title: Interstitial expression of alpha-SMA: an early marker of chronic renal allograft dysfunction.
abstract: BACKGROUND
  Renal myofibroblast infiltration has been shown to be strongly associated with renal function decline in several chronic renal diseases. The purpose of the present study was to investigate whether early detection of myofibroblast infiltration using alpha-smooth-muscle actin (alpha-SMA) expression in time-zero biopsies predicts renal allograft dysfunction.
  
  
  METHODS
  We studied renal tissue from 38 renal transplant patients from whom biopsies had been taken after vascular anastomosis during transplantation to ascertain whether myofibroblasts infiltration predicts renal graft survival. Immunohistochemistry was performed on time-zero biopsies to determine alpha-SMA expression, and this was compared to annual glomerular filtration rate (GFR) variation and other parameters including cold ischaemic time (CIT), donor and recipient age, number of acute rejections, and delayed graft function (DGF). GFR was measured by inulin clearance during of 3 years of follow-up after the transplantation. Progressors were defined as patients with an annual GFR decline >5 ml/min/year.
  
  
  RESULTS
  We found a significant correlation between interstitial alpha-SMA expression in time-zero biopsies and GFR evolution during the post-transplantation course (r=0.60, P<0.001). Although progressors had greater interstitial alpha-SMA expression than non progressors (7.9+/-0.7 vs 4.3+/-0.4%), they showed only a tendency towards higher glomerular alpha-SMA expression. In addition, progressors had more interstitial fibrosis in time-zero biopsies than non-progressors. There was no relationship between alpha-SMA expression and CIT, donor and recipient ages, number of acute rejections, and occurrence of DGF.
  
  
  CONCLUSIONS
  This study suggests that alpha-SMA evaluation in time-zero biopsies, especially the combination of alpha-SMA expression and interstitial fibrosis, can strongly predict chronic renal allograft dysfunctions.
authors.affiliation: Département de Néphrologie, Hôpital Edouard Herriot et EA 645, Laboratoire de Physiologie de l'Environnement, Faculté de Médecine Grange Blanche, Lyon, France.
authors.forename: Chérif
authors.initials: C
authors.lastname: Badid
authors.forename: Alexis
authors.initials: A
authors.lastname: Desmouliere
authors.forename: Daniela
authors.initials: D
authors.lastname: Babici
authors.forename: Aoumeur
authors.initials: A
authors.lastname: Hadj-Aissa
authors.forename: Brigitte
authors.initials: B
authors.lastname: McGregor
authors.forename: Nicole
authors.initials: N
authors.lastname: Lefrancois
authors.forename: Jean Louis
authors.initials: JL
authors.lastname: Touraine
authors.forename: Maurice
authors.initials: M
authors.lastname: Laville
mesh_terms: D000199:Actins / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000032:analysis; D002908:Chronic Disease; D018450:Disease Progression; D005260:Female; D005347:Fibroblasts / Q000473:pathology; D005355:Fibrosis; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000473:pathology / Q000503:physiopathology*; D007674:Kidney Diseases / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000378:metabolism; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000378:metabolism* / Q000473:pathology
chemical_list: D000199:Actins; D015415:Biomarkers