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International study for clinical significance of anti-erythropoietin receptor antibodies as a biomarker candidate in patients with diabetic kidney disease

Research Project

Project/Area Number 20KK0191
Research Category

Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 52:General internal medicine and related fields
Research InstitutionKanazawa University

Principal Investigator

Wada Takashi  金沢大学, その他部局等, その他 (40334784)

Co-Investigator(Kenkyū-buntansha) 遠山 直志  金沢大学, 附属病院, 特任教授 (50624871)
原 章規  金沢大学, 医学系, 准教授 (70507045)
大島 恵  金沢大学, 附属病院, 特任助教 (80802066)
Project Period (FY) 2020-10-27 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2022: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2021: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2020: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Keywords糖尿病性腎臓病 / 抗エリスロポエチン受容体抗体 / 国際共同研究 / バイオマーカー / 糖尿病
Outline of Research at the Start

糖尿病性腎臓病・糖尿病性腎症(腎症)による透析患者は世界的に増加し、病態解明と克服が求められている。腎症など糖尿病臓器合併症は予後不良であり、病態解明と予後を反映するバイオマーカー確立は喫緊の課題である。本研究では、エリスロポエチン受容体(EPOR)に着目し、独自に開発した抗EPOR抗体を国際的糖尿病性腎臓病コホートの血液検体を用いて測定する。さらに、腎症はじめ、心・脳血管障害など全身臓器の予後、総死亡との関連を検討し、病態解析、国際比較を施行する。以上、腎症に代表される糖尿病臓器合併症における抗EPOR抗体の新規国際的バイオマーカーとしての意義の確立を目指す。

Outline of Final Research Achievements

This study was aimed to determine the significance of anti-erythropoietin receptor (EPOR) antibodies, which we have already established, in clinical outcomes and their related risk factors in patients with diabetic nephropathy (diabetic kidney disease) comparing to our Japanese database. We have established international collaborative research team among international cohorts. Our study revealed that higher levels of anti-EPOR antibodies were associated with an increased risk of kidney outcome. In addition, prognostic risk factors including the presence of anti-EPOR antibodies from our Japanese database were closely relevant to those of patients examined. Taken together, these results suggested that anti-EPOR antibodies could be a promising biomarker candidate in predicting kidney disease progression in patients with diabetic nephropathy (diabetic kidney disease).

Academic Significance and Societal Importance of the Research Achievements

本邦では糖尿病性腎症(糖尿病性腎臓病)は透析導入原疾患の第1位である。さらに、諸外国においても、糖尿病の増加とともに、その合併症である腎症の克服は重要な課題である。本研究の学術的な特色は、申請者らが独自に開発した抗エリスロポエチン受容体(EPOR)抗体を用いて国際的糖尿病性腎臓病コホート検体を測定し、腎症の病態や予後との関連を検討した点にある。さらに、本邦の代表的なコホートから得られた成果と病態などの国際比較、検証を行った点にある。本研究は新規国際的バイオマーカーとしての意義の確立を目指すものであり、学術的意義ならびに社会的意義が深い。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (33 results)

All 2022 2021 2020 Other

All Int'l Joint Research (1 results) Journal Article (14 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 14 results,  Open Access: 13 results) Presentation (14 results) (of which Invited: 6 results) Book (4 results)

  • [Int'l Joint Research] University of Groningen(オランダ)

    • Related Report
      2020 Research-status Report
  • [Journal Article] Association between Anti-Erythropoietin Receptor Antibodies and Cardiac Function in Patients on Hemodialysis: A Multicenter Cross-Sectional Study2022

    • Author(s)
      Mochida Yasuhiro, Hara Akinori, Oka Machiko, Maesato Kyoko, Ishioka Kunihiro, Moriya Hidekazu, Oshima Megumi, Toyama Tadashi, Kitajima Shinji, Iwata Yasunori, Sakai Norihiko, Shimizu Miho, Koshino Yoshitaka, Ohtake Takayasu, Hidaka Sumi, Kobayashi Shuzo, Wada Takashi
    • Journal Title

      Biomedicines

      Volume: 10 Issue: 9 Pages: 2092-2092

    • DOI

      10.3390/biomedicines10092092

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intestinal Bacterial Translocation Contributes to Diabetic Kidney Disease.2022

    • Author(s)
      Linh HT, Iwata Y, Senda Y, Sakai-Takemori Y, Nakade Y, Oshima M, Nakagawa-Yoneda S, Ogura H, Sato K, Minami T, Kitajima S, Toyama T, Yamamura Y, Miyagawa T, Hara A, Shimizu M, Furuichi K, Sakai N, Yamada H, Asanuma K, Matsushima K, Wada T.
    • Journal Title

      J Am Soc Nephrol.

      Volume: - Issue: 6 Pages: 1105-1119

    • DOI

      10.1681/asn.2021060843

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Carnitine/organic cation transporter 1 precipitates the progression of interstitial fibrosis through oxidative stress in diabetic nephropathy in mice2021

    • Author(s)
      Makiishi Shohei、Furuichi Kengo、Yamamura Yuta、Sako Keisuke、Shinozaki Yasuyuki、Toyama Tadashi、Kitajima Shinji、Iwata Yasunori、Sakai Norihiko、Shimizu Miho、Hirose-Sugiura Tomoko、Kaneko Shuichi、Kato Yukio、Wada Takashi
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 9093-9093

    • DOI

      10.1038/s41598-021-88724-4

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serum hemoglobin concentration and risk of renal function decline in early stages of diabetic kidney disease: a nationwide, biopsy-based cohort study2021

    • Author(s)
      Yamanouchi M,Furuichi K,Shimizu M,Toyama T,Yamamura Y,Oshima M,Kitajima S,Hara A,Iwata Y,Sakai N,Oba Y,Matsuoka S,Ikuma De,Mizuno H,Suwabe T,Hoshino J Sawa N,Yuzawa Y,Kitamura H,Suzuki Y,Sato H,Uesugi N,Ueda Y,Nishi S,Yokoyama H,Nishino T,Samejima K Kohagura K,Shibagaki Y,Makino H,Matsuo S,Ubara Y,Wada
    • Journal Title

      Nephrology Dialysis Transplantation

      Volume: 37 Issue: 3 Pages: 489-497

    • DOI

      10.1093/ndt/gfab185

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Combined changes in albuminuria and kidney function and subsequent risk for kidney failure in type 2 diabetes2021

    • Author(s)
      Oshima Megumi、ToyaIwata Yasunori、et. al
    • Journal Title

      BMJ Open Diabetes Research & Care

      Volume: 9 Issue: 1 Pages: e002311-e002311

    • DOI

      10.1136/bmjdrc-2021-002311

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Renal, cardiovascular and safety outcomes of canagliflozin in patients with type?2 diabetes and nephropathy in East and South‐East Asian countries: Results from the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation Trial2021

    • Author(s)
      Wada Takashi、Mori‐Anai Kazumi、Kawaguchi Yutaka、Katsumata Hideyuki、Tsuda Hidetaka、Iida Mitsutaka、Arakawa Kenji、Jardine Meg J
    • Journal Title

      Journal of Diabetes Investigation

      Volume: 13 Issue: 1 Pages: 54-64

    • DOI

      10.1111/jdi.13624

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Two-year longitudinal trajectory patterns of albuminuria and subsequent rates of end-stage kidney disease and all-cause death: a nationwide cohort study of biopsy-proven diabetic kidney disease2021

    • Author(s)
      Yamanouchi Masayuki、Iwata Yasunori、et al.
    • Journal Title

      BMJ Open Diabetes Research & Care

      Volume: 9 Issue: 1 Pages: e002241-e002241

    • DOI

      10.1136/bmjdrc-2021-002241

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impact of the relationship between hemoglobin levels and renal interstitial fibrosis on long-term outcomes in type 2 diabetes with biopsy-proven diabetic nephropathy2021

    • Author(s)
      Shimizu Miho、Furuichi Kengo、Kitajima Shinji、Toyama Tadashi、Oshima Megumi、Ogura Hisayuki、Sato Koichi、Nakagawa Shiori、Yamamura Yuta、Miyagawa Taro、Hara Akinori、Iwata Yasunori、Sakai Norihiko、Kitagawa Kiyoki、Yoshimura Mitsuhiro、Yokoyama Hitoshi、Wada Takashi
    • Journal Title

      BMC Nephrology

      Volume: 22 Issue: 1 Pages: 319-319

    • DOI

      10.1186/s12882-021-02510-y

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of canagliflozin versus finerenone on cardiorenal outcomes: exploratory <i>post hoc</i> analyses from FIDELIO-DKD compared to reported CREDENCE results2021

    • Author(s)
      Agarwal Rajiv、Anker Stefan D、Filippatos Gerasimos、Pitt Bertram、Rossing Peter、Ruilope Luis M、Boletis John、Toto Robert、Umpierrez Guillermo E、Wanner Christoph、Wada Takashi、Scott Charlie、Joseph Amer、Ogbaa Ike、Roberts Luke、Scheerer Markus F、Bakris George L
    • Journal Title

      Nephrology Dialysis Transplantation

      Volume: gfab336 Issue: 7 Pages: 1261-1269

    • DOI

      10.1093/ndt/gfab336

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Trajectories of kidney function in diabetes: a clinicopathological update2021

    • Author(s)
      Oshima Megumi、Shimizu Miho、Yamanouchi Masayuki、Toyama Tadashi、Hara Akinori、Furuichi Kengo、Wada Takashi
    • Journal Title

      Nature Reviews Nephrology

      Volume: 17 Issue: 11 Pages: 740-750

    • DOI

      10.1038/s41581-021-00462-y

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison of Circulating Biomarkers in Predicting Diabetic Kidney Disease Progression With Autoantibodies to Erythropoietin Receptor2021

    • Author(s)
      Oshima Megumi、Hara Akinori、Toyama Tadashi、Jun Min、Pollock Carol、Jardine Meg、Harrap Stephen、Poulter Neil、Cooper Mark E.、Woodward Mark、Chalmers John、Perkovic Vlado、Wong Muh Geot、Wada Takashi
    • Journal Title

      Kidney International Reports

      Volume: 6 Issue: 2 Pages: 284-295

    • DOI

      10.1016/j.ekir.2020.10.039

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Nonproteinuric diabetic kidney disease.2020

    • Author(s)
      Yamanouchi M, Furuichi K, Hoshino J, Ubara Y, Wada T.
    • Journal Title

      Clin Exp Nephrol

      Volume: - Issue: 7 Pages: 573-581

    • DOI

      10.1007/s10157-020-01881-0

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinicopathological features of fast eGFR decliners among patients with diabetic nephropathy2020

    • Author(s)
      Furuichi Kengo、Shimizu Miho、Yamanouchi Masayuki、Hoshino Junichi、Sakai Norihiko、Iwata Yasunori、Toyama Tadashi、Kitajima Shinji、Hara Akinori、Wada Takashi et.al.
    • Journal Title

      BMJ Open Diabetes Research & Care

      Volume: 8 Issue: 1 Pages: e001157-e001157

    • DOI

      10.1136/bmjdrc-2019-001157

    • NAID

      120006892782

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of canagliflozin on anaemia in patients with type 2 diabetes and chronic kidney disease: a post-hoc analysis from the CREDENCE trial2020

    • Author(s)
      Oshima Megumi、Neuen Brendon L、Jardine Meg J、Bakris George、Edwards Robert、Levin Adeera、Mahaffey Kenneth W、Neal Bruce、Pollock Carol、Rosenthal Norman、Wada Takashi、Wheeler David C、Perkovic Vlado、Heerspink Hiddo J L
    • Journal Title

      The Lancet Diabetes & Endocrinology

      Volume: 8 Issue: 11 Pages: 903-914

    • DOI

      10.1016/s2213-8587(20)30300-4

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] バイオマーカー開発と産学連携への期待2022

    • Author(s)
      和田隆志
    • Organizer
      日本医療検査科学会 第54回大会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 腎症のバイオマーカー候補2022

    • Author(s)
      原 章規・和田隆志
    • Organizer
      第28回日本糖尿病合併症学会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 腎病理に基づくDKDコホート解析2021

    • Author(s)
      清水美保・古市賢吾・和田隆志
    • Organizer
      第64回日本糖尿病学会年次学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] 糖尿病性腎臓病における腎硬化症の側面2021

    • Author(s)
      清水美保・古市賢吾・和田隆志
    • Organizer
      第64回日本腎臓学会学術総会
    • Related Report
      2021 Research-status Report
  • [Presentation] Strategies for anemia managementin diabetes and chronic kidney disease2021

    • Author(s)
      大島恵・和田隆志
    • Organizer
      第64回日本腎臓学会学術総会
    • Related Report
      2021 Research-status Report
  • [Presentation] 糖尿病性腎臓病:病態と治療2021

    • Author(s)
      和田隆志
    • Organizer
      日本内科学会 第80回東海支部主催生涯教育講演会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 糖尿病性腎臓病:腎病理に基づく現状と課題2021

    • Author(s)
      清水美保・和田隆志
    • Organizer
      第36回日本糖尿病合併症学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 糖尿病性腎臓病の病態を反映する腎病理とバイオマーカー2021

    • Author(s)
      清水美保・古市賢吾・和田隆志
    • Organizer
      第51回日本腎臓学会西部学術大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 糖尿病合併CKDの腎病理2021

    • Author(s)
      清水美保・和田隆志
    • Organizer
      第32回日本糖尿病性腎症研究会
    • Related Report
      2021 Research-status Report
  • [Presentation] The gut-kidney axis in diabetic kidney disease2020

    • Author(s)
      岩田恭宜・中出祐介・和田隆志
    • Organizer
      第63回日本糖尿病学会年次学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] eGFRと尿アルブミンを用いた末期腎不全の代替エンドポイント2020

    • Author(s)
      大島恵・遠山直志・坂井宣彦・和田隆志
    • Organizer
      第50回日本腎臓学会西部学術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] 糖尿病例における腎病変―病態と治療―2020

    • Author(s)
      和田隆志
    • Organizer
      日本糖尿病学会 中国四国地方会第58回総会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 慢性腎臓病と糖尿病性腎臓病:病態と最新治療2020

    • Author(s)
      和田隆志
    • Organizer
      第65回日本透析医学会学術集会・総会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 糖尿病性腎臓病・腎硬化症の診療2020

    • Author(s)
      和田隆志
    • Organizer
      2020年度日本内科学会生涯教育講演会 Bセッション(第2回)
    • Related Report
      2020 Research-status Report
    • Invited
  • [Book] 糖尿病性腎臓病の病態と治療2021

    • Author(s)
      遠山直志・清水美保・古市賢吾・和田隆志
    • Total Pages
      270
    • Publisher
      中外医学社
    • Related Report
      2021 Research-status Report
  • [Book] 糖尿病性腎臓病の病態と治療2021

    • Author(s)
      大島恵・遠山直志・和田隆志
    • Total Pages
      270
    • Publisher
      中外医学社
    • Related Report
      2021 Research-status Report
  • [Book] 腎臓内科Controversy2021

    • Author(s)
      遠山直志・大島恵・清水美保・和田隆志
    • Total Pages
      308
    • Publisher
      中外医学社
    • Related Report
      2021 Research-status Report
  • [Book] 腎臓内科Controversy2021

    • Author(s)
      清水美保・遠山直志・和田隆志
    • Total Pages
      308
    • Publisher
      中外医学社
    • Related Report
      2021 Research-status Report

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Published: 2020-10-29   Modified: 2024-01-30  

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