Despite equivalent efficacy and pretransplantation risk factors for CAN, Neoral was associated with increased allograft fibrosis and significantly higher serum low-density lipoprotein cholesterol levels compared with tacrolimus.

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.

No abstract

No abstract

Aims: The aim of this study was to compare the effect of neoral cyclosporine and tacrolimus‐based therapy on the development of renal allograft fibrosis (chronic allograft nephropathy, CAN) in a prospective randomized trial. Methods: A total of 102 renal transplant patients were randomized to either microemulsion cyclosporine (neoral) or tacrolimus‐based immunosuppression. Renal transplant interstitial fibrosis was quantified using computerized histomorphometric measurement of picrosirius red‐stained 1‐year protocol renal transplant biopsies, and levels of interstitial fibrosis were compared in relation to observed efficacy and toxicity profiles of the two drugs. Results: There was a significant increase in allograft interstitial fibrosis in the neoral treated (sirius red area fraction staining 24.9 ± 11.1) compared to the tacrolimus‐treated patients (15.9 ± 6.5, P = 0.002, Student's t‐test). There was no significant difference in the demographic characteristics between the patient groups or in the incidence of acute (35 per cent tacrolimus versus 36 per cent neoral, P = 0.8, Student's t‐test) or steroid resistant rejection (tacrolimus and neoral 10 per cent, P = 0.9, Student's t‐test). There was a statistical trend (P = 0.07, Chi‐square) towards a higher incidence of insulin resistance in the tacrolimus group (post‐transplant diabetes mellitus, glucose‐tolerance testing). Neoral was associated with a significant increase in total cholesterol (manova, P = 0.03) and LDL levels (manova, P = 0.02). Conclusion: These data suggest that neoral‐based therapy promotes increased interstitial allograft fibrosis compared to tacrolimus in renal transplants in association with a poorer safety profile and equivalent efficacy.