What are the key challenges we face in kidney transplantation today?

Transplantation is more predictable than it was 20 to 30 years ago and innovation over the last 20 years has been rapid, delivering substantial short-term and medium-term improvements. The challenges ahead are to deliver improved results globally in the context of also preventing chronic disease and reducing the costs of treatment. Countries achieving the best rates of transplantation combine deceased and living donors and can transplant more than 50 people per annum per million population, so why can this not be achieved everywhere? The mortality rates have dropped, but they are still up to 10-fold worse than age- and sex-matched controls, such that transplantation ages individuals by 30 years in terms of mortality risk. Cardiovascular disease, infection and malignancy remain the targets if mortality is to normalize. Graft survival rates will not change until the multiple injuries constituting chronic allograft dysfunction and the problems of recurrent disease can be brought to heel. Biomarkers may provide the next innovation to advance outcomes, but early experimental tolerance protocols implemented in clinical practice in at least three centers may deliver results more quickly.