title: Uromodulin and α(1)-antitrypsin urinary peptide analysis to differentiate glomerular kidney diseases.
abstract: OBJECTIVE
  Glomerular kidney disease (GKD) is suspected in patients based on proteinuria, but its diagnosis relies primarily on renal biopsy. We used urine peptide profiling as a noninvasive means to link GKD-associated changes to each glomerular entity.
  
  
  METHODS
  Urinary peptide profiles of 60 biopsy-proven glomerular patients and 14 controls were analyzed by combining magnetic bead peptide enrichment, MALDI-TOF MS analysis, and ClinProTools v2.0 to select differential peptides. Tentative identification of the differential peptides was carried out by HPLC-MS/MS.
  
  
  RESULTS
  The HPLC-MS/MS results suggest that uromodulin (UMOD; m/z: 1682, 1898 and 1913) and α(1)-antitrypsin (A1AT; m/z: 1945, 2392 and 2505) are differentially expressed urinary peptides that distinguish between GKD patients and healthy subjects. Low UMOD and high A1AT peptide abundance was observed in 80-92% of patients with GKD. Proliferative forms of GKD were distinguished from nonproliferative forms, based on a combination of UMOD and A1AT peptides. Nonproliferative forms correlated with higher A1AT peptide levels - focal segmental glomerulosclerosis was linked more closely to high levels of the m/z 1945 peptide than minimal change disease.
  
  
  CONCLUSIONS
  We describe a workflow - urinary peptide profiling coupled with histological findings - that can be used to distinguish GKD accurately and noninvasively, particularly its nonproliferative forms.
authors.affiliation: Department of Nephrology, Germans Trias i Pujol Hospital, Autonomous University of Barcelona, Esfera UAB, Badalona, Spain.
authors.forename: Maribel
authors.initials: M
authors.lastname: Navarro-Muñoz
authors.forename: Meritxell
authors.initials: M
authors.lastname: Ibernon
authors.forename: Josep
authors.initials: J
authors.lastname: Bonet
authors.forename: Vanessa
authors.initials: V
authors.lastname: Pérez
authors.forename: Mari Cruz
authors.initials: MC
authors.lastname: Pastor
authors.forename: Beatriz
authors.initials: B
authors.lastname: Bayés
authors.forename: Juan
authors.initials: J
authors.lastname: Casado-Vela
authors.forename: Maruja
authors.initials: M
authors.lastname: Navarro
authors.forename: Jordi
authors.initials: J
authors.lastname: Ara
authors.forename: Anna
authors.initials: A
authors.lastname: Espinal
authors.forename: Lourdes
authors.initials: L
authors.lastname: Fluvià
authors.forename: Assumpta
authors.initials: A
authors.lastname: Serra
authors.forename: Dolores
authors.initials: D
authors.lastname: López
authors.forename: Ramón
authors.initials: R
authors.lastname: Romero
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis / Q000652:urine; D001706:Biopsy; D003404:Creatinine / Q000097:blood; D003937:Diagnosis, Differential; D005260:Female; D005921:Glomerulonephritis / Q000175:diagnosis* / Q000473:pathology / Q000652:urine*; D006801:Humans; D007668:Kidney / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010928:Placental Lactogen; D040081:Protein Array Analysis / Q000379:methods* / Q000592:standards; D011507:Proteinuria / Q000175:diagnosis / Q000473:pathology / Q000652:urine; D012372:ROC Curve; D012016:Reference Values; D015203:Reproducibility of Results; D020539:Sequence Analysis, Protein; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D058949:Uromodulin / Q000032:analysis / Q000652:urine*; D055815:Young Adult; D000515:alpha 1-Antitrypsin / Q000032:analysis / Q000652:urine*
chemical_list: D015415:Biomarkers; C548612:UMOD protein, human; D058949:Uromodulin; D000515:alpha 1-Antitrypsin; D010928:Placental Lactogen; D003404:Creatinine