Urinary fetuin-A is a novel marker for diabetic nephropathy in type 2 diabetes identified by lectin microarray

• Published in: PloS one 2013-10, Vol.8 (10), p.e77118-e77118
• Main Authors: Inoue, Kentaro, Wada, Jun, Eguchi, Jun, Nakatsuka, Atsuko, Teshigawara, Sanae, Murakami, Kazutoshi, Ogawa, Daisuke, Terami, Takahiro, Katayama, Akihiro, Tone, Atsuhito, Iseda, Izumi, Hida, Kazuyuki, Yamada, Masao, Ogawa, Tomohisa, Makino, Hirofumi
• Format: Article
• Language: English
• Subjects: Affinity chromatography; alpha-2-HS-Glycoprotein - metabolism; alpha-2-HS-Glycoprotein - urine; Alpha-Globulins - metabolism; Alpha-Globulins - urine; Analysis; Biomarkers; Biomarkers - urine; Chromatography; Dentistry; Development and progression; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - complications; Diabetic nephropathies; Diabetic Nephropathies - blood; Diabetic Nephropathies - complications; Diabetic Nephropathies - urine; Diabetic nephropathy; DNA microarrays; Excretion; Female; Glycan; Glycoproteins; Growth factors; Hospitals; Humans; Insulin resistance; Kidney diseases; Lectins; Liquid chromatography; Male; Mass spectrometry; Medical research; Medicine; Metabolism; Microarray Analysis - methods; Middle Aged; Mortality; N-Acetylneuraminic Acid - metabolism; Nephrology; Nephropathy; Patients; Pharmaceutical sciences; Plant Lectins - metabolism; Regression analysis; Risk; Risk factors; Rodents; Type 2 diabetes; University graduates; Urine
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0077118

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