Solid organ transplantation has become the first line of treatment for a growing number of life-threatening pediatric illnesses. With improved survival, research into the long-term outcome of transplant recipients has become important to clinicians. Adherence to medical instructions remains a challenge, particularly in the adolescent population. New immunosuppressant approaches promise to expand organ transplantation in additional directions. Extension of transplantation into replacement of organs such as faces and hands raises complex ethical issues.
The field of solid organ transplantation has grown enormously since 1983, when the widespread availability of effective immunosuppression made what had been surgically possible a viable clinical reality. In the United States, 23,846 solid organ transplants were performed between January and October 2009. As of January 18, 2010, 105,239 people were listed as awaiting transplants in the United States. This article addresses the types of transplants now commonly performed for children, assessment and support of children and families undergoing transplantation, the long-term impact of organ transplantation on children, and new developing areas in organ transplantation.
Pediatric solid organ transplants are still relatively rare. Fewer than 8% of the recipients of solid organ transplants in the United States annually are younger than 18 years according to the 2008 report from the OPTN/SRTR. The annual number of pediatric solid organ transplants has been approximately 2000 children since 1998. Although the wait for an organ that is a match for size and blood type may be longer for young children, the 5-year survival is similar in children and young adults ( Tables 1 and 2 ).
| Organ | Age (y) | |||
|---|---|---|---|---|
| <1 | 1–5 | 6–10 | 11–17 | |
| Heart | 82.8% | 85.9% | 86.8% | 89.7% |
| Liver | 81.1% | 78.1% | 84.4% | 87.4% |
| Kidney | a | 92.7% | 94.7% | 94.1% |
| Intestine | 63.8% | 75.6% | 66.7% | 80.0% |
| Lung | a | a | 88.0% | 78.0% |
a Graft survival not computed because the number of subjects was <10. One-year survival rate is based on 2002–2004 transplants, 3-year survival rates were based on 1999–2002 transplants, 5-year survival rates were based on 1997–2000 transplants.
| Organ | Age (y) | |||
|---|---|---|---|---|
| <1 | 1–5 | 6–10 | 11–17 | |
| Heart | 68.0% | 71.1% | 75.1% | 67.8% |
| Liver | 66.9% | 75.31% | 67.0% | 64.2% |
| Kidney | 100% | 84.2% | 82.2% | a |
| Intestine | 30.8% | 34.7% | 69.2% | a |
| Lung | a | a | 40.7% | 34.6% |
a Graft survival not computed because the number of subjects was <10. One-year survival rate is based on 2002–2004 transplants, 3-year survival rates were based on 1999–2002 transplants, 5-year survival rates were based on 1997–2000 transplants.
Immunosuppression is the critical element in survival of most solid organ transplant recipients. Organs vary as to their levels of immune activity, and subsequently some require more exact matching with the donor and more or different types of immunosuppression. Kidney transplants proved to be feasible in identical twins (for whom immunosuppression was not needed) as early as the 1950s. In the 1960s, non-twin kidney transplants were successful using a combination of azathioprine and prednisone. However, even with immunosuppression, liver transplants almost always resulted in rejection until the introduction of cyclosporine in 1983. Since then, tacrolimus and sirolimus have added options for organ transplantation immunosuppression, and have led to decreased use of prednisone, azathioprine, and cyclosporine. However, posttransplant lymphoproliferative disorder (PTLD), nephrotoxicity, and de novo autoimmune hepatitis remain possible complications of these medications, in addition to the usual risks for decreased immune function. The growth problems associated with chronic steroids have led to attempts to reduce or remove it as a component in immunosuppression regimens for pediatric recipients.
Kidney
Kidney transplants were the earliest of the solid organ transplants to be successful, and they continue to have the best long-term survival. Today the 5-year survival rate for pediatric kidney transplants is more than 90%. Kidney transplantation has several advantages over other solid organ transplantations.
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First, kidney transplantation has a mechanical alternative, dialysis, which can keep a person alive while awaiting a matched organ. Hemodialysis requires visits to an outpatient center three times a week, for hours at a time, and peritoneal dialysis requires connection to an elaborate, sterile set of equipment in the home for 10 hours a night. Patients undergoing dialysis must still watch their salt intake, and the intermittent nature of the dialysis cannot replicate the constant detoxification of a working kidney. Therefore, although both types of dialysis have risks, and impact a patient’s work and social life, dialysis is the reason that, with kidney transplantation, graft failure is not usually equivalent to recipient death.
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Second, kidneys are paired organs, and humans can generally function well with just one, which means that living-related kidney donation has been possible. Using relatives as donors allows better immunologic matching, and therefore decreased risk for rejection. Living-related kidney donation also means the donated organ is taken from a healthy person, and is available when the recipient needs it, not when a matched cadaver is found. Although kidney donation is a major surgical procedure, the risk to the donor is relatively small.
Additionally, because kidneys are paired organs, two recipients can receive organs from one cadaver donor, which has helped to decrease the waiting list relative to other types of solid organ transplants. Anything that decreases the wait time improves the outcome of surgery because it allows the recipient to be healthier at transplantation.
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Third, kidneys are less immune active than some other organs. Although matching of organs by blood type (A, B, AB, or O) and Rh factor (negative or positive) is important, the more-specific HLA typing used for liver and heart transplants seems to be less important in graft rejection for kidney transplants. The difference in 10-year deceased donor kidney survival between the best and worst HLA-matched combinations was 10%, with half-lives ranging from 11.6 to 8.6 years. Some renal transplant recipients have been able to stop taking immunosuppressant medication altogether.
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Fourth, most pediatric kidney transplantations are performed in children older than 6 years, partly because of the illnesses that lead to kidney failure in this population, and partly because of the option of dialysis. This later age at transplantation allows larger organs to be used than would be possible in younger and smaller children, expanding the number of potential donors.
A result of these differences from other organ transplantations is that kidney transplantation has been practiced since the 1950s, and is therefore well established at many centers. More programs are authorized to provide kidney transplantations because more have performed and continue to perform the required number of procedures to be considered “expert.” The number of kidney transplantations in adults related to diabetic nephrology led to combined pancreas and kidney transplantations, primarily in adults. These are now successful, with a 1-year graft survival rate of 85% and 3-year patient survival rate of 90%. Joint kidney and liver transplantations are also relatively common.
Liver
Liver transplantation does not have many of the advantages of kidney transplantation. No mechanical substitute is available for the liver, and the liver is not a paired organ. The liver is active immunologically and must be matched carefully to prevent rejection. Most liver transplantations in children are performed on those younger than 5 years, and most of these are for congenital illness, such as alpha 1-antitrypsin deficiency or biliary atresia. Therefore, the children are small and cannot accommodate an adult liver.
However, the liver is an organ with individual lobes, and people can survive with less than a complete functional liver. Thus, for the reasons described earlier, once the surgical techniques were found to be feasible, partial livers were used for children. Removing just one lobe of the liver allowed donors to continue a healthy life, allowed better-matched relatives to be donors, produced a smaller organ to fit young children, and gave an option to children who would not survive the wait for a deceased donor.
However, one problem was the coercion inherent in being a potential living-related donor. Although this had also been an issue for kidney transplantation, the availability of dialysis reduced some of the time urgency and increased the likelihood of finding another donor. For parents of very small children experiencing liver failure, very few options were available. Programs responded to this by requiring careful assessments of potential donors to see that they qualified as giving true informed consent. That is, they needed to understand the problem, the various alternative treatments (including doing nothing), and the potential consequences of each option, and had to be consenting without undue influence. In reality, parents rarely felt comfortable refusing to be a donor.
Living-related partial liver donation is now uncommon except in areas with little access to deceased donor organs. Although mortality was very low for donors, it was not zero, and the morbidity could be significant, if only involving the loss of a month of employment. New techniques using one cadaver liver for multiple recipients made the use of parental donors less necessary.
Although liver transplantation is performed at major centers worldwide, it is specialized enough that not all medical centers have programs. To maintain a contract with the United Network for Organ Sharing, which oversees distribution of organs, a center must perform a minimum number of transplants and meet criteria on survival, complications, and services provided. Liver transplantation is therefore usually performed at a regional center, with long-term follow-up coordinated though the regional center at the local hospital or clinics.
Liver
Liver transplantation does not have many of the advantages of kidney transplantation. No mechanical substitute is available for the liver, and the liver is not a paired organ. The liver is active immunologically and must be matched carefully to prevent rejection. Most liver transplantations in children are performed on those younger than 5 years, and most of these are for congenital illness, such as alpha 1-antitrypsin deficiency or biliary atresia. Therefore, the children are small and cannot accommodate an adult liver.
However, the liver is an organ with individual lobes, and people can survive with less than a complete functional liver. Thus, for the reasons described earlier, once the surgical techniques were found to be feasible, partial livers were used for children. Removing just one lobe of the liver allowed donors to continue a healthy life, allowed better-matched relatives to be donors, produced a smaller organ to fit young children, and gave an option to children who would not survive the wait for a deceased donor.
However, one problem was the coercion inherent in being a potential living-related donor. Although this had also been an issue for kidney transplantation, the availability of dialysis reduced some of the time urgency and increased the likelihood of finding another donor. For parents of very small children experiencing liver failure, very few options were available. Programs responded to this by requiring careful assessments of potential donors to see that they qualified as giving true informed consent. That is, they needed to understand the problem, the various alternative treatments (including doing nothing), and the potential consequences of each option, and had to be consenting without undue influence. In reality, parents rarely felt comfortable refusing to be a donor.
Living-related partial liver donation is now uncommon except in areas with little access to deceased donor organs. Although mortality was very low for donors, it was not zero, and the morbidity could be significant, if only involving the loss of a month of employment. New techniques using one cadaver liver for multiple recipients made the use of parental donors less necessary.
Although liver transplantation is performed at major centers worldwide, it is specialized enough that not all medical centers have programs. To maintain a contract with the United Network for Organ Sharing, which oversees distribution of organs, a center must perform a minimum number of transplants and meet criteria on survival, complications, and services provided. Liver transplantation is therefore usually performed at a regional center, with long-term follow-up coordinated though the regional center at the local hospital or clinics.
Heart
Hearts are neither paired nor lobed, and are very immunologically active. But an unexpected aspect of heart transplantation has led to some of the most serious concerns about pediatric heart transplants. Although initial survival was excellent, and improving technique led to dramatic improvements in 1-year survival rates after cardiac transplantation, long-term graft survival has been limited by what is called accelerated transplant coronary artery disease or cardiac graft vasculopathy . This condition is an immunologically mediated chronic rejection characterized by progressive fibroproliferative disease, resulting in intimal thickening and occlusion of the grafted coronary vessels. Lipid accumulation in allograft arteries is prominent, with lipoprotein entrapment in the subendothelial tissue, through interactions with proteoglycans. The hope that pediatric organ transplant recipients could undergo just one transplantation and live with that heart for their normal life expectancy is lessened by evidence that significant atherosclerotic disease can be seen in as few as 5 years. This area is one of intense research.
Lung and heart/lung
Cystic fibrosis is one of the most common indications for lung transplantation worldwide, and certainly the most common indication for all pediatric lung transplantations and for bilateral lung transplantation irrespective of age. Outcomes are outstanding when compared with other indications for lung transplantation, and an increasing number of centers now report mean survival of greater than 10 years posttransplant.
Pediatric lung or heart/lung transplantation is also performed to treat congenital heart disease, primary pulmonary hypertension, or pulmonary fibrosis, and has not generally been performed in very young children. Bronchiolitis obliterans remains the major late complication. Survival has not been as good as with liver and heart transplants, but has been improving, at least for some underlying illnesses. Reduced-size transplantation has proven successful, allowing smaller children to undergo transplantation despite the scarcity of small donors. Combined heart and lung transplantation has comparable success with lung transplantation.
Small bowel or multivisceral
Transplantation of the small bowel is performed when the intestine cannot provide the body with sufficient nutrition or hydration. The most common reasons for intestinal failure in children are necrotizing enterocolitis, gastroschisis, intestinal atresia, volvulus, psycho-obstruction, and aganglionosis. Although short-gut syndrome, secondary to surgical correction of the conditions listed earlier, is the most common cause of intestinal failure, short intestinal length is neither necessary nor sufficient to require transplantation.
Transplantation of the small bowel in children had a high initial rate of complications, resulting in a relatively low 5-year survival rate. Although the 1-year survival rate in adults who have undergone small bowel transplantation is now comparable to that of those who have undergone liver and heart transplantations, survival in children is still much less nationally. However, specific centers report 1- and 5-year survival rates of 90% and 77%, respectively. Transplantation of the small bowel has been performed when parenteral nutrition failed. Multivisceral grafts can include donor spleen, large intestine, and small bowel. These patients frequently require intensive care preoperatively and have unique intensive care needs postoperatively. With increasing survival rates, intestinal and multivisceral transplantation have reached the mainstream of medical care. Indications now include neoplastic disease, extensive splanchnic thrombosis, and abdominal catastrophes. Living-donor intestinal transplantation is also being explored as an alternative to minimize death of potential recipients while on the waitlist.
Transplant evaluations
Organs for transplantation are a scarce resource, and therefore allocation is carefully monitored and regulated. Teams of physicians from various specialties assess candidates to ascertain if they are sick enough to need a transplant, well enough to survive the transplant, and able to follow the medical instructions necessary to keep the graft alive. Once patients are listed as good candidates, priority is given to the sickest person in the region on the list who matches the donor organ. The list must be regularly updated to remove anyone who is too sick, lest an organ be “wasted.” For adult patients, the role of the psychiatrist is primarily to evaluate the patient for suitability to be on the list. The psychiatrist generally determines if patients demonstrates signs that they will be nonadherent. In addition to frank psychopathology, determining a history of smoking, illicit drugs, or alcohol abuse requires particular attention.
For most pediatric candidates, because they are young, nonadherence assessment focuses primarily on the parents. This assessment is often performed by social workers rather than psychiatrists or psychologists. Referral for psychiatric assessment in pediatric organ transplantation primarily occurs with adolescents. A Pediatric Transplant Rating Instrument was developed for use in these settings, which assesses the following domains :
- 1.
Knowledge and motivation regarding the transplant
- 2.
History of adherence with medications, appointments, and risks for nonadherence
- 3.
Patient and parental psychiatric and substance abuse history
- 4.
Parental supervision, family conflict, and communication style
- 5.
Financial, logistical, and psychosocial support
- 6.
Relationship with the medical team.
Child psychiatrists or psychologists may also be asked to assess a potential candidate for solid organ transplantation in several other situations.
Suicide Attempt
The classic version of this situation would be a teenager who has taken a handful of acetaminophen and is in acute liver failure. In this case, the acute injury may resolve without need for transplantation, but the assessment must be performed while the patient is alert, before hepatic encephalopathy makes it impossible to assess the situation adequately. The primary goal of this assessment is to determine whether this suicide attempt was serious or a gesture that is unlikely to be repeated. A careful history and mental status examination, with collaboration from family members, can usually determine if the teen has a chronic psychiatric problem. In most cases involving suicide attempts, the psychiatric assessment is advisory, guiding the posttransplant care rather than advising against placing the patient on the list.
Need for a “Family Transplant”
Some unfortunate children have chaotic family situations in addition to a life-threatening illness. Examples of these cases could include young teens who have hepatitis from rape by a stepfather or older teens who has viral endocarditis from their heroin-dealing mother. Although the odds are high that these children will be nonadherent later, many teams have difficulty condemning them to death because of the sins of their parents. The immediate need is to find them a safe place and support system for the pretransplantation waiting period, but this can be difficult because these children generally require more medical care than can be provided in regular foster care settings. Even more difficult is helping these children with long-term survival; evidence suggests that problematic early childhoods are predictive of poor adherence. The family is an important component of transplantation success.
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