Chronic kidney disease (CKD) as a risk factor for cardiovascular diseases: investigation on pathogenesis and development of therapeutic strategy

• Project/Area Number: 19590969
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Kawasaki Medical School
• Principal Investigator: KASHIHARA Naoki Kawasaki Medical School, 医学部, 教授 (10233701)
• Co-Investigator(Kenkyū-buntansha): KOMAI Norio 川崎医科大学, 医学部, 講師 (40368626) ; SATOH Minoru 川崎医科大学, 医学部, 講師 (70449891)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 慢性腎臓病(CKD) / 生活習慣病 / 心血管病 / メタボリックシンドローム / 肥満 / レニン・アンジオテシン系 / 高血圧 / 血管内皮障害 / 慢性腎臓病 / アンジオテンシンII / 虚血 / アルブミン尿 / 一酸化窒素 / 酸化ストレス / 2光子レーザー顕微鏡 / 内皮機能障害 / 糖尿病性腎症

Research Abstract

本邦で慢性腎臓病(Chronic Kidney Disease : CKD)が増加している。その主因は糖尿病、肥満、メタボリックシンドローム等の生活習慣病の増加と高齢化である。CKDは腎不全をもたらすだけでなく、心血管病(CVD)の強い危険因子でもある。本研究では、まずCKDの発症・進展機構の詳細を解明した。特になぜアルブミン尿が出現しCVDを合併するのか、その機構を明らかにした。本研究で得られたCKDの基盤病態の理解は、本症の予防と治療法立案に貢献するものである。

Research Products

• [Journal Article] Oral adsorbent AST-120 ameliorates endothelial dysfunction independent of renal function in rats with subtotal nephrectomy (2009)
  • Author(s): Namikoshi T, Tomita N, Satoh M, Sakuta T, Kuwabara A, Kobayashi S, Higuchi Y, Nishijima F, Kashihara N
  • Journal Title: Hypertens Res 32 Pages: 194-200
  • NAID: 10024829995
  • Peer Reviewed
• [Journal Article] Direct measurement of nitric oxide concentration in CAPDdialysate (2009)
  • Author(s): Mochizuki S, Takayama A, Sasaki T, Horike H, Kashihara N, Ogasawara Y, Kajiya F, Kitawaki T, Oka H
  • Journal Title: Perit Dial Int. 29 Pages: 111-114
  • Peer Reviewed
• [Journal Article] C/EBP- beta modulates transcription of tubuleinterstitial nephritis antigen in obstructive uropathy (2009)
  • Author(s): Xie P, Sun L, Nayak B, Haruna Y, Liu FY, Kashihara N, Kanwar YS
  • Journal Title: J Am Soc Nephrol 20 Pages: 807-819
  • Peer Reviewed
• [Journal Article] Oral adsorbent AST-120 ameliorates endothelial dysfunction independent of renal function in rats with subtotal nephrectomy. (2009)
  • Author(s): Namikoshi T, Tomita N, Satoh M, Sakuta T, Kuwabara A, Kobayashi S, Higuchi Y, Nishijima F, Kashihara N
  • Journal Title: Hypertens Res 32 Pages: 194-200
  • NAID: 10024829995
  • Peer Reviewed
• [Journal Article] Angiotensin II type 1 receptor blocker ameliorates uncoupled endothelial nitric oxide synthase in rats with experimental diabetic nephropathy (2008)
  • Author(s): Satoh M, Fujimoto S, Arakawa S, Yada T, Namikoshi T, Haruna Y, Horike H, Sasaki T, Kashihara N
  • Journal Title: Nephrol Dial Transplant 23 Pages: 3806-13
  • Peer Reviewed
• [Journal Article] Olmesartan ameliorates progressive glomerular injury in subtotal nephrectomized rats through suppression of superoxide production (2008)
  • Author(s): Fujimoto S,Satoh M,Horike H,Hatta H,Haruna Y,Kobayashi S,Namikoshi T,Arakawa S,Tomita N,Kashihara N
  • Journal Title: Hypertens Res 31 Pages: 305-313
  • NAID: 10024359991
  • Peer Reviewed
• [Journal Article] Rap1b GTPase ameliorates glucose-induced mitochondrialdysfunction (2008)
  • Author(s): Sun L, Xie P, Wada J, Kashihara N, Liu FY, Zhao Y, Kumar D, Chugh SS, DaneshFR, Kanwar YS
  • Journal Title: J Am Soc Nephrol 19 Pages: 2293-2301
• [Journal Article] Pioglitazone enhances the antihypertensive and renoprotective effects of candesartan in Zucker obese rats fed a high-protein diet (2008)
  • Author(s): Namikoshi T, TomitaN, Satoh M,Haruna Y, Kobayashi S, Komai N,Sasaki T, Kashihara N
  • Journal Title: Hypertens Res 31 Pages: 745-755
  • NAID: 10021934851
  • Peer Reviewed
• [Journal Article] Blockade of serotonin 2A receptor improves glomerular endothelial function in rats with streptozotocin-induced diabetic nephropathy (2008)
  • Author(s): kobayashi S, Satoh M, Namikoshi T, Haruna Y, Fujimoto S, Arakawa S, Komai N, Tomita N, Sasaki T, Kashihara N
  • Journal Title: Clin Exp Nephrol.Clin Exp Nephrol 12 Pages: 119-125
  • NAID: 10025352144
  • Peer Reviewed
• [Journal Article] Angiotensin II type 1 receptor blocker ameliorates uncoupled endothelial nitric oxide synthase in rats with experimental diabetic nephropathy. (2008)
  • Author(s): Satoh M, Fujimoto S, Arakawa S, Yada T, Namikoshi T, Haruna Y, Horike H, Sasaki T, Kashihara N
  • Journal Title: Nephrol Dial Transplant 23 Pages: 3806-13
  • Peer Reviewed
• [Journal Article] Pioglitazone enhances the antihypertensive and renoprotective effects of candesartan in Zucker obese rats fed a high-protein diet. (2008)
  • Author(s): Namikoshi T, Tomita N, Satoh M, Haruna Y, Kobayashi S, Komai N, Sasaki T, Kashihara N
  • Journal Title: Hypertens Res 31 Pages: 745-755
  • NAID: 10021934851
  • Peer Reviewed
• [Journal Article] Olmesartan ameliorates progressive glomerular injury in subtotal nephrectomized rats through suppression of superoxide production. (2008)
  • Author(s): Fujimoto S, Satoh M, Horike H, Hatta H, Haruna Y, Kobayashi S, Namikoshi T, Arakawa S, Tomita N, Kashihara N
  • Journal Title: Hypertens Res 31 Pages: 305-313
  • NAID: 10024359991
  • Peer Reviewed
• [Journal Article] Blockade of serotonin 2A receptor improves glomerular endothelial function in rats with streptozotocin-induced diabetic nephropathy. Clin Exp Nephrol. (2008)
  • Author(s): Kobayashi S, Satoh M, Na mikoshi T, Haruna Y, Fujimoto S, Arakawa S, Komai N, Tomita N, Sasaki T, Kashihara N
  • Journal Title: Clin Exp Nephrol 12 Pages: 119-125
  • Peer Reviewed
• [Journal Article] Olmesartan ameliorates progressive glomerular injury in subtotal nephrectomized rats through suppression of superoxide production (2008)
  • Author(s): Fujimoto S, et. al.
  • Journal Title: Hypertens Res 31 Pages: 305-313
  • Peer Reviewed
• [Journal Article] Olmesartan ameliorates renovascular injury and oxidative stress in Zucker obese rats enhanced by dietary protein (2007)
  • Author(s): Namikoshi T, et. al.
  • Journal Title: Am J Hypertens 20 Pages: 1086-1091
  • Peer Reviewed
• [Journal Article] Pioglitazone ameliorates endothelial dysfunction in obese rats with neph ropathy (2007)
  • Author(s): Namikoshi T, et. al.
  • Journal Title: Biochem Biophys Res Commun. 361 Pages: 835-840
  • Peer Reviewed
• [Presentation] Uremic Toxins and High Dietary Protein Intake Induce Endo thelial Dysfunction in Rats with Chronic Kidney Didease (2009)
  • Author(s): Namikoshi T, Tomita N, Satoh M, Kuwabara A, Nagasu H, Yorimitsu D, Komai N,Kashihara N
  • Organizer: 第73回日本循環器学会総会・学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-03-20
• [Presentation] Azelnidipin Prevent Renal Dysfunction in Dahl Salt-Sensitive Rats by Suppression of Sympathetic Nerve sysytem (2009)
  • Author(s): Nagasu H, Satoh M, Kuwabara A, Yorimitsu D, Namikoshi T, Tomita N,Sasaki T, Kashihara N
  • Organizer: 第73回日本循環器学会総会・学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-03-20
• [Presentation] Uremic Toxins and High Dietary Protein Intake Induce Endothelial Dysfunction in Rats with Chronic Kidney Didease. (2009)
  • Author(s): Tamehachi Namikoshi, N aruya Tomita, Minoru Satoh, Takeo Sakuta, Atsunori Kuwabara, Hajime Nagasu, Daisuke Yorimitsu, Norio Komai, Naoki Kashihara
  • Organizer: 第73回日本循環器学会総会・学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-03-20
• [Presentation] Azelnidipin Prevent Renal Dysfunction in Dahl Salt-Sensitive Rats by Suppression of Sympathetic Nerve sysytem. (2009)
  • Author(s): Hajime Nagasu, Monoru Satoh, Atsunori Kuwabara, Daisuke Yorimitsu, Tamehachi Namikoshi, Naruya Toinita, Tamaki Sasaki, Naoki Kashihara
  • Organizer: 第73回日本循環器学会総会・学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-03-20
• [Presentation] Angiotensin II Type 1 Receptor Blocker Ameliorates Uncoupled Endothelial Nitric Oxide Synthase in Rats with Streptozotocine Induced Diabetic Nephropathy (2008)
  • Author(s): Satoh M, Fujimoto S, Haruna Y, Yada T,Kuwabara A, Nagasu H,Yorimitsu D, Namikoshi T, Tomita N, Sasaki T, Kashihara N
  • Organizer: American Society of Nephrology 41st Annual Meeting & Scientific Exposition
  • Place of Presentation: Philadelphia, Pennsylvania
  • Year and Date: 2008-11-06
• [Presentation] Oral adsorbent AST-120 ameliorates endothelial dysfunction and alleviates oxidative stress in aorta independent of renal function in subtotally nephrectomized rats (2008)
  • Author(s): Namikoshi T, Tomita N, Satoh M, Sakuta T, Kuwabara A, Nagasu H, Yorimitsu D, Higuchi Y,Nishijima F, Kashihara N
  • Organizer: American Society of Nephrology 41st Annual Meeting & Scientific Exposition
  • Place of Presentation: Philadelphia, Pennsylvania
  • Year and Date: 2008-11-06
• [Presentation] Angiotensin II Type 1Receptor Blocker Ameliorates Uncoupled Endothelial Nitric Oxide Synthase in Rats with Streptozotocine Induced Diabetic Nephropathy. (2008)
  • Author(s): Minoru Satoh, Sohachi Fujimoto, Yoshisuke Haruna, Toyotaka Yada, Atsunori Kuwabara, Hajime Nagasu, Daisuke Yorimitu, Tamehachi Namikoshi, Naruya Tomita, Tamaki Sasaki, Naoki Kashihara
  • Organizer: American Society of Nephrology 41st Annual Meeting & Scientific Exposition
  • Place of Presentation: Philadelphia, Pennsylvania
  • Year and Date: 2008-11-06
• [Presentation] Oral adsorbent AST-120 ameliorates endothelial dysfunction and alleviates oxidative stress in aorta independent of renal function in subtotally nephrectomized rats. (2008)
  • Author(s): Tamehachi Namikoshi, Naruya Tomita, Minoru Satoh, Takeo Sakuta, Atsunori Kuwabara, Hajime Nagasu, Daisuke Yorimitsu, Yuusuke Higuchi, Fuyuhiko Nishijima, Naoki Kashihara
  • Organizer: American Society of Nephrology 41st Annual Meeting & Scientific Exposition
  • Place of Presentation: Philadelphia, Pennsylvania
  • Year and Date: 2008-11-06
• [Presentation] Chronic Kidney disease as a carduovascular risk factor-Analysis by visualization of the in vivo renal microcirculation (2008)
  • Author(s): Satoh M, Kashihara N
  • Organizer: 第34回日本微小循環学会年次総会
  • Place of Presentation: 東京
  • Year and Date: 2008-09-21
• [Presentation] Chronic Kidney disease as a carduovascular risk factor-Analysis by visualization of the in vivo renal microcirc ulation- (2008)
  • Author(s): Minoru Satho, Naoki Kashihara
  • Organizer: 第34回日本微小循環学会年次総会
  • Place of Presentation: 東京
  • Year and Date: 2008-09-21
• [Presentation] 塩酸サルポグレラートの糖尿病モデルにおける腎での活性酸素種(ROS)抑制効果 (2007)
  • Author(s): 小林 伸哉
  • Organizer: 第50回日本腎臓学会学術総会
  • Place of Presentation: 浜松市
  • Year and Date: 2007-05-26