title: Urine proteome analysis may allow noninvasive differential diagnosis of diabetic nephropathy.
abstract: 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.
  
  
  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 CM10 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 β2-microglobulin.
  
  
  CONCLUSIONS
  Our data suggest the presence of a specific urine proteomic signature able to reliably identify type 2 diabetic patients with diabetic glomerulosclerosis.
authors.affiliation: Core Facility of Proteomics and Mass Spectrometry, Department of BioAgroMed, Faculty of Medicine, University of Foggia, Foggia, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Papale
authors.forename: Salvatore
authors.initials: S
authors.lastname: Di Paolo
authors.forename: Riccardo
authors.initials: R
authors.lastname: Magistroni
authors.forename: Olga
authors.initials: O
authors.lastname: Lamacchia
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Di Palma
authors.forename: Angela
authors.initials: A
authors.lastname: De Mattia
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Rocchetti
authors.forename: Luciana
authors.initials: L
authors.lastname: Furci
authors.forename: Sonia
authors.initials: S
authors.lastname: Pasquali
authors.forename: Salvatore
authors.initials: S
authors.lastname: De Cosmo
authors.forename: Mauro
authors.initials: M
authors.lastname: Cignarelli
authors.forename: Loreto
authors.initials: L
authors.lastname: Gesualdo
mesh_terms: D000419:Albuminuria / Q000652:urine; D003928:Diabetic Nephropathies / Q000175:diagnosis* / Q000652:urine*; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D020543:Proteome / Q000032:analysis*
chemical_list: D020543:Proteome