Chronic cyclosporine nephropathy: the Achilles' heel of immunosuppressive therapy.

In the past 15 years, short-term success rates for allografts of kidney, heart, liver, and kidney/pancreas have reached unprecedented levels largely due to cyclosporine-based immunosuppressive regimens. Most transplant centers around the world achieve 85 to 90% one-year graft survival for kidney transplants and very few patients suffer loss of life because of modern medical management [1, 2]. These impressive results with cyclosporine have extended the indications for cyclosporine usage from organ transplantation to the treatment of autoimmune and primary renal diseases. However, nephrotoxicity due to cyclosporine continues to be a major problem [3]. In spite of improved oneand two-year renal allograft graft survival rates, the average half-life of eight years for a cadaver kidney transplant that is functioning at one year has changed little with the addition of cyclosporinebased immunosuppression [4, 1. Conventional wisdom suggests that chronic allograft failure in kidney transplants is largely due to chronic rejection [6]. However, the adverse effects of cyclosporine on long-term kidney structure and function have not been excluded as an important part of the chronic allograft failure syndrome. An important role for cyclosporine on chronic progressive renal dysfunction when used outside the renal transplant situation is well accepted. This communication will review the entity of chronic cyclosporine nephropathy. The current literature about this subject will be analyzed and its presumed pathogenesis will be reviewed with an emphasis on recent studies indicating that cyclosporine-induced renal fibrosis may be an inevitable consequence of effective immunosuppressive therapy.