ORGAN TRANSPLANTS, MEDICAL OVERVIEW OF

The first successful kidney transplant, performed by Dr. Joseph Murray at Boston's Peter Bent Brigham Hospital, took place in 1954. Since then, remarkable advances have occurred in transplantation. Antirejection drugs have dramatically improved success rates, and the vast majority of recipients are restored to well-being and enjoy productive and active lives. Better preservation of organs allows longer storage times, so organs can be transported over greater distances. In addition to kidneys, numerous other organs, including livers, hearts, lungs, and pancreases, are commonly transplanted today. Certain areas remain problematic, however. The control of rejection of transplanted organs is not yet perfect, and post-transplant complications, such as infection and cancer, can still threaten the health of recipients. But the major obstacle remains the inadequate number of organs available to meet the need of potential recipients on the waiting list.

Development of Transplantation

Attempts to transplant a kidney from one person to another began in the 1930s. These attempts were based on laboratory experiments by Alexis Carrel, a researcher who had developed a technique for suturing blood vessels in 1902. These early transplants all failed because the recipient's immune system recognized that the transplanted organ (often called a graft) was a foreign substance. The immune system then attacked and destroyed the organ, a process known as rejection. Success was finally achieved in 1954 because the donor and recipient were identical twins. Identical twins have the same tissue type, so the recipient's immune system perceives the transplant organ as a part of its own body, and rejection does not occur. Because every healthy person has two kidneys, one kidney can be donated from a living person to another person.

An organ or tissue that is transplanted between genetically identical twins is called an isograft. Allografts are organs or tissues that are transplanted between genetically nonidentical people, which occurs when organs or tissues are donated from a deceased person (cadaver donor). An autograft is a tissue transplanted from one part of a person's body to another part, such as when a burn victim has healthy skin grafted from one area of the body to the burned area. A xenograft is an organ or tissue transplanted from a different species, for example, a pig liver transplanted into a human.

During the 1950s, antirejection drugs had not yet been developed, so transplants were limited to kidneys from identical-twin donors. In 1959, however, Murray and his colleagues at Brigham Hospital again achieved a historic feat. They transplanted a kidney from a nonidentical twin to his brother, who had undergone total body X-ray treatment (irradiation). This treatment suppressed the patient's immune response so that his body accepted the new organ, and he lived for twenty-six years after the transplant. Irradiation was also tried with kidney transplants from cadaver donors. For most patients, however, the outcome was fatal because the irradiation weakened their immune systems too much. Although they accepted the transplanted organ, patients died from infection because their natural defenses against bacteria and viruses were reduced. It seemed evident that irradiation for transplantation "was too dangerous to be practical" (Starzl).

During this time, chemical immunosuppression (drug therapy) was being studied. In 1960 the French surgeon René Küss achieved successful nonrelated kidney transplantation using a combination of total-body irradiation, steroids, and 6-mercaptopurine. Azathioprine (also called Imuran) was later derived from 6-mercaptopurine. The combination of azathioprine and prednisone (a type of steroid) to prevent organ rejection, suggested by Sir Roy Calne, was a clinical milestone in 1962, as kidney transplant results improved and fewer side effects occurred.

In 1967 a heart and a liver were each successfully transplanted—the heart by Dr. Christiaan Barnard in Capetown, South Africa, and the liver by Dr. Thomas Starzl in Denver, Colorado. These successful transplants were followed by a flurry of activity as hospitals worldwide rushed to perform transplant surgery. Lung, bowel, and pancreas transplants were all attempted during the 1960s. Most of these attempts failed, however, and many transplant programs were abruptly stopped. Methods of suppressing the immune system were too crude to achieve the fine balance needed to control rejection but avoid fatal infection. By 1975 there were only two liver transplant programs in the world. Starzl was continuing to transplant in Denver, Colorado, and Calne was leading a program in Cambridge, England.

The modern era of transplantation began in the late 1970s and the early 1980s, when drugs to prevent rejection were discovered that were vastly superior to existing ones. The first of these was cyclosporine, a drug that acted much more specifically on the patient's immune system. It primarily affected those cells that were responsible for initiating the rejection process. Other drugs followed, including FK506 and OKT3, which quickly found their place in patient management. The decade of the 1980s witnessed a proliferation of transplant centers worldwide.

Refinements in surgical techniques and better methods to preserve donor organs also contributed to improved patient outcome, and successful kidney, liver, and heart transplants became routine. Lung transplantation was developed at the Toronto General Hospital in Canada, where single-lung transplantation was established in 1983 and double-lung transplantation in 1986. By the year 2000 more than 600,000 organ transplants had been performed worldwide, and transplant centers with special interests accumulated huge experiences that benefited not only their own patients, but those in other centers as well. At the University of Minnesota alone, more than 1,000 pancreas transplants had been performed by 2000 (Sutherland et al.).

Success with bowel transplantation was more difficult to achieve compared to other organs. The intestine has a large number of cells called lymphocytes, which help trigger rejection and also react against the recipient (graft-versus-host disease). Bowel transplantation was not successfully performed until the late 1980s when a patient in Kiel, Germany, and another in Paris, France, had prolonged survival. The first successful combined small-bowel and liver transplant took place at University Hospital (London, Canada) in 1988. Experience from these centers and from Pittsburgh showed that bowel transplants could be worthwhile for selected patients who either had part of their bowel removed or had inadequate bowel function. The antirejection drug FK506 improved the success rate of bowel transplantation, and patients could resume eating a normal diet after their transplant without the need for special intravenous feeding solutions.

Transplantation of islet cells from the pancreas first occurred in the mid-1970s. Rather than transplanting the donor's whole pancreas, the insulin-producing islet cells were removed from the donor pancreas. The cells, injected into the portal vein of the recipient's liver, adhered to the liver. The cells then began producing insulin. For diabetic patients who had to take insulin to stabilize their blood-sugar levels, islet-cell transplantation eliminated or reduced the need for daily insulin injections. Although reports began to emerge of short-term and prolonged insulin independence in 1990 (Scharp et al.), it was not until ten years later that the most significant progress to date was made. The transplant team at the University of Alberta, in Edmonton, Canada, developed a specific protocol of antirejection drugs combined with the transplantation of fresh islets from more than one donor to supply a critical mass of insulin-producing cells (Shapiro et al.). That success has led the National Institutes of Health to sponsor an international trial of islet transplantation using the Edmonton protocol. Because of the inadequate number of cadaver donors, however, animal islet cells, probably from pigs, may be required in the future.

The Cadaver Organ Donor

Traditionally, death has been declared on the basis of cardiopulmonary criteria: The heart stops beating and the patient can no longer breathe. Once the heart stops, oxygen-rich blood is no longer pumped to the body's organs, and the organs' cell functions begin to deteriorate. During the 1960s, organs came either from living donors (for kidneys) or from cadaver donors who were declared dead by the traditional cardiopulmonary criteria (non-heart-beating donors). The first successful liver transplants in 1967 used organs from donors who were removed from ventilators (artificial breathing machines) and pronounced dead after the heart had stopped.

As medical technology progressed and it became possible to maintain bodies after death using mechanical support, doctors needed to determine when a patient could be declared dead. Accordingly, in 1968, an ad hoc committee comprising medical doctors, a lawyer, a philosopher, and a theologian convened at the Harvard Medical School to define acceptable criteria for brain death. They decided that death could be declared by neurologic criteria as well as traditional cardiac criteria. Brain-dead donors, with the assistance of a ventilator, have oxygen circulating in their blood, which maintains the usefulness of organs for transplant. Brain death is declared after a series of tests have been performed. The cause of death, such as trauma, intracerebral hemorrhage, hypoxia, or primary brain tumor, must be known. Patients with potentially reversible conditions, such as hypothermia or drug-induced coma, are not considered potential donors. To be declared brain dead, therefore, a patient must be in an irreversible coma and not respond to pain. There are no brain-stem reflexes, so the patient does not breathe, swallow, or blink. Apnea testing shows that the patient cannot breathe when taken off the ventilator. After death, tests ensure that the deceased patient is a suitable donor, without disease or infection that could possibly be transmitted to the transplant recipient. In 1971 Finland became the first nation to accept the legality of brain-death criteria. Most countries recognize the legal status of brain death and accept brain death as a medical basis to declare death.

Brain-dead donors are preferred for transplant, rather than non-heart-beating donors, because they almost invariably provide better quality organs. When non-heart-beating donors are used, transplants are usually limited to tissues and kidneys, and sometimes the liver. By the time the heart has stopped beating and death is declared through the absence of pulse and respiration, other organs, such as the heart and lungs, are too damaged for transplant. Because of the worldwide shortage of organ donors, however, many countries have explored the possibility of using non-heart-beating donors in addition to brain-dead donors.

Non-heart-beating donors fall into two categories: un-controlled and controlled. Uncontrolled non-heart-beating donors are those in whom death is sudden and unexpected, without any preparatory time to plan for organ removal. Examples are victims of accidents or heart attacks who arrive in hospital emergency rooms in extremis (at the point of death), perhaps after the heart has already stopped beating. They do not respond to resuscitative measures, their lives cannot be saved despite all medical efforts, and they are pronounced dead. Consent for donation has to be obtained urgently, and organ removal is a hasty event, usually performed under far less than ideal circumstances. Still, the organs may have been deprived of blood flow and oxygen for so long that they are irreparably damaged and would not function if transplanted.

Controlled non-heart-beating donors are those in whom death is a planned event. The patient, with a hopeless prognosis, is going to have life support withdrawn because the patient and next of kin wish to forgo any measures or interventions that would prolong life. The patient has previously expressed the wish to donate after death, and consent for donation is obtained prior to death. Surgical removal of organs is timed to occur within minutes of cardiac arrest. In this situation, the organs are generally less damaged than they are with uncontrolled non-heartbeating donors.

Non-heart-beating donors have been used in Spain, the Netherlands, and the United States, although these countries have predominantly used brain-dead donors. Before 1988, when Sweden adopted its brain-death laws, transplant programs retrieved and transplanted livers from donors whose hearts had stopped beating. In 1995 an international workshop on non-heart-beating donors was held in Maastricht, Netherlands, and recommendations were put forward to guide transplant specialists on the use of nonheartbeating donors (Koostra).

The Living Organ Donor

Normal, healthy individuals can donate one of their kidneys or a part of another organ for transplantation. Because of the limited number of cadaver donors and the increasing population of patients developing kidney failure each year, greater use is being made of kidneys from living donors. The best long-term results of kidney transplantation are those achieved with living donors. In countries that typically use cadaver donors, the rate of living donors varies. In the United States, approximately 35 percent of all kidney transplants are from living donors; in Canada, 48 percent; and in the United Kingdom, only 6 percent. Japan has brain death-criteria, but acceptance of the concept for purposes of organ donation has been slow. Consequently, 78 percent of kidney transplants are from living donors.

Advances in minimally invasive surgery now allow kidneys to be removed from living donors through much smaller incisions, allowing for earlier discharge (as early as 48 hours), and shortening the overall recovery period for the donor. The procedure is referred to as laparoscopic kidney removal. Rather than making a long and painful incision over the flank with removal of a rib to retrieve the kidney, slender instruments the diameter of a pencil are inserted into the abdominal cavity through tiny incisions. Carbon dioxide is used to fill the abdominal cavity, which allows the organs to separate from one another. With the use of fiber optics, a camera sees the inside of the abdomen and projects the picture onto a screen for the surgeon. Then the kidney is dissected from its attachments and removed through an incision just large enough for the kidney to fit through the muscles and skin (2 to 3 inches). The donors experience much less pain after the surgery, they recover more quickly, and return to normal activity and employment sooner.

A portion of the liver, lung, pancreas, or bowel can be removed from a living adult and transplanted into a suitably sized recipient, either a child or an adult who is smaller than the donor. Blood-group matching and size matching of the donor and recipient are very important. In most instances, living donors are either genetically related to the recipients or "emotionally related," such as a spouse or close friend. Parent-to-child living-donor liver donation began in the early 1990s, and it has become common in major pediatric transplant centers. A small segment (one-quarter) of the liver is removed from the donor. The use of living liver donors has significantly reduced the number of children dying while on transplant waiting lists. Adult-to-child lung donation is also possible, by removing a lobe of a donor's lung and transplanting it into the chest cavity of a child whose diseased lung has been removed. Living liver donation can also be performed between two adults. Rather than using a small part of the donor liver, as in a parent-to-child transplant, the largest lobe of the liver, which makes up about two-thirds of the organ, is removed and transplanted into a size-matched adult recipient.

Given the severe shortage of donated cadaver organs, relatives, especially parents, may feel compelled to donate. The donor must understand the risks and benefits of donation. Although living donors place themselves at risk, they may experience a psychological benefit from saving, or attempting to save, their loved one's life. In addition, the recipient does not have to wait as long for the transplant and will likely be healthier. This factor, combined with a reduced ischemic time (the length of time the organ has no blood supply) may provide greater success than transplants from cadaver donors. Because the donor and recipient operations can take place simultaneously, the organ does not have to be stored and transported, and ischemia is reduced and organ function is not compromised.

The operative risk of a kidney donor dying is approximately 3 in 10,000 (Najarian et al.). There is general acceptance that the risk is considered low enough to justify the procedure. The risk for a person donating the major portion of the liver is estimated to be much higher, perhaps ten times as high. The exact percentage is not known because no national or international registry has accumulated all the donor data to document the risk. However, deaths have occurred, and some have been widely published in the press (Strong). Experience from individual centers indicates that the chance of a postoperative complication that may interfere with the recovery of the liver donor is as high as one in five patients. Some physicians and surgeons have questioned the justification for living donation that could potentially harm the donor. On the other hand, living donations are an important avenue to reduce the organ shortage. Without living donors, many patients would be denied transplantation.

Organ Retrieval and Preservation

After patients are declared dead and consent has been obtained, they are transferred to an operating room where organs and tissues are removed. Local surgeons may remove organs and send them to a transplant center, or often the transplant team travels to the donor hospital to remove and transport the organs. Surgical teams from different centers may be involved, and each team may remove a different organ before returning by air or ground travel (depending on the distance) to its own transplant center. Organ and tissue recovery is a delicate surgical procedure. Transplant staff are careful to prevent visible disfigurement so that usual funeral arrangements for the donor, including an open casket, are possible.

In the operating room, an incision is made on the donor that extends from the sternal notch (breastbone) to the pelvis. The rib cage and abdomen are retracted so the organs can be seen easily, and the organs are examined for damage or disease that may not have been detected by earlier tests. If the organ appears normal, the surgeon begins to carefully dissect, or cut away, the tissue surrounding the organ. The aorta (the blood vessel through which blood flows from the heart to the rest of the body) is then clamped, and a tube is inserted into it. Through that tube a specially prepared, cold solution (4°C) is infused to flush blood out of each organ and lower the organ's temperature. Cold acts as a metabolic brake, reducing the oxygen requirements of the organ to near zero, thereby helping to preserve the organ. If several organs are to be removed, the procedure takes approximately two to three hours. The heart or lungs are removed first, the liver and small bowel next, followed by the pancreas and kidneys. The kidneys are removed together and then separated—the kidneys are preserved and stored separately so that they can be transplanted into two patients.

Each organ is immersed in cold preservation solution and stored in a sterile container, which is surrounded by ice, and transported in an insulated cooler. Because storage times are limited, recipient surgery has to be timed in relation to the donor procedure. When the donor and recipient are at the same transplant center, the surgeries can be done simultaneously so that organs do not have to be cold-stored for long periods. When the ischemic time is shortened, initial organ function is better after transplant.

Various solutions have been developed to preserve organs, including Collins, Euro-Collins, HTK, and UW solutions. Different solutions can be used for different organs removed from the same donor. There are limits to the time that organs can be stored ("cold ischemic time") before permanent cell damage occurs and the organ cannot be used for transplant. Typically, kidneys are transplanted within 24 hours and livers are transplanted within 12 hours. Heart and lung preservation times remain limited to between 4 to 6 hours.

Whereas most organs are flushed and stored in a cold solution for transport, kidneys can be preserved by two methods: cold storage or machine perfusion. Most often, kidneys are immersed in a cold solution and stored in a sterile container (cold storage). With perfusion, the kidney is attached to a machine that periodically flushes a cold solution through the kidneys until they are transplanted. Long-term results show that kidney transplants are equally successful whether they are cold-stored or machine-perfused.

Organ Distribution

Potential recipients are assessed by transplant teams that evaluate each patient's disease to determine if a transplant is needed, and how quickly it is needed. General criteria are that the potential recipient has a disease for which transplantation is good treatment, and that there are no other health issues that would make a transplant too risky. Transplant centers define their own specific criteria for patient acceptance on waiting lists, such as age and rehabilitation potential. Once on the list, each patient should have an equitable chance of receiving an organ, because policy guidelines have been formulated to ensure appropriate and fair distribution of organs.

Several factors may be considered in selecting the recipient once an organ has been donated: blood group; tissue type (for kidneys); body size of donor and recipient; amount of time the patient has been waiting; proximity to the transplant center; and the patient's current health and "status rating." When their names are added to waiting lists, potential recipients are assigned a status code rating that describes their medical condition. For example, a rating of "1" is given to a patient whose health is stable and who is waiting at home. The highest number, "4," is given to a patient who is on life support in an intensive care unit and may die within days without a transplant. This number or rating changes as the patient's health changes so that the most urgent patients can receive transplants first.

When an organ becomes available, the most suitable recipient on the waiting list is identified through computer and telephone communication between transplant centers and organ procurement agencies. The role of the agencies is to facilitate the procurement of organs after a donor is identified, and assist in the distribution of organs to appropriate recipients according to allocation guidelines. In some countries, such as Canada and the United Kingdom, the agencies are run and funded by governments. In the United States, they are independent organizations that act as arms of the transplant centers. They cover specific geographic regions and charge the transplant centers for the costs they incur. The transplant centers pass on the costs to the recipients' medical insurance. Transplant centers maintain waiting lists of potential recipients for matching with donors in their own region. National waiting lists are also maintained for sharing donor organs between regions, depending on the priority of sick patients. In the United States, the United Network for Organ Sharing (UNOS) maintains a national, computerized list of potential recipients.

In Scandinavia (Norway, Sweden, Finland, and Denmark), Scandiatransplant organizes the exchange of transplant organs. Exchange rules have evolved over time, but transplant organs generally cross international boundaries easily. The UK Transplant Service serves all of Britain and is linked with other agencies in western Europe. In Europe, organ-matching agencies in Italy, France, Spain, and other countries arrange organ distribution according to agreed-upon rules. Eurotransplant, located in the Netherlands, registers potential recipients and distributes organs among the Netherlands, Belgium, Luxembourg, Germany, and Austria.

Rejection and Immunosuppression

After the transplant, the body's attempt to reject the organ is normal, since the function of the immune system is to recognize and attack foreign substances, including a transplanted organ. There are three types of organ rejection: hyperacute rejection; acute rejection; and chronic, long-term rejection. Hyperacute rejection occurs when the recipient's immune system, pre-sensitized by antibodies, immediately recognizes the transplant as foreign. The organ is rejected within minutes to hours. This type of rejection can be avoided if "crossmatch" tests using the donor's and the recipient's blood are performed before the transplant. Although hyperacute rejection can be avoided, acute or chronic rejection may still occur. Acute rejection is characterized by rapid onset, usually several days after the transplant. The closer the match between donor and recipient tissue, the less likely an acute rejection episode will occur. This is particularly important in kidney transplantation. Chronic rejection develops more slowly, occurring many months or years after transplantation, and it gradually compromises function of the graft.

Transplant patients take drugs to suppress the immune response and prevent rejection. Drug therapy (immunosuppression) is usually started during the transplant surgery, and continues after the transplant. Larger doses of drugs are given in the first few weeks after transplantation, when the risk of acute rejection is the greatest. The doses are tapered over time, and most patients need relatively small doses years after their transplant. If acute rejection occurs, the dosage of the patient's regular antirejection drugs may be increased temporarily. Alternatively, other immunosuppressants, such as OKT3, antilymphocyte globulin, or antithymocyte globulin, may be added temporarily to reverse rejection episodes. New immunosuppressants continue to be investigated in clinical trials and animal studies to assess their effectiveness and side effects.

The antirejection drug cyclosporine was first used in transplant patients in 1978. The first clinical studies showed improved patient and organ survival. Until the 1990s, cyclosporine was the mainstay of immunosuppression. Another drug, FK506 (tacrolimus) is a valuable alternative to cyclosporine. Although it is a completely different molecule from cyclosporine, it has a similar effect on the immune system. Either cyclosporine or FK506 is used as baseline immunosuppression in most organ recipients. Prednisone (a steroid) is commonly used as well, but much smaller doses are required because of the effectiveness of cyclosporine and FK506. There are other immunosuppressive drugs that may be added, depending upon specific patient characteristics, the organ transplanted, and the doses of the other drugs being given. Immunosuppression protocols vary among transplant centers, but, as a general principle, drug doses are reduced over time to low levels to minimize the risk of side effects.

Immunosuppression requires a careful balance so that organ rejection is prevented and side effects are minimized. All immunosuppressive drugs have some side effects. Because they affect the body's immune response, white blood cells may be less effective in fighting bacteria and infections. Infections may occur more frequently and be more difficult to treat. The more severe effects may include impaired kidney function, hypertension, or the development of cancer. In some patients, adverse side effects can be minimized or prevented when a combination of drugs is used and a large amount of a single drug is avoided. When large amounts of a

TABLE 1

drug are given, negative side effects, such as impaired kidney function from cyclosporine or weight gain and hypertension from prednisone, may be more likely to occur.

Success of Transplantation

Table 1 shows the survival rates after various organ transplants—success is highest with the kidney and lowest with the bowel. Usually, both patient and graft survival rates are measured. Patient survival rates may be higher because patients may survive even though the transplant fails. This is true especially for kidney recipients who can return to kidney dialysis machines if the graft fails, and pancreas or islet-cell transplant patients, who may resume insulin injections. For other organs, such as the liver, the patient can have a repeat transplant if the first graft fails, and thus patient survival is higher than graft survival. Success rates for a second or third transplant, if a patient is fortunate enough to receive one, are lower, however. When a patient has rejected a kidney transplant, it is often more difficult to find a "match" for a second kidney. The patient's immune system has memory cells and antibodies that persist and would aggressively attack a second transplant if it shared tissue proteins with the first graft.

While the most objective evidence of the success of transplantation is survival, more and more emphasis is appropriately being given to the patient's quality of life. With increasing numbers of recipients entering the second decade after their transplant, long-term goals should be aimed at restoring patients to their pre-illness level of health and social functioning. A major transplant study in the United States reported that 80 to 90 percent of kidney, heart, liver, and pancreas recipients are physically active (Evans). This study also asked transplant recipients to rate their quality of life—their "life satisfaction," "well-being," and "psychological affect." The average scores reported by kidney, heart, liver, and pancreas recipients are similar to scores reported by the general public, indicating a comparable quality of life (see Table 2). Many other studies have also shown that the majority of transplant recipients enjoy a good quality of life and complete rehabilitation (Pinson et al.; Bravata et al.; Ostrowski et al.). Transplantation produces improvement in their physical health, social functioning, and ability to perform daily activities. The sense of wellbeing and satisfaction with life of most recipients is similar to the general public—they are able to return to work, and they enjoy their families without any restriction on their physical activity. Before modern immunosuppression and all of the advances that have occurred in transplantation since the 1980s, recipients led precarious existences. Today, they are encouraged to live lives that are as close to normal as possible. Indeed, every second year the Transplant Olympic Games are held, and hundreds of organ recipients from around the globe compete at a high level.

Transplant recipients are expected to follow good health habits, including regular exercise and appropriate attention to diet and weight. Transplant patients take immunosuppressive drugs to prevent organ rejection for the rest of their lives, although there are occasional patients who have been able to be weaned completely from their immunosuppressive drugs. However, lack of compliance regarding medication is one of the causes for graft loss in the long term. Despite this need for continued medication, patients report remarkable life satisfaction and well-being.

Transplantation Costs and Reimbursement

Transplantation is expensive, as are many other medical therapies and surgical treatments. In view of limited healthcare resources, society must determine the extent of its willingness to fund transplantation. An important consideration, however, is the number of years and quality of life obtained from transplantation. Numerous studies have documented the cost savings of kidney transplantation when compared to its alternative, dialysis. It is widely recognized that transplantation is the most cost-effective treatment for end-stage kidney disease. Although transplantation initially costs more than dialysis, the costs are fully recouped within three years after surgery (Loubeau et al.). Other studies report that liver and heart transplantation are also cost effective. The cost effectiveness of lung transplantation is limited by its lower survival rates and high costs (Anyanwu et al.).

In the United States, funding through Medicare and Medicaid has provided coverage for many kinds of transplants at approved transplant centers. Approved centers must have performed at least a specified number of transplants with a certain level of success to receive these funds. Medicare has been the primary provider of kidney transplant coverage, although coverage has also been provided for certain patients requiring bone marrow, cornea, heart, or liver transplants. Medicaid coverage has varied from state to state, but usually bone marrow, cornea, kidney, and liver transplants have been covered. Heart transplants have been widely available, but coverage for heart-lung, lung, and pancreas transplants has been limited. Most states have covered the cost of organ retrieval, and every state has paid for antirejection drugs for the first year after the transplant. During the 1990s, drug coverage increased, and new transplant patients now have coverage for three years.

In the United States, private insurance and the patient's own financial resources are often necessary. Even when public and private insurance covers transplantation, patients may only be partially reimbursed. The total costs for organ retrieval, surgery, and follow-up healthcare may not be reimbursed, so the patient may have substantial medical bills to pay.

In Canada, provincial health programs cover the costs of organ retrieval, transplant surgery, and medical care. The major cost for recipients is transportation to the transplant center, which may be located in another province. The antirejection drug cyclosporine is paid for for all transplant recipients by a government-sponsored program. Costs are paid as long as patients take the drug, regardless of the socioeconomic status of patients. If patients take other immunosuppressive drugs, these costs may be completely or partially reimbursed by work benefits, private insurance, or special plans for patients with limited finances. Long-term follow-up care is covered by the patient's provincial healthcare plan.

TABLE 2

In Europe, according to European Economic Community (EEC) agreements, patients may be eligible for transplant in other countries, with their own governments paying the costs. Patients from countries outside the EEC may also receive transplants, but they have to pay the costs themselves. As more programs have developed, however, fewer patients need to travel to other countries for their transplants.

Expanding the Pool of Cadaveric Organs

Given the success of transplants, and the prevalence of diseases that result in organ failure, more patients are being referred for transplant surgery. The inadequate supply of organs, however, limits the number of transplants, so waiting lists continue to grow (see Figure 1). Transplant programs, therefore, continue to expand their criteria for acceptable organs and are trying innovative ways to procure more organs. One prime example is the use of organs from donors who are older than ideal. As a person ages, hardening of the arteries occurs to greater or lesser degrees in almost everyone, accompanied by deterioration in the function of various organs. Less-than-perfect donor organs have been used, and studies have shown that they can function adequately when certain criteria are met (Wall et al.; Loebe et al.). For example, both kidneys from an older cadaver donor can be transplanted into one patient, and this can provide the recipient with an adequate mass of functioning kidney tissue. The liver is affected by aging much less than other organs, and livers from donors in their seventies, and even eighties, can be successfully transplanted when other variables are satisfactory. For unknown reasons, the blood vessels that feed the liver are rarely affected by hardening of the arteries. Unsuitable hearts, which would not usually be used, have been transplanted as "biological bridges" in urgent situations until a suitable heart has been found.

FIGURE 1

The liver from a cadaver donor can be split in two for transplant into two suitably sized patients. The procedures are technically complex, however, and there is a greater risk of complications. The applicability of this procedure is also limited by the need for multiple surgical teams operating simultaneously. Additional constraints are those imposed by limited preservation times, especially if the intended recipients are located in different transplant centers. Nevertheless, good results are obtainable. The practice of domino transplantation allows a recipient's healthy organ to be removed and transplanted into another patient. For example, when a patient needs a double-lung transplant, he or she may receive a combined heart-lung transplant because it is easier technically to include the donor heart with the transplant as opposed to just the lungs. In this situation, the healthy heart of the recipient can be transplanted into another recipient rather than being discarded. So the recipient of the lungs is both a donor (heart) and a recipient (lungs and heart).

Transplant specialists face dilemmas when less-than-optimal donor organs are offered for transplantation. Obviously, they want the best outcome for their recipients, but the lack of donor organs may force them to make compromises. And while doctors must do what they can to make effective use of donated organs, society must also do its part to maximize organ donation rates. Even if organs were donated from every potential cadaveric donor, however, the supply would still not satisfy the need. Thus, other alternatives such as mechanical hearts and animals as sources for organs have to be explored.

calvin r. stiller (1995)

revised by calvin r. stiller

william j. wall

SEE ALSO: Artificial Hearts and Cardiac Assist Devices; Body: Cultural and Religious Perspectives; Cybernetics; Death, Definition and Determination of; Dialysis, Kidney; Healthcare Resources, Allocation of; Informed Consent; Life, Quality of; Organ and Tissue Procurement; Organ Transplants, Socio-cultural Aspects of; Technology

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