Most HUS patients who receive kidney transplants require 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 intravenous “induction therapy” such as rabbit antithymocyte globulin (ATG) while starting oral 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 immune-suppressive medications for kidney transplant recipients?
Calcineurin inhibitors include cyclosporine (brand-name: Neoral) and tacrolimus (brand-name: Prograf). These are powerful medications that need to be prescribed and monitored by physicians who are well-schooled in drug-interactions, proper dosing, and side-effects. Blood levels need to be monitored. Drug-interactions pose a significant risk because the metabolism and clearance of both cyclosporine and tacrolimus are decreased by more than 2 dozen other medications, which can result in toxic blood levels. Conversely, there are about half a dozen other medications that accelerate metabolism and decrease blood levels, thereby increasing the risk of acute rejection.
Because these medications can cause microvascular injury (a feature of HUS), there was once a reluctance to use them in patients whose ESRD was caused by HUS. It is now recognized that calcineurin inhibitors can be safely used, and that recurrence of HUS is uncommon.
The side-effects of these medications are numerous. Both cyclosporine and tacrolimus 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, both of which are special concerns for adolescent girls.
Mycophenolate Mofetil (CellCept): A popular agent often combined with calcineurin inhibitors. It 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.
Glucocorticoids: Long-term use of cortisone-related drugs (e.g., prednisone, methylprednisolone) is no longer required for most patients. In fact, at least with children, steroid side effects such as “moon faces”, abdominal and intracapsular 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.
Newer experimental anti-rejection therapies: For the most part, the newer therapies are designed to eliminate, or at least reduce the need for powerful anti-rejection medications and their associated, often severe, side effects. The goal is to induce immune tolerance, that is, to induce the recipient’s immune system to coexist with the foreign tissue (renal graft) while still maintaining its ability to respond appropriately to infectious agents (various types of germs).
Studies, infusing cells from the prospective donor’s bone marrow are encouraging. One group of doctors at a major medical center has successfully transitioned four of five kidney transplant patients off the usual regimen of anti-rejection drugs. They first weakened the patient’s immune system with drugs and medications, and then infused the donors’ bone marrow at the time of renal graft surgery. They used anti-rejection medication initially, but were able to successfully wean four of the five patients off drugs by about one year. Another team from a leading transplant center is harvesting stem cells from the prospective donor’s bone marrow and infusing them into prospective recipients. Stem cells in the bone marrow can mature into cells (T-cells, plasma cells) that are important in the immune response. The hope is that the recipient’s immune system will gradually tolerate (get used to) the stem cells and the renal graft. The preliminary results are encouraging.