Before, during and after transplantation: an overview

Vital organs such as the liver and kidneys can become damaged because of the following:

• chronic infections that attack the liver (such as hepatitis B virus and hepatitis C virus)
• inflammation
• exposure to harmful substances (such as in cases of alcohol abuse)
• toxicity of medications
• diabetes
• higher-than-normal blood pressure

As these organs degrade, waste products can build up in the blood and circulate, causing complications and weakening overall health.

The first step in finding out more about transplantation options is a referral from a physician to a transplantation centre. These are usually located in major regional hospitals.

Evaluation

The process of evaluation by the transplant team can take several weeks, as different specialists are seen. For instance, in the case of a liver transplant, the specialists that can be involved include:

• liver transplant surgeons
• liver specialists (hepatologists)
• infectious disease specialists
• nurses
• social workers
• psychologists

In the case of a kidney transplant, a nephrologist (a doctor who specializes in kidney care) and kidney surgeon will be part of the team.

As part of the assessment, overall health and in particular the health of other key organs (heart, lungs and so on) will be checked to confirm not only that a transplant is needed but that a person’s health is strong enough to withstand surgery and potential ensuing complications.

A psychological assessment will also take place to ensure that potential transplant recipients are mentally and emotionally ready for living with a transplanted organ. Generally, people who are active substance users are excluded from transplant programs. People who have recovered from addiction are usually required to be off substances for at least six months or longer, depending on the substance use and the transplant program.

Social stability is an important requirement for long-term success after transplantation because an intensive degree of monitoring, medication adherence and self-care is needed.

Each transplant centre may have its own criteria for people who are ideal candidates for transplantation. Usually these criteria are similar within a region. As there is a shortage of organs suitable for transplant, eligible candidates for transplantation are placed on a waiting list.

Where do donated organs come from?

Organs are often removed or harvested from people who have suffered severe and fatal injuries as a result of accidents or trauma to the head. After vital organs are harvested, they are placed in a solution that helps to nourish and maintain them and packed in ice. In this way, harvested organs can be maintained for between 12 and 20 hours and must be transplanted within that time. Sometimes a healthy family member or a friend can donate an organ or part of an organ if he or she is a suitable genetic match.

Balancing needs

People in need of organs who are severely ill are usually prioritized for transplantation. Medical centres also try to balance people’s needs and take into account which patients on the waiting list are most likely to have the fewest transplant-related complications so that recipients can provide a hospitable host for the donated organ to survive. To help deal fairly with the needs of many different ill people, transplant centres often use a rating system. In the case of people waiting for liver transplants, this is called MELD—the model for end-stage liver disease. MELD involves an equation that takes into account the following lab values:

• bilirubin
• creatinine
• time for blood to clot

MELD scores are very useful in predicting which patients are likely to survive the transplantation process.

Matching an organ to a person

A person’s suitability for a donated organ depends on several factors, such as the following:

• matching the recipient’s blood type (A, B, AB and so on) with the donor’s blood type
• a similarity of immunologic markers (called HLA factors) on the cells of the recipient’s immune system and on those of the donor’s – the more closely the recipient and donor can be immunologically matched, the greater the chances of long-term transplantation success.
• cross-match test – even if there is a match based on blood type and HLA, there is still the possibility that the recipient’s blood could have antibodies that can attack the donor’s tissue. These antibodies arise most commonly because the recipient has been exposed to another person’s tissues through blood transfusion. To rule out the presence of these antibodies, a small sample of blood is drawn from the recipient and white blood cells from a potential donor are exposed to the recipient’s blood. If the donor’s white blood cells are subsequently injured as a result of exposure to the recipient’s blood, this is called a positive cross match and strongly suggests that transplanted tissue from the donor will most likely be severely attacked by the recipient’s immune system. If no damage to the donor’s white blood cells occurs then the result is called a negative cross match and the recipient’s body is less likely to mount a strong attack against the new organ.

Surgery

The surgery involved in an organ transplant is complex and is done under general anesthesia. Removing a damaged liver is complex because the organ is inflamed and there is an increased risk for complications, such as bleeding. Veins and arteries have to be closed off and then reconnected to the new organ. During surgery, levels of many important substances, including glucose and calcium, fall to very low levels and body temperature also falls. These changes cause stress on the body but are successfully managed by the transplant team. Liver transplantation usually takes about three or four hours, while kidney transplantation can take up to 12 hours.

After the transplant

Because removing and transplanting vital organs is a major undertaking and because someone who has failing organs will usually be in some degree of ill health and immune-suppressing drugs must be administered, the recipient of a transplant can develop complications after surgery. Some complications are minor, others are major; some are short-term and others are long-term.

Depending on the results of the operation, transplant recipients usually stay in the hospital for about one week after surgery, as the transplant team performs intensive monitoring and tests to ensure that the new organ is working and that there are not any serious complications. Sometimes longer stays in the hospital are necessary.

After surgery the kidneys may temporarily become overwhelmed from the combination of injury caused by surgery and the toxicity of exposure to immunosuppressive medicines, particularly cyclosporine (Neoral, Sandimmune). So mechanical filtration of the blood (dialysis) may be temporarily needed for some recipients of a transplanted kidney.

As with any major surgery, bleeding can occur. Also, the new organ may carry cells of the donor’s immune system and once these enter the circulation of the recipient, they can attack his or her red blood cells. This can cause a shortage of red blood cells in the recipient and so blood transfusion(s) may be necessary.

Other non-infection-related complications can include depression and seizures.

Most people who receive a transplanted organ feel better immediately. However, despite an improvement in energy, alertness and possibly mood, it may take several months for a person to regain his or her strength.

Infections

It is common for people to get infections after a transplant. Most of these infections can be treated quickly and suppressed. In the first month after transplantation, infections may appear in the following locations:

• abdomen
• genitals and tubes through which urine flows
• lungs

After the first month, other infections may appear but taking certain drugs called antimicrobials (antibiotics, antifungals and antivirals) can prevent or treat these infections. Commonly used antimicrobial agents include:

• azithromycin (Zithromax) – helps to prevent infection by bacteria called MAC (Mycobacterium avium complex)
• Bactrim/Septra (trimethoprim-sulfamethoxazole) – helps to prevent common pneumonias, particularly PCP (Pneumocystis pneumonia), to which HIV-positive people are susceptible
• fluconazole (Diflucan) – helps to prevent some fungal infections
• valganciclovir (Valcyte) – is used to prevent or treat viral infections, particularly those caused by CMV (cytomegalovirus)

Rejection

Despite good pre-transplant tests to ensure a good match between donor and recipient, the host’s immune system will attack the new organ unless immunosuppressive medicines are taken. These attacks on the new organ are called rejection. Episodes of rejection can still occur despite the use of immunosuppressive drugs as the transplant team seeks to find a balance between suppressing the immune system so that the new organ can survive but not suppressing it so much that the recipient develops serious infections and other complications.

Signs of rejection can include fever and pain in the area where the new organ has been implanted. However, note that rejection, at least initially, may not result in symptoms. This is another reason why frequent and regular check-ups, including blood tests, are essential after transplantation.

CAT scans or even a biopsy of the liver or kidney may be necessary to be certain that rejection is occurring. When an episode of rejection is suspected, the transplant team may temporarily intensify immunosuppression, often with methylprednisone.

Life after transplant

After transplantation, many people eventually return to the activities that they used to enjoy before they became ill and needed a transplant. The transplant team provides advice to patients about staying healthy when they are ready to leave the hospital. Here are just a few general tips for staying healthy:

• Keep all appointments with your transplant team. Initially it may seem like you have frequent appointments to see different specialists or to have blood drawn, but after the first six months, if you are doing well, you will find that the transplant teams does not need to see you as often.
• If you suspect that an episode of rejection is occurring, contact your transplant team right away.
• Get advice from a registered dietician about eating a nutritious diet and ask your transplant team about what exercises are right for you.
• Avoid tobacco, alcohol and use of other substances.
• Always consult your transplant doctors about the medicines that you are taking, both over the counter and prescription. This is particularly important because many drugs can interfere with your transplant medicines and therefore your health.
• Always discuss the potential use of any supplements (including herbs) with your transplant team. Herbs are particularly troublesome because they can interfere with many medicines, including those used in transplantation and HIV care.
• Take all of your medicines exactly as prescribed. If you have difficult doing this, talk to your nurse or pharmacist as soon as possible.
• Continue to practice safer sex so as to minimize your exposure to germs.

REFERENCES:

1. Trullas JC, Cofan F, Tuset M, et al. Renal transplantation in HIV-infected patients: 2010 update. Kidney International. 2011 Jan 19. [Epub ahead of print].
2. Carpenter CB, Milford EL, Sayegh MH. Chapter 276. Transplantation in the Treatment of Renal Failure. Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J: Harrison’s Principles of Internal Medicine, 17th ed. McGraw-Hill Companies, Inc.; 2008.
3. Finberg R, Fingeroth J. Chapter 126. Infections in Transplant Recipients. Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J: Harrison’s Principles of Internal Medicine, 17th ed. McGraw-Hill Companies, Inc.; 2008.
4. Dienstag JL, Chung RT. Chapter 304. Liver Transplantation. Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J: Harrison’s Principles of Internal Medicine, 17th ed. McGraw-Hill Companies, Inc.; 2008.