title: C5b-9 glomerular deposition and tubular alpha3beta1-integrin expression are implicated in the development of chronic lesions and predict renal function outcome in immunoglobulin A nephropathy.
abstract: OBJECTIVE
  Tubular atrophy is one of the factors predicting poor outcome of renal function in primary immunoglobulin A nephropathy (IgAN). However, the development of tubular atrophy is a late phenomenon during the disease progression. It would be useful to identify early factors that potentially result in renal damage and could be used as early predictors of renal outcome.
  
  
  METHODS
  Forty-eight patients with IgAN were examined retrospectively. All patients had a renal biopsy at the beginning of the study. Histological parameters were reviewed and immunohistochemistry was performed on cryostat sections. Monoclonal antibodies used were against C5b-9, alpha3beta1-integrin, transforming growth factor-beta1 (TGF-beta1) and alpha-smooth muscle actin (alpha-SMA), and the results were correlated with histological data and long-term outcome of renal function.
  
  
  RESULTS
  In the glomeruli the extent of C5b-9 deposition had significant positive correlations with the degree of focal glomerulosclerosis (p=0.005), tubular atrophy (p=0.003), interstitial inflammation (p=0.005) and tubular expression of alpha3beta1 (p=0.0001). alpha3beta1 tubular expression correlated positively with the severity of proteinuria (p=0.01), number of glomerular and tubulointerstitial myofibroblasts, and the degree of tubular atrophy (p=0.0001) and interstitial monocyte infiltration (p =0.005). Tubular alpha3beta1 expression and the degree of tubular atrophy had significant implications in the development of renal failure at the beginning and at the end of follow-up, respectively.
  
  
  CONCLUSIONS
  Glomerular deposition of C5b-9 may participate in the development of glomerulosclerosis in IgAN. Furthermore, its positive correlation with the intensity of tubular alpha3beta1-integrin suggests a possible implication in the development of tubulointerstitial fibrosis.
authors.affiliation: Nephrology Department, Aristotle University of Thessaloniki, Thessaloniki, Greece. mstangou@math.com
authors.forename: Maria
authors.initials: M
authors.lastname: Stangou
authors.forename: Efstathios
authors.initials: E
authors.lastname: Alexopoulos
authors.forename: Afroditi
authors.initials: A
authors.lastname: Pantzaki
authors.forename: Maria
authors.initials: M
authors.lastname: Leonstini
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Memmos
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001284:Atrophy; D001706:Biopsy; D002908:Chronic Disease; D015938:Complement Membrane Attack Complex / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D005355:Fibrosis; D005922:Glomerulonephritis, IGA / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D039201:Integrin alpha3beta1 / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology; D007684:Kidney Tubules / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012598:Sclerosis; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D055815:Young Adult
chemical_list: D015938:Complement Membrane Attack Complex; D039201:Integrin alpha3beta1; D053773:Transforming Growth Factor beta1