By Thomas G. Peters, MD, FACS

All patients who receive an organ transplant are considered for some form of treatment to prevent rejection of the organ. Over the course of the last 20 or 30 years, the treatment plans for transplant patients have changed dramatically. For kidney transplant patients, the choices of medicines and various combinations of drugs have led to remarkably good outcomes with expectations that almost every kidney transplant should work. This does not mean that rejection cannot or does not occur. However, it is far rarer than it used to be, and it is much more easily treated and reversed than in the past. All patients who are placed on transplant medicines must follow the treatment plan as closely as possible. The importance of such compliance is highlighted by the fact that the most common cause of rejection in modern kidney transplantation is that the patient does not follow the medication treatment plan.

Most transplant centers have excellent treatment plans, or “protocols,” which define the way they use the various anti-rejection medicines. Patients may hear that a particular transplant center has a “Cyclosporin-based protocol,” or “Rapamune-based protocol,” or other such name. The term “protocol,” as used in day-to-day medicine, simply means a defined treatment plan. For some centers, and in some patient populations, these treatment plans do not change much from patient-to-patient. In other instances, protocols are designed so that a center would use different drugs in different types of patients or would change drugs for any particular patient as time went on. Interestingly, very few kidney transplant centers have exactly the same treatment plan or drug protocol. This, in itself, should not be troublesome since a variety of known drug combinations have worked well to preserve kidney function after transplantation.

The medications that prevent rejection can be given to patients just before a kidney transplant, although that does not often occur. All patients are started on some type of medicine at the time of or shortly after the kidney transplant operation. Medicines are scheduled usually for once or twice a day doses, and the timing of certain medications remains an important part of treatment. The selection of drugs and various doses is a bit different in the immediate post-transplant period while the patient is in the hospital, as compared to the outpatient/long-term care setting. In addition, medicines given in the hospital are monitored by staff so patients have a lesser role in directing their own drug use. For that reason, we will consider the common medicines patients take at home.

Medications used principally in the outpatient setting are often given in some combination so that patients are taking two or three anti-rejection drugs. These medications usually have several different names for the very same drug. The following summary of outpatient medications will list the several names of any given drug, but will use the most common name employed by both patients and caregivers.

Cyclosporin A (CyA, Neoral, Gengraf, SangCya, Sandimmune) Cyclosporin is a drug that inhibits production of certain types of cells that can cause rejection. It is usually taken twice daily. Side effects of cyclosporin include high blood pressure, tremor (shakes), hair growth, overgrowth of gum tissue, increased levels of cholesterol and damage to the liver or kidney. These side effects, however, can usually be controlled by careful monitoring and dose adjustment. The monitoring includes blood tests to measure the amount of Cyclosporin in the blood, and such tests are usually done 11 to 12 hours after taking the evening or nighttime dose. Many drugs interact with Cyclosporin, as does grapefruit juice. Cyclosporin is in common usage for kidney and other organ transplants. As a rule, most patients would be taking either Cyclosporin or Prograf.

Prograf (Tacrolimus, FK506) Prograf is also a drug that prevents certain cells from causing rejection. Like Cyclosporin, it is usually given in a morning and evening dose. Side effects include high blood pressure, diabetes, “shakes,” headache, nausea and kidney toxicity. These problems also can be addressed by monitoring drug levels and adjusting dosage. Prograf does not cause hair growth, but may cause hair to fall out. It does not have the same effect on gum overgrowth as Cyclosporin does. It shares many of the same drug and food interactions with Cyclosporin. Prograf is monitored in the same fashion as Cyclosporin and sometimes substituted for that drug.

Imuran (Azathioprine) Imuran is one of the longest-used immunosuppressants, and it works by reducing certain blood cell populations that can cause rejection. Imuran is usually given once daily, and its side effects are low blood cell counts, liver toxicity and intestinal-related problems. The drug is not usually measured with blood tests, but rather patients on Imuran are followed by doing complete blood counts at regular intervals. If certain blood cell counts are too low, the dose is lowered or the drug discontinued. Imuran is being used less frequently than in past years, and is often replaced by a newer drug called CellCept.

CellCept (MMF, Mycophenolate Mofetil) CellCept is a drug that is now more frequently used in treatment plans as a substitute for Imuran. CellCept prevents certain cells from being produced in a slightly different way from Imuran and is believed to be a more effective drug at preventing rejection. It is usually given twice daily and blood levels of the drug are measured at some but not all transplant centers. It has few side effects, but it can depress blood cell development and cause abdominal pain, vomiting and diarrhea in some patients. Those problems are addressed by lowering the dose. Like Imuran, CellCept has few drug interactions and it is generally well tolerated.

Prednisone (Deltasone, Methylprednisolone, steroids) Prednisone and similar steroid medications continue to be used in most patients who receive organ transplants. Steroids reduce inflammation, which is part of rejection. Ordinarily, Prednisone is given once daily, and the dose may be decreased over time as the patient enjoys a successful transplant. Prednisone has many side effects including a change in appearance of the patient by development of a rounded face. In addition, Prednisone may be accompanied by a tendency towards diabetes, hypertension, joint problems, cataracts, stomach ulcers, acne and weight gain. There are few drug interactions with Prednisone, and blood levels are seldom measured. Many centers are attempting to minimize Prednisone dose in modern kidney transplantation.

Rapamune (Sirolimus) Rapamune is a drug that prevents certain cells from activating a rejection response. It is taken once daily, and drug levels are measured at most centers about 23 hours after the last dose. Side effects can include high blood pressure, joint pain, blood cell depression, diarrhea, acne, joint pain and cholesterol elevation. Rapamune does interact with a number of other drugs, as well as grapefruit juice and most of its side effects and dosing can be managed by following drug levels. Rapamune may often substitute for any of the above-mentioned drugs and can be given in combination with almost any one or two anti-rejection medicines.

Some general side effects are common to most of the above drugs, since they all suppress the immune system. The most common of these is a risk to infection. Transplant patients on anti-rejection drugs are “unable to reject germs,” since the natural response to infection is quite similar to the natural response to an organ transplant. Therefore, all transplant patients seem to be more prone to more common infections such as flu and pneumonia, as well as very uncommon infections such as certain parasites and fungal organisms. It is commonly recommended that any new illness associated with fever, chills or other signs of infection be reported immediately to the transplant center. Caregivers can then determine if the patient needs to be hospitalized, seen immediately or advised to attend the next scheduled clinic visit. Other potential problems related to drug combinations and transplant surgery include bleeding (low blood platelet count), blood clots, interactions with other drugs and development of certain types of cancer. While most new cancers in transplant patients are simple skin lesions, persons who take immunosuppressive medications are more prone to certain types of leukemia/lymphoma, sarcoma and skin related malignancy.  

While this may appear to make kidney transplantation a very risky endeavor, principally because of the medicines, adjustment and monitoring of the medicines allows for safe treatment in most patients. In fact, the difficulties patients have with kidney transplant anti-rejection medicine are more often related to not taking the medicines properly (skipping doses) than it is to using the medications as directed. Compliance in medication usage has been shown to be safe and effective. All transplant patients should work with their transplant teams to develop an understanding of their drugs and how they must be used. The outcomes of good kidney function and healthy living for transplant patients are really due to the effective and safe use of modern medications that prevent rejection.

Dr. Peters is a transplant surgeon at the Jacksonville Transplant Center at Shands Jacksonville Medical Center, Jacksonville, Florida. He also serves on the AAKP Board of Directors and Medical Advisory Board.

The Dear Doctor column provides readers with an opportunity to submit renal related health questions to healthcare professionals who specialize in the area of concern. The answers are not to be construed as a diagnosis and therefore, altercations in current healthcare should not occur until the patient's physician is consulted.

This article originally appeared in the November 2003 issue of aakpRENALIFE Vol. 19, No. 3.

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