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Overview of Transplantation

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by Martin Hertl, MD, PhD, Paul S. Russell, MD

Transplantation is the removal of living, functioning cells, tissues, or organs from the body and then their transfer back into the same body or into a different body.

The most common type of transplantation is a blood transfusion (see Overview of 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.

Organ transplantation, unlike blood transfusion, involves major surgery, the use of drugs to suppress the immune system (immunosuppressants), and the possibility of transplant rejection and 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 life. These procedures have most of the same risks as organ transplantation. They are still experimental.

Donors

A tissue or organ donor can be a living person—related to the recipient or not—or a person who has recently died (deceased donor).

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 a part of the liver or a lung. 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. 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 (see Brain Death).

One donor can provide several people with transplants. For example, one donor could provide two corneas, a pancreas, two kidneys, two liver segments, two lungs, 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.

Did You Know...

  • One deceased donor can provide two corneas, a pancreas, two kidneys, two liver segments, two lungs, and a heart.

Organ 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 their tissue type and other information. When organs become available, that information is entered and a match is made.

Organs are allocated first among 12 geographic regions, then among local organ procurement organizations. If no recipient in the first region is suitable, organs are reallocated to recipients in other regions. For some organs (liver or heart), the recipient is chosen based on how severe the recipient's disorder is. For other organs (kidney, lung, or intestine), the recipient is chosen based on how severe the disorder is, how long the person has been on the waiting list, or both.

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 (see Biology of the Immune System:White blood cells), 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 (see Table: Controlling Diseases by Purifying the Blood ) and intravenous immune globulin have been used to remove or suppress the antibodies and thus make transplantation possible when a close match is not available. 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. The decision 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.

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.

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)

Dexamethasone

Prednisolone

Prednisone

Atherosclerosis

Excess hair on the face

Facial puffiness

Fragile skin

High blood pressure

High blood sugar levels (as occur in diabetes mellitus)

Muscle weakness

Osteoporosis

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)

Antilymphocyte globulin

Antithymocyte globulin

Severe allergic (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 )

Basiliximab

Daclizumab

Severe allergic (anaphylactic) reactions

Given by vein

Used at the time of transplantation or for rejection episodes

Muromonab (OKT3)

Fever

Shaking (rigors)

Joint and muscle pain

Nausea and vomiting

Diarrhea

Possibly low blood pressure

Given by vein

Used at the time of transplantation or for rejection episodes

Severe side effects usually occurring only after the first few doses

Calcineurin inhibitors (drugs that inhibit the production and activation of white blood cells )

Cyclosporine

Diabetes

Excessive hairiness (hirsutism)

Gout

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

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

Rapamycins (drugs that inhibit the production and activity of white blood cells )

Everolimus

Sirolimus

Accumulation of fluid (edema) in the legs

Anemia

High blood pressure

Increased levels of cholesterol and other fats

Low potassium levels

Lung damage

Rash

Slow healing of wounds

Given by mouth

Used with corticosteroids or cyclosporine in people who have received a kidney or liver transplant

Everolimus usually given to people who have received a heart transplant

Mitotic inhibitors (drugs that suppress cell division and thus the production of white blood cells )

Azathioprine

Allergic reactions (in some people)

Fatigue

Hepatitis (rare)

Increased risk of infection

Low white blood cell count

Nausea

Tendency to bleed

Vomiting

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

Mycophenolate mofetil

Diarrhea

Increased risk of infection

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

*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.

White blood cells help the body recognize and destroy foreign cells.

Complications After Transplantation

Complications that can occur after transplantation include

  • Rejection

  • Infections

  • Cancer

  • Kidney problems

  • Atherosclerosis

  • Graft-versus-host disease

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.

Some complications are related to the use of immunosuppressants. 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.

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. Such infections may be caused by bacteria (such as Listeria or Nocardia), viruses (such as cytomegalovirus or Epstein-Barr virus), fungi (such as Pneumocystis jirovecii or Aspergillus), or parasites (such as Toxoplasma). 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.

Cancers due to immunosuppression 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.

Kidney problems develop in about 15 to 20% of people with a transplanted organ, particularly the small intestine. The kidneys become less able to remove waste products, which then build up in the blood. High doses of immunosuppressants (particularly cyclosporine and tacrolimus) may contribute to the development of these problems, as can the physical stress of transplantation surgery.

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.

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.

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.

Other complications that can result from use of immunosuppressants (especially corticosteroids) include osteoporosis and stunted growth in children. Doctors test most people for osteoporosis before transplantation is done.

Resources In This Article

Drugs Mentioned In This Article

  • Generic Name
    Select Brand Names
  • AFINITOR
  • SIMULECT
  • ORAPRED, PRELONE
  • OZURDEX
  • PROGRAF
  • RAYOS
  • NEORAL, SANDIMMUNE
  • IMURAN
  • RAPAMUNE
  • MEDROL