Anti-rejection therapy
Since all kidneys except those from an identical twin are recognized as “foreign” by the recipient’s immune system, it is necessary to use immunosuppressive medications to reduce the risk of rejection.
It is now common to start with immediate “induction therapy”, such as rabbit antithymocyte globulin (ATG), while starting anti-rejection medications (e.g., cyclosporine, mycophenolate mofetil). Compared to previous decades, today’s powerful immunosuppressants are responsible for markedly improved short term graft survival.
What are these medications?
- Calcineurin inhibitors: Calcineurin inhibitors (cyclosporine [e.g., Neoral], tacrolimus [Prograf]) are powerful medications that need to be prescribed and monitored by physicians who are well-schooled in the various drug interactions, proper dosing, and side effects. Blood levels need to be monitored. It is imperative to know that the metabolism and clearance of cyclosporine and tacrolimus are reduced by more than two dozen other medications, which can result in toxic blood levels. Conversely, there are about half a dozen other medications that accelerate metabolism and reduce blood levels, thereby increasing the risk of acute rejection.
Since these medications can cause microvascular injury (a feature of HUS), there was at one time a reluctance to use them in patients whose ESRD was caused by HUS. It is now recognized that calcineurin inhibitors can be used in those who had D+HUS, and that recurrence of HUS in the renal graft is uncommon.
Side affects are numerous. Both can be toxic to the renal graft and cause graft dysfunction. If toxicity is progressive in spite of careful monitoring of blood levels, and is verified by renal graft biopsy, cautious withdrawal of cyclosporine/tacrolimus may be necessary. Hyperkalemia (elevated blood potassium concentration), diarrhea, headache, hypertension, elevated blood lipid levels (cholesterol, triglyceride), and tremor are common side effects. Tacrolimus is more likely to cause diabetes mellitus, but less likely to cause hypertrichosis (excessive hair growth) and gum hypertrophy, a special concern for adolescent girls.
- Mycophenolate Mofetil (CellCept): Mycophenolate mofetil (MMF) is a popular agent that is often combined with calcineurin inhibitors and has largely replaced azathioprine (Imuran) as an adjunctive immunosuppressive medication. The side effect profile includes pancytopenia (reduced white, red, and platelet cells) and increased opportunistic infections and malignancies.
- Sirolimus (Rapamune): A newer drug, Sirolimus, combined with Cyclosporine, has not been shown to improve graft survival, and may even decrease it. The ability to inhibit cell growth, however, makes it an attractive agent in those with post-transplant cancer. Its side effects include increased opportunistic infections and elevated blood lipid levels.
- Steroids: The long term use of cortisone related drugs (e.g., prednisone, methprednisolone) is no longer required for most patients. In fact, at least with children, steroid side effects such as “moon” faces, abdominal and intrascapular fat, emotional instability, stretch marks, diabetes, bone damage, and poor linear growth are all largely a thing of the past. Many pediatric transplant programs taper LRD recipients off prednisone very rapidly, and some do not use them at all, except perhaps as induction therapy.