Solid organ transplantation (that includes heart, lungs, liver, kidney, pancreas and small intestine) has been revolutionized by the discovery and refinement of multiple immunosuppressive and anti-rejection medications that keep these organs alive for prolonged periods of time after they are transplanted. Approximately, 25,000 or more transplants are performed in the US every year and survival rates approach 90 % or above at 1 year and 75 % at 5 years, depending on the organ that is transplanted. Modern anti-rejection drugs have made graft loss due to acute rejection almost obsolete in the current era.
However, the other side of this coin is that more patients are now alive who have been taking anti-rejection medications after their transplants. This has led to a new problem – morbidity due the side effects of these medications taken over a prolonged period of time. For example, it is estimated that almost 10 % of patients will progress to dialysis or needing a kidney transplant due to the side effects of a certain class of anti-rejection medication called calcineurin inhibitors.
Current immunosuppressive regimens are usually made up of two or more medications, mainly to increase the effectiveness of both medications and decrease their side effects
Listed below are the medications grouped by their mechanism of action and their side effects.
- Antibodies: include alemtuzumab, thymoglobulin and others. These bind to different proteins called antibodies in a recipient’s blood that would otherwise attack and destroy the organ.
Side effects include severe opportunistic infections like fungal or viral infections, allergic reactions, fevers, low blood cell counts and breathing difficulties.
- Antimetabolites: include azathioprine and mycophenolate. These work by blocking the DNA and RNA in cells that attack the organ, called lymphocytes.
Side effects include gastrointestinal intolerance and infetions
- Cacineurin inhibitors: include cyclosporine and tacrolimus. These are the mainstay of immune suppressive medications in this era due to their effectiveness in preventing organ rejection. They work by blocking certain proteins in the blood known as cytokines, which in turn blocks an enzyme called calcineurin which then inactivates the T and B lymphocytes from attacking the organ.
Side effects include glucose intolerance, headaches, kidney failure and seizures, to name a few.
- Corticosteroids: were the first drugs used in the early days and remain as one of the main drugs in use today . They have multiple mechanisms by which they work to prevent organ rejection.
Side effects include problems with wound healing, increased rates of infections, weight gain, development of diabetes and high blood pressure and osteoporosis.
- Co-stimulation blockers: are newer medications but are not used very frequently
- Proliferation inhibitors (MTOR-inhibitors): include sirolimus, a newer class of medication, and work by blocking intra-cellular proteins, which blocks the activation of T cells and hence prevents organ rejection.
Side effects include low blood counts, joint pains, high cholesterol levels, diarrhea and poor wound healing.