Experimental study for the regression of chronic kidney disease and mineral bone disorder(CKD-MBD)

• Project/Area Number: 20590985
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Showa University
• Principal Investigator: AKIZAWA Tadao Showa University, 医学部, 教授 (40102339)
• Co-Investigator(Kenkyū-buntansha): OGATA Hiroaki 昭和大学, 医学部, 講師 (30296959) ; MIZOBUCHI Masahide 昭和大学, 医学部, 助教 (90465203)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 慢性腎臓病ミネラル骨代謝異常症 / 二次性副甲状腺機能亢進症 / 腎性骨異栄養症 / 異所性石灰化 / 慢性炎症 / エラスチン / 慢性腎不全 / CKD-MBD / 動脈硬化 / カルシウム受容作動薬 / bisphosphonate / 線維性骨炎

Research Abstract

To regress the pathological findings resulted from chronic kidney disease mineral and bone disorder (CKD-MBD), it may be effective to directly inject the active vitamin D or its analogue into parathyroid gland and to systemically administrate vitamin D and/or calcimimetics for enlarged parathyroid gland and high turn-over bone disease. But it is difficult to regress ectopic vascular calcification by these methods. It may be important to prevent inflammatory process and elastin degradation for regression. Further studies are urgently required to clarify this point.

Research Products

• [Journal Article] Mineral Metabolism Management in Hemodialysis Patients with Secondary Hyperparathyroidism in Japan : Baseline Data from the MBD-5D. (2011)
  • Author(s): Fukagawa M, Komaba H, Onishi Y, Fukuhara S, Akizawa T, Kurokawa K
  • Journal Title: Am J Nephrol 33(5) Pages: 427-437
  • Peer Reviewed
• [Journal Article] Mineral and bone disorders outcomes study for Japanese chronic kidney disease stage 5D patients : rationale and study design. (2011)
  • Author(s): Fukuhara S, Akizawa T, Fukagawa M, Onishi Y, Yamaguchi T, Hasegawa T, Kurokawa K
  • Journal Title: Ther Apher Dial. 15(2) Pages: 169-75
  • Peer Reviewed
• [Journal Article] Detection of peripheral artery disease by duplex ultrasonography among hemodialysis patients. (2010)
  • Author(s): Ogata H, Kumata-Maeta C, Shishido K, Mizobuchi M, Yamamoto M, Koiwa F, Kinugasa E, Akizawa T
  • Journal Title: Clin J Am Soc Nephrol. 5(12) Pages: 2199-206
  • Peer Reviewed
• [Journal Article] Impact of fibroblast growth factor 23 on lipids and atherosclerosis in hemodialysis patients. (2010)
  • Author(s): Ashikaga E, Honda H, Suzuki H, Hosaka N, Hirai Y, Sanada D, Nakamura M, Nagai H, Matsumoto K, Kato N, Mukai M, Watanabe M, Takahashi K, Shishido K, Akizawa T.
  • Journal Title: Ther Apher Dial. 14(3) Pages: 315-22
  • Peer Reviewed
• [Journal Article] Development of a technique for introduction of an expressed complementary deoxyribonucleic acid into parathyroid cells by direct injection. (2010)
  • Author(s): Shiizaki K, Hatamura I, Fukagawa M, Nakazawa E, Saji F, Watanabe Y, Akizawa T, Kusano E
  • Journal Title: Endocrinology. 151(8) Pages: 4031-8
  • Peer Reviewed
• [Journal Article] Involvement of alpha-klotho and fibroblast growth factor receptor in the development of secondary hyperparathyroidism. (2010)
  • Author(s): Kumata C, Mizobuchi M, Ogata H, Koiwa F, Nakazawa A, Kondo F, Kadokura Y, Kinugasa E, Akizawa T
  • Journal Title: Am J Nephrol. 31(3) Pages: 230-8
  • Peer Reviewed
• [Journal Article] Myocardial effects of VDR activators in renal failure. (2010)
  • Author(s): Mizobuchi M, Nakamura H, Tokumoto M, Finch J, Morrissey J, Liapis H, Slatopolsky E
  • Journal Title: J Steroid Biochem Mol Biol. 121(1-2) Pages: 188-92
  • Peer Reviewed
• [Journal Article] Novel markers of left ventricular hypertrophy in uremia. (2010)
  • Author(s): Nakamura H, Tokumoto M, Mizobuchi M, Ritter CS, Finch JL, Mukai M, Slatopolsky E
  • Journal Title: Am J Nephrol. 31(4) Pages: 292-302
  • Peer Reviewed
• [Journal Article] Development of a technique for introduction of an expressed complementary deoxyribonucleic acid into parathyroid cells by direct injection. (2010)
  • Author(s): Shiizaki K, et al
  • Journal Title: Endocrinology Volume: 151 Pages: 4031-4038
  • Peer Reviewed
• [Journal Article] Detection of peripheral artery disease by duplex ultrasonography among hemodialysis patients. (2010)
  • Author(s): Ogata H, et al
  • Journal Title: Clin J Am Soc Nephrol. Volume: 5 Pages: 2199-2206
  • Peer Reviewed
• [Journal Article] Involvement of alpha-klotho and fibroblast growth factor receptor in the development of secondary hyperparathyroidism. (2010)
  • Author(s): Kumata C, et al
  • Journal Title: Am J Nephrol Volume: 31 Pages: 230-238
  • Peer Reviewed
• [Journal Article] Involvement of alpha-klotho and fibroblast growth factor receptor in the development of secondary hyperparathyroidism (2010)
  • Author(s): Kumata C
  • Journal Title: Am J Nephrol. 31 Pages: 230-238
  • Peer Reviewed
• [Journal Article] Elastin degradation accelerates phosphate-induced mineralization of vascular smooth muscle cells. (2009)
  • Author(s): Hosaka N, Mizobuchi M, Ogata H, Kumata C, Kondo F, Koiwa F, Kinugasa E, Akizawa T
  • Journal Title: Calcif Tissue Int. 85(6) Pages: 523-9
  • Peer Reviewed
• [Journal Article] Improvement of impaired calcium and skeletal homeostasis in vitamin D receptor knockout mice by a high dose of calcitriol and maxacalcitol. (2009)
  • Author(s): Shiizaki K, Hatamura I, Imazeki I, Moriguchi Y, Sakaguchi T, Saji F, Nakazawa E, Kato S, Akizawa T, Kusano E
  • Journal Title: Bone. 45(5) Pages: 964-71
  • Peer Reviewed
• [Journal Article] Vitamin D and vascular calcification in chronic kidney disease. (2009)
  • Author(s): Mizobuchi M, Ogata H, Koiwa F, Kinugasa E, Akizawa T
  • Journal Title: Bone. 45 Suppl 1
  • Peer Reviewed
• [Journal Article] KRN1493 Study Group. Long-term cinacalcet HCl treatment improved bone metabolism in Japanese hemodialysis patients with secondary hyper-parathyroidism. (2009)
  • Author(s): Shigematsu T, Akizawa T, Uchida E, Tsukamoto Y, Iwasaki M, Koshikawa S
  • Journal Title: Am J Nephrol. 29(3) Pages: 230-6
  • Peer Reviewed
• [Journal Article] Vascular calcification : the killer of patients with chronic kidney disease. (2009)
  • Author(s): Mizobuchi M, Towler D, Slatopolsky E
  • Journal Title: J Am Soc Nephrol. 20(7) Pages: 1453-64
  • Peer Reviewed
• [Journal Article] Calcium-sensing receptor expression is regulated by glial cells missing-2 in human parathyroid cells. (2009)
  • Author(s): Mizobuchi M, Ritter CS, Krits I, Slatopolsky E, Sicard G, Brown AJ
  • Journal Title: J Bone Miner Res. 24(7) Pages: 1173-9
  • Peer Reviewed
• [Journal Article] Blockage of the renin-angiotensin system attenuates mortality but not vascular calcification in uremic rats : sevelamer carbonate prevents vascular calcification. (2009)
  • Author(s): Tokumoto M, Mizobuchi M, Finch JL, Nakamura H, Martin DR, Slatopolsky E
  • Journal Title: Am J Nephrol. 29(6) Pages: 582-91
  • Peer Reviewed
• [Journal Article] Combination therapy with paricalcitol and enalapril ameliorates cardiac oxidative injury in uremic rats. (2009)
  • Author(s): Husain K, Ferder L, Mizobuchi M, Finch J, Slatopolsky E
  • Journal Title: Am J Nephrol. 29(5) Pages: 465-72
  • Peer Reviewed
• [Journal Article] Comparison of oral falecalcitriol and intravenous calcitriol in hemodialysis patients with secondary hyperparathyroidism : a randomized, crossover trial. (2009)
  • Author(s): Ito H, Ogata H, Yamamoto M, Takahashi K, Shishido K, Takahashi J, Taguchi S, Kinugasa E
  • Journal Title: Clin Nephrol. 71(6) Pages: 660-8
  • Peer Reviewed
• [Journal Article] Elastin degradation accelerates phosphate-induced mineralization of vascular smooth muscle cells (2009)
  • Author(s): Hosaka N
  • Journal Title: Calcif Tissue Int 85 Pages: 523-529
  • Peer Reviewed
• [Journal Article] Improvement of impaired calcium and skeletal homeostasis in vitamin D receptor knockout mice by a high dose of calcitriol and maxacalcitol (2009)
  • Author(s): Shiizaki K
  • Journal Title: Bone 45 Pages: 964-971
  • Peer Reviewed
• [Journal Article] Vitamin D and vascular calcification in chronic kidney disease (2009)
  • Author(s): Mizobuchi M
  • Journal Title: Bone 45
  • Peer Reviewed
• [Journal Article] K Study Group. Impact of cinacalcet hydrochloride on bone histology in patients with secondary hyperparathyroidism. (2008)
  • Author(s): Yajima A, Akizawa T, Tsukamoto Y, Kurihara S, Ito A
  • Journal Title: Ther Apher Dial. 12 Suppl 1
  • Peer Reviewed
• [Journal Article] Proliferating potential and apoptosis in the development of secondary hyperparathyroidism : a study based on Ki-67 immunohistochemical staining and the terminal dUTP nick-end labeling assay. (2008)
  • Author(s): Wada Y, Kunimura T, Sato S, Hisayuki T, Sato M, Imataka H, Yamashita N, Akizawa T, Moroboshi T
  • Journal Title: Ther Apher Dial. 12(4) Pages: 319-28
  • Peer Reviewed
• [Journal Article] Molecular and morphological approach of uremia-induced hyperplastic parathyroid gland following direct maxacalcitol injection. (2008)
  • Author(s): Shiizaki K, Hatamura I, Nakazawa E, Ogura M, Masuda T, Akizawa T, Kusano E
  • Journal Title: Med Mol Morphol. 41(2) Pages: 76-82
  • Peer Reviewed
• [Journal Article] Mortality risk for dialysis patients with different levels : the Dialysis Outcomes and Practice Patterns Study (DOPPS). (2008)
  • Author(s): Tentori F, Blayney MJ, Albert JM, Gillespie BW, Kerr PG, Bommer J, Young EW, Akizawa T, Akiba T, Pisoni RL, Robinson BM, Port FK
  • Journal Title: Am J Kidney Dis. 52(3) Pages: 519-30
  • Peer Reviewed
• [Journal Article] Highly concentrated calcitriol and its analogues induce apoptosis of parathyroid cells and regression of the hyperplastic gland--study in rats. (2008)
  • Author(s): Shiizaki K, Hatamura I, Negi S, Sakaguchi T, Saji F, Imazeki I, Kusano E, Shigematsu T, Akizawa T
  • Journal Title: Nephrol Dial Transplant. 23(5) Pages: 1529-36
  • Peer Reviewed
• [Journal Article] Direct injection of calcitriol or its analog improves abnormal gene expression in the hyperplastic parathyroid gland in uremia. (2008)
  • Author(s): Shiizaki K, Fukagawa M, Yuan Q, Hatamura I, Nii-Kono T, Saji F, Shigematsu T, Akizawa T
  • Journal Title: Am J Nephrol. 28(1) Pages: 59-66
  • Peer Reviewed
• [Journal Article] Molecular and morphological approach of uremia-induced hyperplastic parathyroid gland following direct maxacalcitol injection. (2008)
  • Author(s): Shiizaki K, Hatamura I, Akizawa T, et al
  • Journal Title: Med Mol Morphol. 41 Pages: 76-82
  • Peer Reviewed
• [Journal Article] Clinical study of cinacalcet in Japan. (2008)
  • Author(s): Akizawa T, Koshikawa S
  • Journal Title: Ther Apher Dial 12
  • Peer Reviewed
• [Journal Article] Proliferating potential and apoptosis in the development of secondary hyperparathyroidism : a study based on Ki-67 immunohistochemical staining and the terminal dUTP nick-end labeling assay. (2008)
  • Author(s): Wada Y, Kunimura T, Akizawa T, Moroboshi T, et, al
  • Journal Title: Ther Apher Dial 12 Pages: 319-328
  • Peer Reviewed
• [Journal Article] Involvement of Matrix Metalloproteinase-2 in the Development of Medial Layer Vascular Calcification in Uremic Rats.
  • Author(s): Chiaki Kumata, 1 Masahide Mizobuchi, Hiroaki Ogata, Fumihiko Koiwa, Fumiko Kondo, Eriko Kinugasa, Tadao Akizawa
  • Journal Title: Ther Apher Dial. 15(Supplement 1) Pages: 18-22
  • Peer Reviewed
• [Presentation] Involvement of Matrix Metalloproteinase-2 in the Development of Aortic Calcification in Uremic Rats (2010)
  • Author(s): Kumata C, et al
  • Organizer: 43rd Annual Meeting of American Society of Nephrology
  • Place of Presentation: Denver USA
  • Year and Date: 2010-11-19
• [Presentation] A Vitamin D Analog Inhibits VSMC Mineralization Induced by TNF-α and Phosphate (2010)
  • Author(s): Aoshima Y, et al
  • Organizer: 43rd Annual Meeting of American Society of Nephrology
  • Place of Presentation: Denver USA
  • Year and Date: 2010-11-18
• [Presentation] (2010)
  • Organizer: 第43回米国腎臓学会
• [Presentation] Both Type I Membrane Klotho and Fibroblast Growth Factor Receptor Are Decreased in Secondary Hyperparathyroidism (2009)
  • Author(s): Tadao Akizawa
  • Organizer: American Society of Nephrology
  • Place of Presentation: SanDiego USA
  • Year and Date: 2009-10-30
• [Presentation] (2009)
  • Organizer: 第42回米国腎臓学会
• [Presentation] Effect of elastin degradation on the mineralization of vascular smooth muscle cells (2008)
  • Author(s): Hosaka N, Mizobuchi M, Akizawa T, et. al
  • Organizer: 米国腎臓学会
  • Place of Presentation: Philadelphia
  • Year and Date: 2008-11-07
• [Presentation] (2008)
  • Organizer: 第41回米国腎臓学会