Rescue therapy with mycophenolate mofetil. Mycophenolate Mofetil Renal Refractory Rejection Study Group.

In three international phase III trials, MMF has been demonstrated to reduce the frequency and severity of acute renal allograft rejection episodes. As a treatment for acute refractory renal allograft rejection, MMF is also now showing strong promise in phase I and phase II trials. The mechanism of MMF to selectively inhibit purine synthesis in T- and B-lymphocytes results in a number of pathways in which it can interfere with deleterious immune responses in solid-organ transplant patients: inhibiting T- and B-cell activation and proliferation, inhibiting the glycosylation of adhesion molecules, and inhibiting the production of antibodies and possibly cytokines. The result is a new drug that not only can be used to prevent acute rejection episodes but, in contrast to other drugs such as azathioprine, can also be used to treat refractory acute rejection episodes. MMF may also have additional long-term benefits in that it is less mutagenic or carcinogenic than azathioprine, and it appears to suppress allograft arteriosclerosis and chronic rejection (see accompanying articles in this issue). Our own experience with MMF leads us to conclude that MMF treatments will soon become a standard, valuable alternative therapy for acute refractory allograft rejection.