The spectrum of long-term renal transplantation: Outcomes, complications, and clinical studies

Abstract

Successful long-term renal transplantation has been achieved, albeit in limited numbers, even with immunosuppression consisting primarily of prednisone and azathioprine used in the 1960s. Substantial improvements in immunosuppression marked by the introduction of cyclosporine in 1984 and later by tacrolimus, mycophenolate mofetil, sirolimus, thymoglobulin, and anti-CD25 monoclonal antibodies were followed by lower rates of acute rejection, better 1-year patient and allograft survivals, and, after some delay, improved half-life (T1/2) for the grafts. However, these successes, which focused on the allografts, were possible only because of parallel advances being made in the management of a wide range of complications affecting immunosuppressed renal transplant recipients. These complications include cardiovascular disease and its risk factors (hypertension, hypercholesterolemia, diabetes mellitus, hyperhomocysteinemia); a wide range of infections including the major viral liver diseases hepatitis B and C; malignancies, particularly posttransplant lymphoproliferative disease and skin cancers; musculoskeletal diseases, especially osteoporosis; posttransplant erythrocytosis; and allograft-related problems such as proteinuria, recurrent and de novo renal diseases, and transplant renal artery stenosis. Coronary heart disease is the dominant cause of patient mortality, and chronic allograft nephropathy, with both immune and nonimmune components, is the major cause of allograft loss. It now appears that risk factors for coronary heart disease are also basically the same risk factors for progressive renal failure. Consequently, therapies designed to be cardioprotective are also renoprotective. Accordingly, in addition to more potent immunosuppressants, the concurrent use of medications designed to control coronary heart disease and progressive renal failure simultaneously will likely be the approach to improving the likelihood of even greater, long-term successes for both the transplant recipient and the allograft.