Overview of Transplantation
The most common type of transplantation is a blood transfusion. Blood transfusions are used to treat millions of people each year. More typically, transplantation refers to the transfer of organs (solid organ transplants) or tissues.
Transplants may consist of
The transplanted tissues may be
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Cells, as in stem cell transplantation
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Part of an organ, as in some liver transplantations or lung transplantations
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Entire organs, as in heart transplantation or kidney transplantation
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More than one tissue (called composite transplants)
Organ transplantation, unlike blood transfusion, involves major surgery, the use of drugs to suppress the immune system (immunosuppressants, including corticosteroids), and the possibility of infection, transplant rejection, and other serious complications, including death. However, for people whose vital organs have failed, organ transplantation may offer the only chance of survival.
Some procedures, such as hand or face transplantation, may greatly improve a person's quality of life but are not done to save a life. These procedures have most of the same risks as organ transplantation. They are highly specialized and done infrequently but are no longer considered experimental.
Donors
A tissue or organ donor can be
Tissues and organs from living donors are preferable because they are usually healthier. Stem cells (from bone marrow or blood) and kidneys are the tissues most often donated by living donors. Usually, a kidney can be safely donated because the body has two kidneys and can function well with only one. Living donors can also donate only a part of the liver or a lung or a pancreas. Organs from living donors are usually transplanted within minutes of being removed. In the United States, being paid to donate an organ is illegal, but reimbursement for cells and tissues is allowed.
Some organs, such as the heart, obviously cannot be taken from living donors.
Organs from deceased donors usually come from people who previously agreed to donate organs. In many states, people can indicate their willingness to donate organs on their driver’s license, although family members are also consulted even when donor status is indicated on the license. Permission for donation also may be obtained from the deceased’s closest family member when the deceased’s wishes are unknown. Deceased donors can be otherwise healthy people who have been in a major accident, as well as those who died of a medical disorder that does not affect the organ being donated. Doctors do not take the potential for organ donation into account when deciding whether to recommend withdrawal of life support from people who are terminally ill or who are brain dead.
One deceased donor can provide several people with transplants. For example, one donor could provide two corneas, a pancreas, two kidneys, two liver segments, two lungs, a small intestine, and a heart. When people die, organs deteriorate quickly. Some organs last only a few hours outside the body. Other organs, if kept cold, can last a few days.
Organ Matching and Distribution
In the United States, a national organization (United Network for Organ Sharing) matches donors and recipients for transplantation through the use of a computer database. The database includes all people who are on a waiting list for a transplant, along with information about their blood and tissue types, distance from the donor hospital, and how severe their disorder is. Other information is included based on what organ a person needs. When organs become available, that information is entered and a match is made. Organs are then distributed once the criteria for transplantation of a specific organ type have been met.
Pretransplantation Screening
Because transplantation is somewhat risky and donor organs are scarce, potential recipients are screened for factors that may affect the likelihood of success.
Tissue matching
The immune system normally attacks foreign tissue, including transplants. This reaction is called rejection. Rejection is triggered when the immune system recognizes certain molecules on the surface of a cell as foreign. These cell-surface molecules are called antigens.
For blood transfusions, rejection is relatively easily avoided because red blood cells have only three main antigens on their surface. These antigens determine the blood type and are called A, B, and Rh. Doctors test to make sure that antigens in the donor blood and the recipient blood are a complete match.
For organ transplantation, however, many antigens are involved. These antigens are called human leukocyte antigens (HLA), or the major compatibility complex (MHC). They occur on the surface of every cell in the body. Each person has unique HLA, which determine the tissue type. Ideally, the donor’s tissue type exactly matches the recipient’s tissue type. However, a perfect HLA match is extremely rare, and some people are too ill to wait for a highly compatible donor. In these cases, doctors sometimes use donor tissue that is not an exact match but that is a close match. A close HLA match between the donor and recipient reduces the likelihood and severity of rejection and improves the long-term outcome. However, because immunosuppressant therapy has become more effective, the success of transplantation is less affected by the degree of matching.
Before transplantation, the recipient’s blood is screened for antibodies against the tissues of the donor. The body may have produced such antibodies in response to a blood transfusion, a previous transplant, or a pregnancy. If these antibodies are present, transplantation may not be possible because immediate, severe rejection will occur. Plasma exchange and intravenous immune globulin (IVIG) have been used to remove or suppress the antibodies and thus make transplantation possible when a close match is not available. (IVIG is antibodies obtained from blood that is collected from people with a normal immune system.) These treatments are expensive but seem promising.
Donor screening
Donors are screened for cancer and infections, which can be transmitted during transplantation. Doctors screen donors for cancer by thoroughly reviewing their medical history and carefully inspecting the organ in the operating room at the time of organ recovery. Organs containing cancers are obviously not used for transplantation. Whether or not to use organs from donors who previously had cancer in another organ is based on the likelihood that cancer cells are still present or have spread to the organ being transplanted.
Most bacterial infections are evident to doctors based on the donor’s overall health and have often been diagnosed and treated even before the decision to donate. If treatment has been adequate, organ transplantation is safe, although the recipient may be given additional antibiotic treatment.
To prevent transmission of viral infections, which are often not so obvious, doctors usually test the donor’s blood for certain viral infections. These infections include those due to cytomegalovirus (CMV), Epstein-Barr virus (EBV), hepatitis B and C viruses, human immunodeficiency virus (HIV), and human T-cell lymphotropic virus (HTLV). Some viral infections in the donor, such as HIV infection, mean that transplantation cannot be done unless the infection can be controlled. Other viral infections, such as CMV and EBV infections, do not prevent transplantation, but the recipient must take antiviral drugs afterward.
Recipient screening
Recipients are also screened for cancer and infections, and their general health is evaluated. Because organ transplant recipients are given immunosuppressants in high doses at the time of transplantation, recipients who have active infections or cancers cannot undergo transplantation until these conditions are controlled or cured. Taking immunosuppressants could make an infection or cancer worse.
People with poor overall health, certain viral infections, or other medical problems in addition to malfunction of the organ requiring transplantation are less likely to do well with a transplant. The decision to transplant is based on the person’s specific circumstances, including age.
Psychosocial screening is done because the lifelong regimen of drugs, treatments, and follow-up visits required to keep a transplanted organ functioning is quite demanding, and not all people are willing or able to comply. In addition to nurses and doctors, psychiatrists and social workers are involved to help people and their families understand the long-term commitment and difficulties involved in accepting a transplant. Everybody’s input is important in determining whether organ transplantation is right for a person.
Suppression of the Immune System
Even if tissue types are closely matched, transplanted organs, unlike transfused blood, are usually rejected unless measures are taken to prevent rejection. Rejection results from an attack by the recipient's immune system on the transplanted organ. Rejection can be mild and easily controlled or severe, resulting in destruction of the transplanted organ.
Rejection can usually be controlled with drugs called immunosuppressants, which suppress the immune system and the body’s ability to recognize and destroy foreign substances. With the use of immunosuppressants, the transplanted organ is more likely to survive.
Immunosuppressants must be taken indefinitely. High doses are usually necessary only during the first few weeks after transplantation or during an episode of rejection. After that, smaller doses can usually prevent rejection (called maintenance immunosuppression). Doses of immunosuppressants may need to be reduced further if recipients develop serious infections or if the drug has troublesome side effects, but reducing the dose of the immunosuppressant increases the risk of rejection.
At the first sign of rejection, doctors increase the dose of the immunosuppressant, change the type of immunosuppressant, or add an another immunosuppressant.
Different types of immunosuppressants target different parts of the immune system. Thus, several drugs may be used together. Some drugs, such as corticosteroids, suppress the immune system as a whole. Others have different ways of inhibiting the production and activity of white blood cells. White blood cells help the body recognize and destroy foreign cells, such as those in a transplanted organ.
Drugs Used to Prevent Transplant Rejection
Drug |
Possible Side Effects* |
Comments |
Corticosteroids (potent anti-inflammatory drugs that suppress the immune system as a whole) |
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Dexamethasone Prednisolone Prednisone |
Excess hair on the face Facial puffiness Fragile skin High blood sugar levels (as occur in diabetes mellitus) Muscle weakness Stomach ulcers Water retention |
Given by vein in high doses at the time of transplantation Gradual reduction of the dose to a maintenance dose taken by mouth, usually indefinitely |
Polyclonal immunoglobulins (antibodies directed toward particular cells of the immune system) |
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Antilymphocyte globulin Antithymocyte globulin |
Severe allergic reactions (anaphylactic reactions) with fever and chills, usually occurring only after the first or second dose Sometimes a reaction to the foreign proteins in the drug, causing fever, rash, and joint pain (serum sickness) Sometimes kidney problems |
Given by vein Used at the time of transplantation with other immunosuppressants so that those drugs can be used in lower, safer doses Also used for rejection episodes |
Monoclonal antibodies (antibodies that target and suppress white blood cells†) |
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Basiliximab |
Severe allergic (anaphylactic) reactions |
Given by vein Used at the time of transplantation or for rejection episodes The only antibody of its type still available |
Calcineurin inhibitors (drugs that inhibit the production and activation of white blood cells†) |
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Cyclosporine |
Excessive hairiness (hirsutism) Gum enlargement High blood pressure Increased levels of cholesterol and other fats Increased risk of lymphoma Kidney damage Liver damage Nerve damage Tremor |
Given by mouth Used at the time of transplantation and for maintenance immunosuppression in people who have received an organ transplant Can be used alone but is usually given with other drugs that help prevent rejection |
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Tacrolimus |
Diabetes Diarrhea Gout Hair loss Headache High blood pressure Increased levels of cholesterol and other fats Increased risk of lymphoma Insomnia Kidney damage Liver damage Nausea Nerve damage Tremor |
Given by mouth Used at the time of transplantation and for maintenance immunosuppression in people who have received an organ transplant Used for rejection episodes |
Rapamycins (drugs that inhibit the production and activity of white blood cells†) |
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Everolimus Sirolimus |
Accumulation of fluid (edema) in the legs Anemia High blood pressure Increased levels of cholesterol and other fats Lung damage Rash Slow healing of wounds |
Given by mouth Used with corticosteroids or cyclosporine for maintenance in people who have received a kidney or liver transplant Everolimus: Used to prevent rejection of a kidney or liver transplant |
Mitotic inhibitors (drugs that suppress cell division and thus the production of white blood cells†) |
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Azathioprine |
Fatigue Fever and rash (hypersensitivity reaction) Hepatitis (rare) Low white blood cell count |
Given by mouth Used at the time of transplantation and for maintenance immunosuppression in people who have received an organ transplant Often used with low doses of calcineurin inhibitors |
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Mycophenolate mofetil |
Diarrhea Increased risk of lymphoma Low white blood cell count Nausea Vomiting |
Given by mouth Used for maintenance immunosuppression in people who have received an organ transplant Used with corticosteroids and cyclosporine or tacrolimus |
OT-cell costimulatory blocker (drug that suppresses activation and proliferation of white blood cells)† |
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Belatacept |
Constipation Dizziness Headache Increased hunger Increased risk of lymphoma Increased urination |
Given by injection Used to prevent rejection of kidney transplants Increases risk of certain viral infections and viral disorders Rarely used in kidney transplant recipients who are at increased risk of kidney damage caused by use of calcineurin inhibitors |
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* All of these drugs increase the risk of infections. Also, they can all cause allergic reactions, but the risk is higher with some of them. |
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† White blood cells help the body recognize and destroy foreign cells. |
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Pregnancy and Transplantation
Many immunosuppressants are unsafe for fetuses, so transplantation cannot be done during pregnancy. However, some women who have received a transplant may be able to get pregnant and have healthy babies once the function of their transplanted organ is stable. The immunosuppressants they are taking can be specially adjusted or switched if needed.
Complications After Transplantation
Complications that can occur after transplantation include
The use of immunosuppressants can lead to some complications. In addition to suppressing the immune system’s reaction to the transplanted organ, these drugs also reduce the ability of the immune system to fight infections and to destroy cancer cells. Thus, transplant recipients are at increased risk of developing infections and certain cancers.
Rejection
Rejection, if it occurs, often begins soon after transplantation but can occur after weeks, months, or even years.
Symptoms of rejection vary depending on which organ was transplanted and when rejection occurs. If rejection occurs soon after transplantation, symptoms may include fever, chills, nausea, fatigue, and sudden changes in blood pressure.
Infections
Several factors increase the risk of infections for transplant recipients:
Infections that may develop in transplant recipients include the same ones that might develop in any person recovering from surgery. Such infections include infection of the surgical site or the transplanted organ, pneumonia, and urinary tract infections.
Transplant recipients are also at risk of unusual (opportunistic) infections that affect mainly people with a weakened immune system. Opportunistic infections may be caused by
After transplantation, most people are given antimicrobial drugs to help prevent infections. After 6 months, the risk of infections goes back to what it was before transplantation in about 80% of people.
Cancer
Certain cancers are more likely to develop when immunosuppressants are taken a long time, as occurs after transplantation. Such cancers include certain skin cancers, lymphoma, cervical cancer, and Kaposi sarcoma.
Treatment is similar to that for people who do not have transplants. But sometimes during treatment for cancer, immunosuppressants are stopped or the doses are decreased.
Atherosclerosis
Atherosclerosis (deposits of fatty material in arteries) may develop because some immunosuppressants cause levels of cholesterol and other fats (lipids) to increase. These fats may accumulate in the walls of arteries and reduce or block blood flow, causing a heart attack or stroke.
Atherosclerosis typically develops about 15 years after kidney transplantation.
Kidney problems
Gout
Gout is common, particularly after heart or kidney transplantation. It can be severe and progress rapidly, particularly if people have had gout before transplantation or if they take cyclosporine or tacrolimus.
Graft-versus-host disease
Graft-versus-host disease occurs when white blood cells (the graft) from the donor attack the recipient's (the host) tissues. This disorder most commonly occurs in recipients of stem cell transplants but can occur in recipients of liver or small intestine transplants.
Symptoms may include fever, rash, jaundice, vomiting, diarrhea, abdominal pain, weight loss, and increased risk of infections. These reactions can be fatal. However, certain drugs such as methylprednisolone can eliminate or reduce the severity of graft-versus-host disease in the recipient.
Osteoporosis and stunted growth
Use of immunosuppressants (especially corticosteroids) can result in osteoporosis in people who are at risk of developing osteoporosis before transplantation. These people include those who have a sedentary lifestyle, who use tobacco and alcohol, or who have kidney disease.
In children, use of immunosuppressants can result in stunted growth.
Doctors test most people for osteoporosis before transplantation is done. Sometimes doctors give transplant recipients vitamin D or drugs that prevent bone loss (such as bisphosphonates) to help prevent bone loss.
Donor complications
Living donors are also at risk of complications. Some of these complications are those that may occur after any surgery, such as infection and bleeding. Some additional complications depend on which organ has been removed. Donors may also be at risk of emotional and mental complications, so transplant teams carefully evaluate potential donors before a person is selected as a donor.
More Information
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United Network for Organ Sharing: Information about how donated organs are matched with transplant candidates
Drugs Mentioned In This Article
| Generic Name | Select Brand Names |
|---|---|
methylprednisolone |
MEDROL |
immune globulin |
Gammagard S/D |
Dexamethasone |
OZURDEX |
Mycophenolate |
Mycophenolate |
Azathioprine |
IMURAN |
Cyclosporine |
NEORAL, SANDIMMUNE |
Prednisolone |
ORAPRED, PRELONE |
Basiliximab |
SIMULECT |
Belatacept |
NULOJIX |
Prednisone |
RAYOS |
Tacrolimus |
PROGRAF |
Everolimus |
AFINITOR |
Sirolimus |
RAPAMUNE |
