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


Su Chi Lim, Dept of Medicine, Khoo Teck Puat Hospital, 90 Yishun Central, Singapore 768828, Republic of Singapore. E-mail:


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.