Clinical renal transplantation: where are we now, what are our key challenges?

Today transplant patients have a risk of death a log order higher than someone of the same age but without end-stage renal failure and a prognosis akin to the normal population with a diagnosis of cancer. Graft losses are mostly from chronic allograft nephropathy, and death arises from cardiac disease, malignancy, and infection. Most immunosuppression protocols are designed to minimize acute allograft rejection, through heavy induction strategies, powerful but toxic maintenance therapies, and equally powerful and expensive prophylaxis against resultant infections. However, despite all efforts, the 20-year survival of renal allografts has not improved much over the past 30 years. New metrics and new thinking are needed to change the long-term outcomes. The biological consequences of immunosuppression currently require a balance between controlling the allograft response and reducing toxicity. To improve, we must both control rejection and remove the long-term problems of toxicity and infection. In the early period after transplantation, we need maximum immunosuppressive efficacy with minimal ischemia-reperfusion injury. Later, we need less immunosuppressive efficacy, to avoid risk factors for chronic toxicity, cardiovascular disease, and malignancy. One of the key challenges for the next few years will be to learn how to individualize therapy using surveillance biopsies and then to validate and use noninvasive technologies to guide therapeutic decisions. There is also an urgent need to determine the relevant early indicators for measuring long-term success to help design better management strategies. The multiplicity of alternatives testifies to the absence of a single dominant strategy.