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2013 Fiscal Year Final Research Report

Factors Increasing Interstitial Fibrosis and Its Reduction with Personalized Dosing of Immunosuppressive Drugs after Kidney Transplantation

Research Project

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Project/Area Number 23592378
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Urology
Research InstitutionAkita University

Principal Investigator

SATOH Shigeru  秋田大学, 医学部, 教授 (80187195)

Co-Investigator(Kenkyū-buntansha) MIURA Maastomo  秋田大学, 医学部, 教授 (30265194)
KOMATSUDA Atsushi  秋田大学, 医学部, 准教授 (70272044)
INOUE Takamitsu  秋田大学, 医学部, 講師 (60375243)
NUMAKURA Kazuyuki  秋田大学, 医学部, 助教 (90566415)
Project Period (FY) 2011 – 2013
Keywords腎移植 / 移植腎線維増生 / 臨床因子 / 遺伝子多型 / 免疫抑制薬 / カルシニュリン阻害薬 / 個別投与量設計
Research Abstract

Patients with CYP3A5*1 allele (CYP3A5 expressers) require a higher daily tacrolimus dose than those with CYP3A5*3/*3 genotype (non-expressers) in order to maintain target trough levels. Recently, we reported that renal cortical interstitial fibrosis (IF) from 0-hour to 1-year post-transplantation increased in non-expressers than CYP3A5 expressers. Therefore, we have started to a personalized initial dosing regimen of tacrolimus based on the CYP3A5 polymorphism. Initial oral doses of tacrolimus were 0.20mg/kg for CYP3A5 expressers and 0.10mg/kg for non-expressers. In the non-personalized regimen, all patients received 0.20mg/kg of tacrolimus.
In results, the personalized medicine of tacrolimus based on the CYP3A5 polymorphism may decrease the pharmacokinetic difference between two groups, and it may contribute better graft function in non-expressers in the early post-transplantation. We are analyzing the 1-year post-transplant outcome and IF.

  • Research Products

    (21 results)

All 2013 2012 2011

All Journal Article (13 results) (of which Peer Reviewed: 9 results) Presentation (7 results) Book (1 results)

  • [Journal Article] Pharmaceutical and genetic determinants for interindividual differences of tacrolimus bioavailability in renal transplant recipients2013

    • Author(s)
      Niioka T, Kagaya H, Miura M, Numakura K, Saito M, Inoue T, Habuchi T, Satoh S
    • Journal Title

      Eur J Clin Pharmacol

      Volume: 69 Pages: 1659-1665

    • Peer Reviewed
  • [Journal Article] A limited sampling strategy to estimate the area under the concentration-time curve of tacrolimus modified-release once-daily preparation in renal transplant recipients2013

    • Author(s)
      Niioka T, Miura M, Kagaya H, Saito M, Numakura K, Habuchi T, Satoh S
    • Journal Title

      Ther Drug Monit

      Volume: 35 Pages: 228-232

    • Peer Reviewed
  • [Journal Article] 腎移植患者における免疫抑制剤の個別化療法2013

    • Author(s)
      三浦昌朋, 佐藤 滋
    • Journal Title

      日病薬誌

      Volume: 49 Pages: 1061-1065

  • [Journal Article] グラセプタのトラフ値はプログラフと同等か?2013

    • Author(s)
      佐藤 滋, 新岡丈典, 加賀谷英彰, 沼倉一幸, 井上高光, 斎藤 満, 小峰直樹, 秋濱 晋, 成田伸太郎, 土谷順彦, 羽渕友則, 三浦昌朋
    • Journal Title

      日本臨床腎移植学会雑誌

      Volume: 1 Pages: 78-81

    • Peer Reviewed
  • [Journal Article] タクロリムスの薬物動態・薬理遺伝学2013

    • Author(s)
      佐藤 滋
    • Journal Title

      今日の移植

      Volume: 26 Pages: 351-358

  • [Journal Article] 腎移植の適応. 特集 腎移植治療の最前線2013

    • Author(s)
      佐藤 滋
    • Journal Title

      泌尿器外科

      Volume: 26 Pages: 1605-1610

  • [Journal Article] Comparison of pharmacokinetics and pharmacogenetics of once- and twice-daily tacrolimus in the early stage after renal transplantation2012

    • Author(s)
      Niioka T, Satoh S, Kagaya H, Numakura K, Inoue T, Saito M, Narita S, Tsuchiya N, Habuchi T, Miura M
    • Journal Title

      Transplantation

      Volume: 94 Pages: 1013-101

    • Peer Reviewed
  • [Journal Article] Influence of NAT2 polymorphisms on sulfamethoxazole pharmacokinetics in renal transplant recipients2012

    • Author(s)
      Kagaya H, Miura M, Niioka T, Saito M, Numakura K, Habuchi T, Satoh S
    • Journal Title

      Antimicrob Agents Chemother

      Volume: 56 Pages: 825-829

    • Peer Reviewed
  • [Journal Article] Impact of the CYP3A4*1G polymorphism and its combination with CYP3A5 genotypes on tacrolimus pharmacokinetics in renal transplant patients2011

    • Author(s)
      Miura M, Satoh S, Kagaya H, Saito M, et al
    • Journal Title

      Pharmacogenomics

      Volume: 12 Pages: 977-984

    • Peer Reviewed
  • [Journal Article] Monitoring of mycophenolic acid predose concentration in the maintenance phase more than one year after renal transplantation2011

    • Author(s)
      Miura M, Niioka T, Kato S, Kagaya H, Saito M, Habuchi T, Satoh S
    • Journal Title

      Ther Drug Monit

      Volume: 33 Pages: 295-302

    • Peer Reviewed
  • [Journal Article] Factors increasing quantitative interstitial fibrosis from 0 hr to 1 year in living kidney transplant patients receiving tacrolimus2011

    • Author(s)
      Miura Y, Satoh S, Saito M, Numakura K, Inoue T, Obara T, Tsuruta H, Narita S, Horikawa Y, Tsuchiya N, Komatsuda A, Kagaya H, Miura M, Habuchi T
    • Journal Title

      Transplantation

      Volume: 91 Pages: 78-85

    • Peer Reviewed
  • [Journal Article] Pharmacogenetic determinants for interindividual difference of tacrolimus pharmacokinetics 1 year after renal transplantation2011

    • Author(s)
      Miura M, Niioka T, Kagaya H, Saito M, Hayakari M, Habuchi T, Satoh S
    • Journal Title

      J Clin Pharm Ther

      Volume: 36 Pages: 208-216

    • Peer Reviewed
  • [Journal Article] 薬物動態 、薬力学および薬理遺伝学に基づくミコフェノール酸の個別化療法の確立2011

    • Author(s)
      三浦昌朋, 佐藤 滋
    • Journal Title

      臨床薬理の進歩

      Volume: 別冊 Pages: 90-98

  • [Presentation] Lack of clinical factors increasing quantitative interstitial fibrosis after renal transplantation under a lower target trough strategy of tacrolimus2013

    • Author(s)
      Komine, N., Satoh, S., Numakura, K., Saito, M., Inoue, T., Narita, S., Miura, Y., Tsuchiya, N., Kagaya, H., Miura, M., Habuchi, H.
    • Organizer
      The 108th Annunal Meeting of the American Urological Association
    • Place of Presentation
      San Diego,USA
    • Year and Date
      20130500
  • [Presentation] Pharmacokinetics and CYP3A5 pharmacogenetics for once- versus twice-daily tacrolimus from first dosing day to 1 year post-transplantation2013

    • Author(s)
      Satoh, S., Niioka, T., Kagaya, H., Numakura, K., Saito, M., Inoue, T., Komine, N., Akihama, S., Narita, S., Tsuchiya, T., Habuchi, T., Miura, M.
    • Organizer
      The 13rd Annunal Meeting of the American Transplant Congress
    • Place of Presentation
      Seattl
    • Year and Date
      20130500
  • [Presentation] 遺伝子多型解析を基にした移植免疫抑制剤投与量2012

    • Author(s)
      佐藤 滋
    • Organizer
      第9回岐阜腎不全研究会
    • Place of Presentation
      岐阜(特別講演)
    • Year and Date
      20121200
  • [Presentation] Personalized initial dose of tacrolimus based on CYP3A5 polymorphism and its impact on 1-month graft function: a preliminary experience2012

    • Author(s)
      Satoh S, Numnakura K, Maita S, Obara T, Inoue T, Narita S, Horikawa Y, Tsuchiya N, Habuchi T, Kagaya H, Miura M.
    • Organizer
      24 th International Congress of the Transplantation Society
    • Place of Presentation
      Berlin
    • Year and Date
      20120700
  • [Presentation] MMF 血中濃度測定の現状Global Consensus と最近の研究動向2011

    • Author(s)
      佐藤 滋
    • Organizer
      第47回日本移植学会総会
    • Place of Presentation
      仙台(特別講演)
    • Year and Date
      20111000
  • [Presentation] タクロリムス薬物動態に及ぼすCYP3A4*1G遺伝子多型の影響とCYP3A5*1/*3との比較2011

    • Author(s)
      佐藤 滋、三浦昌朋、加賀谷英彰、沼倉一幸、斎藤 満、土谷順彦、羽渕友則
    • Organizer
      第47回日本移植学会総会
    • Place of Presentation
      仙台
    • Year and Date
      20111000
  • [Presentation] Basiliximab induction therapy combined with a lower target trough level of tacrolimus and low dose of mycophenolate mofetil decreased interstitial fibrosis at 1-year posttransplantation and improved the 5-year graft survival2011

    • Author(s)
      Satoh S, Numakura K, Saito M, Miura Y, Obara T, Tsuruta H, Inoue T, Narita S, Horikawa Y, Tsuchiya N, Habuchi T, Kagaya H, Miura M
    • Organizer
      The 106th Annual Meeting of the American Urological Association
    • Place of Presentation
      Washington DC
    • Year and Date
      20110500
  • [Book] ミコフェノール酸モフェチル.腎疾患治療マニュアル 2013-2014 腎と透析2013

    • Author(s)
      佐藤 滋, 三浦昌朋((編)腎と透析編集委員会)
    • Total Pages
      727-730
    • Publisher
      東京医学社, 東京(74 増刊号)

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Published: 2015-07-16  

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