Modern medicine has revolutionised the field of transplantation. While the first human deceased kidney transplant took place in 1933, a mismatch in patient and donor blood groups resulted in patient mortality after just two days. The first successful kidney transplant was achieved in monozygotic twins in 1954 when immunosuppression was not available, but fortunately not needed in this instance.
The development of pharmacological immunosuppression started in 1959 when 6-mercaptourine was shown to dampen immune responses and prolong rabbit skin allograft survival. The subsequent discovery of the 6-mercaptourine derivative azathioprine in 1960 went on to form the basis of conventional immunosuppressive therapy, in conjunction with high-dose prednisolone, from 1966 to 1978.
Ciclosporin, a CNI, inhibits IL-2 synthesis and reduces cytotoxic T cell maturation. In 1978, clinical trials with ciclosporin began and its incorporation into immunosuppressive regimens spread worldwide from 1982. Subsequently, tacrolimus, a CNI that is 100 times more potent than ciclosporin, showed reduced acute rejection, improved graft survival, and became the standard of care. More recently, a range of new treatments with differing mechanisms of action have been introduced. These include antiproliferative agents such as mycophenolate mofetil, mTOR inhibitors, interleukin-2 (IL-2) inhibitors, and a range of biologics (Shrestha et al., 2015).
The balance between organ rejection and the negative side-effects of immunosuppression is often a difficult one to strike, with a significant burden of mortality directly relating to the immunosuppression accomplished in order to keep the transplant functioning. Interventions such as induction therapy can enable sparing of potentially toxic agents, while in this section we also discuss other options for immunosuppression.
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