TGF-β1 expression in renal allograft rejection and cyclosporine A toxicity

Background. To assess short- and long-term influence of the TGF-beta(1) on renal allografts. Methods. Expression of TGF-beta(1) 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-beta(1), 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-beta(1), expression that patients with CsA toxicity exhibited significantly higher grade of tubular TGF-beta(1) expression than patients with AR (P < 0.05) and CAN (P < 0.05). A significant difference was found between the grades of tubular TGF-beta(1) expression in regards to graft function of cases with AR and CsA toxicity (P < 0.05). Higher grade tubular TGF-beta(1) expression showed better graft function during 6 months. Besides the degree of renal TGF-beta(1) 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-beta(1) expression. Conclusions. Despite the short-term posttransplantation tubule-repairing effects of TGF-beta(1), the overall effects of TGF-beta(1) in the kidney seem to be negative that increased expression of TGF-beta(1) promotes IF and vasculopathy associated with CAN.