title: Urinary fetuin-A is a novel marker for diabetic nephropathy in type 2 diabetes identified by lectin microarray.
abstract: We analyzed the urine samples of patients with type 2 diabetes at various stages of diabetic nephropathy by lectin microarray to identify a biomarker to predict the progression of diabetic nephropathy. Japanese patients with type 2 diabetes at various stages of nephropathy were enrolled and we performed lectin microarray analyses (n = 17) and measured urinary excretion of fetuin-A (n = 85). The increased signals of urine samples were observed in Siaα2-6Gal/GalNAc-binding lectins (SNA, SSA, TJA-I) during the progression of diabetic nephropathy. We next isolated sialylated glycoproteins by using SSA-lectin affinity chromatography and identified fetuin-A by liquid chromatography-tandem mass spectrometer. Urinary excretion of fetuin-A significantly increased during the progression of albuminuria (A1, 0.40 ± 0.43; A2, 0.60 ± 0.53; A3 1.57 ± 1.13 ng/gCr; p = 7.29 × 10(-8)) and of GFR stages (G1, 0.39 ± 0.39; G2, 0.49 ± 0.45; G3, 1.25 ± 1.18; G4, 1.34 ± 0.80 ng/gCr; p = 3.89 × 10(-4)). Multivariate logistic regression analysis was employed to assess fetuin-A as a risk for diabetic nephropathy with microalbuminuria or GFR<60 mL/min. Fetuin-A is demonstrated as a risk factor for both microalbuminuria and reduction of GFR in diabetic nephropathy with the odds ratio of 4.721 (1.881-11.844) and 3.739 (1.785-7.841), respectively. Collectively, the glycan profiling analysis is useful method to identify the urine biomarkers and fetuin-A is a candidate to predict the progression of diabetic nephropathy.
authors.affiliation: Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Kita-ku, Okayama, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Inoue
authors.forename: Jun
authors.initials: J
authors.lastname: Wada
authors.forename: Jun
authors.initials: J
authors.lastname: Eguchi
authors.forename: Atsuko
authors.initials: A
authors.lastname: Nakatsuka
authors.forename: Sanae
authors.initials: S
authors.lastname: Teshigawara
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Murakami
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ogawa
authors.forename: Takahiro
authors.initials: T
authors.lastname: Terami
authors.forename: Akihiro
authors.initials: A
authors.lastname: Katayama
authors.forename: Atsuhito
authors.initials: A
authors.lastname: Tone
authors.forename: Izumi
authors.initials: I
authors.lastname: Iseda
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Hida
authors.forename: Masao
authors.initials: M
authors.lastname: Yamada
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Ogawa
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Makino
mesh_terms: D000510:Alpha-Globulins / Q000378:metabolism / Q000652:urine; D015415:Biomarkers / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000097:blood / Q000150:complications / Q000652:urine*; D005260:Female; D006801:Humans; D008297:Male; D046228:Microarray Analysis / Q000379:methods*; D008875:Middle Aged; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D037121:Plant Lectins / Q000378:metabolism*; D012306:Risk; D060749:alpha-2-HS-Glycoprotein / Q000378:metabolism / Q000652:urine*
chemical_list: D000510:Alpha-Globulins; D015415:Biomarkers; D037121:Plant Lectins; C016001:alpha-1-microglobulin; D060749:alpha-2-HS-Glycoprotein; D019158:N-Acetylneuraminic Acid