Investigation on the mechanisms of association of chronic kidney disease(CKD) and cardiovascular diseases.

2011 Fiscal Year Final Research Report

• Project/Area Number: 21591047
• 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 川崎医科大学, 医学部, 教授 (10233701)
• Co-Investigator(Kenkyū-buntansha): TOMITA Naruya 川崎医科大学, 医学部, 准教授 (70314432) ; SATOH Minoru 川崎医科大学, 医学部, 講師 (70449891)
• Project Period (FY): 2009 – 2011
• Keywords: 慢性腎臓病 / アルブミン尿 / 内皮障害 / グライコカリックス

Research Abstract

Albuminuria is strongly associated with cardiovascular diseases. Endothelial dysfunction has been speculated to be involved in the pathogenesis of albuminuria. We have successfully developed a novel in vivo imaging technique which enables us to visualize microcirculation and permeability change in the kidney. Using this technique, we found hyperfiltration of macromolecules precede albuminuria. We also demonstrated endothelial dysfunction, indicated by the loss of glycocalyx along the glomerular vascular wall and uncoupling of eNOS is deeply involved in this condition.

Research Products

• [Journal Article] Azelnidipine attenuates glomerular damage in Dahl salt-sensitive rats by suppressing sympathetic nerve activity (2012)
  • Author(s): Nagasu, H, Satoh, M, Fujimoto, S, Tomita, N, Sasaki, T & Kashihara, N
  • Journal Title: Hypertens Res Volume: 35 Pages: 348-55
• [Journal Article] Endothelial dysfunction promotes the transition from compensatory renal hypertrophy to kidney injury after unilateral nephrectomy in mice (2012)
  • Author(s): Nagasu, H, Satoh, M, Kidokoro, K, Nishi, Y, Channon, KM, Sasaki, T & Kashihara, N
  • Journal Title: Am J Physiol Renal Physiol Volume: 302 Pages: F1402-8
• [Journal Article] Overexpression of klotho protein modulates uninephrectomy-induced compensatory renal hypertrophy by suppressing IGF-I signals (2011)
  • Author(s): Nagasu, H, Satoh, M, Kuwabara, A, Yorimitsu, D, Kidokoro, K, Nishi, Y, Tomita, N, Sasaki, T & Kashihara, N
  • Journal Title: Biochem Biophys Res Commun
• [Journal Article] Comparison of combination therapy of olmesartan plus azelnidipine or hydrochlorothiazide on renal and vascular damage in SHR/NDmcr-cp rats (2011)
  • Author(s): Nagasu, H, Satoh, M, Yorimitsu, D, Tomita, N, Sasaki, T & Kashihara, N
  • Journal Title: Kidney Blood Press Res Volume: 34 Pages: 87-96
• [Journal Article] Mitochondrial damage-induced impairment of angiogenesis in the aging rat kidney (2011)
  • Author(s): Satoh, M, Fujimoto, S, Horike, H, Ozeki, M, Nagasu, H, Tomita, N, Sasaki, T & Kashihara, N
  • Journal Title: Lab Invest Volume: 91 Pages: 190-202
• [Journal Article] Clear Correlation of Tetrahydrobiopterin with Nitric Oxide Bioavailability in Continuous Ambulatory Peritoneal Dialysis (2010)
  • Author(s): Mochizuki, S, Takayama, A, Sasaki, T, Yada, T, Endo, K, Horike, H, Kashihara, N, Ogasawara, Y & Kajiya, F
  • Journal Title: Blood Purif Volume: 30 Pages: 96-97
• [Journal Article] Renal denervation reduces glomerular injury by suppressing NAD(P) H oxidase activity in Dahl salt-sensitive rats (2010)
  • Author(s): Nagasu, H, Satoh, M, Kuwabara, A, Yorimitsu, D, Sakuta, T, Tomita, N & Kashihara, N
  • Journal Title: Nephrol Dial Transplant
• [Journal Article] Involvement of the renin-angiotensin system in the development of vascular damage in a rat model of arthritis : effect of angiotensin receptor blockers (2010)
  • Author(s): Sakuta, T, Morita, Y, Satoh, M, Fox, DA & Kashihara, N
  • Journal Title: Arthritis Rheum Volume: 62 Pages: 1319-28
• [Journal Article] Mitochondrial damage-induced impairment of angiogenesis in the aging rat kidney (2010)
  • Author(s): Satoh, M, Fujimoto, S, Horike, H, Ozeki, M, Nagasu, H, Tomita, N, Sasaki, T & Kashihara, N
  • Journal Title: Lab Invest
• [Journal Article] Oxidative Stress in Diabetic Nephropathy (2010)
  • Author(s): Kashihara, N, Haruna, Y, Kondeti, VK & Kanwar, YS
  • Journal Title: Curr Med Chem Volume: 17(34) Pages: 4256-69
• [Journal Article] Telmisartan improves endothelial dysfunction and renal autoregulation in Dahl salt-sensitive rats (2010)
  • Author(s): Satoh, M, Haruna, Y, Fujimoto, S, Sasaki, T & Kashihara, N
  • Journal Title: Hypertens Res Volume: 33 Pages: 135-42
• [Journal Article] Deterioration of glomerular endothelial surface layer induced by oxidative stress is implicated in altered permeability of macromolecules in Zucker fatty rats (2010)
  • Author(s): Kuwabara, A, Satoh, M, Tomita, N, Sasaki, T & Kashihara, N
  • Journal Title: Diabetologia Volume: 53 Pages: 2056-65
• [Journal Article] In vivo visualization of glomerular microcirculation and hyperfiltration in streptozotocin-induced diabetic rats (2010)
  • Author(s): Satoh, M, Kobayashi, S, Kuwabara, A, Tomita, N, Sasaki, T & Kashihara, N
  • Journal Title: Microcirculation Volume: 17 Pages: 103-12
• [Journal Article] Erythropoietin Enhances Hydrogen Peroxide-Mediated Dilatation of Canine Coronary Collateral Arterioles during Myocardial Ischemia in Dogs in Vivo (2010)
  • Author(s): Yada, T, Shimokawa, H, Hiramatsu, O, Satoh, M, Kashihara, N, Takaki, A, Goto, M, Ogasawara, Y & Kajiya, F
  • Journal Title: Am J Physiol Heart Circ Physiol
• [Presentation] Endothelial Cell Interacted with Podocyte and Mesangial Cells Via NAD(P) H Oxidase (2012)
  • Author(s): Nagasu, H, Satoh, M, Kidokoro, K, Kashihara, N
  • Organizer: 49th ERA-EDTA Congress
  • Place of Presentation: Paris, France
  • Year and Date: 2012-05-25
• [Presentation] Preservation of Endothelial GTP Cyclohydrolase I Activity and Improvement of Renal Nitric Oxide Availability Prevent the Development of Diabetic Nephropathy (2012)
  • Author(s): Kidkoro, K, Satoh, M, Nagasu, H, Nishi, Y, Ihoriya, C, Kadoya, H, Yada, T, Keith M Channon, Sasaki, T, Kashihara N
  • Organizer: 49th ERA-EDTA Congress
  • Place of Presentation: Paris, France
  • Year and Date: 2012-05-25
• [Presentation] The Glycocalyx (2011)
  • Author(s): Kashihara, N
  • Organizer: Third International Symposium on Albuminuria
  • Place of Presentation: Groningen, the Netherlands
  • Year and Date: 2011-11-30
• [Presentation] Implications of Oxidative Stress Derived from Endothelial NAD(P) H Oxdase in the Development of Diabetic Nephropathy (2011)
  • Author(s): Nagasu, H, Satoh, M, Kuwabara, A, Kidokoro, K, Tomita, N, Sasaki, T, Kashihara, N
  • Organizer: American Society of Nephrology Kidney Week 2011
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2011-11-11
• [Presentation] Cyclic GMP Dependent Protein Kinase-Akt Pathway is Essential for Compensatory Renal Hypertrophy and Maintenance Renal Function After Unilateral Nephrectomy (2011)
  • Author(s): Nagasu, H, Satoh, M, Kidokoro, K, Tomita, N, Sasaki, T, Kashihara, N
  • Organizer: World Congress of N ephrology 2011
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2011-04-10
• [Presentation] Nitric Oxide Induces Tubular Cell Hypertrophy Via Cyclic GMP-Dependedent Protein Kinase in Rat Compensatory Renal Hypertrophy (2010)
  • Author(s): Nagasu, H, Satoh, M, Tomita, N, Sasaki, T, Kashihara, N
  • Organizer: American Society of Nephrology Renal Week 2010
  • Place of Presentation: Denver, USA
  • Year and Date: 2010-11-19