Electrophoretic methods for analysis of urinary polypeptides in IgA-associated renal diseases

Electrophoresis. 2007 Dec;28(23):4469-83. doi: 10.1002/elps.200700237.

Abstract

We evaluated the utility of SDS-PAGE/Western blot and CE coupled with MS (CE-MS) for detection of urinary polypeptide biomarkers of renal disease in patients with IgA-associated glomerulonephritides. In a reference cohort of 402 patients with various renal disorders and 207 healthy controls, we defined CE-MS patterns of renal damage and IgA nephropathy (IgAN). In a blinded analysis of a separate cohort of patients with IgAN (n = 10), Henoch-Schoenlein purpura (HSP) with nephritis (n = 10), and IgA-associated glomerulonephritis due to hepatitis C virus (HCV)-induced cirrhosis (n = 9), and healthy controls (n = 12), we compared SDS-PAGE/Western blot and CE-MS against clinical urinalysis for detection of urinary proteins/polypeptides. Urinalysis indicated proteinuria for 50, 90, and 33% of patients, respectively, and for none of the healthy controls. SDS-PAGE/Western blot showed urinary polypeptides abnormality for 90, 80, and 67% of patients, respectively, and for none of the healthy controls. CE-MS indicated a Renal Damage Pattern in 80, 80, and 100 of patients, respectively, and in 17% of healthy controls, with the more specific IgAN Pattern in 90, 90, and 1%, respectively, and in none of the healthy controls. Based on differences in CE-MS patterns, the disease mechanisms may differ among various IgA-associated glomerulonephritides. These exploratory findings should be evaluated in a prospective study with contemporaneous renal biopsy and urinary testing. If validated, it may be feasible to adapt the CE-MS methodology to develop novel tests to detect renal injury at earlier stages, assess clinical manifestations, and monitor responses to therapy in patients with IgA-associated renal diseases.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / urine
  • Biopsy / methods
  • Child
  • Child, Preschool
  • Creatinine / blood
  • Electrophoresis, Capillary / methods*
  • Electrophoresis, Polyacrylamide Gel / methods*
  • Fibrosis / immunology
  • Fibrosis / urine
  • Glomerulonephritis, IGA / immunology
  • Glomerulonephritis, IGA / urine*
  • Hepatitis C / immunology
  • Hepatitis C / urine
  • Humans
  • IgA Vasculitis / immunology
  • IgA Vasculitis / urine
  • Immunoglobulin A / isolation & purification
  • Immunoglobulin A / urine*
  • Mass Spectrometry
  • Middle Aged
  • Peptides / isolation & purification
  • Peptides / urine*
  • Predictive Value of Tests
  • Proteinuria / urine*
  • Sensitivity and Specificity

Substances

  • Biomarkers
  • Immunoglobulin A
  • Peptides
  • Creatinine