyama, Hiroshi Watanabe, Toru Maruyama, Junichiro J. Kazama, Ichiei Narita
  • Organizer: The 14th Asian Pacific Congress of Nephrology
  • Place of Presentation: SHINAGAWA PRINCE HOTEL 10-30 Takanawa 4-chome, Minato-ku, Tokyo, 108-8611 Japan
  • Year and Date: 2014-05-16
• [Presentation] Indoxyl sulfate inhibits efflux and promote production of inflammatory cytokine of macrophage (2013)
  • Author(s): Matuso K, Yamamoto S, Kazama JJ, Kawamura K, Wakasugi M, Narita I
  • Organizer: WCN 2013 Satellite Symposium Kidney and Lipids
  • Place of Presentation: ヒルトン福岡
• [Presentation] インドキシル硫酸はマクロファージの炎症反応と細胞毒性を促進する (2013)
  • Author(s): 松尾浩司、山本卓、風間順一郎、川村和子、若杉三奈子、成田一衛
  • Organizer: 第58回日本透析医学会
  • Place of Presentation: 福岡国際会議場
• [Presentation] Inhibition of renin-angiotensin system was associated with lower hospitalization rate due to bone fracture in haemodialysis patients with secondary hyperparathyroidism (2013)
  • Author(s): Suguru Yamamoto, Ryo Kido, Yoshihiro Onishi, Shingo Fukuma, Tadao Akizawa, Masafumi Fukagawa, Junichiro J. Kazama, Ichiei Narita, Shunichi Fukuhara
  • Organizer: 50th ERA-EDTA congress
  • Place of Presentation: トルコ
• [Presentation] Inhibition of renin-angiotensin system was associated with lower hospitalization rate due to bone fracture in haemodialysis patients with secondary hyperparathyroidism
  • Author(s): Suguru Yamamoto, Ryo Kido, Yoshihiro Onishi, Shingo Fukuma, Tadao Akizawa, Masafumi Fukagawa, Junichiro J. Kazama, Ichiei Narita, Shunichi Fukuhara
  • Organizer: 50th ERA-EDTA
  • Place of Presentation: Istanbul, Turkey
• [Presentation] Indoxyl surfate promote THP-1 cell inflammation and reduce cholesterol efflux
  • Author(s): Koji Matsuo, Suguru Yamamoto, Kazuko Kawamura,Minako Wakasugi, Junichiro J. Kazama, Ichiei Narita
  • Organizer: WCN satellite symposium. Kidney and Lipid
  • Place of Presentation: ヒルトン福岡シーホーク, Fukuoko, Japan
• [Presentation] インドキシル硫酸はマクロファージの炎症反応と細胞毒性を促進する
  • Author(s): 松尾浩司、山本卓、川村和子、若杉三奈子、風間順一郎、成田一衛
  • Organizer: 日本透析医学会
  • Place of Presentation: 福岡国際会議場 福岡県
• [Presentation] レニンーアンギオテンシン系の阻害は二次性副甲状腺機能亢進症を合併した血液透析患者の骨折による入院頻度を抑制する
  • Author(s): 山本卓、木戸亮、大西良浩、福間真悟、秋澤忠男、 深川雅史、風間順一郎、成田一衛、福原俊一
  • Organizer: 日本透析医学会
  • Place of Presentation: 福岡国際会議場 福岡県
• [Presentation] Oral activated charcoal adsorbent, AST-120, induced continuous reduction of protein-bound uremic toxins in maintenance hemodialysis patients. A randomized crossover trial
  • Author(s): Suguru Yamamoto, Kentaro Omori, Koji Matsuo, Yoshimitsu Takahashi, Kazuko Kawamura, Minako Wakasugi, Hiroki Maruyama, Junichiro J. Kazama, and Ichiei Narita
  • Organizer: American Society of Nephrology
  • Place of Presentation: Atlanta, USA
• [Book] 透析療法ネクスト (2014)
  • Author(s): 山本卓、深川雅史
  • Total Pages: 7
  • Publisher: 医学図書出版
• [Book] 腎と透析 (2014)
  • Author(s): 山本卓、成田一衛
  • Total Pages: 4
  • Publisher: 東京医学社
• [Book] Dialysis-Related Amyloidosis: Pathogenesis and Clinical Features in Patients Undergoing Dialysis Treatment (2013)
  • Author(s): Suguru Yamamoto, Junichiro James Kazama, Hiroki Maruyama and Ichiei Narita
  • Total Pages: 17
  • Publisher: INTECH