慢性腎臓病ミネラル骨代謝異常症(CKD-MBD)退縮をめざした実験的研究

• 研究課題/領域番号: 20590985
• 研究種目: 基盤研究(C)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 腎臓内科学
• 研究機関: 昭和大学
• 研究代表者: 秋澤 忠男 昭和大学, 医学部, 教授 (40102339)
• 研究分担者: 緒方 浩顕 昭和大学, 医学部, 講師 (30296959) ; 溝渕 正英 昭和大学, 医学部, 助教 (90465203)
• 研究期間 (年度): 2008 – 2010
• 研究課題ステータス: 完了 (2010年度)
• 配分額: 4,420千円 (直接経費: 3,400千円、間接経費: 1,020千円); 2010年度: 910千円 (直接経費: 700千円、間接経費: 210千円); 2009年度: 1,430千円 (直接経費: 1,100千円、間接経費: 330千円); 2008年度: 2,080千円 (直接経費: 1,600千円、間接経費: 480千円)
• キーワード: 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

研究概要

慢性腎臓病ミネラル骨代謝異常症を構成する二次性副甲状腺機能亢進症、線維性骨炎については、活性型ビタミンD製剤の副甲状腺内局注と引き続く全身投与や、calcimimeticsの積極的使用により退縮の実現できる可能性が示された。しかし異所性血管石灰化の退縮はこれらの手段で達成は困難で、炎症の抑制、エラスチン代謝の制御など、新たな手段の構築が必要と考えられた。

研究成果

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