Adipocytokine zinc α2 glycoprotein (ZAG) as a novel urinary biomarker for normo-albuminuric diabetic nephropathy.
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.
Diabetes Centre, Khoo Teck Puat Hospital School of Chemical and Life Sciences, Nanyang Polytechnic, Singapore. lim.su.chi@alexandrahealth.com.sg
S C
SC
Lim
D Q
DQ
Liying
W C
WC
Toy
M
M
Wong
L Y
LY
Yeoh
C
C
Tan
D
D
Lau
C
C
Tan
T
T
Subramaniam
C F
CF
Sum
D054392:Adipokines / Q000378:metabolism*; D000419:Albuminuria / Q000652:urine; D044466:Asian People / Q000706:statistics & numerical data; D015415:Biomarkers / Q000652:urine; D015153:Blotting, Western; D002352:Carrier Proteins / Q000652:urine*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000652:urine; D003928:Diabetic Nephropathies / Q000453:epidemiology / Q000503:physiopathology / Q000652:urine*; D015180:Electrophoresis, Gel, Two-Dimensional; D005453:Fluorescence; D005919:Glomerular Filtration Rate; D006023:Glycoproteins / Q000652:urine*; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D012680:Sensitivity and Specificity; D000090203:Zn-Alpha-2-Glycoprotein
D054392:Adipokines; D015415:Biomarkers; D002352:Carrier Proteins; D006023:Glycoproteins; C488891:AZGP1 protein, human; D000090203:Zn-Alpha-2-Glycoprotein