Vimentin expression and myofibroblast infiltration are early markers of renal dysfunction in kidney transplantation: an early stage of chronic allograft dysfunction?

Transplant Proc. 2010 Nov;42(9):3482-8. doi: 10.1016/j.transproceed.2010.06.014.

Abstract

Introduction: 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.

Conclusion: Fibrogenesis mechanisms occur very early after transplantation and are risk factors for long-term renal function deterioration.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • Biopsy
  • Brazil
  • Chi-Square Distribution
  • Creatinine / blood
  • Early Diagnosis
  • Epithelial-Mesenchymal Transition*
  • Female
  • HLA Antigens / immunology
  • Humans
  • Kaplan-Meier Estimate
  • Kidney / metabolism*
  • Kidney / pathology*
  • Kidney / physiopathology
  • Kidney Diseases / diagnosis*
  • Kidney Diseases / etiology
  • Kidney Diseases / metabolism
  • Kidney Diseases / pathology
  • Kidney Diseases / physiopathology
  • Kidney Function Tests
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Myofibroblasts / pathology*
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Risk Assessment
  • Risk Factors
  • Severity of Illness Index
  • Time Factors
  • Transplantation, Homologous
  • Treatment Outcome
  • Vimentin / metabolism*

Substances

  • Biomarkers
  • HLA Antigens
  • Vimentin
  • Creatinine