Adipocytokine zinc α2 glycoprotein (ZAG) as a novel urinary biomarker for normo-albuminuric diabetic nephropathy

• Published in: Diabetic medicine Vol. 29; no. 7; pp. 945 - 949
• Main Authors: Lim, S. C., Liying, D. Q., Toy, W. C., Wong, M., Yeoh, L. Y., Tan, C., Lau, D., Subramaniam, T., Sum, C. F.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.07.2012; Blackwell
• Subjects: Adipokines - metabolism; albuminuria; Albuminuria - urine; Asian Continental Ancestry Group - statistics & numerical data; Associated diseases and complications; Biological and medical sciences; biomarker; Biomarkers - urine; Blotting, Western; Carrier Proteins - urine; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - urine; Diabetes. Impaired glucose tolerance; Diabetic Nephropathies - epidemiology; Diabetic Nephropathies - physiopathology; Diabetic Nephropathies - urine; diabetic nephropathy; Electrophoresis, Gel, Two-Dimensional; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Feeding. Feeding behavior; Fluorescence; Fundamental and applied biological sciences. Psychology; Glomerular Filtration Rate; Glycoproteins - urine; Humans; Kidney - metabolism; Male; Mass Spectrometry; Medical sciences; Middle Aged; Sensitivity and Specificity; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; zinc α2 glycoprotein; Endocrinopathy; Kidney disease; Urine; Obesity; Urinary system disease; Nutrition; Diabetes mellitus; Nutrition disorder; Glycoprotein; Albumin; Biological marker; Metabolic diseases; Adipokine; biomarker; Zinc; albuminuria; Concomitant disease; Diabetic nephropathy; Endocrinology; Nutritional status; zinc α
• ISSN: 0742-3071; 1464-5491
• DOI: 10.1111/j.1464-5491.2011.03564.x

Diabet. Med. 29, 945–949 (2012) Objective  A substantial proportion of diabetic nephropathy individuals are non‐albuminuric. Using a proteomic approach, we searched for novel urinary biomarkers. Methods  We studied three groups (n = 6 per group) of males with Type 2 diabetes: (1) normal renal function; (2) classical diabetic nephropathy (urinary albumin–creatinine ratio > 1000 mg/g and glomerular filtration rate < 60 ml/min.1.73 m2) and (3) non‐albuminuric diabetic nephropathy (glomerular filtration rate < 60 ml/min.1.73 m2 and urinary albumin–creatinine ratio < 30 mg/g). We used two‐dimensional fluorescence differential gel electrophoresis, matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry peptide identification and western blot validation in the study. Results  Sixty protein spots were differentially abundant between the non‐albuminuric and macro‐albuminuric subjects (> 2.5‐fold, P < 0.05). In the non‐albuminuric subjects, in addition to previously reported α1‐microglobulin, the next most interesting spot (upregulated 3.44‐fold, P = 0.0026) was human zinc‐α2‐glycoprotein, a novel adipose‐cytokine associated with glomerular injury. This was confirmed by western blot and replicated in female diabetic nephropathy subjects. Conclusions  From our preliminary results, human zinc‐α2‐glycoprotein may be a novel urinary biomarker for non‐albuminuric diabetic nephropathy.