Answer: Beginning with the transplant operation, every transplant recipient must take medications to prevent the immune system from recognizing the transplanted organ as a foreign invader that should be attacked and eliminated – the process called rejection. Although there is now a variety of improved immunosuppressive medications from which to choose, all may cause side effects that are medically undesirable. Additionally, the medications are quite expensive and only partially reimbursed even when Medicare and/or private insurance coverage is available. To minimize the cost and complications of long-term care, reduction of the total amount of immunosuppression used to maintain the protected immunologic state of a transplanted organ is obviously appealing to both the patient and the transplant physician.

Unfortunately, there is no direct means of determining the strength of an individual’s immune system. While we can accurately measure many processes in the functioning human body, such as the “amount” of kidney function (blood and urine measurements of creatinine are used to assess the “glomerular filtration rate”) or the production rate of red blood cells (blood measurements of the number of cells and the level of the stimulatory hormone erythropoietin), no specific indicator of immune strength has been identified.  Without a direct measure, we are forced to rely on circumstantial evidence to assume whether too much, too little or just the right amount of immunosuppression to fit the patient’s needs is being used. When the immune system is overly suppressed, infections, malignancies and wound healing may become severe problems. But when the level of immunosuppression is insufficient, rejection and ultimately loss of the transplanted organ may occur. 

TOO MUCH IMMUNOSUPPRESSION

• Multiple infections
• Failure to heal wounds
• Lymphoma
• Other malignancy

Too Little Immunosuppression

• Rejection

Determination of the combination and amount of immunosuppressive drugs to be taken by an individual patient (we commonly call this the “immunosuppressive cocktail”) is based on the knowledge accumulated by the collective community of transplant physicians and surgeons, by the personal experience of the specific treating doctor and by the specific medical needs of the individual patient. With the large number of medications available today, there is usually more than one reasonable drug combination that might be selected and you should expect that different physicians may not make exactly the same choices. Nevertheless, the principles used to prescribe and adjust the immunosuppressive regimen are generally shared by most transplant doctors. We know that there are a number of medical factors associated with increased strength of the immune system’s response to the transplanted organ. Previous exposure of the recipient’s immune system to proteins (antigens) from other human beings through blood transfusion, pregnancy or an earlier transplant may have stimulated the production of antibodies directed at those proteins, a state called “sensitization” in transplant jargon (the extent of sensitization is measured with the “PRA” ranging from a low of zero to a high of 100). If a recipient is sensitized, has had a previous transplant, is younger than 60 years, African-American or has an immunologically active disease such as lupus, you are considered a “higher risk” patient because it may be more difficult to establish and maintain an adequate level of immunosuppression.

With newer immunosuppressive medications introduced during the late 1990’s, rejection is prevented in the majority of patients. In this setting, a collective interest has developed within the transplant community, in reducing the dosage of some of the medications, particularly steroids, that are associated with particularly challenging side effects. In order to fully appreciate the safety of these interventions, transplant centers have initiated several promising clinical trials of these approaches. For the most part the first patients to be included in these attempts are those considered to be at relatively low risk of rejection. As we await the outcomes of these studies, patients will need to rely on the judgment of their own transplant doctors.

As explained above, it is tempting to seek the lowest level of immunosuppression that your immune system requires to prevent you from rejecting your kidney transplant. Yet, without a specific indicator to follow, and still awaiting the results of studies, your doctor must rely on the experiences gained from treating other patients and from the clues your body provides. For those patients who have none of the high risk factors and have never experienced rejection, your doctor will be relatively comfortable lowering the doses to a minimum level. If you have had one or more episodes of rejection or you have one of the medical factors that generally increase your risk of rejection, your doctor is likely to be reluctant to aggressively lower the doses of your immunosuppressive medication. On the other hand, if you have developed more than one of the signs of too much immunosuppression, it may be necessary to do so.

As always, the most important thing to remember is that you should expect your doctor to communicate directly with you about the approach they use to suppress your immune system. In return, you must be precise and reliable in taking exactly the prescribed doses of all medications. You should ask whether or not you are at high risk of rejection, should be familiar with the most common side effects of the specific medications you are taking and should understand the strategy behind each alteration made in your immunosuppressive regimen. If your doctor is lowering the dose, you should understand why the change is being made and whether there will be a significant risk of rejection. With a good level of understanding it is entirely reasonable to indicate your preference regarding your level of comfort with the selected approach to your doctor.

Answer provided by Dr. Amy Friedman, Department of Surgery at Yale University School of Medicine in New Haven, Connecticut. She also serves on the AAKP 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 aakpRENALIFE, March 2003 Volume 18 Number 5. 

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