title: Vimentin expression and myofibroblast infiltration are early markers of renal dysfunction in kidney transplantation: an early stage of chronic allograft dysfunction?
abstract: BACKGROUND
  The objective of this study was to show the morphologic characteristics of allograft renal biopsies in renal transplant patients with stable renal function, which can potentially be early markers of allograft dysfunction, after 5 years of follow-up.
  
  
  METHODS
  Forty-nine renal transplant patients with stable renal function were submitted to renal biopsies and simultaneous measurement of serum creatinine (Cr). Histology was evaluated using Banff scores, determination of interstitial fibrosis by Sirius red staining and immunohistochemical study of proximal tubule and interstitial compartment (using cytokeratin, vimentin, and myofibroblasts as markers). Biopsies were evaluated according to the presence or absence of the epitheliomesenchymal transition (EMT). The interstitial presence of myofibroblasts and tubular presence of vimentin was also analyzed simultaneously. Renal function was measured over the follow-up period to estimate the reduction of graft function.
  
  
  RESULTS
  Median posttransplant time at enrollment was 105 days. Patients were followed for 64.3 ± 8.5 months. The mean Cr at biopsy time was 1.44 ± 0.33 mg/dL, and after the follow-up it was 1.29 ± 0.27 mg/dL. Nine patients (19%) had a reduction of their graft function. Eleven biopsies (22%) had tubulointerstitial alterations according to Banff score. Seventeen biopsies (34%) presented EMT. Fifteen biopsies (32%) had high interstitial expression of myofibroblasts and tubular vimentin. Using Cox multivariate analysis, HLA and high expression of interstitial myofibroblasts and tubular vimentin were associated with reduction of graft function, yielding a risk of 3.3 (P = .033) and 9.8 (P = .015), respectively.
  
  
  CONCLUSIONS
  Fibrogenesis mechanisms occur very early after transplantation and are risk factors for long-term renal function deterioration.
authors.affiliation: Division of Nephrology, Universidade Federal de São Paulo. Hospital do Rim e Hipertensão. Fundação Oswaldo Ramos, São Paulo, Brazil. anacmatos@terra.com.br
authors.forename: A C Carvalho
authors.initials: AC
authors.lastname: de Matos
authors.forename: N O Saraiva
authors.initials: NO
authors.lastname: Câmara
authors.forename: E J
authors.initials: EJ
authors.lastname: Tonato
authors.forename: M de Souza
authors.initials: Mde S
authors.lastname: Durão Júnior
authors.forename: M F
authors.initials: MF
authors.lastname: Franco
authors.forename: L A Ribeiro
authors.initials: LA
authors.lastname: Moura
authors.forename: A
authors.initials: A
authors.lastname: Pacheco-Silva
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D001938:Brazil; D016009:Chi-Square Distribution; D003404:Creatinine / Q000097:blood; D042241:Early Diagnosis; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D007674:Kidney Diseases / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D058628:Myofibroblasts / Q000473:pathology*; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014746:Vimentin / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D006680:HLA Antigens; D014746:Vimentin; D003404:Creatinine