In vitro studies done on human proximal tubular epithelial cells showed no direct cytotoxicity of cyclosporine A. The 15-year results of an open randomized trial comparing cyclosporine withdrawal... Show moreIn vitro studies done on human proximal tubular epithelial cells showed no direct cytotoxicity of cyclosporine A. The 15-year results of an open randomized trial comparing cyclosporine withdrawal and conversion to azathioprine with continued cyclosporine treatment after kidney allograft transplantation are presented. The results show that allograft function is better preserved after conversion and that a lower incidence of chronic allograft nephropathy is reported. Chronic kidney allograft rejection elicits a more pronounced fibrotic response than does chronic cyclosporine nephrotoxicity. During chronic cyclosporine nephrotoxicity collagen III and IV are preferentially accumulated in the tubulointerstitium. Early increases in the deposition of collagen I, with collagen III and IV, were more specific for CR. The cortical mRNA levels of laminin beta 2 and TGF-beta 1 are higher in chronic cyclosporine nephrotoxicity than in chronic allograft rejection and can be used to discriminate between these two entities. Show less
