Multicentric validation of proteomic biomarkers in urine specific for diabetic nephropathy

• Published in: PloS one 2010-10, Vol.5 (10), p.e13421-e13421
• Main Authors: Alkhalaf, Alaa, Zürbig, Petra, Bakker, Stephan J L, Bilo, Henk J G, Cerna, Marie, Fischer, Christine, Fuchs, Sebastian, Janssen, Bart, Medek, Karel, Mischak, Harald, Roob, Johannes M, Rossing, Kasper, Rossing, Peter, Rychlík, Ivan, Sourij, Harald, Tiran, Beate, Winklhofer-Roob, Brigitte M, Navis, Gerjan J
• Format: Article
• Language: English
• Subjects: Biological markers; Biomarkers; Biomarkers - urine; Biotechnology/Protein Chemistry and Proteomics; Capillary electrophoresis; Cardiovascular disease; Case-Control Studies; Collagen (type I); Coronary vessels; Diabetes; Diabetes and Endocrinology/Type 2 Diabetes; Diabetes mellitus; Diabetes therapy; Diabetic nephropathies; Diabetic Nephropathies - urine; Diabetic nephropathy; Diabetic retinopathy; Diabetics; Diagnosis; Diagnostic systems; Disease prevention; Electrophoresis, Capillary; Ethics; Humans; Identification; Internal medicine; Kidney diseases; Kidneys; Laboratories; Limit of Detection; Mass Spectrometry; Mass spectroscopy; Medical research; Medicine; Metabolism; Nephrology/Chronic Kidney Disease; Nephropathy; Patients; Peptides; Proteomics; Retinopathy; Scientific imaging; Type 2 diabetes; Urine
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0013421

Urine proteome analysis is rapidly emerging as a tool for diagnosis and prognosis in disease states. For diagnosis of diabetic nephropathy (DN), urinary proteome analysis was successfully applied in a pilot study. The validity of the previously established proteomic biomarkers with respect to the diagnostic and prognostic potential was assessed on a separate set of patients recruited at three different European centers. In this case-control study of 148 Caucasian patients with diabetes mellitus type 2 and duration ≥5 years, cases of DN were defined as albuminuria >300 mg/d and diabetic retinopathy (n = 66). Controls were matched for gender and diabetes duration (n = 82). Proteome analysis was performed blinded using high-resolution capillary electrophoresis coupled with mass spectrometry (CE-MS). Data were evaluated employing the previously developed model for DN. Upon unblinding, the model for DN showed 93.8% sensitivity and 91.4% specificity, with an AUC of 0.948 (95% CI 0.898-0.978). Of 65 previously identified peptides, 60 were significantly different between cases and controls of this study. In