Improvement of nephrotoxicity, hypertension, and lipid metabolism after conversion of kidney transplant recipients from cyclosporine to tacrolimus.

AFTER cyclosporine (CyA) was introduced as an immunosuppressant in organ transplantation in 1978, the 1-year graft survival rates of patients undergoing liver, kidney, or heart transplantation were improved by about 20%. Since the middle of 1985, CyA-based primary immunosuppression has been used in nearly all transplantation centers in Europe and in the United States. Despite improved 1-year graft survival rates in patients receiving CyA, chronic transplant rejection continues to be a serious problem, and CyA-related nephrotoxicity is an additional difficulty. Several risk factors in the pathogenesis of chronic graft rejection are being discussed. These discussions center on the question whether chronic transplant rejection is an immunological or nonimmunological process. Investigators postulating an immunological pathogenesis have demonstrated that patients experiencing severe acute rejection episodes in the early posttransplant period are more prone to chronic graft rejection. On the other hand, animal studies and the analysis of clinical trials in kidney transplantation have revealed that—independent of immunological factors—disorders of lipid metabolism and arterial hypertension produce changes indistinguishable from chronic rejection from a clinical and histopathologic point of view. An immunosuppressive agent 10 to 100 times as potent as CyA has been available with the introduction of tacrolimus (TAC) in the early 1990s. Multicenter studies performed in the United States and in Europe have shown that the incidence of acute rejection is much lower in liver and kidney graft recipients treated with TAC than in patients under CyA-based immunosuppression. Furthermore, TAC was found to improve the lipid metabolism of liver transplant patients receiving primary TAC immunosuppression, as compared with those on CyA. The lower incidence of rejection episodes and the TACinduced improvement of lipid metabolism demonstrated in multicenter studies prompted us, in January 1997, to switch successfully transplanted kidney graft recipients with worsening lipid metabolism from CyA to TAC. The aim was to determine whether a 6-month treatment with TAC was effective in improving the lipid metabolism in this selected group of patients, without increasing the incidence of rejection and infection.