Sirolimus: a potential option for the prevention of chronic allograft nephropathy

Abstract

O ver the past few decades, the continued progress in basic science, clinical medicine, and imnmnopharmacology has engendered exciting improvements in the field of renal transplantation. Today this procedure offers longer patient survival, improved quality' of life, and reduced medical expenses compared with dialysis. Consequently, renal transplantation is the theralu of choice for patients with end-stage renal disease. After the introduction ofcyclosporine into clinical practice in the early 1980s, l-year graft smMval rates in renal transplantation improved from 60% to between 80% and 90%, and patient survival increased to more than 90%? However, the incidence of acute graft rejection in the first 6 months remained high; approximately 40% of transplant recipients had at least 1 episode of acute rejection, w-' In the 1990s, the introduction of the new inamunosuppressive agents tacrolimus and mycophenolate mofetil led to a decrease in the incidence of acute rejection? .4 Although current l-year rates of patient and graft survival are excellent (95% and 90%, respectively), longterm results remain limited, and the results have not significantly improved in the last several years. ~:~ Consequently, a progressive increase in the waiting list for renal transplantation has been detected in all countries. Two reasons could explain the lack of long-term improvement in renal transplantation-chronic allograft nephropathy (CAIN) and death with a functioning graft, as a result of cardiovascular diseasesJ 1,7 Both remain leading causes of the late loss of renal allografts, resuhing in an annual rate of loss of 3% to 5%. For these reasons, strategies that may improve long-term results of renal transplantation, especially the prevention of CAIN, have become a priority in renal transplantation.