Multicentric validation of proteomic biomarkers in urine specific for diabetic nephropathy

Alkhalaf, A. et al. (2010) Multicentric validation of proteomic biomarkers in urine specific for diabetic nephropathy. PLoS ONE, 5(10), e13421. (doi: 10.1371/journal.pone.0013421)



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Background: 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). Methodology/Principal Findings: 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 <10% of cases and controls classification by proteome analysis not entirely resulted in the expected clinical outcome. Analysis of patient's subsequent clinical course revealed later progression to DN in some of the false positive classified DN control patients. Conclusions: These data provide the first independent confirmation that profiling of the urinary proteome by CE-MS can adequately identify subjects with DN, supporting the generalizability of this approach. The data further establish urinary collagen fragments as biomarkers for diabetes-induced renal damage that may serve as earlier and more specific biomarkers than the currently used urinary albumin.

Item Type:Articles
Additional Information:This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Glasgow Author(s) Enlighten ID:Mischak, Professor Harald
Authors: Alkhalaf, A., Zürbig, P., Bakker, S.J.L., Bilo, H.J.G., Cerna, M., Fischer, C., Fuchs, S., Janssen, B., Medek, K., Mischak, H., Roob, J.M., Rossing, K., Rossing, P., Rychlík, I., Sourij, H., Tiran, B., Winklhofer-Roob, B.M., Navis, G.J., and Federici, M.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN (Online):1932-6203
Published Online:01 January 2010
Copyright Holders:© 2010 Alkhalaf et al
First Published:First published in PLoS ONE 2010 5(10): e13421
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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