Development of novel biomarkers for early detection of diabetic nephropathy

• Project/Area Number: 24790535
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Applied pharmacology
• Research Institution: Jichi Medical University
• Principal Investigator: HOSOHATA Keiko 自治医科大学, 医学部, 助教 (10547962)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 糖尿病性腎症 / バイオマーカー / Kim-1 / OLETFラット / 腎臓学 / アルブミン / 尿細管 / 医療薬学 / ２型糖尿病 / 腎臓 / 慢性腎臓病（CKD) / 尿中アルブミン / OLETF ラット / 尿細管障害

Research Abstract

Using spontaneous type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats, we examined temporal pattern of novel tubular markers in the urine for early diagnosis and evaluation of the severity of diabetic nephropathy. Urinary kidney injury molecule-1 (Kim-1) showed significant elevation before increase in albuminuria and N-acetyl-beta-D-glucosaminidase (NAG) in the OLETF rats with histopathologically proven renal tubular injury, compared with non-diabetic controls, Long-Evans Tokushima Otsuka (LETO) rats. In addition, urinary human KIM-1 showed elevation in type 2 diabetic patients with nephropathy compared with nondiabetic patients. Thus, urinary Kim-1 is a useful biomarker for the detection of early stage of type 2 diabetic nephropathy.

Research Products

• [Journal Article] Urinary Kim-l is a sensitive biomarker for the early stage of diabetic nephropathy in Otsuka Long Evans Tokushima Fatty rats (2014)
  • Author(s): Hosohata K, Ando H, Takeshita Y, Misu H, Takamura T, Kaneko S, Fujimura A
  • Journal Title: Diab Vasc Dis Res Volume: 11 Pages: 243-250
  • Peer Reviewed
• [Journal Article] Association between CYP3A5 genotypes in graft liver and increase in tacrolimus biotransformation by steroid treatment in living-donor liver transplant patients (2014)
  • Author(s): Hosohata K, Uesugi M, Hashi S, Hosokawa M, Inui K, Matsubara K, Ogawa K, Fujimoto Y, Kaido T, Uemoto S and Masuda S
  • Journal Title: Drug Metab Pharmacokinet Volume: 29 Pages: 83-89
  • NAID: 130004463348
  • Peer Reviewed
• [Journal Article] Early detection of renal injury using urinary vanin-1 in rats with experimental colitis (2014)
  • Author(s): Hosohata K, Ando H, Fujimura A
  • Journal Title: J Appl Toxicol Volume: 34 Pages: 184-190
  • Peer Reviewed
• [Journal Article] Urinary Kim-1 is a sensitive biomarker for the early stage of diabetic nephropathy in Otsuka Long-Evans Tokushima Fatty rats (2014)
  • Author(s): Hosohata K, Hitoshi Ando, Yumie Takeshita, Hirofumi Misu, Toshinari Takamura, Shuichi Kaneko, and Akio Fujimura
  • Journal Title: Diabetes & Vascular Disease Research Volume: in press Issue: 4 Pages: 243-250
  • DOI: 10.1177/1479164114531299
  • Peer Reviewed
• [Journal Article] Association between <i>CYP3A5</i> Genotypes in Graft Liver and Increase in Tacrolimus Biotransformation from Steroid Treatment in Living-donor Liver Transplant Patients (2014)
  • Author(s): Hosohata K, Uesugi M, Hashi S, Hosokawa M, Inui KI, Matsubara K, Ogawa K, Fujimoto Y, Kaido T, Uemoto S, Masuda S.
  • Journal Title: Drug Metabolism and Pharmacokinetics Volume: 29 Issue: 1 Pages: 83-89
  • DOI: 10.2133/dmpk.DMPK-13-RG-060
  • NAID: 130004463348
  • ISSN: 1347-4367, 1880-0920
  • Peer Reviewed
• [Journal Article] Relationship between the receptor occupancy profile and pleiotropic effects of angiotensin II receptor blockers (2013)
  • Author(s): Ando H, Ushijima K, Hosohata K, Saito T, Fujimura A
  • Journal Title: Br J Clin Pharmacol Volume: 75 Pages: 415-422
  • Peer Reviewed
• [Journal Article] Dosing time - dependent effect of raloxifene on plasma plasminogen activator inhibitor-1 concentrations in post - menopausal women with osteoporosis (2013)
  • Author(s): Ando H, Otoda T, Ookami H, Nagai Y, Inano A, Takamura T, Ushijima K, Hosohata K, Matsushita E, Saito T, Kaneko S, Fujimura A
  • Journal Title: Clin Exp Pharmacol Physiol Volume: 40 Pages: 227-232
  • Peer Reviewed
• [Journal Article] Relationship between the receptor occupancy profile and pleiotropic effects of angiotensin II receptor blockers. (2013)
  • Author(s): Ando H, Ushijima K, Hosohata K, Saito T, and Fujimura A.
  • Journal Title: Br J Clin Pharmacol. Volume: 75 Issue: 2 Pages: 415-422
  • DOI: 10.1111/j.1365-2125.2012.04358.x
  • Peer Reviewed
• [Journal Article] Early detection of renal injury using urinary vanin-1 in rats with experimental colitis. (2013)
  • Author(s): Hosohata K, Ando H, and Fujimura A.
  • Journal Title: J Appl Toxicol. Volume: in press Issue: 2 Pages: 184-190
  • DOI: 10.1002/jat.2849
  • Peer Reviewed
• [Journal Article] Dosing time-dependent effect of raloxifene on plasma plasminogen activator inhibitor-1 concentrations in post-menopausal women with osteoporosis (2013)
  • Author(s): H Ando, T Otoda, H Ookami, Y Nagai, A Inano, T Takamura, K Ushijima, K Hosohata, E Matsushita, T Saito, S Kaneko, A Fujimura
  • Journal Title: Clin Exp Pharmacol Physiol Volume: 40(3) Issue: 3 Pages: 227-32
  • DOI: 10.1111/1440-1681.12055
  • Peer Reviewed
• [Journal Article] Urinary vanin-1 as a novel biomarker for early detection of drug-induced acute kidney injury (2012)
  • Author(s): Hosohata K, Ando H, Fujimura A
  • Journal Title: J Pharmacol Exp Ther Volume: 341 Pages: 656-662
  • NAID: 130005008682
  • Peer Reviewed
• [Journal Article] Urinary vanin-1 as a novel biomarker for early detection of drug-induced acute kidney injury. (2012)
  • Author(s): Hosohata K, Ando H, and Fujimura A.
  • Journal Title: J Pharmacol Exp Ther. Volume: 341 Issue: 3 Pages: 656-662
  • DOI: 10.1124/jpet.112.192807
  • NAID: 130005008682
  • Peer Reviewed
• [Journal Article] Temsirolimus induces surfactant lipid accumulation and lung inflammation in mice
  • Author(s): Washino S, Ando H, Ushijima K, Hosohata K, Kumazaki M, Mato N, Sugiyama Y, Kobayashi Y, Fujimura A, and Morita T
  • Journal Title: Am J Physiol Lung Cell Mol Physiol Volume: (in press)
  • Peer Reviewed
• [Presentation] Elevations of urinary vanin-1 and neutrophil gelatinase-associated lipocalin precede the appearance of albuminuria in spontaneously hypertensive rats (2013)
  • Author(s): Hosohata K, Ando H, Yoshioka D, and Fujimura A
  • Organizer: The 5th International Conference on Fixed Combination in the Treatment of Hypertension, Dyslipidemia and Diabetes Mellitus, Bangkok
  • Place of Presentation: Thailand
• [Presentation] Elevations of urinary vanin-1 and neutrophil gelatinase-associated lipocalin precede the appearance of albuminuria in spontaneously hypertensive rats (2013)
  • Author(s): Hosohata K, Ando H, Yoshioka D, and Fujimura A.
  • Organizer: The 5th International Conference on Fixed Combination in the Treatment of Hypertension, Dyslipidemia and Diabetes Mellitus.
  • Place of Presentation: Bangkok, Thailand
• [Presentation] Urinary vanin-1 as a kidney-specific biomarker under multiorgan damages (2012)
  • Author(s): Hosohata K, Ando H, and Fujimura A
  • Organizer: 日本薬物動態学会第27回年会
  • Place of Presentation: 千葉
• [Presentation] 薬物性腎障害を早期に検出するためのバイオマーカーvanin-1の同定 (2012)
  • Author(s): 細畑圭子、安藤仁、藤村昭夫
  • Organizer: 第39回日本トキシコロジー学会学術年会
  • Place of Presentation: 仙台
• [Presentation] 薬物性腎障害を早期に検出するためのバイオマーカーvanin-1の同定 (2012)
  • Author(s): 細畑圭子、安藤 仁、藤村昭夫
  • Organizer: 第39回日本毒性学会学術年会
  • Place of Presentation: 宮城県仙台市
• [Presentation] Urinary vanin-1 as a kidney-specific biomarker under multiorgan damages (2012)
  • Author(s): Keiko Hosohata, Hitoshi Ando, and Akio Fujimura
  • Organizer: 日本薬物動態学会第27回年会
  • Place of Presentation: 東京都
• [Book] 薬物による治療.がん患者さんの口腔ケアをはじめましょう (2013)
  • Author(s): 細畑圭子、藤村昭夫
  • Publisher: 学建書院
• [Book] がん患者さんの口腔ケアをはじめましょう (2013)
  • Author(s): 細畑圭子、藤村昭夫
  • Publisher: 学建書院
• [Remarks]
  • URL: http://jglobal.jst.go.jp/search.