Uromodulin and α(1)-antitrypsin urinary peptide analysis to differentiate glomerular kidney diseases

Kidney Blood Press Res. 2012;35(5):314-25. doi: 10.1159/000335383. Epub 2012 Mar 7.

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 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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / analysis
  • Biomarkers / urine
  • Biopsy
  • Creatinine / blood
  • Diagnosis, Differential
  • Female
  • Glomerulonephritis / diagnosis*
  • Glomerulonephritis / pathology
  • Glomerulonephritis / urine*
  • Humans
  • Kidney / pathology
  • Male
  • Middle Aged
  • Placental Lactogen
  • Protein Array Analysis / methods*
  • Protein Array Analysis / standards
  • Proteinuria / diagnosis
  • Proteinuria / pathology
  • Proteinuria / urine
  • ROC Curve
  • Reference Values
  • Reproducibility of Results
  • Sequence Analysis, Protein
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Uromodulin / analysis
  • Uromodulin / urine*
  • Young Adult
  • alpha 1-Antitrypsin / analysis
  • alpha 1-Antitrypsin / urine*

Substances

  • Biomarkers
  • UMOD protein, human
  • Uromodulin
  • alpha 1-Antitrypsin
  • Placental Lactogen
  • Creatinine