TGF-beta1 expression in renal allograft rejection and cyclosporine A toxicity

Transplantation. 2005 Dec 27;80(12):1681-5. doi: 10.1097/01.tp.0000185303.92981.d6.

Abstract

Background: To assess short- and long-term influence of the TGF-beta1 on renal allografts.

Methods: Expression of TGF-beta1 and TNF-alpha, and the proportion of macrophages and eosinophils in interstitium were evaluated in 64 cases including five cases with nonrejected kidneys (NRK), 18 cases with acute rejection (AR), 26 cases with chronic allograft nephropathy (CAN), and 15 cases with acute cyclosporine A (CsA) toxicity. Follow-up biopsies of all cases with AR and CsA toxicity were evaluated for development of interstitial fibrosis (IF) and graft atherosclerosis (GAS). Additionally, influence of tubular-TGF-beta1 expression on graft function during 6 months after the diagnostic biopsy was evaluated.

Results: A significant differences was seen between rejected kidneys and acute CsA toxicity in regards of tubular TGF-beta1 expression that patients with CsA toxicity exhibited significantly higher grade of tubular TGF-beta1 expression than patients with AR (P<0.05) and CAN (P<0.05). A significant difference was found between the grades of tubular TGF-beta1 expression in regards to graft function of cases with AR and CsA toxicity (P<0.05). Higher grade tubular TGF-beta1 expression showed better graft function during 6 months. Besides the degree of renal TGF-beta1 expression was positively correlated with development of diffuse IF and GAS (P<0.05) that the risk of the IF and GAS was higher in cases with grade 2 renal TGF-beta1 expression.

Conclusions: Despite the short-term posttransplantation tubule-repairing effects of TGF-beta1, the overall effects of TGF-beta1 in the kidney seem to be negative that increased expression of TGF-beta1 promotes IF and vasculopathy associated with CAN.

MeSH terms

  • Adult
  • Antibodies, Monoclonal
  • Biopsy
  • Creatinine / blood
  • Cyclosporine / adverse effects*
  • Female
  • Graft Rejection / immunology
  • Graft Rejection / pathology*
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Kidney Transplantation / immunology
  • Kidney Transplantation / pathology*
  • Kidney Tubules / pathology
  • Macrophages / pathology
  • Male
  • Retrospective Studies
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta1
  • Transplantation, Homologous
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Immunosuppressive Agents
  • TGFB1 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Cyclosporine
  • Creatinine