What is the role of mycophenolate acid in immunosuppression after solid organ transplantation?

Updated: Jan 04, 2016
  • Author: Bethany Pellegrino, MD; Chief Editor: Mary C Mancini, MD, PhD, MMM  more...
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Answer

Answer

Inhibitors of nucleotide synthesis (purine synthesis [IMDH] inhibitors)

Mycophenolate acid

Mycophenolate acid inhibits the enzyme inosine monophosphate dehydrogenase (IMDH; required for guanosine synthesis) and impairs B- and T-cell proliferation, sparing other rapidly dividing cells (because of the presence of guanosine salvage pathways in other cells). This agent is used for maintenance immunosuppression and chronic rejection.

Adverse effects include nausea, vomiting, diarrhea, leukopenia, anemia, and thrombocytopenia.

In current practice, tacrolimus and mycophenolate mofetil are considered more efficient than cyclosporine A and mycophenolate mofetil, but recent studies have challenged this assumption. With antithymocyte globulins and steroids, clinically suspected acute rejections did not differ between cyclosporine A//azathioprine and tacrolimus/mycophenolate mofetil arms. Cyclosporine A/azathioprine allowed a low acute rejection rate, but tacrolimus/mycophenolate mofetil seemed to be a better regimen regarding severe secondary outcomes.

Among a cohort of patients being followed long term, mycophenolate mofetil appeared to be highly efficient for preventing both allograft rejection episodes and the development of coronary artery stenoses early after heart transplantation. Mycophenolate mofetil also significantly improved the survival of heart transplant recipients compared with azathioprine, despite a greater incidence of infections linked to mycophenolate mofetil therapy.

A study from the National Adult Solitary Renal Transplant Recipients database from 1998 to 2006 evaluated patient death and graft loss, complications, and renal function. One-year acute rejection rates were reduced for patients on mycophenolate mofetil versus azathioprine (10% vs 13%, P< .01); there were no statistically significant differences for malignancies, renal function, or BK virus infection at 1 year. The primary findings suggested that the association of mycophenolate mofetil with improved outcomes may not be apparent in patients also receiving tacrolimus.

Outcomes after lung transplantation did not meaningfully vary between those assigned to cyclophosphamide/mycophenolate mofetil compared with tacrolimus/azathioprine combined with IL-2 inhibitor induction therapy.

A retrospective study has shown that mycophenolate mofetil rescue therapy improves the long-term kidney graft survival compared with azathioprine despite high early rejection rates, and it avoids the negative impact of acute rejections on graft survival.

In a study done in cadaveric kidney transplantation, patients treated with mycophenolate mofetil have increased risk for the development of CMV disease. However, the disease course was less severe and was less frequently accompanied with deterioration of renal function in comparison to the azathioprine group.

The mycophenolate, steroid-sparing, multicenter, prospective, randomized, parallel-group trial compared acute rejections and adverse events in recipients of cadaver kidney transplants. The study concluded that in recipients of cadaver kidney transplants given cyclosporin microemulsion, mycophenolate mofetil offers no advantages over azathioprine in preventing acute rejections and is about 15 times more expensive.

Trough levels and AUC values are increased with concurrent administration of tacrolimus.


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