Molecular analyses of chronic renal allograft injuries

• Project/Area Number: 25461237
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Kanazawa Medical University
• Principal Investigator: YOKOYAMA Hitoshi 金沢医科大学, 医学部, 教授 (50191531)
• Co-Investigator(Kenkyū-buntansha): ADACHI Hiroki 金沢医科大学, 医学部, 助教 (10350761) ; ATSUMI Hirokatsu 金沢医科大学, 医学部, 助教 (70460342)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 腎移植 / 移植腎機能障害 / アディポサイトカイン / non-classical HLA分子 / 膠原繊維 / 抗HLA抗体 / 糸球体線維化 / non classical HLA分子 / アデポサイトカイン

Outline of Final Research Achievements

We constructed the cohort of 132 renal allograft transplanted patients, and analyzed the outcomes of renal and actuarial survival. As the results, 1) Serum high- and low-molecular-weight adiponectin (ADPN) fractions were related to the development of both cardiovascular diseases and post-transplant diabetes, and renal allograft function. 2) The gamma;-H2AX (a marker of double-strand DNA breaks) and Collagen type VI expression in renal allograft glomeruli were positively correlated with the duration of the post-renal transplant period. 3) The alteration of Th1, Th2, Th17, Treg (Foxp3+) subsets and non-classical HLA-G5 molecules were found in the early stage of allograft transplantation. In addition, higher serum HLA-G5 level was selected as a protective factor for renal allografts after 60 months.
Conclusion: In Japanese renal allograft recipients, ADPN fractions and non-classical HLA -G molecules were significant factors for the long-term allograft survival and complications.

Research Products

• [Journal Article] DNA double-strand breaks induced intractable glomerular fibrosis in renal allografts. (2016)
  • Author(s): Matsui Y, Sunatani Y, Hayashi N, Okino K, Okushi Y, Mukai K, Adachi H, Yamaya H, Iwabuchi K, Yokoyama H
  • Journal Title: Clin. Exp. Nephrol. Volume: 20 Issue: 3 Pages: 479-488
  • DOI: 10.1007/s10157-015-1174-3
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Clinicopathological Characteristics of M-type Phospholipase A2 Receptor (PLA2R)-Related Membranous Nephropathy in Japanese (2015)
  • Author(s): Norifumi Hayashi, Shin’ichi Akiyama, Hiroshi Okuyama, Yuki Matsui, Hiroki Adachi, Hideki Yamaya, Shoichi Maruyama, Enyu Imai, Seiichi Matsuo, Hitoshi Yokoyama
  • Journal Title: Clinical and Experimental Nephrology Volume: 印刷中 Issue: 5 Pages: 797-803
  • DOI: 10.1007/s10157-014-1064-0
  • Peer Reviewed
• [Journal Article] Different association of cigarette smoking with GFR estimated from serum creatinine and that from serum cystatin C in the general population. (2015)
  • Author(s): Yamada Y, Noborisaka Y, Ishizaki M, Yamazaki M, Honda R, Yokoyama H, Kakuma T.
  • Journal Title: Clin Exp Nephrol. Volume: 19 Issue: 4 Pages: 669-677
  • DOI: 10.1007/s10157-014-1058-y
  • Peer Reviewed
• [Journal Article] Clinicopathological characteristics of M-type phospholipase A2 receptor (PLA2R)-related membranous nephropathy in Japanese. (2014)
  • Author(s): 4.Hayashi N, Akiyama S, Okuyama H, Matsui Y, Adachi H, Yamaya H, Maruyama S, Imai E, Matsuo S, Yokoyama H.
  • Journal Title: Clin Exp Nephrol Volume: Epub Issue: 5 Pages: 804-814
  • DOI: 10.1007/s10157-014-1067-x
  • Peer Reviewed
• [Journal Article] Outcomes of primary nephrotic syndrome in elderly Japanese: (2014)
  • Author(s): Yokoyama H, Sugiyama H, Narita I, Saito T, Yamagata K, Nishio S, Fujimoto S, Mori N, Yuzawa Y, Okuda S, Maruyama S, Sato H, Ueda Y, Makino H, Matsuo S
  • Journal Title: Clin Exp Nephrol Volume: Epub Issue: 3 Pages: 496-505
  • DOI: 10.1007/s10157-014-1022-x
  • Peer Reviewed / Open Access
• [Journal Article] A multicenter cross-sectional study of circulating soluble urokinase receptor in Japanese patients with glomerular disease (2014)
  • Author(s): Wada T, Nangaku M, Maruyama S, Imai E, Shoji K, Kato S, Endo T, Muso E, Kamata K, Yokoyama H, Fujimoto K, Obata Y, Nishino T, Kato H, Uchida S, Sasatomi Y, Saito T, Matsuo S.
  • Journal Title: Kidney Int Volume: 85 Issue: 3 Pages: 641-8
  • DOI: 10.1038/ki.2013.544
  • Peer Reviewed / Open Access
• [Journal Article] Long-term outcomes of Japanese type 2 diabetic patients with biopsy-proven diabetic nephropathy. (2013)
  • Author(s): Shimizu M, Furuichi K, Toyama T, Kitajima S, Hara A, Kitagawa K, Iwata Y, Sakai N, Takamura T, Yoshimura M, Yokoyama H, Kaneko S, Wada T and Kanazawa Study Group for Renal Diseases and Hypertension.
  • Journal Title: Diabetes Care Volume: 36 Issue: 11 Pages: 3655-3662
  • DOI: 10.2337/dc13-0298
  • Peer Reviewed
• [Journal Article] Research Group of Diabetic Nephropathy, Ministry of Health, Labour, and Welfare of Japan. Japan Diabetic Nephropathy Cohort Study : study design, methods, and implementation (2013)
  • Author(s): Furuichi K1, Shimizu M, Toyama T, Koya D, Koshino Y, Abe H, Mori K, Satoh H, Imanishi M, Iwano M, Yamauchi H, Kusano E, Fujimoto S, Suzuki Y, Okuda S, Kitagawa K, Iwata Y, Kaneko S, Nishi S, Yokoyama H, Ueda Y, Haneda M, Makino H, Wada T
  • Journal Title: Clin Exp Nephrol Volume: 17 Issue: 6 Pages: 819-826
  • DOI: 10.1007/s10157-013-0778-8
  • Peer Reviewed
• [Presentation] Adiponectin fractions influences the development of cardiovascular disease in Japanese renal transplant recipients. (2015)
  • Author(s): Adachi H, Matsui Y, Hayashi N, Fujimoto K, Imura J, Yamaya H, Yokoyama H
  • Organizer: The Annual of American Society of Nephrology
  • Place of Presentation: San Diego (USA)
  • Year and Date: 2015-11-03
  • Int'l Joint Research
• [Presentation] DNA double strand breaks induced collagen type VI secretion of glomerular endothelial cells in renal allografts. (2015)
  • Author(s): Matsui Y, Hayashi N, Imura J, Fujimoto K, Adachi H, Yamaya H, Yokoyama H
  • Organizer: The Annual of American Society of Nephrology
  • Place of Presentation: San Diego (USA)
  • Year and Date: 2015-11-03
  • Int'l Joint Research
• [Presentation] DNA double strand breaks accelerated collagen type VI secretion of glomerular endothelial cells. (2015)
  • Author(s): Matsui Y, Sunatani Y, Iwabuchi K, Yokoyama H
  • Organizer: ERA-EDTA Congress
  • Place of Presentation: London (England)
  • Year and Date: 2015-05-28
  • Int'l Joint Research
• [Presentation] DNA double strand brakes induced intractable glomerular fibrosis in renal allografts (2014)
  • Author(s): Y.Matsui, H.Atsumi, J.Imura, K.Fujimoto, H.Adachi, H.Okuyama, H.Yamaya, H.Yokoyama
  • Organizer: The Annual of American Sociey of Nephrology
  • Place of Presentation: Philadelphia (United State of America)
  • Year and Date: 2014-11-12 – 2014-11-16
• [Presentation] 長期移植腎における糸球体線維化の検討 (2014)
  • Author(s): 藤本圭司, 沖野一晃, 大串勇気, 向井清孝, 正島季代, 松井佑樹, 渥美浩克, 足立浩樹, 奥山 宏, 山谷秀喜, 横山 仁
  • Organizer: 第57回日本腎臓学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-07-04 – 2014-07-06
• [Presentation] 膜性PhospholipaseA2受容体 (PLA2R) 関連膜性腎症の臨床病理学的検討 (2014)
  • Author(s): 林 憲史, 松井佑樹, 藤本圭司, 渥美浩克, 足立浩樹, 奥山 宏, 山谷秀喜, 横山 仁, 秋山真一, 丸山彰一, 今井圓裕, 松尾清一
  • Organizer: 第57回日本腎臓学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-07-04 – 2014-07-06
• [Presentation] ネフローゼ症候群におけるsuPARの意義 (2014)
  • Author(s): 藤本圭司, 沖野一晃, 大串勇気, 向井清孝, 正島季代, 松井佑樹, 渥美浩克, 足立浩樹, 奥山 宏, 山谷秀喜, 横山 仁
  • Organizer: 第57回日本腎臓学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-07-04 – 2014-07-06
• [Presentation] 難治性ネフローゼ症候群の実際と治療 (2014)
  • Author(s): 横山 仁
  • Organizer: 第111回日本内科学会講演会
  • Place of Presentation: 東京国際フォーラム（東京都，千代田区）
  • Year and Date: 2014-04-12
  • Invited
• [Presentation] Angiotensin II receptor blockers protected renal allografts in Japanese (Sub-analysis of I-LORD study) (2013)
  • Author(s): H.Yokoyama
  • Organizer: World Congress of Nephrology 2013
  • Place of Presentation: Hong-Kong (China)
• [Presentation] Circulating Soluble Urokinase Receptor Levels in Primary Nephrotic Syndrome Predict the Response to Therapy (2013)
  • Author(s): K.Fujimoto, K.Mukai, Y.Okushi, K.Okino, H.Atsumi, H.Adachi, H.Okuyama, H.Yamaya, H.Yokoyama
  • Organizer: The Annual Meeting of American Society of Nephrology 2013
  • Place of Presentation: Atlanta (USA)
• [Presentation] Intact PTH and FGF23 levels of cinacalcet pre-test predict refractory hyperparathyroidism in hemodialysis patients (2013)
  • Author(s): A.Saito, H.Yokoyama, H.Okuyama, H.Yamaya, I.Ishikawa
  • Organizer: The Annual Meeting of American Society of Nephrology 2013
  • Place of Presentation: Atlanta (USA)