Introduction

As medical technology advances, more children–including the extremely premature and those with genetic syndromes–are surviving with multiple medical comorbidities, sometimes including chronic kidney disease (CKD) [1]. Many of these children have irreversible physical and/or neurodevelopmental disabilities due to their underlying condition and are medically fragile. Some of these children depend on external life-sustaining support for feeding and/or ventilation. When these medically complex children near end-stage kidney disease (ESKD), health care providers are faced with difficult decisions about whether kidney transplantation is appropriate.

Kidney transplantation is usually the desired goal of treatment in children with ESKD due to its ability to improve length and quality of life (QOL), cognition, and CKD-related morbidities [2]. However, transplantation is not without its own complications, including immediate risks related to the surgery and anesthesia and long-term risks related to infections, malignancy, and the need for lifetime medication monitoring. In those with comorbidities, the benefits gained by transplantation may be difficult to ascertain due to uncertainties about the long-term prognosis of the underlying conditions and the medical interventions used to treat them. As well, transplantation remains a limited resource, with the number of people in need of organs far exceeding the supply of donors. Therefore, discussions around transplantation often include the element of resource allocation.

There are extremely limited data regarding transplantation in children with multiple comorbidities. With a lack of consistent policies or evidence-based guidelines, transplantation centers are left to somewhat subjective decision making regarding transplantation candidacy for such medically complex children. This lack of uniformity leaves room for misinterpretation of the decision-making process by patients and families, health care providers, and the public. Recently, several transplantation candidacy decisions have been scrutinized in the media [3, 4]. In these circumstances, public debate has centered on whether certain disabilities should be considered contraindications to transplantation and whether decisions not to transplant because of comorbidities are discriminatory.

This paper provides a theoretical framework for health care professionals to work through an ethical, systematic, and rational process for evaluating transplantation candidacy in medically complex children. Whereas this work is intended to serve as a foundation for structuring the decision-making process of transplantation candidacy, it must be emphasized that each transplant evaluation must be individualized.

Historical context

Neurodevelopmental disability and its relationship to transplantation candidacy has long been an area for debate. In the early days of solid-organ transplantation, neurodevelopmental disability was generally accepted as a contraindication to transplantation, assuming that the disability could result in reduced capacity to adhere to the complex posttransplant medical regimen or that expected QOL was so low as to warrant transplantation exclusion [5–7]. It was not until the mid-1990s that patients with significant developmental disabilities were able to win legal battles to be listed for solid organ transplants [8, 9]. A study by Levenson and Olbrisch from that era found that many transplant physicians felt that low intelligence quotient (IQ) (< 50 for some, 50–70 for others) should be either an absolute or relative contraindication to transplantation [10].

There is a perceived lack of access to transplantation in the disabled community. A web-based survey of people with disabilities and solid organ disease, conducted in 2004 by the National Working Group on Disability and Transplantation, found that 80 % of respondents believed that people with disability are discriminated against regarding access to transplantation [6]. Seemingly obvious and fixable issues, such as transplant clinics located in non-wheelchair-accessible areas, were identified, but more insidious barriers, such as a negative attitude toward disability, perceived inability to cope with rigors of transplantation, and financial/insurance factors, also played a role.

Transplant societies have generally been reluctant to consider reduced mental capacity an absolute contraindication to transplantation. The American Society of Transplant Physicians developed clinical guidelines that recognize the importance of the psychosocial assessment to determine transplantation candidacy but admit that this assessment can be very subjective. It emphasized the importance of ensuring “that recipient selection is not unduly influenced by outcome predictors of questionable value” [11]. Specifically, guidelines state that “cognitive disability should only pose a contraindication to transplantation when the disability is so severe that it precludes treatment compliance which cannot be compensated for with family or caregiver support.” The Canadian Society of Transplantation’s transplant eligibility guidelines state that “cognitive or neurodevelopmental delay is not an absolute contraindication to renal transplantation in children” and explain that transplantation can result in an improvement in QOL for recipients and their families, including recipients with disabilities [12]. In contrast, the Veneto region of northern Italy has codified IQ as an absolute or relative contraindication to transplantation, depending on the severity of the disability [13].

Many centers do transplant children with disabilities, but it is clear that the profession continues to struggle with this issue. In a 2008 study by Richards and colleagues, 38 % of transplantation centers surveyed stated that they had denied listing a child for organ transplantation solely on the basis of a coexisting developmental disability, but none of the centers had formalized criteria for how disability should be weighed in transplantation decision making [14]. The survey respondents varied widely on whether they thought disability should be a consideration in transplant listing, with 44 % stating that it should always/usually be a consideration and 39 % that it should never/rarely be considered.

There is no literature on kidney transplantation outcomes in children with other significant medical comorbidities (e.g., tracheostomy or severe feeding difficulties). Anecdotally, a handful of ventilator-dependent children have undergone kidney transplantation with short-term success, but in many pediatric transplantation centers, dependence on ventilation is considered a relative contraindication due to concerns about increased risk of infection [15]. Many premature children have a history of necrotizing enterocolitis and small-bowel resection and are dependent on gastric or gastrojejunal feeds or intravenously administered alimentation. Whereas these children would not benefit from kidney transplantation alone, they may be candidates for multivisceral transplantation ,including small bowel, liver, and kidney, as long as there are no other contraindications to the transplantation process [16, 17].

Ethical considerations

The two competing ethical considerations in organ allocation are equity and utility. Equity mandates that all individuals be treated equally; no one individual’s life is considered more valuable than that of another. Utility requires that organs, especially from the deceased-donor pool, be allocated efficiently in order to maximize benefit. Decisions to allocate organs based on degree of matching, for example, are utility based because they prioritize those with a better expected graft survival over those whose graft survival is expected to be lower. In contrast, wait-list priority is an example of equity-based allocation.

Commonly accepted medical contraindications to transplantation incorporate utility by excluding individuals whose diseases can be expected to recur after transplantation (e.g., untreated vasculitis), diseases that may be worsened by posttransplant immunosuppression (e.g., uncontrolled infections with HIV, hepatitis B, and malignancies), and diseases that make surgery unsafe for the patient (e.g., severe heart disease) [12]. There are generally no explicit contraindications to transplantation based on anticipated QOL after a medically successful transplantation.

Utility-based arguments against transplantation for children with comorbidities may not be supported by available data. There are certainly some children whose diseases are so severe that their lives may not improve, even with a successful transplant. For others, however, there are data, albeit limited, suggesting that their outcomes can be similar to those of other children without disabilities. Ohta and colleagues compared transplantation outcomes in a group of Japanese children with varying degrees of intellectual and motor disabilities to their general transplant recipient group [18]. These 25 children were followed for a median of 20 (range 1–187) months and had transplantation outcomes similar to those of the general population (100 % patient and graft survival in the disabled group compared with 87 % graft survival and 98 % patient survival at 5 years in the general group). They also noted posttransplant improvements in QOL for both patients and their caregivers in almost every case in both groups. A summary of kidney transplantation outcomes in patients with Trisomy 21, some of whom had physical comorbidities, revealed similar graft outcomes to the general population. Lost grafts were due to infection or progression of cardiorespiratory disease; ability to adhere to the medical regimen did not seem to play a significant role [19]. Galante found similar graft survival (though slightly lower patient survival) at 5 years in kidney transplant patients with intellectual disabilities [20]. A review by Martens et al. summarized cases from several major transplantation centers, which also suggested that outcomes of transplantation recipients with developmental disabilities were similar to the general transplantation population [5]. Of course, these studies only included children who were actually transplanted, and they may not be reflective of the pool of children who could have been eligible. Nevertheless, these data provide some evidence that children with disabilities can fare well after kidney transplantation as long as sufficient family and community support exists.

If survival rates are similar for a select group of children with comorbidities, why might some consider severe physical or developmental disabilities as contraindications to transplantation? Some suggest that QOL for individuals with significant comorbidities posttransplantation would not be as good as for others, so organs should be saved for those who can get better use from them [21, 22]. QOL determinations, however, should be approached with caution. Health care providers often perceive the QOL of their patients quite differently than do the patients themselves and their family members, even for those experienced in treating children with serious health conditions [23–25]. To base such an important decision on a measure known to be flawed is both unwise and unfair.

Some comorbidities may shorten the length of life and therefore might be a reason to limit transplantation eligibility in particular cases. For adults with ESKD, national kidney allocation policy changes have increasingly focused on trying to better match anticipated graft longevity with recipient longevity so that the potential survival of every transplanted organ can be realized within biological reason [26]. It seems reasonable from a utility perspective to set some limit for life expectancy below which transplantation might be inappropriate. Whereas the Organ Procurement and Transplant Network (OPTN) and United Network for Organ Sharing (UNOS) Ethics Committee do not set arbitrary limits on eligibility, they do state that “transplantation should be carefully considered if the candidate’s reasonable life expectancy with a functioning graft, based on factors such as age or comorbid conditions, is significantly shorter than the reasonably expected ‘life span’ of the transplanted organ” [27]. It may be difficult to apply this concept in many pediatric cases, however, because even within a known condition, there is substantial heterogeneity in comorbidities. Consequently, prognosis estimates can vary widely. Also, as scientific technology advances, children with complex conditions are surviving longer, so historic estimates of life expectancy may no longer be accurate. For example, Trisomy 18 was once considered a universally lethal diagnosis in the newborn period; however, with increasing access to heart surgery and other high-technology interventions, some children with Trisomy 18 are surviving longer into childhood [28]. Yet, in instances in which comorbidities significantly increase the risk of failure of the transplanted organ, transplantation may be precluded. For example, patients with ESKD with significantly impaired cardiac output who are not eligible for heart transplants may not be suitable candidates for kidney transplantation alone.

Even if it could be shown that children with comorbidities do worse than children without them, it may still be appropriate in some situations to list those children for transplantation. Several studies suggest that the public does not want a utilitarian perspective to dominate in allocation decisions. Koch uses the analogy of a lifeboat to describe the allocation issue in transplantation [29]. He describes a focus-group study done with members of the public, health care professionals, and members of the local Down syndrome chapter in Toronto, ON, Canada. The groups were asked to consider several factors in allocation, including whether intelligence should be a factor in ranking wait list recipients. Whereas all groups recognized the importance of utility in allocation, they rejected the concept that intelligence was a valid way to rank recipients. In Koch’s lifeboat analogy, respondents recognized that many issues other than intelligence were important in allocation and felt that “equality should reign because the skills of survival are varied and the needs of the passengers numerous.” Similar studies involving allocation decisions confirm that the public is generally willing to sacrifice some utility in order to ensure equity [30–32].

It is important to recognize that the biases against disabled individuals are deeply entrenched and not always obvious, even to those who are making these difficult decisions. An analysis of recipient evaluation committees for liver transplantation candidates found that whereas the evaluation process was fairly consistent and committees were well meaning, judgments about social worth often inserted themselves in the decision-making process [33]. For example, the authors cited that committees commonly considered education and intelligence in the assessments of a patient’s ability to carry out necessary treatment plans. Lack of clear and explicit policies for assessing transplantation eligibility was cited as one of the reasons for making ambiguous decisions. The authors emphasized the need for written policies to guide decision making and promote transparency and consistency, and they recommended a designated patient advocate to eliminate confusion about committee members’ roles.

The disabled community has long been victim to the “invidious prejudices” regarding QOL and social worth from the public and the transplantation community [34]. In a profession that must recognize and wrestle with the ignoble shadows of the Seattle (God) Committee, who meted out dialysis chairs based partly on social-worth criteria, we should remember the words of George Annas, who cautioned: “to prevent the gulf between those ‘who have’ and ‘have not’ from widening, we must make every reasonable attempt to develop medical criteria that are objective and independent of social-worth categories” [35]. In the absence of strong evidence of poor outcomes in those with comorbidities, equity favors listing over nonlisting in many situations.

Another question that frequently arises is whether the donor source should influence transplantation candidacy decision making. Some would be more likely to accept a living-donor kidney for a child with multiple comorbidities and avoid taking an organ from the deceased-donor pool. Others might urge a potential living donor to avoid taking on the risk of donation if the perceived benefits were less than for a child with isolated kidney disease. A complete discussion of the ethical differences between living and deceased donation and of the principles behind deceased-donor allocation is beyond the context of this paper, but a few points should be emphasized. As we argued above, children with comorbidities can and do experience benefit from transplantation in some cases and should not be judged on social-worth criteria to at least become potential candidates for the pool of deceased organs along with other ESKD patients. For living donors, the medical risks to the donor are the same regardless of the recipient’s medical status, but the complex interplay among the acceptable donor risks, anticipated donor benefits, and expected recipient risks and benefits does need to be considered. If a child is deemed an appropriate kidney transplantation candidate even with associated comorbidities, both donor and recipient could benefit from living donation. For example, the parent who is able to donate to his or her child might benefit from seeing that child enjoying improved health after transplantation. It seems reasonable, however, to ensure that the donor and/or advocate is aware of the patient’s medical complexities as part of the donor’s informed consent process, as is recommended in other situations that may affect recipient outcome [36].

Benefits and burdens

We have argued why some children with comorbidities should be considered transplantation candidates and how listing can be consistent with the principles of equity and utility. At the individual level, however, it is clear that transplantation may benefit some children but may not be the right choice for all. A careful analysis of benefits and burdens of transplantation and how they can be affected by the child’s comorbidities can be helpful in determining whether transplantation is appropriate. Wilkinson suggested a model for intellectual disability in neonates that may be useful in determining how other disabilities can affect transplantation eligibility [37]. He describes three ways that disability can affect the benefits and burdens of a proposed intervention:

  1. 1.

    Disability so severe that the concept of benefits and burdens becomes meaningless (e.g., a child who is so disabled that he/she cannot interact with/experience the world or interact with his/her parents in some situations).

  2. 2.

    Disability that increases burdens by increasing suffering that cannot be alleviated, even with additional supports (e.g., some children may be excessively miserable in the hospital environment or suffer intractable pain that cannot be managed).

  3. 3.

    Disability that decreases the benefits of life that could otherwise be enjoyed (e.g., a child whose other disabilities will severely limit their enjoyment or length of life posttransplant).

If we accept a model such as Wilkinson’s, we would proceed with transplantation evaluation in cases in which benefits outweigh burdens but forgo it in cases in which the balance is unfavorable. A child’s and family’s attitude and behavior toward the health care interventions should be also be assessed: some may want to pursue all available interventions; others may decline transplantation as a treatment option. Whatever the final decisions, it needs to be clear to both health care providers and to the patient and family that the decision is being made based on the child’s particular situation and prognosis and not on the child’s perceived social worth.

Legal considerations

Though this paper deals primarily with ethical issues of transplantation eligibility, it is prudent to have a basic understanding of the potential legal implications of these decisions. The law supports a nondiscriminatory approach to listing individuals with medical complexities for transplantation unless their nonrenal disease can be shown to impair significantly the benefits realized from a kidney transplant. Several authors examined how the Americans with Disabilities Act (ADA) affects listing decisions and generally concluded that disability can only legally be considered in allocation decisions when it compromises a person’s ability to derive benefit from the transplant or if the program cannot operate without some sort of discriminatory practice (e.g., severe heart disease may be considered a disability but could also make transplant surgery extremely risky and thus be considered a reasonable contraindication to transplantation) [38–40]. The US Centers for Medicare and Medicaid Condition of Participation (482.90) mandates that transplantation centers must have a fair and nondiscriminatory patient-selection process for determining transplantation candidacy [40]. In the state of New Jersey in the United States, recent legislation explicitly prohibits discrimination in transplantation eligibility for people with physical or mental disability and provides for an expedited court process for those who feel that the law’s provisions were not upheld [41]. Similar disability legislation exists in other countries, making this issue important for pediatric nephrologists worldwide [42, 43]. Nevertheless, as the resources for managing disability and societal attitudes vary from country to country, the framework we propose may have greater applicability to transplantation centres in the Western world vs other regions.

Suggested approach

For clinicians faced with these challenging cases, we offer a practical approach based on medical, ethical, and legal considerations:

  1. 1.

    Individualized evaluation

    When a medically complex child presents for transplantation evaluation, it is important for clinicians to have a fair, nondiscriminatory, and transparent process for assessing transplantation eligibility. Clinicians should conduct a careful and thorough analysis of all the disabilities, and consideration should be given to those which can be expected to improve after transplantation. Wide consultation with other subspecialists (neurology, developmental pediatrics, pulmonology, gastroenterology, nutrition, etc.) is necessary to best predict prognosis and make an individualized plan to address these issues both before and after transplantation. It is important to seek social worker and/or psychologist perspectives about the child and family to help clarify expectation of posttransplant life. Where possible, a patient advocate should be identified in order to help the family understand and navigate the evaluation process. This individual should serve as the patient liaison with the medical providers to ensure each case is presented to the selection committee in an unbiased and comprehensive manner. The information gained by the advocate can help both families and health care providers to reach a consensus about what is best for an individual child. The child should be involved in the decision-making process whenever possible.

    It is appropriate to move forward with transplantation candidacy when a patient can be expected to experience significant benefits over burdens, even if not every potential benefit will be realized. If barriers are identified, it should be determined whether they are intrinsic and insurmountable (e.g., uncorrectable comorbidities that severely limit life expectancy) or whether they are improvable with increased supports (e.g., extra supervision and support to help manage medications). If additional supports can decrease burdens and increase benefits, then every reasonable effort should be made to provide and advocate for those supports so that the transplantation evaluation can proceed.

    When comorbitiy burdens cannot be overcome and outweigh the benefits of transplantation, then it is appropriate to preclude transplantation as a therapeutic option. This does not mean that dialysis cannot be considered or continued, because the benefit/burden considerations in starting or continuing dialysis may be very different from those for transplantation. As is often the decision in adults with ESKD, children could potentially benefit from the extended lifespan and improved health that dialysis provides, even when transplantation is not desirable or achievable. Whereas transplantation is the usual endpoint for ESKD in childhood, it need not be the only endpoint.

    We purposely did not list absolute contraindications to transplantation, as the importance of individualized assessment must be emphasized. Different children with the same syndrome, genetic diagnosis, or disability may have a very different balance between burdens and benefits. Legal challenges to the ADA confirm that individuals with disabilities must be evaluated on their individual opportunities, not by the class of individuals to which they belong [39].

  2. 2.

    Individualized transplantation care plan

    Careful planning needs to be given to how the transplantation procedure will fit into the management of the child’s comorbidities and vice versa. For example, some suggest that reduction in immunosuppression may be necessary for transplantation recipients with Trisomy 21, as their immune systems may be weaker than those of other ESKD patients [18]. Alterations may need to be made to anesthesia to accommodate patients with cardiorespiratory issues, and patients may need longer intensive care monitoring posttransplant than a typical transplantation recipient. Thorough consideration should be given to the possible impact on the child’s other health conditions of medications and monitoring involved with transplantation (e.g., a child with a tracheostomy may be at higher risk of respiratory infections posttransplant).

  3. 3.

    Clear communication

    Clear communication between health care providers and families is crucial, starting from the transplant referral through evaluation and decision making. Caregivers must understand the steps involved in the decision-making process and how the ultimate decision of acceptance or denial of transplantation eligibility is assessed. If transplantation is deemed inappropriate for a particular child, the reasons for this decision must be clearly explained to the family (and child, where appropriate) and plans for alternative therapy addressed early in the communication. It may be prudent to involve other professionals, such as ombudsmen and ethics and legal consultants if such a decision is being considered, particularly if a decision is contrary to the family’s wishes. This conversation would best be conducted with a clinician who has already established a relationship of trust with the child and family. It should be emphasized that the decision is being made because of the balance of benefits and burdens of transplantation and not because of the perceived value of the child’s life. Conversely, children and/or their families may opt against transplantation in some situations in which the health care team feels it would be appropriate to proceed. Continued discussion around the child’s and family’s values and goals may help clarify why the choice is being made.

  4. 4.

    Systematic process for conflict resolution

    Transplantation centers should establish a due and systematic process for conflict resolution if there is discrepancy between health care providers and the family, between different family members, or between the family and the child. Additional medical consultations, as well as pastoral care or palliative care consultation may be appropriate. A multidisciplinary team including support for the family from both inside and outside the institution in conjunction with involvement of the hospital ethics committee can be highly beneficial. Additionally, psychological counseling for the patient and caregivers should be offered. In rare cases, when there is discordance between clinicians’ advocacy for transplantation against the wishes of a parent/caregiver, clinicians may need to resort to legal remedies, but conflict resolution is always preferred [44].

    Transplantation centers should be encouraged to establish an appeals process and offer an automatic second opinion at another transplantation center, or some other means of double-checking these difficult decisions. Offering these outlets permits patients and their families the opportunity to feel that the health care team places the patients’ best interests as the foremost priority.

  5. 5.

    Reassessment as appropriate

    Transplantation eligibility can be dynamic and can and should be reassessed if there is a change in the patient’s medical condition.

We also offer some tools to help health care teams evaluate these difficult cases. Table 1 outlines some questions to consider in the evaluation of a child with multiple comorbidities. Although not an exhaustive list, it can serve as a starting point for some of these discussions. Figure 1 is a decision tree for evaluating transplantation candidacy in children with multiple comorbidities to help teams organize their approach to evaluation.

Table 1 Questions to consider in the kidney transplantation evaluation of a child with multiple comorbidities
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Fig. 1
figure 1

Decision tree to evaluate transplantation candidacy in children with multiple comorbidities ᅟ

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Need for additional research

There is a clear need for additional research to inform evidence-based decision making of individual risk–benefit balance in transplantation eligibility. The modified Charlson Comorbidity Index and a Frailty Index, developed by Garonzik-Wang and colleagues, has been linked to outcomes in adult transplantation candidates and recipients [45, 46]. The “Comorbidity Software” is one in the family of tools to inform decision making at national, state, and community levels [47]. No such comorbidity scores or frailty measures exist for children with ESKD, and current studies are challenged by small, heterogeneous populations of patients. Nevertheless, research endeavors should attempt to identify ways to better predict patient and graft survival based on objective measures of illness severity in medically complex and fragile children. Whereas these aggregate data should not be used as a substitute for individualized assessment, they can be helpful in framing prognosis discussions.

There is a crucial need to collect data both on children for whom transplantation is pursued and for whom transplantation is deemed inappropriate. Currently, publication and media bias focuses attention on the exceptional successes of transplantation in patients with highly complex conditions; however, there is a lack of failure acknowledgement. There is also lack of discourse of patients and families who have opted against transplantation and experienced positive outcomes. At the local level, regular debriefings about each case can help guide decision-making processes. As medical technology and scientific interventions continue to advance, long-term outcomes for children with complex medical conditions are likely to continue to improve, and the risks of transplantation and the risk–benefit ratios may change. Thus, we must continue to revisit transplantation eligibility criteria on an ongoing basis.

An appeal for further engagement

Finally, we appeal to the pediatric transplantation community to engage with each other and with other stakeholders to share insights and experience in order to inform consensus guidelines. We must gather expertise from transplantation ethicists and multidisciplinary transplantation teams as well as patients and family members, particularly for patients with medically complex conditions. Formal policies are needed to ensure transparency and consistency. As we continue to gather data, we should also work together to define key research questions that will further ensure practices that promote equity and utility for all patients, regardless of disability.