Chronic maintenance immunosuppression in renal transplantation: the unrealized goal of improved long-term outcomes

Major improvements in short-term renal transplant allograft outcomes by reductions in early graft loss due to rejection have been largely achieved with improved induction and maintenance immunosuppression drugs in the last 25 years. The hope that this would translate into improved long-term graft outcomes has not been realized. The rate of graft loss after one year has not appreciably improved over that same period. Graft losses due to immunologic, drug nephrotoxic da-mage, and death with graft function remain the principle causes of graft failure. In this review, first, the risk and benefits of currently available maintenance immunosuppression and the data regarding chronic maintenance immunosuppression strategies and long-term graft and patient outcomes will be assessed. Second, the predictive value of short-term surrogate markers for long-term graft outcomes will be reviewed and critiqued. Third, mitigating trade-offs inherent in chronic immunosuppression that impede improvement in long-term outcomes will be discussed. Finally, future ways of improving long-term graft and patient outcomes will be explored.