Chronic Renal Allograft Damage: Existing Challenges (2011)

INTRODUCTION Manuel Arias In the early years after the clinical application of renal transplantation using azathioprine/prednisone-based immunosuppression (IS) and managing young donors and recipients, there were little doubts that both early and late failures were because of immune rejection of the graft. After the emerging of cyclosporine A (CsA), and even more after tacrolimus (TAC) and mycophenolate mofetil (MMF), the excellent control of the alloimmune response in the immediate posttransplant period allowed us to consider that all graft losses were mainly due to nonimmunologic causes, principally nephrotoxicity caused by calcineurin inhibitors (CNIs). In recent years, better posttransplant immune monitoring has revealed that the alloreactive response, especially the humoral response, remains throughout the life of the graft. The oversimplification that early failures have an immunologic cause and late failures have a nonimmunologic cause may lead to dangerous therapeutic decisions. Nowadays, more than 90% of recipients keep their kidneys for at least 1 year. However, the annual rate of allograft failure beyond the first year has remained relatively constant (1, 2). CNI-based immunosuppressive protocols with CsA and TAC, including antiproliferative immunosuppressants and corticosteroids, can reach significantly low acute rejection (AR) rates and excellent graft survival. Despite short-term success, side effects of drug and long-term attrition of graft function still constitute significant problems. 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