Excretion of complement proteins and its activation marker C5b-9 in IgA nephropathy in relation to renal function

BMC Nephrol. 2011 Nov 23;12:64. doi: 10.1186/1471-2369-12-64.

Abstract

Background: Glomerular damage in IgA nephropathy (IgAN) is mediated by complement activation via the alternative and lectin pathways. Therefore, we focused on molecules stabilizing and regulating the alternative pathway C3 convertase in urine which might be associated with IgAN pathogenesis.

Methods: Membrane attack complex (MAC), properdin (P), factor H (fH) and Complement receptor type 1 (CR1) were quantified in urine samples from 71 patients with IgAN and 72 healthy controls. Glomerular deposition of C5, fH and P was assessed using an immunofluorescence technique and correlated with histological severity of IgAN and clinical parameters. Fibrotic changes and glomerular sclerosis were evaluated in renal biopsy specimens.

Results: Immunofluorescence studies revealed glomerular depositions of C5, fH and P in patients with IgAN. Urinary MAC, fH and P levels in IgAN patients were significantly higher than those in healthy controls (p < 0.001), but CR1 was significantly lower than that in healthy controls (p < 0.001). Urinary MAC and fH levels were positively correlated with serum creatinine (sCr), urinary N-acetyl-β-D-glucosaminidase (u-NAG), urinary β2 microglobulin (u-Bm), urinary protein (p < 0.001), interstitial fibrosis (MAC: p < 0.01, fH: p < 0.05) and the percentage of global glomerular sclerosis (p < 0.01). Urinary P was positively correlated with u-NAG, u-Bm, and urinary protein (p < 0.01).

Conclusions: Complement activation occurs in the urinary space in IgAN and the measurement of levels of MAC and fH in the urine could be a useful indicator of renal injury in patients with IgAN.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers
  • Complement Activation*
  • Complement Factor H / urine
  • Complement Membrane Attack Complex / urine*
  • Complement Pathway, Alternative
  • Complement System Proteins / analysis
  • Female
  • Fibrosis
  • Glomerulonephritis, IGA / immunology*
  • Glomerulonephritis, IGA / physiopathology
  • Glomerulonephritis, IGA / urine
  • Humans
  • Kidney / physiopathology*
  • Kidney Glomerulus / chemistry
  • Kidney Glomerulus / pathology
  • Male
  • Middle Aged
  • Properdin / urine
  • Receptors, Complement / analysis
  • Young Adult

Substances

  • Biomarkers
  • Complement Membrane Attack Complex
  • Receptors, Complement
  • Properdin
  • Complement Factor H
  • Complement System Proteins