%0 Journal Article
%T Cyclosporine: A Review
%A Dustin Tedesco
%A Lukas Haragsim
%J Journal of Transplantation
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/230386
%X The discovery and use of cyclosporine since its inception into clinical use in the late 1970s has played a major role in the advancement of transplant medicine. While it has improved rates of acute rejection and early graft survival, data on long-term survival of renal allografts is less convincing. The finding of acute reversible nephrotoxicity and nephrotoxicity in nonrenal transplants has since led to the widely accepted view that there is a chronic more irreversible component to this agent as well. Since that time, there has been intense interest in finding protocols which seek to minimize and even avoid the use of calcineurin inhibitors altogether. We seek to review cyclosporine in terms of its mechanism of action, pathophysiologic, and histologic features associated with acute and chronic nephrotoxicity and recent studies looking to avoid its toxic side effects. 1. Introduction Discovered in the lab of Sandoz in Switzerland in 1972, cyclosporine (CsA) has since revolutionized transplant medicine. Initially discovered while searching for novel antifungal agents, it was found to have many immunologic properties that made it an attractive agent for immunosuppression following renal and other solid organ transplants. With the premise that cell-mediated immunity was involved in autoimmune and chronic inflammatory conditions, Borel set up a series of experiments using antiinflammatory, immunosuppressant, and antimitotic medications to examine their effects on lymphocyte-mediated lysis of presensitized and na£żve effector cells. In these experiments, it was found that cyclosporine inhibited both in vitro cell-mediated lysis as well as lymphocyte sensitization by allogeneic target cells [1]. It was this work and others by Borel that exhibited the cell-mediated specificity of cyclosporine, theoretically lending itself to a far better side effect profile than the current immunosuppressive agents in use at that time. Subsequently, a European multicenter trial demonstrated one-year graft survival of 72% and 52% in recipients of cadaveric renal transplants allocated to receive either cyclosporine or azathioprine and steroids, respectively, for immunosuppression. Such promising results helped lead to clinical approval of CsA for use in the early 1980s [2]. With improved rates of acute rejection and one-year graft survival, cyclosporine has become a mainstay for immune suppression of renal and other solid organ transplants. A review from Hariharan et al. published in 2000 looking at graft survival in more than 93,000 transplants from 1988 to 1996 revealed
%U http://www.hindawi.com/journals/jtrans/2012/230386/