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

Diabet Med. 2012 Jul;29(7):945-9. doi: 10.1111/j.1464-5491.2011.03564.x.

Abstract

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 m(2) ) and (3) non-albuminuric diabetic nephropathy (glomerular filtration rate < 60 ml/min.1.73 m(2) 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 α(1) -microglobulin, the next most interesting spot (upregulated 3.44-fold, P = 0.0026) was human zinc-α(2) -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-α(2) -glycoprotein may be a novel urinary biomarker for non-albuminuric diabetic nephropathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipokines / metabolism*
  • Albuminuria / urine
  • Asian People / statistics & numerical data
  • Biomarkers / urine
  • Blotting, Western
  • Carrier Proteins / urine*
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / urine
  • Diabetic Nephropathies / epidemiology
  • Diabetic Nephropathies / physiopathology
  • Diabetic Nephropathies / urine*
  • Electrophoresis, Gel, Two-Dimensional
  • Fluorescence
  • Glomerular Filtration Rate
  • Glycoproteins / urine*
  • Humans
  • Kidney / metabolism*
  • Male
  • Mass Spectrometry
  • Middle Aged
  • Sensitivity and Specificity

Substances

  • AZGP1 protein, human
  • Adipokines
  • Biomarkers
  • Carrier Proteins
  • Glycoproteins