title: Diagnosis of Alport syndrome--search for proteomic biomarkers in body fluids.
abstract: BACKGROUND
  The hereditary kidney disease Alport syndrome (AS) has become a treatable disease: intervention with angiotensin-converting enzyme (ACE)-inhibitors delays end stage renal failure by years. The efficiency of ACE inhibition depends on the onset of therapy-the earlier the better. Therefore, early diagnosis has become increasingly important. To date, robust diagnosis requires renal biopsy and/or expensive genetic analysis, which is mostly performed late after onset of the profound clinical symptoms of this progressive renal disease. Thus, disease biomarkers enabling low-invasive screening are urgently required.
  
  
  METHODS
  Fourteen potential proteomic candidate markers (proteins) identified in a previous study in sera from patients exhibiting manifest AS were evaluated in the plasma, serum, and urine collected from a cohort of 132 subjects, including patients with AS and other nephropathies and healthy controls. Quantitation was performed by immunoassays.
  
  
  RESULTS
  The serum and plasma levels of none of the 14 proteins evaluated were significantly different among the three groups and therefore could not be used to discriminate between the groups. In contrast, the levels of various biomarker combinations in the urine were significantly different between AS patients and healthy controls. Importantly, some combinations had the potential to discriminate between AS and other nephropathies.
  
  
  CONCLUSIONS
  These findings open a window of opportunity for the sensitive and specific early diagnosis of AS. Our results increase the potential for larger scale evaluation of an increased number of patients.
authors.affiliation: Department of Pediatric Nephrology, Children's Hospital, Friedrich Schiller University Jena, Jena, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Pohl
authors.forename: Karin
authors.initials: K
authors.lastname: Danz
authors.forename: Oliver
authors.initials: O
authors.lastname: Gross
authors.forename: Ulrike
authors.initials: U
authors.lastname: John
authors.forename: Johannes
authors.initials: J
authors.lastname: Urban
authors.forename: Ludwig
authors.initials: L
authors.lastname: Patzer
authors.forename: Sandra
authors.initials: S
authors.lastname: Habbig
authors.forename: Markus
authors.initials: M
authors.lastname: Feldkötter
authors.forename: Oliver
authors.initials: O
authors.lastname: Witzke
authors.forename: Mario
authors.initials: M
authors.lastname: Walther
authors.forename: Heidrun
authors.initials: H
authors.lastname: Rhode
mesh_terms: D051722:ADAM Proteins / Q000032:analysis; D015415:Biomarkers / Q000032:analysis*; D005353:Fibronectins / Q000032:analysis; D006801:Humans; D007118:Immunoassay; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D008565:Membrane Proteins / Q000032:analysis; D009218:Myosins / Q000032:analysis; D009394:Nephritis, Hereditary / Q000175:diagnosis*; D040901:Proteomics / Q000379:methods*
chemical_list: D015415:Biomarkers; D005353:Fibronectins; C498718:MYO10 protein, human; D008565:Membrane Proteins; D051722:ADAM Proteins; C068490:ADAM8 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D009218:Myosins