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Organ Transplants, Immunosuppressive Drugs, and Associated Dental Management Guidelines

ORGAN TRANSPLANTS OVERVIEW AND FACTS

Organ transplantation has come a long way from the first transplant done in the early 1950s. Most organ transplants initially had been allografts or tissues from genetically nonidentical donors. This accounted for the less-than-satisfactory outcomes with organ transplants. Now, with newer trends, the live, related-donor rates have increased, accounting for an improved outcome and greater hope for organ transplantations. The success rates for organ transplants have also increased tremendously with the discovery of immunosuppressants cyclosporine and tacrolimus (Prograf). These drugs have improved the survival rates in transplanted patients.

Care post organ transplant has also seen some changes in the way the patients are managed. The trend now is to keep the patient’s immunity at a specific optimal level, such that the need for immunosuppression drugs is decreased. This improves the recipient’s immune system response in helping to ward off infections or deal with infections. Some transplant centers are now providing the patient with steroid-free and calcineurin-inhibitor–free immunosuppressions. The short-term results with these new strategies have been promising thus far, but the long-term outcome data need to show that this process is truly a move in the right direction. The physician now can utilize ImmuKnow, an assay to assess immune system function from a single blood drop. The test measures the vitality of the patient’s immune system, thus allowing the physician to better manage the patient’s response to infection thereby personalizing the care to prevent organ rejection. These newer methods of care will definitely lower the cost of medications in the future and prolong the organ recipient’s life. The major organs transplanted today are bone marrow, heart, lungs, pancreas, liver, and kidneys.

Kidney Transplant Facts

Dialysis is a very expensive option in the long run for renal failure patients. A kidney transplant is also expensive at first, but overall it has a lower yearly maintenance cost compared with dialysis. With kidney transplant, the quality of life improves for the patient and there is also an improvement of uremia, anemia, peripheral neuropathy, and autonomic neuropathy. A kidney transplant can double the life span of kidney failure patients.

The transplanted kidney can be obtained from a cadaver—50% of transplants utilize this source—a live related donor, or a live distant/unrelated donor. Kidneys obtained from a live donor are much better than those obtained from a nonliving or cadaveric donor.

Liver Transplant Facts

A liver transplant is much more complicated than a kidney transplant because of the complexity of the surgical procedure. To prioritize a patient on the liver transplant list, the severity of a liver failure patient’s status is assessed using the model of end-stage liver disease (MELD) criteria. The MELD criteria evaluate the following tests: bilirubin, PT/INR, and serum creatinine. The serum creatinine is the most sensitive mortality-risk indicator of liver failure.

Cells Responsible for Prevention of Organ Rejection

The following cells constitute the cell-mediated defenses for the prevention of organ rejection:

TYPES OF IMMUNOSUPPRESSION

Post-transplant immunosuppression includes the giving of a combination of drugs to prevent rejection of the transplanted organ, but how and when these drugs are given is based on a patient’s individual situation. Depending on these factors, the approaches could include:

• Induction immunosuppression
• Maintenance immunosuppression
• Anti-rejection immunosuppression

Induction Immunosuppression

In this approach, all medications are given in very high doses immediately after transplantation as to prevent any acute rejection. The drugs may be continued for the first 30 days after transplant, but they are not used long term for immunosuppressive maintenance. Medications often used for this type of immunosuppression include methylprednisolone, atgam, thymoglobulin, OKT3, basiliximab, or daclizumab.

Maintenance Immunosuppression

In maintenance immunosuppression, all immunosuppressive medications are given before, during, or after transplant with the intention to maintain their use long term. Drugs often used for this type of immunosupression include prednisone, cyclosporine, tacrolimus, mycophenolate mofetil, azathioprine, or rapamycin.

Anti-Rejection Immunosuppression

In this approach, all immunosuppressive medications are given to treat an acute rejection episode during the initial post-transplant period or during a specific follow-up period, usually up to 30 days after the diagnosis of acute rejection. Medications used include methylprednisolone, atgam, OKT3, thymoglobulin, basiliximab, or daclizumab.

IMMUNOSUPPRESSANT DRUGS

Immunosuppressants currently available are azathioprine, basiliximab, cyclosporine, daclizumab, muromonab-CD3, mycophenolic acid, mycophenolate mofetil, prednisone, sirolimus, and tacrolimus. These drugs do cause side effects, but the physician may control these adverse effects by changing doses or switching medications. The maintenance immunosuppression drugs will be discussed because they are the most commonly used of all the anti-rejection drugs. The drugs discussed are:

AZATHIOPRINE (IMURAN)

Mechanism of Action

Azathioprine is an antimetabolite that decreases inflammation and interferes with the growth of rapidly dividing cells. It has a generalized effect on bone marrow and inhibits the production of blood-forming cells, thus preventing rejection. Azathioprine inhibits the white blood cells causing leucopenia and thrombocytopenia. Always assess the CBC prior to instituting dental treatment in patients on azathioprine (Imuran).

Side Effects

Common side effects experienced by the patient are cold hands and feet; loss of appetite, upset stomach, diarrhea, and vomiting; fever; mouth sores; sore throat; and unusual bleeding or bruising.

CYCLOSPORINE (SANDIMMUNE)

Cyclosporine is used for the management of organ transplants, severe psoriasis, and rheumatoid arthritis.

Mechanism of Action

Cyclosporine decreases the production of interleukins, resulting in decreased replication of helper and killer T cells.

Facts

Cyclosporine is extensively metabolized by the cytochrome P450 enzyme system in the liver. It is not unusual for the BUN and serum creatinine levels to be elevated during therapy if the cyclosporine levels are not kept in check.

Cyclosporine can therefore cause hypertension if the levels are not regulated well. Nephrotoxicity has occurred in patients receiving high doses of cyclosporine. Cyclosporine levels are monitored regularly every four to six weeks. Avoid nephrotoxic drugs in patients on cyclosporine. Cyclosporine is known to cause gingival hyperplasia.

Antibiotics Alert

Macrolides increase cyclosporine toxicity by increasing the intestinal absorption and inhibiting the biliary absorption of cyclosporine.

Antifungal Alert

Fluconazole (Diflucan) also increases cyclosporine toxicity, and the mechanism of action is unknown.

Analgesics Alert

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