title: Identification and validation of six proteins as marker for endemic nephropathy.
abstract: Endemic nephropathy (EN) is defined as a slow progressive renal tubulointestitial disease that mainly occurs in the restricted areas of the Balkan Peninsula. The complexity of the pathogenesis of EN makes its earlier diagnosis very difficult. Urine samples from healthy volunteers from EN regions, EN patients with proteinuria less than 150 mg/L and EN patients with proteinuria more than 150 mg/L, patients with acute kidney injury, patients with diabetic nephropathy and healthy volunteers from Germany were collected. The urinary proteome analyses were performed using 2-D DIGE and mass spectrometry. The validation of biomarkers was investigated by two approaches (Western blot (WB) and dot blot) in successively increasing size - and partially overlapping - sample sets. Comparative and statistical analyses of the proteomics data from the different patient groups allowed the identification of six proteins (alpha-1-microglobulin, alpha-2-glycoprotein-1, beta-2-microglobulin, mannose-binding-lectin-2, protection-of-telomeres-protein-1, and superoxide-dismutase [Cu-Zn]), which were able to discriminate EN with low and high proteinuria from the other groups with high significance (p<0.05). The reliability of the identified proteins as EN marker was underlined with high statistical significance using WB analyses (sensitivity 66.7-98% and specificity 70-100%), whereas the dot blot analyses revealed a decrease in the sensitivity and specificity of these biomarkers.
authors.affiliation: Department of Nephrology and Rheumatology, University Medical Centre, Georg-August University Goettingen, Goettingen, Germany.
authors.forename: Ivana
authors.initials: I
authors.lastname: Pešić
authors.forename: Vladisav
authors.initials: V
authors.lastname: Stefanović
authors.forename: Gerhard A
authors.initials: GA
authors.lastname: Müller
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Müller
authors.forename: Rade
authors.initials: R
authors.lastname: Cukuranović
authors.forename: Olaf
authors.initials: O
authors.lastname: Jahn
authors.forename: Vladmila
authors.initials: V
authors.lastname: Bojanić
authors.forename: Michael
authors.initials: M
authors.lastname: Koziolek
authors.forename: Hassan
authors.initials: H
authors.lastname: Dihazi
mesh_terms: D054392:Adipokines; D000328:Adult; D000368:Aged; D000510:Alpha-Globulins / Q000652:urine; D001449:Balkan Nephropathy / Q000175:diagnosis* / Q000652:urine*; D015415:Biomarkers / Q000652:urine*; D015153:Blotting, Western; D002352:Carrier Proteins / Q000652:urine; D015180:Electrophoresis, Gel, Two-Dimensional; D006023:Glycoproteins / Q000652:urine; D006801:Humans; D015151:Immunoblotting; D037601:Mannose-Binding Lectin / Q000652:urine; D008875:Middle Aged; D011507:Proteinuria / Q000652:urine; D040901:Proteomics / Q000379:methods*; D012680:Sensitivity and Specificity; D000089804:Shelterin Complex; D013482:Superoxide Dismutase / Q000652:urine; D034501:Telomere-Binding Proteins / Q000652:urine; D000090203:Zn-Alpha-2-Glycoprotein
chemical_list: D054392:Adipokines; D000510:Alpha-Globulins; D015415:Biomarkers; D002352:Carrier Proteins; D006023:Glycoproteins; D037601:Mannose-Binding Lectin; D000089804:Shelterin Complex; D013482:Superoxide Dismutase; D034501:Telomere-Binding Proteins; C488891:AZGP1 protein, human; D000090203:Zn-Alpha-2-Glycoprotein; C440849:POT1 protein, human; C016001:alpha-1-microglobulin