title: Toward Noninvasive Diagnosis of IgA Nephropathy: A Pilot Urinary Metabolomic and Proteomic Study.
abstract: IgA nephropathy is diagnosed by renal biopsy, an invasive procedure with a risk of significant complications. Noninvasive approaches are needed for possible diagnostic purposes and especially for monitoring disease activity or responses to treatment. In this pilot project, we assessed the utility of urine samples as source of biomarkers of IgA nephropathy. We used spot urine specimens from 19 healthy controls, 11 patients with IgA nephropathy, and 8 renal-disease controls collected on day of renal biopsy. Urine samples were analyzed using untargeted metabolomic and targeted proteomic analyses by several experimental techniques: liquid chromatography coupled with mass spectrometry, immunomagnetic isolation of target proteins coupled with quantitation by mass spectrometry, and protein arrays. No single individual biomarker completely differentiated the three groups. Therefore, we tested the utility of several markers combined in a panel. Discriminant analysis revealed that combination of seven markers, three metabolites (dodecanal, 8-hydroxyguanosine, and leukotriene C4), three proteins (α1-antitrypsin, IgA-uromodulin complex, and galactose-deficient IgA1), and heparan sulfate, differentiated patients with IgA nephropathy from patients with other renal diseases and healthy controls. Future studies are needed to validate these preliminary findings and to determine the power of these urinary markers for assessment of responses to therapy.
authors: First Faculty of Medicine, Department of Nephrology, Charles University and General University Hospital in Prague, Prague 2, Czech Republic.
authors: Michaela
authors: M
authors: Neprasova
authors: First Faculty of Medicine, Department of Nephrology, Charles University and General University Hospital in Prague, Prague 2, Czech Republic.
authors: Dita
authors: 0000-0002-6733-2857
authors: D
authors: Maixnerova
authors: Departments of Microbiology and Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors: Jan
authors: 0000-0002-9211-6670
authors: J
authors: Novak
authors: Departments of Microbiology and Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors: Colin
authors: 0000-0002-4033-1360
authors: C
authors: Reily
authors: Departments of Microbiology and Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors: Bruce A
authors: 0000-0001-5781-1021
authors: BA
authors: Julian
authors: University of Chemistry and Technology, Technická 5, 166 28 Prague 6, Czech Republic; Essence Line, Plzeňská 130/221, 150 00 Prague 5, Czech Republic.
authors: Jan
authors: 0000-0002-3301-4842
authors: J
authors: Boron
authors: Essence Line, Plzeňská 130/221, 150 00 Prague 5, Czech Republic.
authors: Petr
authors: 0000-0002-9193-8138
authors: P
authors: Novotny
authors: University of Chemistry and Technology, Technická 5, 166 28 Prague 6, Czech Republic.
authors: Miloslav
authors: M
authors: Suchanek
authors: First Faculty of Medicine, Department of Nephrology, Charles University and General University Hospital in Prague, Prague 2, Czech Republic.
authors: Vladimir
authors: V
authors: Tesar
authors: University of Chemistry and Technology, Technická 5, 166 28 Prague 6, Czech Republic.
authors: Petr
authors: 0000-0003-0351-3795
authors: P
authors: Kacer
mesh_terms: D000328:Adult; D000368:Aged; D000447:Aldehydes / Q000652:urine; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D005260:Female; D005922:Glomerulonephritis, IGA / Q000473:pathology / Q000652:urine*; D006151:Guanosine / Q000031:analogs & derivatives / Q000652:urine; D006497:Heparan Sulfate / Q000652:urine; D006801:Humans; D007070:Immunoglobulin A / Q000652:urine; D017997:Leukotriene C4 / Q000652:urine; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D020543:Proteome; D058949:Uromodulin / Q000652:urine; D000515:alpha 1-Antitrypsin / Q000652:urine
chemical_list: D000447:Aldehydes; D015415:Biomarkers; D006151:Guanosine; D006497:Heparan Sulfate; D007070:Immunoglobulin A; D017997:Leukotriene C4; D020543:Proteome; D058949:Uromodulin; D000515:alpha 1-Antitrypsin; C046215:8-hydroxyguanosine