Progress in Transplantation: Will It Be Achieved in Big Steps or by Marginal Gains?

A wish for progress in transplantation assumes that there are needs not met by the currently available therapy and that the barriers to resolving the problems can be surmounted. There are 5 major unmet needs: the potential to avoid transplantation either by prevention of disease or provision of an alternative to natural biological organ replacement; geographic heterogeneity of access to, and quality of, transplantation; availability of transplantation to those in need of it; survival of the patient and the transplant; and the avoidance of adverse effects of immunosuppression. During the past 50 years, there have been advances on at least 4 of these 5 fronts that illustrate the interplay of "big steps" and "marginal gains" in the following areas: surgical technique, testing the immunologic barriers, introduction of chemical and biological immunosuppression, and prophylaxis for microbial infections. The potential for further improvement comes in 5 major areas: blood biomarkers for monitoring of rejection, drug-free transplantation through the development of stable tolerance, eliminating the impact of ischemia-reperfusion injury, xenotransplantation of porcine kidneys, and finally, the possibility of autologous regeneration of functioning kidney tissue to treat advanced kidney disease.