Proteomic identification of urinary biomarkers of diabetic nephropathy.
OBJECTIVE
Diabetic nephropathy is a serious complication of both type 1 and type 2 diabetes, and, unless arrested, leads to end-stage renal disease. Current diagnosis consists of urine assays of microalbuminuria, which have inadequate specificity and sensitivity.


METHODS
We used proteomic analyses to identify novel biomarkers of nephropathy in urine from type 2 diabetic patients with demonstrated normo-, micro-, or macroalbuminuria. Samples were analyzed by fluorescence two-dimensional (2-D) differential in-gel electrophoresis (DIGE), and protein identification was performed by liquid chromatography-tandem mass spectrometry.


RESULTS
2-D DIGE analysis of the urinary proteome in diabetes with nephropathy identified 195 protein spots representing 62 unique proteins. These proteins belonged to several functional groups, i.e., cell development, cell organization, defense response, metabolism, and signal transduction. Comparisons between control and diabetic subjects with different stages of renal dysfunction revealed the differential expression of several proteins. Spot volume quantification identified 7 proteins that were progressively upregulated with increasing albuminuria and 4 proteins that exhibited progressive downregulation. The majority of these potential candidate biomarkers were glycoproteins.


CONCLUSIONS
These data demonstrate the ability of proteomic analyses to reveal potential biomarkers for diabetic nephropathy in urine, an important step forward in advancing accurate diagnosis and our understanding of disease mechanisms.
Rao
Paturi V
PV
Department of Endocrinology and Metabolism, Nizam's Institute of Medical Sciences University, Hyderabad, India.
Lu
Xinfang
X
Standley
Melissa
M
Pattee
Patrick
P
Neelima
Gundupalle
G
Girisesh
Gudige
G
Dakshinamurthy
K V
KV
Roberts
Charles T
CT
Nagalla
Srinivasa R
SR
D000419:Albuminuria; D015415:Biomarkers / Q000652:urine*; D002853:Chromatography, Liquid; D003404:Creatinine / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000652:urine*; D003928:Diabetic Nephropathies / Q000652:urine*; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D013058:Mass Spectrometry; D011507:Proteinuria / Q000652:urine*; D020543:Proteome; D012016:Reference Values
D015415:Biomarkers; D020543:Proteome; D003404:Creatinine