Uromodulin and α<inf>1</inf>-antitrypsin urinary peptide analysis to differentiate glomerular kidney diseases

Maribel Navarro-Muñoz, Meritxell Ibernon, Josep Bonet, Vanessa Pérez, Mari Cruz Pastor, Beatriz Bayés, Juan Casado-Vela, Maruja Navarro, Jordi Ara, Anna Espinal, Lourdes Fluvià, Assumpta Serra, Dolores López, Ramón Romero

Research output: Contribution to journalArticleResearchpeer-review

16 Citations (Scopus)

Abstract

Background/Aims: 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 α1- 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. Conclusion: 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. Copyright © 2012 S. Karger AG.
Original languageEnglish
Pages (from-to)314-325
JournalKidney and Blood Pressure Research
Volume35
Issue number5
DOIs
Publication statusPublished - 1 Jun 2012

Keywords

  • α -Antitrypsin 1
  • Glomerular kidney disease
  • MALDI-TOF MS analysis
  • Peptide profiling
  • Proteinuria
  • Urine proteomics
  • Uromodulin

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