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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.

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 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.

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References
1.
Papale M, Pedicillo M, Thatcher B, Di Paolo S, Lo Muzio L, Bufo P . Urine profiling by SELDI-TOF/MS: monitoring of the critical steps in sample collection, handling and analysis. J Chromatogr B Analyt Technol Biomed Life Sci. 2007; 856(1-2):205-13. DOI: 10.1016/j.jchromb.2007.06.001. View

2.
Lapolla A, Seraglia R, Molin L, Williams K, Cosma C, Reitano R . Low molecular weight proteins in urines from healthy subjects as well as diabetic, nephropathic and diabetic-nephropathic patients: a MALDI study. J Mass Spectrom. 2009; 44(3):419-25. DOI: 10.1002/jms.1520. View

3.
Christensen P, Larsen S, Horn T, Olsen S, Parving H . Renal function and structure in albuminuric type 2 diabetic patients without retinopathy. Nephrol Dial Transplant. 2001; 16(12):2337-47. DOI: 10.1093/ndt/16.12.2337. View

4.
Mazzucco G, Bertani T, Fortunato M, Bernardi M, Leutner M, Boldorini R . Different patterns of renal damage in type 2 diabetes mellitus: a multicentric study on 393 biopsies. Am J Kidney Dis. 2002; 39(4):713-20. DOI: 10.1053/ajkd.2002.31988. View

5.
Merchant M, Perkins B, Boratyn G, Ficociello L, Wilkey D, Barati M . Urinary peptidome may predict renal function decline in type 1 diabetes and microalbuminuria. J Am Soc Nephrol. 2009; 20(9):2065-74. PMC: 2736765. DOI: 10.1681/ASN.2008121233. View