Development of metabolomic biomarkers for early detection of acute kidney injury in kidney transplantation.

• Project/Area Number: 24591219
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Fujita Health University
• Principal Investigator: YUZAWA Yukio 藤田保健衛生大学, 医学部, 教授 (00191479)
• Co-Investigator(Kenkyū-buntansha): AKIYAMA Shin'ichi 名古屋大学, 医学(系)研究科(研究院), 講師 (20500010) ; HAYASHI Hiroki 藤田保健衛生大学, 医学部, 助教 (10378086) ; HASEGAWA Midori 藤田保健衛生大学, 医学部, 教授 (40298518) ; KUSAKA Mamoru 藤田保健衛生大学, 医学部, 教授 (40309141) ; MARUYAMA Shoichi 名古屋大学, 医学(系)研究科(研究院), 准教授 (10362253) ; SATO Waichi 藤田保健衛生大学, 医学部, 准教授 (90508920) ; SOGA Tomoyoshi 慶応義塾大学, 環境情報学部, 教授 (60228217) ; 曽我 朋義 慶應義塾大学, 環境情報学部, 教授 (60338217)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: AKIバイオマーカー / メタボローム解析 / 腎移植 / AKI: acute kidney injury / 急性腎傷害

Outline of Final Research Achievements

We have established the level of urinary midkine as an early biomarker of acute kidney injury (AKI). Furthermore, recent advances on metabolomics allowed us to identify metabolomic biomarkers for prediction of AKI. This study aimed to develop metabolomics biomarkers for early detection of AKI after renal transplantation by elucidating the detailed molecular mechanism of AKI at the metabolite level. A simultaneous metabolomics analysis with capillary electrophoresis-time of flight-mass spectrometry was conducted on urine samples from subjects who had undergone the surgery with renal ischemia reperfusion at the time of renal transplantation. Our metabolomic profiling identified novel biomarker candidates for early prediction of ischemic AKI in kidney transplantation.

Research Products

• [Journal Article] Long-term effects of spironolactone in peritoneal dialysis patients. (2014)
  • Author(s): Ito Y, Mizuno M, Suzuki Y, Tamai H, Hiramatsu T, Ohashi H, Ito I, Kasuga H, Horie M, Maruyama S, Yuzawa Y, Matsubara T, Matsuo S; on behalf of the Nagoya Spiro Study Group.
  • Journal Title: J Am Soc Nephrol Volume: 25(5) Pages: 1094-102
  • DOI: 10.1681/asn.2013030273
  • Peer Reviewed
• [Journal Article] Enzymatic sialylation of IgA1 o-glycans: implications for studies of IgA nephropathy. (2014)
  • Author(s): Takahashi K, Raska M, Stuchlova Horynova M, Hall SD, Poulsen K, Kilian M, Hiki Y, Yuzawa Y, Moldoveanu Z, Julian BA, Renfrow MB, Novak J.
  • Journal Title: PLoS One. Volume: 9(2)
  • DOI: 10.1371/journal.pone.0099026
  • Peer Reviewed / Open Access
• [Journal Article] Deficiency of growth factor midkine exacerbates necrotizing glomerular injuries in progressive glomerulonephritis. (2013)
  • Author(s): Kojima H, Kosugi T, Sato W, Sato Y, Maeda K, Kato N, Kato K, Inaba S, Ishimoto T, Tsuboi N, Matsuo S, Maruyama S, Yuzawa Y, Kadomatsu K
  • Journal Title: Am J Pathol. Volume: 182(2) Pages: 410-419
  • DOI: 10.1016/j.ajpath.2012.10.016
  • Peer Reviewed
• [Journal Article] Comparison of Kidney Disease: Improving Global Outcomes and Acute Kidney Injury Network criteria for assessing patients in intensive care units. (2013)
  • Author(s): Shinjo H, Sato W, Imai E, Kosugi T, Hayashi H, Nishimura K, Nishiwaki K, Yuzawa Y, Matsuo S, Maruyama S
  • Journal Title: Clin Exp Nephrol. Volume: 999 Pages: 999-999
  • Peer Reviewed
• [Journal Article] CD147/basigin reflects renal dysfunction in patients with acute kidney injury. (2013)
  • Author(s): Nagaya H, Kosugi T, Maeda-Hori M, Maeda K, Sato Y, Kojima H, Hayashi H, Kato N, Ishimoto T, Sato W, Yuzawa Y, Matsuo S, Kadomatsu K, Maruyama S
  • Journal Title: Clin Exp Nephrol. Volume: 999 Pages: 999-999
  • Peer Reviewed
• [Journal Article] エビデンスに基づくCKD診療ガイドライン2013 (2013)
  • Author(s): 木村 健二郎, 松尾 清一, 湯澤 由紀夫, 他106名, エビデンスに基づくCKD診療ガイドライン2013作成委員会, 日本腎臓学会
  • Journal Title: 日本腎臓学会誌 Volume: 55(5) Pages: 585-860
• [Journal Article] Deficiency of growth factor midkine exacerbates necrotizing glomerular injuries in progressive glomerulonephritis. (2013)
  • Author(s): Kojima H, Kosugi T, Sato W, Sato Y, Maeda K, Kato N, Kato K, Inaba S, Ishimoto T, Tsuboi N, Matsuo S, Maruyama S, Yuzawa Y, Kadomatsu K
  • Journal Title: The American Journal of Pathology Volume: 182(2) Pages: 410-9
  • Peer Reviewed
• [Journal Article] DNA hypermethylation and inflammatory markers in incident Japanese dialysis patients. (2012)
  • Author(s): Kato S
  • Journal Title: Nephron Extra Volume: 2(1) Pages: 159-68
  • DOI: 10.1159/000339437
  • Peer Reviewed
• [Journal Article] Autologous cell therapy for cisplatin-induced acute kidney injury by using non-expanded adipose tissue-derived cells. (2012)
  • Author(s): Yasuda K, Ozaki T, Saka Y, Yamamoto T, Gotoh M, Ito Y, Yuzawa Y, Matsuo S, Maruyama S
  • Journal Title: Cytotherapy. Volume: 14(9) Pages: 1089-100
  • Peer Reviewed
• [Presentation] AKI; diagnosis and future prospect“Organ drosstalk in acute kidney injury” (2014)
  • Author(s): Yukio Yuzawa
  • Organizer: The 59th Congress of the Japanese Society for Dialysis Therapy
  • Place of Presentation: Yokohama, Japan (PACIFICO Yokohama)
  • Year and Date: 2014-07-04 – 2014-07-06
  • Invited
• [Presentation] Treatment of IgA nephropathy“The first comprehensive evidence-based clinical guideline for IgA nephropathy in Japan (2014)
  • Author(s): Yukio Yuzawa
  • Organizer: 1st Oxford Conference on IgA Nephropathy
  • Place of Presentation: Oxford, UK (Magdalen College School)
  • Year and Date: 2014-06-25 – 2014-06-26
  • Invited
• [Presentation] Acute Kidney Injury “Urinary Biomarker for Acute Kidney Injury (AKI) (2014)
  • Author(s): Yukio yuzawa, Hiroki Hayashi, Midori Hasegawa
  • Organizer: The 14th Asian Pacific Congress of Nephrology
  • Place of Presentation: Tokyo, Japan (Shinagawa Prince Hotel)
  • Year and Date: 2014-05-14 – 2014-05-17
  • Invited
• [Presentation] Urinary neutrophil gelatinase-associated lipocalin as a biomarker of cardiovascular events in chronic kidney disease. (2013)
  • Author(s): Midori Hasegawa, Junichi Ishii, Fumihiko Kitagawa, Hiroshi Takahashi, Kyoko Kanayama and Yukio Yuzawa
  • Organizer: World Congress of Nephrology 2013
  • Place of Presentation: Hong Kong
• [Presentation] IgA Antibodies to Glomerular Endothelial Cells in Patients with Lupus Nephritis: Correlations with Renal Injury. (2013)
  • Author(s): Kazuo Takahashi, Ayako Kondo, Daisuke Hirano, Shin’ichi Akiyama, Hiroki Hayashi, Shigehisa Koide, Midori Hasegawa, Yoshiyuki Hiki, Shunji Yoshida, Keiji Miura, Yukio Yuzawa
  • Organizer: Kidney Week 2013 (American Society of Nephrology)
  • Place of Presentation: Atlanta,Georgia,USA
• [Presentation] A Retrospective Study on Outcome of MPO-ANCA Associated Vasculitis in Renal Replacement Therapy. (2013)
  • Author(s): Midori Hasegawa, Kyoko Hattori, Kazuo Takahashi, Hiroki Hayashi, Shigehisa Koide, Yukio Yuzawa.
  • Organizer: Kidney Week 2013 (American Society of Nephrology)
  • Place of Presentation: Atlanta,Georgia,USA
• [Presentation] Distant Effects of AKI on Lung Injuries by Soluble Mediators in Broncho-Alveolar Lavage Fluid in Patients with Acute Lung Injury / Acute Respiratory Distress Syndrome. (2012)
  • Author(s): Hiroki Hayashi, Sachiyo Suzuki, Kensuke Kataoka, Yasuhiro Kondoh, Hiroyuki Taniguchi, Daisuke Sugiyama, Kunihiro Nishimura, Waichi Sato, Shoichi Maruyama, Seiichi Matsuo, Yukio Yuzawa
  • Organizer: ERA-EDTA Congress 2012
  • Place of Presentation: Paris, France
• [Presentation] 教育講演「AKI のバイオマーカー」 (2012)
  • Author(s): 湯澤由紀夫
  • Organizer: 第42回日本腎臓学会西部学術大会
  • Place of Presentation: 沖縄県宜野湾市
  • Invited
• [Presentation] ランチョンシンポジウム2：臓器連関障害を救済するための急性血液浄化療法の位置付け (2012)
  • Author(s): 湯澤由紀夫
  • Organizer: 第23回日本急性血液浄化学会学術集会
  • Place of Presentation: 埼玉県大宮市
  • Invited
• [Book] 尿検査教本From 2013 (第1章)総論 急性腎障害AKIの考え方と尿バイオマーカー (2013)
  • Author(s): 湯澤 由紀夫長谷川 みどり, 林 宏樹
  • Total Pages: 999
  • Publisher: 臨床病理レビュー
• [Book] Annual Review 腎臓 2012: 2. 肺・腎連関 CKDにおけるRAS活性化を介する機能的な腎・肺連関 Critical Care Nephrology における腎・肺クロストーク AKI後のALI/ARDS発症に重要な因 (2012)
  • Author(s): 湯澤由紀夫, 林宏樹
  • Total Pages: 10
  • Publisher: 中外医学社
• [Book] EBM 腎臓病の治療 2011-2012: III急性腎不全 1. 急性腎不全のバイオマーカーは何がよいでしょうか？ (2012)
  • Author(s): 林 宏樹, 湯澤由紀夫
  • Total Pages: 6
  • Publisher: 中外医学社
• [Remarks] 藤田保健衛生大学医学部腎内科学
  • URL: http://www.fujita-hu.ac.jp/~jinzou/index.html
• [Remarks] 藤田保健衛生大学医学部腎内科学ホームページ
  • URL: http://www.fujita-hu.ac.jp/~jinzou/index.html