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Mitigating Risk of Immunosuppression by Immune Monitoring: Are We There?

The advent of the calcineurin inhibitors (CNIs), cyclosporine and tacrolimus, heralded a new era in transplantation. The introduction of cyclosporine in the late 1980s reduced the rejection rates in kidney allograft recipients from approximately 80% to approximately 40%with a concomitant improvement in graft survival to more than 80% in the first year after transplant. This opened a new era in transplantation, allowing kidney transplantation to become amore mainstream option for patients with end-stage renal failure. It also allowed the development and expansion of other solid organ transplants including liver, heart, lungs, and intestine. They also allowed for the first time successful transplantation of skin containing vascularized composite organs such as upper extremities and face. The benefits of reduced rejection rates and improved early allograft survival weremet with a challenge in long-term graft survival. Calcineurin inhibitor toxicity is considered an impediment to long-term survival for both kidney and other organ transplant recipients. In our own program, in response to a high prevalence of polyoma virus nephropathy, a modest decrease of tacrolimus target levels by 2 ng/mL resulted in a significant decrease in polyoma virus nephropathy and beneficial effects on metabolic profiles and renal allograft histology (Figure 1). This benefit was not without consequences. There was a numerical increase in rejection rates. This highlighted the importance of finding a method of determining which recipients would benefit from a decrease in immunosuppression without the increased risk of rejection. We, as in other programs, used pretransplant characteristics in an attempt to achieve the goal of reaping the benefit of reduced immunosuppression without increasing the risk of acute rejection or increasing the rate of de novo donor-specific antibodies. Currently, this has resulted in the application of 4 different immunosuppressive regimens deployed at the time of transplantation based on age, presence of preformed donor-specific antibodies, andHLA