Sequential protocol biopsies from renal transplant recipients show an increasing expression of active TGF β

Chronic allograft nephropathy (CAN) is a major cause of graft loss after renal transplantation. Implicated in the pathogenesis of this complication is overproduction of the cytokine transforming growth factor beta (TGF β). In this study we measured changes in CAN's expression in stable patients early after transplantation, and studied links with established risk factors for CAN, such as delayed graft function, acute rejection, and cyclosporine exposure. We took biopsies from 40 renal allografts at time of transplantation (pre-perfusion), and then, using ultrasound guidance, at 1 week and 6 months after transplantation. An immunofluorescence technique was used to stain sections for active TGF β. These were then assessed by semi-quantitative scanning laser confocal microscopy. There was very little variation in active TGF-β expression among patients in their pre-perfusion biopsies. Expression had increased by 1 week and then very significantly by 6 months (P<0.0001). Patients who suffered delayed graft function had increased TGF-β expression at both time points. There was no difference regarding donor type, acute rejection, and immunosuppressive drug (cyclosporine or tacrolimus). There was no correlation between the amount of TGF-β expression at any time-point and isotope glomerular filtration rate (GFR) at 12 months. This study demonstrated that in a group of stable renal allograft recipients, TGF-β expression in the kidney increased after transplantation. As the study used protocol biopsies, this increase is unlikely to be due to acute events, and probably represents a genuine increase.