Role and Action of New Stimulants and inhibitors on Bone Metabolism in Chronic Kidney Disease

2008 Fiscal Year Final Research Report

• Project/Area Number: 19590950
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Kobe University
• Principal Investigator: FUKAGAWA Masafumi Kobe University, 医学部附属病院, 准教授 (00211516)
• Co-Investigator(Kenkyū-buntansha): HAMADA Yasuhiro 神戸大学, 医学部附属病院, 特定助教 (30397830)
• Project Period (FY): 2007 – 2008
• Keywords: 人工透析学 / 骨代謝

Research Abstract

慢性腎臓病(Chronic Kidney Disease: CKD)とその最大の原因である糖尿病における骨代謝異常の機序,特に骨の副甲状腺ホルモン(PTH)に対する抵抗性と骨芽細胞機能抑制の発症機序について検討したところ,尿毒症物質であるインドキシル硫酸が有機酸トランスポーターを通じて細胞内に入り,酸化ストレスを惹起して,PTHの作用を減弱させることを示した.また,酸化ストレスは,糖尿病における骨芽細胞機能低下にも大きな役割を果たしていることが,糖尿病動物モデルや抗酸化物質過剰発現マウスを用いた実験で明らかになった.これらの知見は,CKDおける骨回転の調節異常の治療法につながると考えられる.

Research Products

• [Journal Article] The calcimimetic R-568 retards progression of uremia-enhanced vascular calcification and atherosclerosis in apolipoprotein E deficient (apoE-/-) mice. Atherosclerosis (2009)
  • Author(s): Ivanovski O, Nikolov IG, Joki N, Caudrillier A, Phan O, Mentaverri R, Maizel J, Nguyen-Khoa T, Fukagawa M, Kamel S, Lacour B, Drueke TB, Massy Z
  • Pages: 0
  • Peer Reviewed
• [Journal Article] Oral charcoal adsorbent (AST-120) prevents the progression of cardiac damage in chronic kidney disease through the suppression of oxidative stress. Nephrol Dial Transplant (2009)
  • Author(s): Fujii H, Nishijima F, Goto S, Sugano M, Yamato H, Kitazawa R, Kitazawa S, Fukagawa M
  • Pages: 0
  • Peer Reviewed
• [Journal Article] Pharmacokinetic target for ciclosporin A-based regimens in renal transplantation: Implications of maintaining 1,25-dihydroxyvitamin D3 synthesis. Clin Transplant (2009)
  • Author(s): Sato T, Fukagawa M, Uchida K, Katayama A, Nagasaka T, Matsuoka S, Goto N, Tominaga Y, Kobayashi T, Nakao A
  • Journal Title: 23 Pages: 368-374
  • Peer Reviewed
• [Journal Article] Thioredoxin-1 overexpression in transgenic mice attenuates streptozotocin-induced diabetic oeteoporosis: A novel role of oxidative stress and therapeutic implications. Bone (2009)
  • Author(s): Hamada Y, Fujii H, Kitazawa R, Yodoi J, Kitazawa S, Fukagawa M
  • Journal Title: 44 Pages: 936-941
  • Peer Reviewed
• [Journal Article] Cinacalcet (KRN 1493) effectively decreases serum intact PTH level with favorable control of serum phohphorus and calcium levels in Japanese dialysis patients. Nephrol Dial Transplant (2008)
  • Author(s): Fukagawa M, Yumita S, Akizawa T, Uchida E, Tsukamoto Y, Iwasaki M, Koshikawa S, and KRN1493 study group
  • Journal Title: 23 Pages: 328-335
  • Peer Reviewed
• [Journal Article] Direct calcitriol or its analogue injection improves abnormal gene expression of hyperplastic parathyroid gland in secondary hyperparathyroidism. Am J Nephrol (2008)
  • Author(s): Shiizaki K, Fukagawa M, Yuan Q, Hatamura I, Nii-Kono T, Saji F, Shigematsu T, Akizawa T
  • Journal Title: 28 Pages: 59-66
  • Peer Reviewed
• [Journal Article] Bone formation in the newly established non-obese type 2 diabetic model rats; Spontaneously Diabetic Torii (SDT) rats. Bone (2008)
  • Author(s): Fujii H, Hamada Y, Fukagawa M
  • Journal Title: 42 Pages: 372-379
  • Peer Reviewed
• [Journal Article] Effects of serum levels of calcium, phosphorus, and intact PTH on survival in chronic hemodialysis patients in Japan. Ther Aphr Dial (2008)
  • Author(s): Nakai S, Akiba T, Kazama JJ, Yokoyama K, Fukagawa M. Tominaga Y, Iseki K, Tsubakihara Y
  • Journal Title: 12 Pages: 49-54
  • Peer Reviewed
• [Journal Article] Alteration of duodenal iron absorption in adenine-induced renal failure rats: a possible mechanism of iron deficiency in chronic kidney disease patients with erythropoietin treatment. Nephrol Dial Transplant (2008)
  • Author(s): Hamada Y, Nii-Kono T, Moriguchi Y, Higuchi M, Fukagawa M
  • Journal Title: 23 Pages: 1886-1891
  • Peer Reviewed
• [Journal Article] Serum hepcidin as an indicator of iron status in dialysis patients. Ther Aphr Dial (2008)
  • Author(s): Tsuchihashi D, Abe T, Komaba H, Fujii H, Hamada Y, Nii-Kono T, Tanaka M, Fukagawa M
  • Journal Title: 12 Pages: 226-231
  • Peer Reviewed
• [Journal Article] Putative role of asymmetric dimethylarginine in microvascular disease of kidney and heart in hypertensive patients, Am J Hypertension (2008)
  • Author(s): Fujii H, Takiuchi S, Kawano Y, Fukagawa M
  • Journal Title: 21 Pages: 650-656
  • Peer Reviewed
• [Journal Article] Putative role of endothelial lipase in cardiovascular disease in dialysis patients with malnutrition and inflammation. Am J Nephrol (2008)
  • Author(s): Fujii H, Fukuda A, Tanaka M, Kojima Y, Ishida T, Hirata K, Fukagawa M
  • Journal Title: 28 Pages: 974-981
  • Peer Reviewed
• [Journal Article] Percutaneous ethanol injection therapy for advanced renal hyperparathyroidism in Japan: A 2004 survey by the Japanese Society for Parathyroid Intervention. NDT Plus (Supple) (2008)
  • Author(s): Kakuta T, Fukagawa M, Kitaoka M, Koiwa F, Onoda N, Tominaga Y, Akizawa T, Kurokawa K
  • Journal Title: 1 Pages: iii21-iii25
  • Peer Reviewed
• [Journal Article] Long-term prognosis (over 5 years) of parathyroid function in chronic dialysis patients after PEIT guided by ultrasonography. NDT Plus (Supple) (2008)
  • Author(s): Tanaka R, Kakuta T, Koiwa F, Fukagawa M, Saito A
  • Journal Title: 1 Pages: iii29-iii34
  • Peer Reviewed
• [Journal Article] Association between long-term efficacy of cinacalcet and parathyroid gland volume in haemodialysis patients with secondary hyperparathyroidism. NDT Plus (Supple) (2008)
  • Author(s): Tanaka M, Nakanishi S, Komaba H, Itoh K, Matsushita K, Fukagawa M
  • Journal Title: 1 Pages: iii49-iii53
  • Peer Reviewed
• [Journal Article] The whole-PTH/intact-PTH ratio is a useful predictor of severity of secondary hyperparathyroidism. NDT Plus (Supple) (2008)
  • Author(s): Tanaka M, Komaba H, Itoh K, Matsushita K, Matsushita K, Hamada Y, Fujii H, Fukagawa M
  • Journal Title: 1 Pages: iii59-iii62
  • Peer Reviewed
• [Journal Article] Relationship between the weight of parathyroid glands and their secretion of parathyroid hormone in hemodialysis patients with secondary hyperparathyroidism. Ther Aphre Dial (2008)
  • Author(s): Kakuta T, Tanaka R, Kanai G, Miyamoto Y, Inagaki M, Suzuki H, Fukagawa M, Saito A
  • Journal Title: 12 Pages: 385-390
  • Peer Reviewed
• [Journal Article] Reduced dialysate calcium improves mineral metabolism in hemodialysis patients. Clin Nephrol (2007)
  • Author(s): Fujimori A, Yorifuji M, Sakai M, Fukagawa M
  • Journal Title: 67 Pages: 20-24
  • Peer Reviewed
• [Journal Article] A Possible role of thioredoxine interacting protein in the pathogenesis of streptozotocin-induced diabetic nephropathy. Kobe J Med Sci (2007)
  • Author(s): Hamada Y, Fukagawa M
  • Journal Title: 53 Pages: 53-61
  • Peer Reviewed
• [Journal Article] Indoxyl sulfate induced skeletal resistance to PTH in osteoblastic cells, Kidney Int (2007)
  • Author(s): Nii-Kono T, Iwasaki Y, Yamato H, Fukagawa M
  • Journal Title: 71 Pages: 738-743
  • Peer Reviewed
• [Journal Article] Histomorphometric analysis of diabetic osteopenia in streptozotocin-induced diabetic mice: a possible role of oxidative stress. Bone (2007)
  • Author(s): Hamada Y, Kitazawa S, Kitazawa R, Fujii H, Kasuga M, Fukagawa M
  • Journal Title: 40 Pages: 1408-1414
  • Peer Reviewed
• [Journal Article] Overexpression of thioredoxin 1 in transgenic mice suppresses development of diabetic nephropathy. Nephrol Dial Transplant (2007)
  • Author(s): Hamada Y, Miyata S, Nii-Kono T, Kitazawa R, Kitazawa S, Higo S, Fukunaga M, Ueyama S, Nakamura H, Yodoi J, Fukagawa M, Kasuga M
  • Journal Title: 22 Pages: 1547-1557
  • Peer Reviewed
• [Journal Article] Fibroblast growth factor-23 (FGF-23) in patints with transient hypoparathyroidism: Its important role in serum phosphate regulation. Endocrine J (2007)
  • Author(s): Yamashita H, Yamazaki Y, Hasagawa H, Yamashita T, Fukumoto S, Shigematsu T, Kazama JJ, Fukagwa M, Noguchi S
  • Journal Title: 54 Pages: 465-470
  • Peer Reviewed
• [Journal Article] Relationship between parathyroid hormone and cardiac abnormalities in chronic dialysis patients without cardiac disease, Internal Med (2007)
  • Author(s): Fujii H, Kim J-I, Abe T, Umezu M, Fukagawa M
  • Journal Title: 46 Pages: 1507-1512
  • Peer Reviewed
• [Presentation] V International Symposium: Advances in Bone and Mineral Disorders in CKD (2009)
  • Author(s): Fukagawa M
  • Organizer: FGF23, phosphate, and VDRE in dialysis
  • Place of Presentation: Oviedo, Spain
  • Year and Date: 2009-05-20
• [Presentation] Workshop of Earthquake Related AKI, co-organized ISN COMGAN & Chinese Society of Nephrology (2008)
  • Author(s): Fukagawa M
  • Organizer: Nephrology in earthquakes: Sharing experiences and information
  • Place of Presentation: Chengdu, China
  • Year and Date: 2008-12-16
• [Presentation] Vitamin D receptor activator (VDRA) treatment attenuate increased oxidative stress in hemodialysis patients (2008)
  • Author(s): Tanaka M, Tokunaga T, Komaba H, Itoh K, Matsushita K, Maruyama T, Otagiri M, Fukagawa M
  • Organizer: America Society of Nephrology
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2008-11-07
• [Presentation] Functional induction of target genes in parathyroid cell by direct injection (2008)
  • Author(s): Shiizaki K, Hatamura I, Nakazawa E, Saji F, Imazu Y, Watanabe Y, Ueda Y, Fukagawa M, Akizawa T, Kusano E
  • Organizer: American Society of Nephrology
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2008-11-07
• [Presentation] Different roles of oxidative stress and asymmetric dimethylarginine for the progression of diabetic nephropathy in the newly established non-obese type 2 diabetic model rata: Spontaneously Diabetic Torii (SDT) rats (2008)
  • Author(s): Fujii H, Hamada Y, Komaba H, Kitazawa R, Kitazawa S, Fukagawa M
  • Organizer: American Society of Nephrology
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2008-11-07
• [Presentation] Sevelamer hydrochloride elevates serum homocysteine levels through inhibiting absorption of folic acid in chronic dialysis (2008)
  • Author(s): Goto S, Fujii H, Kim J-I, Fukagwa M
  • Organizer: American Society of Nephrology
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2008-11-07
• [Presentation] Putative roles of receptors for AGEs (RAGE) in bone metabolism under non-diabetic and diabetic (2008)
  • Author(s): Hamada Y, Goto S, Komaba H, Fujii H, Fukagawa M
  • Organizer: American Society of Nephrology
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2008-11-07
• [Presentation] Treatment of various rebal involvements associated with multicentric Castleman's disease with anti-interleukin-6 receptor antibody (Tocilzumab) (2008)
  • Author(s): Komaba H, Nakazawa T, Tsuji G, Yamaguchi Y, Kumagai S, Fukagawa M
  • Organizer: American Society of Nephrology
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2008-11-07
• [Presentation] Kidney dysfunction distuebs collagen maturation in adynamic bone disease as assessed by confocal laser raman spectroscopy (2008)
  • Author(s): Iwasaki Y, Yamato H, Fukagawa M
  • Organizer: American Society for Bone and Mineral Research
  • Place of Presentation: Montreal, Canada
  • Year and Date: 2008-09-14
• [Presentation] Functional induction of target genes in parathyroid cell by direct injection technique (2008)
  • Author(s): Shiizaki K, Hatamura I, Nalazawa E, Iwazu Y, Watanabe Y, Fukagawa M, Akizawa T, Kusano E
  • Organizer: American Society for Bone and Mineral Research
  • Place of Presentation: Montreal Canada
  • Year and Date: 2008-09-14
• [Presentation] FGF-23 in CKD, ectopic calcification, post-transplantation hypophosphatemia, and nephrolitiasis. (2008)
  • Author(s): Fukagawa M
  • Organizer: Symposium, XLV ERA-EDTA Congress
  • Place of Presentation: Stockholm, Sweden
  • Year and Date: 2008-05-12
• [Presentation] CKD-MBD in diabetes: from bench to bedside (2008)
  • Author(s): Fukagawa M
  • Organizer: Updates on CKD-MBD, Korea University
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2008-04-26
• [Presentation] PTH assay: from pronciple to practice (2008)
  • Author(s): Fukagawa M
  • Organizer: Updates on CKD-MBD, Korea University, Seoul
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2008-04-26
• [Presentation] Asymmetric dimethylarginine reflects an incipient atherosclerosis in both kidney and heart (2007)
  • Author(s): Fujii H, Takiuchi S, Kawano Y, Fukagawa M
  • Organizer: ERA-EDTA Congress
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2007-06-22
• [Presentation] Randomized, placebo-controlled trial of cinacalcet (KRN1493) in Japanese dialysis patients with more severe hyperparathyroidism and longer dialysis (2007)
  • Author(s): Fukagawa M, Yumita S, Akizawa T, Tsukamoto Y, Uchida E, Iwasaki M, Koshikawa S
  • Organizer: ERA-EDTA Congress
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2007-06-22
• [Presentation] 1-84PTH/intact PTH ratio is a useful predictor of the severity of secondary hyperparathyroidism (2007)
  • Author(s): Tanaka M, Itoh K, Matsushita K, Matsushita K, Hamada Y, Fujii H, Fukagawa M
  • Organizer: ERA-EDTA Congress
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2007-06-22
• [Book] Fluid & Electrolyte Disorders, in 2008 Current Medical Diagnosis & Treatment(McPhee SJ, Papadakis, MA) (2009)
  • Author(s): Cho KC, Fukagawa M, Kurokawa K
  • Total Pages: 766-794
  • Publisher: Lange Medical Books/McGrow Hill, New York
• [Book] Fluid & Electrolyte Disorders, in 2008 Current Medical Diagnosis & Treatment(McPhee SJ, Papadakis, MA) (2008)
  • Author(s): Fukagawa M, Kurokawa K, Papadakis MA
  • Total Pages: 757-784
  • Publisher: Lange Medical Books/McGrow Hill, New York
• [Book] (2008)
  • Author(s): Fukagawa M, Tanaka M
  • Publisher: Hypophosphatemia, Encyclopedic reference of molecular mechanism of disease,
• [Book] Fluid & Electrolyte Disorders, in 2007 Current Medical Diagnosis & Treatment(Tierney LM Jr, McPhee SJ,Papadakis MA) (2007)
  • Total Pages: 887-913
  • Publisher: Lange Medical Books/McGrow Hill, New York
• [Book] Imaging of intervension pf parathyroid hyperplasia, in Spectrum of Renal Osteodystrophy and Vascular Caicification in Uremia( Olgaar K, Silver J, Salusky I)
  • Author(s): Komaba H, Tanaka M, Fukagawa M
  • Publisher: Oxford University Press