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This Article Full Text Full Text (PDF) 088260.Supplemental Data All Versions of this Article: clinchem.2007.088260v1 53/9/1636    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (12) Citing Articles via Google Scholar Google Scholar Articles by Dihazi, H. Articles by Strutz, F. Search for Related Content PubMed PubMed Citation Articles by Dihazi, H. Articles by Strutz, F. Related Collections Proteomics and Protein Markers

Characterization of Diabetic Nephropathy by Urinary Proteomic Analysis: Identification of a Processed Ubiquitin Form as a Differentially Excreted Protein in Diabetic Nephropathy Patients

¹ Department of Nephrology and Rheumatology, Georg-August-University Medical Center, Goettingen, Germany.
² Indivumed GmbH Center for Cancer Research at the Israelitisches Krankenhaus, Hamburg, Germany.
³ Department of Clinical Chemistry, Georg-August-University Medical Center, Goettingen, Germany.

^aAddress correspondence to this author at: Department of Nephrology and Rheumatology, Georg-August University Göttingen, Robert-Koch-Strasse 40, D-37075 Goettingen, Germany. Fax 049-551-3991039; e-mail dihazi{at}med.uni-goettingen.de.

Background: Identification of markers for prediction of the clinical course of diabetic nephropathy remains a major challenge in disease management. We established a proteomics approach for identification of diabetic nephropathy-related biomarkers in urine.

Methods: We used SELDI-TOF mass spectrometry and SAX2 protein arrays to compare protein profiles from urine of 4 defined patient groups. Samples from patients with type 2 diabetes (DM; n = 45) without nephropathy and without microalbuminuria (DM-WNP), patients with DM with macro- or microalbuminuria (DM-NP; n = 38), patients with proteinuria due to nondiabetic renal disease (n = 34), and healthy controls (n = 45) were analyzed. Anionic exchange, reversed-phase fractionation, gel electrophoresis, and mass spectrometry were used to isolate and identify proteins with high discriminatory power.

Results: A protein with m/z 6188 (P <0.0000004) was strongly released in the urine of healthy controls, patients with proteinuria due to nondiabetic disease, and DM-WNP in contrast to DM-NP patients. An m/z 14 766 protein (P <0.00008) was selectively excreted in the urine of DM-NP patients, whereas the protein with m/z 11 774 (P <0.000004) was significantly excreted by patients with proteinuria and DM-NP. The m/z 11 774 and m/z 14 766 mass peaks were identified as ß₂-microglobulin and UbA52, a ubiquitin ribosomal fusion protein, respectively. The protein with m/z 6188 was identified as a processed form of ubiquitin.

Conclusion: The release of high amounts of UbA52 in urine of DM-NP patients could serve as a diagnostic marker, whereas the lack of the short form of ubiquitin raises interesting questions about the pathophysiology.

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