Renal renin-angiotensin system and tubular prorenin endocytosis in diabetic nephropathy with microalbuminuria

• Project/Area Number: 23591214
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: The University of Tokyo
• Principal Investigator: TOJO Akihiro 東京大学, 医学部附属病院, 講師 (50292917)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 糖尿病性腎症 / レニン・アンジオテンシン系 / アルブミン / プロレニン / アンジオテンシン / 微量アルブミン尿

Research Abstract

Glomerular filtration of prorenin and angiotensinogen were increased as similar to that of albumin in early stage diabetic nephropathy with microalbuminuria, and the increased tubular reabsorption of prorenin and angiotensinogen contributed to the enhanced renal renin-angiotensin system in diabetic nephropathy. Suppression of tubular reabsorption of prorenin can be a new target to prevent progression of diabetic nephropathy.

Research Products

• [Journal Article] Urinary and glomerular podocytes in patients with chronic kidney diseases. (2014)
  • Author(s): Hanamura K, Tojo A, Fujita T.
  • Journal Title: Clin Exp Nephrol Volume: 18 Issue: 1 Pages: 95-103
  • DOI: 10.1007/s10157-013-0814-8
  • Peer Reviewed
• [Journal Article] Doppler ultrasonography and hypertensive target organ damage. (2014)
  • Author(s): Tojo A
  • Journal Title: Anadolu Kardiyol Derg Volume: 14 Pages: 1-2
  • DOI: 10.5152/akd.2013.12677
• [Journal Article] Autoimmune disorder phenotypes in HVCN1 gene deficient mice. (2013)
  • Author(s): Sasaki M, Tojo A, Okochi Y, Miyawaki N, Kamimura D, Yamaguchi A, Murakami M, Okamura Y.
  • Journal Title: Biochem J Volume: 450 Issue: 2 Pages: 295-301
  • DOI: 10.1042/bj20121188
  • Peer Reviewed
• [Journal Article] The role of adrenomedullin in the renal NADPH oxidase and (pro)renin in diabetic mice. (2013)
  • Author(s): Hayashi, M., Tojo, A., Shimosawa, T., and Fujita, T.
  • Journal Title: J Diabetes Res Volume: - Pages: 134395-134395
  • DOI: 10.1155/2013/134395
  • Peer Reviewed
• [Journal Article] The role of the kidney in protein metabolism: the capacity of tubularlysosomal proteolysis in nephrotic syndrome (2013)
  • Author(s): Tojo A
  • Journal Title: Kidney Int Volume: 84 Issue: 5 Pages: 861-863
  • DOI: 10.1038/ki.2013.284
  • Peer Reviewed
• [Journal Article] Mechanisms of glomerular albumin filtration and tubular reabsorption. (2012)
  • Author(s): Tojo A, Kinugasa S
  • Journal Title: Int J Nephrol Volume: 2012 Pages: 1-9
  • DOI: 10.1155/2012/481520
  • Peer Reviewed
• [Journal Article] Application of low-vacuum scanning electron microscopy for renal biopsy specimens (2012)
  • Author(s): Miyazaki H, Uozaki H, Tojo A, Hirashima S, Inaga S, Sakuma K, Morishita Y, Fukayama M.
  • Journal Title: Pathol Res Pract Volume: 208 Issue: 9 Pages: 503
  • DOI: 10.1016/j.prp.2012.05.006
  • URL: https://pure.teikyo.jp/en/publications/add93dff-4c66-42e1-9f5f-8c329e251f6b
  • Peer Reviewed
• [Journal Article] Acute tubulointerstitial nephritis with an autoantibody response against carbonic anhydrase II. (2012)
  • Author(s): Tojo A, Miyashita K, Kinugasa S, Takemura T, Goto A.
  • Journal Title: Am J Med Sci Volume: 345(5) Issue: 5 Pages: 407-408
  • DOI: 10.1097/maj.0b013e318272f1a6
  • Peer Reviewed
• [Journal Article] The resistive index is a marker of renal function, pathology, prognosis, and responsiveness to steroid therapy in chronic kidney disease patients. (2012)
  • Author(s): Hanamura K, Tojo A, Kinugasa S, Asaba K, Fujita T.
  • Journal Title: Int J Nephrol Volume: 2012 Pages: 1-9
  • DOI: 10.1155/2012/139565
  • Peer Reviewed
• [Journal Article] Successful treatment of antineutrophil cytoplasmic antibody-associated vasculitis with eicosapentaenoic acid. (2012)
  • Author(s): Hirahashi J, Jo A, Ueda K, Tojo A, Fujita T
  • Journal Title: Ann Intern Med Volume: 156(10) Pages: 755-756
  • Peer Reviewed
• [Journal Article] A case of de novo focal segmental glomerulosclerosis occurred one and half years after kidney transplantation supposed to be caused by calcineurin inhibitor (2012)
  • Author(s): Ikeda Y, Nangaku M, Ishibashi Y, Hirohama D, Uozaki H, Tojo A, Ishikawa A, Fujita T
  • Journal Title: Clin Transplant Volume: 26 Issue: SUPPL.24 Pages: 76
  • DOI: 10.1111/j.1399-0012.2012.01640.x
  • Peer Reviewed
• [Journal Article] Mechanisms of glomerular albumin filtration and tubular reabsorption (2012)
  • Author(s): Akihiro Tojo, Satoshi Kinugasa
  • Journal Title: International Journal of Nephrology Volume: in press
  • Peer Reviewed
• [Journal Article] Selective albuminuria via podocyte albumin transport in puromycin nephrotic rats is attenuated by an inhibitor of NADPH oxidase (2011)
  • Author(s): Kinugasa S, Fujita T, et al.
  • Journal Title: Kidney Int. Volume: 80 Issue: 12 Pages: 1328-1338
  • DOI: 10.1038/ki.2011.282
  • Peer Reviewed
• [Journal Article] Detection of myeloperoxidase in membranous nephropathy-like deposits in patients with anti-neutrophil cytoplasmic antibody-associated glomerulonephritis (2011)
  • Author(s): Hanamura K, Tojo A, Kinugasa S, Asaba K, Onozato ML, Uozaki H, Fukayama M, Fujita T
  • Journal Title: Human Pathology Volume: 42 Issue: 5 Pages: 649
  • DOI: 10.1016/j.humpath.2010.08.020
  • Peer Reviewed
• [Presentation] Effect of angiotensin receptor blockade on sodium-glucose co-transporters and renal gluconeogenesis in diabetic rats (2013)
  • Author(s): Tojo A, Kinugasa S
  • Organizer: The American Society of Nephrology, Kidney Week 2013
  • Place of Presentation: Atlanta, GA, USA
• [Presentation] The reduction and morphological alterations of podocyte slits cause acute kidney injury in minimal change nephrotic syndrome (2013)
  • Author(s): Kinugasa S, Asaba K, Nangaku M, Tojo A
  • Organizer: The American Society of Nephrology, Kidney Week 2013
  • Place of Presentation: Atlanta, GA, USA
• [Presentation] 糖尿病ラットにおけるSGLT2と糖新生 (2013)
  • Author(s): 藤乗嗣泰、衣笠哲史、渡邉隆史
  • Organizer: 第56回日本腎臓学会学術総会
  • Place of Presentation: 東京
• [Presentation] 糖尿病ラットにおけるSGLT2と腎糖新生のアンジオテンシン受容体遮断薬による調節 (2013)
  • Author(s): 藤乘嗣泰、衣笠哲史
  • Organizer: 第45回日本臨床分子形態学会総会
  • Place of Presentation: 福岡
• [Presentation] 糖尿病におけるSGLT2と腎糖新生とアンジオテンシン受容体遮断薬の効果 (2013)
  • Author(s): 藤乗嗣泰、衣笠哲史
  • Organizer: 第36回日本高血圧学会総会
  • Place of Presentation: 大阪
• [Presentation] Effect of angiotensin receptor blockade on sodium-glucose co-transporters and renal gluconeogenesis in diabetic rats. (2013)
  • Author(s): Tojo A, Kinugasa S
  • Organizer: The American Society of Nephrology, Kidney Week 2013
  • Place of Presentation: Atlanta, Georgia, USA
• [Presentation] The reduction and morphological alterations of podocyte slits cause acute kidney injury in minimal change nephrotic syndrome (2013)
  • Author(s): Kinugasa S, Asaba K, Nangaku M, Tojo A
  • Organizer: The American Society of Nephrology, Kidney Week 2013
  • Place of Presentation: Atlanta, Georgia, USA
• [Presentation] Quantitative evaluation of renal cortical fibrosis and renal prognosis in IgA nephropathy and focal segmental glomerulosclerosis. (2013)
  • Author(s): Iida F, Asaba K, Kinugasa S, Ishibashi Y, Nangaku M, Tojo A
  • Organizer: The American Society of Nephrology, Kidney Week 2013
  • Place of Presentation: Atlanta, Georgia, USA
• [Presentation] 急性腎障害を合併した微小変化型ネフローゼ症候群はたこ足細胞スリットの減少と狭小化を呈する (2013)
  • Author(s): 衣笠哲史、浅羽研介、花村菊乃、南学正臣、藤乗嗣泰
  • Organizer: 第56回日本腎臓学会学術総会
  • Place of Presentation: 東京
• [Presentation] 腎予後予測における画像解析による線維化面積評価について (2013)
  • Author(s): 飯田英和、浅羽研介、川端知晶、衣笠哲史、花村菊乃、石橋由孝、藤乗嗣泰
  • Organizer: 第56回日本腎臓学会学術総会
  • Place of Presentation: 東京
• [Presentation] Resistive index正常高値のCKD患者ではステロド治療が有効である (2013)
  • Author(s): 花村菊乃、衣笠哲史、浅羽研介、南学正臣、藤田敏郎、藤乗嗣泰
  • Organizer: 第56回日本腎臓学会学術総会
  • Place of Presentation: 東京
• [Presentation] Negative stainingによる透過型電顕で診断し得たNail-Patella症候群 (2013)
  • Author(s): 藤乘嗣泰、衣笠哲史、福田覚、山田秀臣、新谷裕加子、深山正久
  • Organizer: 第45回日本臨床分子形態学会総会
  • Place of Presentation: 福岡
• [Presentation] Increased Renal Uptake of Exogenous Human Prorenin and Angiotensinogen Enhances the Renal Renin-Angiotensin System in Diabetic Rats (2012)
  • Author(s): Kinugasa S, Tojo A, Hirata Y, et al
  • Organizer: The American Society of Nephrology, Kidney Week 2012
  • Place of Presentation: San Diego, USA
• [Presentation] Significance of Foot Process Effacement in Minimal Change Disease with Acute Kidney Injury in Humans and Animal Models (2012)
  • Author(s): Tojo A, Asaba K
  • Organizer: The American Society of Nephrology, Kidney Week 2012
  • Place of Presentation: San Diego, USA
• [Presentation] Streptozotocin糖尿病モデルにおける腎組織レニン・アンジオテンシンの役割 (2012)
  • Author(s): 衣笠哲史、藤乗嗣泰、高橋将文、藤田敏郎
  • Organizer: 第55回日本腎臓学会学術総会
  • Place of Presentation: 横浜
• [Presentation] Streptozotocin糖尿病ラットにおけるヒトプロレニン・アンジオテシノーゲン投与後の腎内局在と生理作用 (2012)
  • Author(s): 衣笠哲史、藤乗嗣泰、高橋将文、平田恭信、藤田敏郎
  • Organizer: 第35回日本高血圧学会総会
  • Place of Presentation: 名古屋
• [Presentation] Significance of Foot Process Effacement in Minimal Change Disease with Acute Kidney Injury in Humans and Animal Models. (2012)
  • Author(s): Tojo A, Asaba K
  • Organizer: The American Society of Nephrology, Kidney Week 2012
  • Place of Presentation: San Diego, USA
• [Presentation] Increased Renal Uptake of Exogenous Human Prorenin and Angiotensinogen Enhances the Renal Renin-Angiotensin System in Diabetic Rats. (2012)
  • Author(s): Kinugasa S, Tojo A, Hirata Y
  • Organizer: The American Society of Nephrology, Kidney Week 2012
  • Place of Presentation: San Diego, USA
• [Presentation] 急性腎障害を呈する微小変化型ネフローゼ症候群の臨床的・病理学的特徴 (2012)
  • Author(s): 浅羽研介、藤乗嗣泰、衣笠哲史、花村菊乃、宇於崎宏、藤田敏郎
  • Organizer: 第55回日本腎臓学会学術総会
  • Place of Presentation: 横浜
  • Invited
• [Presentation] Electron microscopic observation of mechanisms of proteinuria in various glomerular diseases (2011)
  • Author(s): Tojo A, Kinugasa S, Fujita T
  • Organizer: World Congress of Nephrology 2011
  • Place of Presentation: Vancouver, Canada
• [Presentation] 糖尿病におけるAdrenomedullinのレニン・アンジオテンシン系に及ぼす影響 (2011)
  • Author(s): 藤乗嗣泰、林道夫、下澤達雄、藤田敏郎
  • Organizer: 第34回日本高血圧学会総会
  • Place of Presentation: 栃木
• [Presentation] Electron microscopic observation of mechanisms of proteinuria in various glomerular diseases (2011)
  • Author(s): Akihiro Tojo, Satoshi Kinugasa, Toshiro Fujit
  • Organizer: World Congress of Nephrology
  • Place of Presentation: Vancouver, Canada
• [Presentation] Clinical significance of podocytes excreted in urine in various glomerular diseases (2011)
  • Author(s): Kikuno Hanamura, Akihiro Tojo, Satoshi Kinugasa, Kensuke Asaba, Toshiro Fujita
  • Organizer: World Congress of Nephrology
  • Place of Presentation: Vancouver, Canada
• [Presentation] Mechanism of selective proteinuria in minimal change nephrotic syndrome (2011)
  • Author(s): Satoshi Kinugasa, Akihiro Tojo, Tatsuo Sakai, Masafumi Takahashi, Yasunobu Hirata, Toshiro Fujita
  • Organizer: ASN Kidney Week 2011
  • Place of Presentation: Philadelphia, PA, USA
• [Book] Paraneoplastic glomerulopathy associated with renal cell carcinoma. Chapter 7 in the Renal Tumor (2013)
  • Author(s): Tojo A. Edited by Jindong Chen
  • Total Pages: 208
  • Publisher: InTech
• [Book] Paraneoplastic glomerulopathy associated with renal cell carcinoma. Chapter 7 in Renal Tumor (2013)
  • Author(s): Tojo A
  • Total Pages: 208
  • Publisher: INTECH
• [Book] Renal Tumor (2013)
  • Author(s): Tojo A, edited by Jundong Chen
  • Total Pages: 208
  • Publisher: InTechOpen