Transplantation
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Organ transplantation is the moving of an organ from one body to another or from a donor site on the patient’s own body, for the purpose of replacing the recipient’s damaged or absent organ. The emerging field of regenerative medicine is allowing scientists and engineers to create organs to be re-grown from the patient’s own cells (stem cells, or cells extracted from the failing organs). Organs and/or tissues that are transplanted within the same person’s body are called autografts. Transplants that are recently performed between two subjects of the same species are called allografts. Allografts can either be from a living or cadaveric source.
Organs that can be transplanted are the heart, kidneys, eyes, liver, lungs, pancreas, intestine, and thymus. Tissues include bones, tendons (both referred to as musculoskeletal grafts), cornea, skin, heart valves, and veins. Worldwide, the kidneys are the most commonly transplanted organs, followed closely by the liver and then the heart. The cornea and musculoskeletal grafts are the most commonly transplanted tissues; these outnumber organ transplants by more than tenfold. Organ donors may be living, or brain dead. Tissue may be recovered from donors who are cardiac dead – up to 24 hours past the cessation of heartbeat. Unlike organs, most tissues (with the exception of corneas) can be preserved and stored for up to five years, meaning they can be “banked”. Transplantation raises a number of bioethical issues, including the definition of death, when and how consent should be given for an organ to be transplanted and payment for organs for transplantation. Other ethical issues include transplantation tourism and more broadly the socio-economic context in which organ harvesting or transplantation may occur. A particular problem is organ trafficking. Some organs, such as the brain, cannot yet be transplanted in humans. In the United States of America, tissue transplants are regulated by the U.S. Food and Drug Administration (FDA) which sets strict regulations on the safety of the transplants, primarily aimed at the prevention of the spread of communicable disease. Regulations include criteria for donor screening and testing as well as strict regulations on the processing and distribution of tissue grafts. Organ transplants are not regulated by the FDA. Transplantation medicine is one of the most challenging and complex areas of modern medicine. Some of the key areas for medical management are the problems of transplant rejection, during which the body has an immune response to the transplanted organ, possibly leading to transplant failure and the need to immediately remove the organ from the recipient. When possible, transplant rejection can be reduced through serotyping to determine the most appropriate donor-recipient match and through the use of immunosuppressant drugs. Types of transplant Autograft Transplant of tissue to the same person. Sometimes this is done with surplus tissue, or tissue that can regenerate, or tissues more desperately needed elsewhere (examples include skin grafts, vein extraction for CABG, etc.) Sometimes an autograft is done to remove the tissue and then treat it or the person, before returning it (examples include stem cell autograft and storing blood in advance of surgery). In a rotationplasty a distal joint is used to replace a more proximal one, typically a foot and ankle joint is used to replace a knee joint. The a patient’s foot is severed and reversed, the knee removed, and the tibia joined with the femur. Allograft and allotransplantation An allograft is a transplant of an organ or tissue between two genetically non-identical members of the same species. Most human tissue and organ transplants are allografts. Due to the genetic difference between the organ and the recipient, the recipient’s immune system will identify the organ as foreign and attempt to destroy it, causing transplant rejection. Isograft A subset of allografts in which organs or tissues are transplanted from a donor to a genetically identical recipient (such as an identical twin). Isografts are differentiated from other types of transplants because while they are anatomically identical to allografts, they do not trigger an immune response. Xenograft and xenotransplantation A transplant of organs or tissue from one species to another. An example is porcine heart valve transplant, which is quite common and successful. Another example is attempted piscine-primate (fish to non-human primate) transplant of islet (i.e. pancreatic or insular tissue) tissue. The latter research study was intended to pave the way for potential human use, if successful. However, xenotransplantion is often an extremely dangerous type of transplant because of the increased risk of non-compatibility, rejection, and disease carried in the tissue. Split transplants Sometimes a deceased-donor organ, usually a liver, may be divided between two recipients, especially an adult and a child. This is not usually a preferred option because the transplantation of a whole organ is more successful. Domino transplants In patients with cystic fibrosis, where both lungs need to be replaced, it is a technically easier operation with a higher rate of success to replace both the heart and lungs of the recipient with those of the donor. As the recipient’s original heart is usually healthy, it can then be transplanted into a second recipient in need of a heart transplant. Another example of this situation occurs with a special form of liver transplant in which the recipient suffers from familial amyloidotic polyneuropathy, a disease where the liver slowly produces a protein that damages other organs. The recipient’s liver can then be transplanted into an older patient for whom the effects of the disease will not necessarily contribute significantly to mortality. This term also refers to a series of living donor transplants in which one donor donates to the highest recipient on the waiting list and the transplant center utilizes that donation to facilitate multiple transplants. These other transplants are otherwise impossible due to blood type or antibody barriers to transplantation. The “Good Samaritan” kidney is transplanted into one of the other recipients, whose donor in turn donates his or her kidney to an unrelated recipient. Depending on the patients on the waiting list, this has sometimes been repeated for up to six pairs, with the final donor donating to the patient at the top of the list. This method allows all organ recipients to get a transplant even if their living donor is not a match to them. This further benefits patients below any of these recipients on waiting lists, as they move closer to the top of the list for a deceased-donor organ. Johns Hopkins Medical Center in Baltimore and Northwestern University’s Northwestern Memorial Hospital have received significant attention for pioneering transplants of this kind. In February 2012 the last link in a record sixty-person domino chain of thirty kidney transplants was completed. Major organs and tissues transplanted Thoracic organs
Organ donors may be living, or brain dead. Brain dead means the donor must have received an injury (either traumatic or pathological) to the part of the brain that controls heartbeat and breathing. Breathing is maintained via artificial sources, which, in turn, maintains heartbeat. Once brain death has been declared the person can be considered for organ donation. Criteria for brain death vary. Because less than 3% of all deaths in the U.S. are the result of brain death, the overwhelming majority of deaths are ineligible for organ donation, resulting in severe shortages. Tissue may be recovered from donors who are cardiac dead. That is, their breathing and heartbeat has ceased. They are referred to as cadaveric donors. In general, tissues may be recovered from donors up to 24 hours past the cessation of heartbeat. In contrast to organs, most tissues (with the exception of corneas) can be preserved and stored for up to five years, meaning they can be “banked.” Also, more than 60 grafts may be obtained from a single tissue donor. Because of these three factors—the ability to recover from a non-heart beating donor, the ability to bank tissue, and the number of grafts available from each donor—tissue transplants are much more common than organ transplants. The American Association of Tissue Banks estimates that more than one million tissue transplants take place in the United States each year. Living In “living donors”, the donor remains alive and donates a renewable tissue, cell, or fluid (e.g. blood, skin), or donates an organ or part of an organ in which the remaining organ can regenerate or take on the workload of the rest of the organ (primarily single kidney donation, partial donation of liver, small bowel). Regenerative medicine may one day allow for laboratory-grown organs, using patient’s own cells via stem cells, or healthy cells extracted from the failing organs. Deceased Deceased (formerly cadaveric) are donors who have been declared brain-dead and whose organs are kept viable by ventilators or other mechanical mechanisms until they can be excised for transplantation. Apart from brain-stem dead donors, who have formed the majority of deceased donors for the last twenty years, there is increasing use of Donation after Cardiac Death Donors (formerly non-heart beating donors) to increase the potential pool of donors as demand for transplants continues to grow. These organs have inferior outcomes to organs from a brain-dead donor; however given the scarcity of suitable organs and the number of people who die waiting, any potentially suitable organ must be considered. Reasons for donation and ethical issues Living related donors Living related donors donate to family members or friends in whom they have an emotional investment. The risk of surgery is offset by the psychological benefit of not losing someone related to them, or not seeing them suffer the ill effects of waiting on a list. Paired exchange A “paired-exchange” is a technique of matching willing living donors to compatible recipients using serotyping. For example a spouse may be willing to donate a kidney to their partner but cannot since there is not a biological match. The willing spouse’s kidney is donated to a matching recipient who also has an incompatible but willing spouse. The second donor must match the first recipient to complete the pair exchange. Typically the surgeries are scheduled simultaneously in case one of the donors decides to back out and the couples are kept anonymous from each other until after the transplant. Paired exchange programs were popularized in the New England Journal of Medicine article “Ethics of a paired-kidney-exchange program” in 1997 by L.F. Ross. It was also proposed by Felix T. Rapport in 1986 as part of his initial proposals for live-donor transplants “The case for a living emotionally related international kidney donor exchange registry” in Transplant Proceedings. A paired exchange is the simplest case of a much larger exchange registry program where willing donors are matched with any number of compatible recipients. Transplant exchange programs have been suggested as early as 1970: “A cooperative kidney typing and exchange program.” The first pair exchange transplant in the U.S. was in 2001 at Johns Hopkins Hospital. The first complex multihospital kidney exchange involving 12 patients was performed in February 2009 by The Johns Hopkins Hospital, Barnes-Jewish Hospital in St. Louis and Integris Baptist Medical Center in Oklahoma City. Another 12-patient multihospital kidney exchange was performed four weeks later by Saint Barnabas Medical Center in Livingston, New Jersey,Newark Beth Israel Medical Center and New York-Presbyterian Hospital. Surgical teams led by Johns Hopkins continue to pioneer in this field by having more complex chain of exchange such as eight-way multihospital kidney exchange. In December 2009, a 13 organ 13 recipient matched kidney exchange took place, coordinated through Georgetown University Hospital and Washington Hospital Center, Washington DC. Paired-donor exchange, led by work in the New England Program for Kidney Exchange as well as at Johns Hopkins University and the Ohio OPOs may more efficiently allocate organs and lead to more transplants. Good Samaritan Good Samaritan or “altruistic” donation is giving a donation to someone not well-known to the donor. Some people choose to do this out of a need to donate. Some donate to the next person on the list; others use some method of choosing a recipient based on criteria important to them. Web sites are being developed that facilitate such donation. It has been featured in recent television journalism that over half of the members of the Jesus Christians, anAustralian religious group, have donated kidneys in such a fashion. Compensated donation In compensated donation, donors get money or other compensation in exchange for their organs. This practice is common in some parts of the world, whether legal or not, and is one of the many factors driving medical tourism. In the United States, The National Organ Transplant Act of 1984 made organ sales illegal. In the United Kingdom, the Human Organ Transplants Act 1989 first made organ sales illegal, and has been superseded by the Human Tissue Act 2004. In 2007, two major European conferences recommended against the sale of organs. Recent development of web sites and personal advertisements for organs among listed candidates has raised the stakes when it comes to the selling of organs, and have also sparked significant ethical debates over directed donation, “good-Samaritan” donation, and the current U.S. organ allocation policy. Bioethicist Jacob M. Appel has argued that organ solicitation on billboards and the internet may actually increase the overall supply of organs. Two books, Kidney for Sale By Owner by Mark Cherry (Georgetown University Press, 2005); and Stakes and Kidneys: Why markets in human body parts are morally imperative by James Stacey Taylor: (Ashgate Press, 2005); advocate using markets to increase the supply of organs available for transplantation. In a 2004 journal article Economist Alex Tabarrok argues that allowing organ sales, and elimination of organ donor lists will increase supply, lower costs and diminish social anxiety towards organ markets. Iran has had a legal market for kidneys since 1988, and the market price is of the order of US$1,200 for the recipient.The Economistand the Ayn Rand Instituteapprove and advocate a legal market elsewhere. They argued that if 0.06% of Americans between 19 and 65 were to sell one kidney, the national waiting list would disappear (which, the Economist wrote, happened in Iran). The Economist argued that donating kidneys is no more risky than surrogate motherhood, which can be done legally for pay in most countries. In Pakistan, 40 percent to 50 percent of the residents of some villages have only one kidney because they have sold the other for a transplant into a wealthy person, probably from another country, said Dr. Farhat Moazam of Pakistan, at a World Health Organization conference. Pakistani donors are offered $2,500 for a kidney but receive only about half of that because middlemen take so much. In Chennai, southern India, poor fishermen and their families sold kidneys after their livelihoods were destroyed by the Indian Ocean tsunami on December 26, 2004. About 100 people, mostly women, sold their kidneys for 40,000–60,000 rupees ($900–$1,350). Thilakavathy Agatheesh, 30, who sold a kidney in May 2005 for 40,000 rupees said, “I used to earn some money selling fish but now the post-surgery stomach cramps prevent me from going to work.” Most kidney sellers say that selling their kidney was a mistake. In Cyprus in 2010 police closed a fertility clinic under charges of trafficking in human eggs. The Petra Clinic, as it was known locally, imported women from Ukraine and Russia for egg harvesting and sold the genetic material to foreign fertility tourists. This sort of reproductive trafficking violates laws in the European Union. In 2010 thePulitzer Center on Crisis Reporting and the magazine Fast Company explored illicit fertility networks in Spain, the United States and Israel. Allocation of donated organs The overwhelming majority of deceased-donor organs in the United States are allocated by federal contract to theOrgan Procurement and Transplantation Network (OPTN), held since it was created by the Organ Transplant Act of 1984 by the United Network for Organ Sharing or UNOS. (UNOS does not handle donor cornea tissue; corneal donor tissue is usually handled by various eye banks.) UNOS allocates organs based on the method considered most fair by the scientific leadership in the field. For kidneys, for instance, that is by waiting time; for livers, it is by MELD (Model of End-Stage Liver Disease), an empirical score based on lab values indicative of the sickness of the patient from liver disease. Experiencing somewhat increased popularity, but still very rare, is directed or targeted donation, in which the family of a deceased donor (often honoring the wishes of the deceased) requests an organ be given to a specific person. If medically suitable, the allocation system is subverted, and the organ is given to that person. In the United States, there are various lengths of waiting due to the different availabilities of organs in different UNOS regions. In other countries such as the UK, only medical factors and the position on the waiting list can affect who receives the organ. If this is not the desired person, it is noted that this puts them higher on the list. One of the more publicized cases of this type was the 1994 Chester and Patti Szuber transplant. This was the first time that a parent had received a heart donated by one of their own children. Although the decision to accept the heart from their recently killed child was not an easy decision, the Szuber family agreed that giving Patti’s heart to her father would have been something that she would have wanted. Access to organ transplantation is one reason for the growth of medical tourism. Forced donation There have been various accusations that certain authorities are harvesting organs from those the authorities deem undesirable, such as prison populations. The World Medical Association stated. that individuals in detention are not in the position to give free consent to donate their organs Illegal dissection of corpses is a form of body-snatching and may have taken place to obtain allografts. According to the Chinese Deputy Minister of Health, Huang Jiefu, approximately 95% of all organs used for transplantation are from executed prisoners. The lack of public organ donation program in China is used as a justification for this practice. However reports in Chinese media raised concerns if executed criminals are the only source for organs used in transplants. In October 2007, bowing to international pressure, the Chinese Medical Association agreed on a moratorium of commercial organ harvesting from condemned prisoners, but did not specify a deadline. China agreed to restrict transplantations from donors to their immediate relatives. People in other parts of the world are responding to this availability of organs, and a number of individuals (including US and Japanese citizens) have elected to travel to China or India as medical tourists to receive organ transplants which may have been sourced in what might be considered elsewhere to be unethical ways (see later). Organ transplantation in different countries Demographics Despite efforts of international transplantation societies, it is not possible to access an accurate source on the number, rates and outcomes of all forms of transplantation globally; the best that we can achieve is estimations. This is not a sound basis for the future and thus one of the crucial strategies for the Global Alliance in Transplantation is to foster the collection and analysis of global data.
In addition to the citizens waiting for organ transplants in the US and other developed nations, there are long waiting lists in the rest of the world. More than 2 million people need organ transplants in China, 50,000 waiting in Latin America (90% of which are waiting for kidneys), as well as thousands more in the less documented continent ofAfrica. Donor bases vary in developing nations. Traditionally, Muslims believe body desecration in life or death to be forbidden, and thus many reject organ transplant. However most Muslim authorities nowadays accept the practice if another life will be saved. In Latin America the donor rate is 40–100 per million per year, similar to that of developed countries. However, in Uruguay, Cuba, and Chile, 90% of organ transplants came from cadaveric donors. Cadaveric donors represent 35% of donors in Saudi Arabia. There is continuous effort to increase the utilization of cadaveric donors in Asia, however the popularity of living, single kidney donors in India yields India a cadaveric donor prevalence of less than 1 pmp. Organ transplantation in China has taken place since the 1960s, and China has one of the largest transplant programmes in the world, peaking at over 13,000 transplants a year by 2004. Organ donation, however, is against Chinese tradition and culture, and involuntary organ donation is illegal under Chinese law. China‘s transplant programme attracted the attention of international news media in the 1990s due to ethical concerns about the organsand tissue removed from the corpses of executed criminals being commercially traded for transplants. With regard to organ transplantation in Israel, there is a severe organ shortage due to religious objections by some rabbis who oppose all organ donations and others who advocate that a rabbi participate in all decision making regarding a particular donor. One third of all heart transplants performed on Israelis are done in the Peoples’ Republic of China; others are done in Europe. Dr. Jacob Lavee, head of the heart-transplant unit, Sheba Medical Center, Tel Aviv, believes that “transplant tourism” is unethical and Israeli insurers should not pay for it. The organization HODS (Halachic Organ Donor Society) is working to increase knowledge and participation in organ donation among Jews throughout the world. Transplantation rates also differ based on race, sex, and income. A study done with patients beginning long term dialysis showed that the sociodemographic barriers to renal transplantation present themselves even before patients are on the transplant list. For example, different groups express definite interest and complete pretransplant workup at different rates. Previous efforts to create fair transplantation policies had focused on patients currently on the transplantation waiting list. Comparative costs One of the driving forces for illegal organ trafficking and for “transplantation tourism” is the price differences for organs and transplant surgeries in different areas of the world. According to the New England Journal of Medicine, a human kidney can be purchased in Manila for $1000–$2000, but in urban Latin America a kidney may cost more than $10,000. Kidneys in South Africa have sold for as high as $20,000. Price disparities based on donor race are a driving force of attractive organ sales in South Africa, as well as in other parts of the world. In China, a kidney transplant operation runs for around $70,000, liver for $160,000, and heart for $120,000 .Although these prices are still unattainable to the poor, compared to the fees of the United States, where a kidney transplant may demand $100,000, a liver $250,000, and a heart $860,000, Chinese prices have made China a major provider of organs and transplantation surgeries to other countries. In India, a kidney transplant operation runs for around as low as $5000. Safety Compensation for donors also increases the risk of introducing diseased organs to recipients because these donors often yield from poorer populations unable to receive health care regularly and organ dealers may evade disease screening processes. The majority of such deals include one major payment and no follow up care for the donor. Some cases argue that there is a possibility of 1:18 to acquire HIV from such transplants. In November 2007, the CDC reported the first-ever case of HIV and Hepatitis C being simultaneously transferred through an organ transplant. The donor was a 38-year-old male, considered “high-risk” by donation organizations, and his organs transmitted HIV and Hepatitis C to four organ recipients, none of whom had been told he was “high-risk.” Experts say that the reason the diseases did not show up on screening tests is probably because they were contracted within three weeks before the donor’s death, so antibodies would not have existed in high enough numbers to detect. The crisis has caused many to call for more sensitive screening tests, which could pick up antibodies sooner. Currently, the screens cannot pick up on the small number of antibodies produced in HIV infections within the last 90 days or Hepatitis C infections within the last 18–21 days before a donation is made. NAT (nucleic acid testing) is now being done by many organ procurement organizations and is able to detect antibodies for HIV and Hepatitis C within seven to ten days of exposure to the virus. Organ transplant laws Both developing and developed countries have forged various policies to try to increase the safety and availability of organ transplants to their citizens. Brazil, France, Italy, Poland and Spain have ruled all adults potential donors with the “opting out” policy, unless they attain cards specifying not to be. However, whilst potential recipients in developing countries may mirror their more developed counterparts in desperation, potential donors in developing countries do not. The Indian government has had difficulty tracking the flourishing organ black market in their country and have yet to officially condemn it. Other countries victimized by illegal organ trade have implemented legislative reactions. Moldova has made international adoption illegal in fear of organ traffickers. China has made selling of organs illegal as of July 2006 and claims that all prisoner organ donors have filed consent. However, doctors in other countries, such as the United Kingdom, have accused China of abusing its high capital punishment rate. Despite these efforts, illegal organ trafficking continues to thrive and can be attributed to corruption in healthcare systems, which has been traced as high up as the doctors themselves in China, Ukraine, and India, and the blind eye economically strained governments and health care programs must sometimes turn to organ trafficking. Some organs are also shipped to Uganda and the Netherlands. This was a main product in the triangular trade in 1934. Starting on May 1, 2007, doctors involved in commercial trade of organs will face fines and suspensions in China. Only a few certified hospitals will be allowed to perform organ transplants in order to curb illegal transplants. Harvesting organs without donor’s consent was also deemed a crime. On June 27, 2008, Indonesian, Sulaiman Damanik, 26, pleaded guilty in Singapore court for sale of his kidney to CK Tang’s executive chair, Mr Tang Wee Sung, 55, for 150 million rupiah (S$ 22,200). The Transplant Ethics Committee must approve living donor kidney transplants. Organ trading is banned in Singapore and in many other countries to prevent the exploitation of “poor and socially disadvantaged donors who are unable to make informed choices and suffer potential medical risks.” Toni, 27, the other accused, donated a kidney to an Indonesian patient in March, alleging he was the patient’s adopted son, and was paid 186 million rupiah (20,200 US). Upon sentence, both would suffer each, 12 months in jail or 10,000 Singapore dollars (7,600 US) fine. In an article appearing in the Econ Journal Watch, April 2004. Economist Alex Tabarrok examined the impact of direct consent laws on transplant organ availability. Tabarrok found that social pressures resisting the use of transplant organs decreased over time as the opportunity of individual decisions increased. Tabarrok concluded his study s |
