Urine Proteome Analysis May Allow Noninvasive Differential Diagnosis of Diabetic Nephropathy

作者：Papale Massimo; Di Paolo Salvatore; Magistroni Riccardo; Lamacchia Olga; Di Palma Anna Maria; De Mattia Angela; Rocchetti Maria Teresa; Furci Luciana; Pasquali Sonia; De Cosmo Salvatore; Cignarelli Mauro; Gesualdo Loreto^*

来源：Diabetes Care, 2010, 33(11): 2409-2415.

DOI：10.2337/dc10-0345

OBJECTIVE- Chronic renal insufficiency and/or proteinuria in type 2 diabetes may stem from chronic renal diseases (CKD) other than classic diabetic nephropathy in more than one-third of patients. We interrogated urine proteomic profiles generated by surface-enhanced laser desorption/ionization-time of flight/mass spectrometry with the aim of isolating a set of biomarkers able to reliably identify biopsy-proven diabetic nephropathy and to establish a stringent correlation with the different patterns of renal injury.
RESEARCH DESIGN AND METHODS- Ten micrograms of urine proteins from 190 subjects (20 healthy subjects, 20 normoalbuminuric, and 18 microalbuminuric diabetic patients and 132 patients with biopsy-proven nephropathy: 65 diabetic nephropathy, 10 diabetic with nondiabetic CKD [nd-CKD], and 57 nondiabetic with CKD) were run using a CM 10 ProteinChip array and analyzed by supervised learning methods (Classification and Regression Tree analysis).
RESULTS- The classification model correctly identified 75% of patients with normoalbuminuria, 87.5% of those with microalbuminuria, and 87.5% of those with diabetic nephropathy when applied to a blinded testing set. Most importantly, it was able to reliably differentiate diabetic nephropathy from nd-CKD in both diabetic and nondiabetic patients. Among the best predictors of the classification model, we identified and validated two proteins, ubiquitin and beta(2-)microglobulin.
CONCLUSIONS- Our data suggest the presence of a specific urine proteomic signature able to reliably identify type 2 diabetic patients with diabetic glomerulosclerosis.

• 出版日期2010-11