It is a favorite assertion of the authors that clinical transplantation is an excellent example of “medical ethics in practice.” Perhaps this is best demonstrated by the processes of organ allocation where a balance must be struck between allocation that…
Introduction There are far more eligible kidney transplant candidates worldwide than there are organs available. Kidney exchange, also referred to as paired kidney donation, has become strongly established over the past decade as a modality for facilitating living kidney donation…
Naturally occurring antibodies against blood group antigens and acquired alloantibodies against donor human leukocyte antigens (HLAs; secondary to a prior kidney transplant, blood transfusions, or pregnancy) may pose major barriers to a successful renal transplantation. Because approximately 20% of renal…
Acknowledgments The work from the authors’ own laboratories described in this review was supported by grants from The Wellcome Trust, Medical Research Council, British Heart Foundation, The Deutsche Forschungsgemeinschaft, and The European Union ONE Study, Optistem, TRIAD, AFACTT (European Union…
Small Molecules Leflunomide and Malononitrilamides Leflunomide, initially developed as an agriculture herbicide, was explored as an immunosuppressant because of its ability to inhibit the enzyme dihydroorotate dehydrogenase. The potential of leflunomide as an immunosuppressant in the field of transplantation was…
Renal transplantation is the preferred treatment for most end-stage renal diseases. Transplantation’s success, however, has been counterbalanced, by its dependence on immunosuppressive drugs with their related infectious, metabolic, and malignant complications. Consequently, a common goal throughout the history of clinical…
Sirolimus and its closely related analog everolimus are potent immunosuppressive agents that impair lymphocyte activation and proliferation by inhibiting the mammalian target of rapamycin (mTOR), also known as the mechanistic target of rapamycin. The mTOR inhibitors emerged in the 1990s…
Although the improved outcomes over the past 60+ years in kidney transplantation have been related to a number of factors, the effect of immunosuppression has perhaps been the most significant. The advent of the calcineurin inhibitors (CNIs), first cyclosporine and…
Introduction When the first renal transplants were being performed in the early 1960s the immunosuppressive properties of corticosteroids were already noted, and steroids were successfully used to reverse episodes of acute rejection. In his 1964 book, Starzl described the use…
Introduction Whereas calcineurin inhibitors (cyclosporine and tacrolimus) block early signaling events and cytokine production, both azathioprine and mycophenolates, often termed antiproliferatives, exert effects downstream in the cell cycle, interfering with cytokine-dependent signals and lymphocyte proliferation. Azathioprine, usually in combination with…