Urinary Proteomics in Diabetes and CKD : Journal of the American Society of Nephrology (original) (raw)

BRIEF COMMUNICATION

Rossing, Kasper*; Mischak, Harald†; Dakna, Mohammed†; Zürbig, Petra†; Novak, Jan‡; Julian, Bruce A.‡, §; Good, David M.‖; Coon, Joshua J.‖, ¶; Tarnow, Lise*; Rossing, Peter* on behalf of the PREDICTIONS Network

*Steno Diabetes Center, Gentofte, Denmark; †Mosaiques Diagnostics, Hannover, Germany; Departments of ‡Microbiology and §Medicine, University of Alabama at Birmingham, Birmingham, Alabama; and Departments of ‖Chemistry and ¶Biomolecular Chemistry, University of Wisconsin-Madison, Madison, Wisconsin

Correspondence: Dr. Kasper Rossing, Steno Diabetes Center, Niels Steensens Vej 2, DK 2820 Gentofte, Denmark. Phone: +45-4443-7310; Fax: +45-4443-8747; E-mail: [email protected]

Accepted January 13, 2008

Received September 21, 2007

Abstract

Urinary biomarkers for diabetes, diabetic nephropathy, and nondiabetic proteinuric renal diseases were sought. For 305 individuals, biomarkers were defined and validated in blinded data sets using high-resolution capillary electrophoresis coupled with electrospray-ionization mass spectrometry. A panel of 40 biomarkers distinguished patients with diabetes from healthy individuals with 89% sensitivity and 91% specificity. Among patients with diabetes, 102 urinary biomarkers differed significantly between patients with normoalbuminuria and nephropathy, and a model that included 65 of these correctly identified diabetic nephropathy with 97% sensitivity and specificity. Furthermore, this panel of biomarkers identified patients who had microalbuminuria and diabetes and progressed toward overt diabetic nephropathy over 3 yr. Differentiation between diabetic nephropathy and other chronic renal diseases reached 81% sensitivity and 91% specificity. Many of the biomarkers were fragments of collagen type I, and quantities were reduced in patients with diabetes or diabetic nephropathy. In conclusion, this study shows that analysis of the urinary proteome may allow early detection of diabetic nephropathy and may provide prognostic information.