Introduction
There are several organ allocation systems used in various countries. They all call attention to the main challenge created by the scarcity of deceased donor kidneys: the need to balance equity with efficiency (medical utility).Footnote 1, Footnote 2, Footnote 3 Put differently, each system, in its way, seeks to strike a balance between the utilitarian argument—the idea that each organ should be transplanted in the patient for whom it will last the longestFootnote 4—and the principle of equity, which requires that each individual who could benefit from a transplant ought to have a comparable opportunity to receive one.Footnote 5 The two principles are often in conflict yet can also converge, and the distinction between them is not always clear-cut. Moreover, it is not straightforward to measure the trade-off between efficiency and equity, as it is easier to quantify the former (e.g., according to recipient survival, years added to life compared to dialysis, kidney graft survival, quality of life, or averting the ineffective use of a scarce resource) than to quantify the latter. Even when quantification methods are available, it is difficult for decisionmakers to identify the measures that best capture the concepts of “benefit,” “efficiency,” and “equity,” which are poorly defined both in theory and in practice.Footnote 6
Although efficiency and equity are technical terms with slippery meanings and complex applications, it is important to differentiate between them and not to showcase all the challenging traits under a unified list. Efficiency and equity are opposite and conflicting forces in a complicated and delicate system. Nonetheless, these contradictory traits must coexist; hence, it is essential to acknowledge them separately to understand the difficulty of finding equilibrium. In what follows, we elaborate on some of the factors that might inform a decisionmaker’s evaluation of the extent to which a given allocation scheme is efficient or equitable. The “Efficiency Considerations” section specifies the efficiency considerations. We present the characteristics that challenge the utility trait and display health improvement measures, such as quality-adjusted life-years (QALYs) and disability-adjusted life-years (DALYs). In the “Equity Considerations’ section, we depict the equity considerations by emphasizing the factors considered to design equitable allocation policies. The “Suggestions” section offers suggestions that hold the potential to generate a fairer allocation policy. The “Summary: Efficiency versus Equity” section summarizes the trade-offs between efficiency and equity in kidney allocation policies.
Efficiency Considerations
Laws, rules, and regulations governing organ allocation formulate clear and explicit reference to the “best” use of organs in terms of waste reduction and avoidance and acknowledge the need to allocate organs under sound medical judgment. Yet, there is still substantial controversy regarding how much relative weight organ allocation schemes should give to each kind of benefit. For example, does utility indicate increasing the number of years lived posttransplantation? The amount of pain and suffering alleviated by transplantation? The number of lives saved by transplantation?Footnote 7, Footnote 8 Currently, decisionmakers take the following characteristics into account when evaluating efficiency, although few features present a challenge to the efficiency trait.
Age
Exclusion from eligibility for transplantation based on age alone can arguably be considered unfair. Nonetheless, age is often used as a proxy for medical efficiency, given that life expectancy for older transplant patients is shorter than that for younger recipients. Thus, the “gain of years” that senior candidates can achieve from a transplant (compared to remaining on dialysis) is less than that for younger recipients. However, given that age demographics are shifting in developed countries, and older individuals are beginning to make up a more significant relative portion of the population, it seems likely that the conception that those over 60 years of age are “elderly” will progressively be challenged.Footnote 9, Footnote 10, Footnote 11 In particular, the assumption that age is an adequate proxy for utility, and the idea that it is acceptable to refuse transplantation on the criterion of age alone, will no longer be valid.Footnote 12, Footnote 13
Obesity
The prevalence of overweight and obesity at the time of transplantation has risen by 60% among kidney transplant candidates.Footnote 14 Numerous studiesFootnote 15, Footnote 16, Footnote 17, Footnote 18 have established a connection between overweight/obesity and significant comorbidities in kidney transplant patients. Among obese patients (i.e., body mass index [BMI] of ≥30 kg/m2), the rate of skin and soft tissue complications are enhanced, chiefly wound infections, wound dehiscence, and anastomotic and perinephric complications (e.g., lymphocele formation, hematoma, and vascular). Moreover, delayed graft function is higher, hence contributing to a longer length of stay following transplant. Systemic complications such as new-onset diabetes after transplant and cardiac outcomes also appear to be increased in the obese population. Therefore, elevated BMI in the setting of kidney transplantation has been linked with increased transplant-related complications, apprehensions about inferior rates of graft and patient survival, and higher transplantation costs.Footnote 19, Footnote 20 Owing to the aforementioned concerns, obese patients wait longer for kidney transplantation and develop increased morbidity while on the waiting list.Footnote 21, Footnote 22
The practice and current guidelines concerning obese patients are relatively vague and tremendously flexible internationally, nationally, and sometimes even within the same department.Footnote 23 Thus, due to the correlated technical complexity, surgical complications, and outcomes-related worries, transplant programs may place restrictions on selecting obese patients for transplantation or can inflict a maximal BMI eligibility threshold for transplant.Footnote 24, Footnote 25
With that said, observational studies and scientific evidence imply that transplantation among obese transplant patients poses survival advantages and improves life quality in contrast to wait-listed obese transplant candidates.Footnote 26, Footnote 27, Footnote 28 Furthermore, even though obesity negatively influences access to transplantation, current studiesFootnote 29, Footnote 30 seem to support a neutral influence of obesity on the long-term graft and patient survival, and some even state that after transplantation, short- and long-term outcomes are quite satisfactory.Footnote 31
To sum up, since it is hard to detect body composition restrictions that impede clinical gain from kidney transplantation, obesity should be treated as one risk factor and not be seen as an independent and additional obstacle for transplant listing. Yet, a nihilist point of view (i.e., listing everybody regardless of the degree of obesity) appears equally inept. Therefore, obesity should not constitute an utter contraindication or an exclusion criterion to transplantation; however, individualized risk assessment is required.Footnote 32, Footnote 33, Footnote 34
Diabetes Mellitus
Reduced recipient survival in preexisting diabetes mellitus, particularly type 2 diabetes, has been consistently reported. Death-censored graft survival is generally similar to other groups of patients, and the inferior result is ascribed to increased cardiovascular events. Nonetheless, the prognosis for diabetic patients on dialysis therapy is poor and remains a prominent risk factor for mortality.Footnote 35, Footnote 36
Frailty
Frailty is present in up to 35% of patients with end-stage renal disease (ESRD). It is a condition distinct from comorbidity and disability, clinically expressed as reduced resistance to stressors and decreased physiologic reserve. Frailty is associated with falls, hospitalizations, poor cognitive function, poorer health-related quality of life, and mortality. Moreover, it is allied with inferior outcomes on dialysis and poor outcomes posttransplant, including delirium, delayed graft function, a longer length of stay, early hospital readmission, immunosuppression intolerance, and even mortality. Therefore, frailty is likely to be manifested in decreased access to kidney transplantation, even though some frail patients with ESRD can benefit from transplants over chronic dialysis. Hitherto, clinicians encounter difficulty identifying which patients are frail, whereas patients find it hard to report their frailty status accurately.Footnote 37, Footnote 38
To conclude, frailty is associated with an inferior chance of listing, a lesser transplant rate, and higher wait-list mortality. However, it is a possibly modifiable candidate feature. It could be amended and optimized prior to transplantation (e.g., via prehabilitation and intensive exercise therapy), thus improving candidates’ health.Footnote 39, Footnote 40, Footnote 41
FSGS Recurrence
Recurrence of focal segmental glomerulosclerosis (FSGS) in the allograft ensues in 30%–50% of patients and is associated with inferior renal allograft survival compared with patients transplanted for other causes of ESRD.Footnote 42, Footnote 43 It is the most common primary glomerular disorder in the dialysis population, with a prevalence of 4%.Footnote 44, Footnote 45 FSGS is the prominent factor of nephrotic syndrome in the adult population. It is labeled primary (i.e., idiopathic) when a precise cause cannot be detected or secondary due to various etiologies like genetic, viral-related, drug-induced, or adaptive. By and large, only primary FSGS recurs following kidney transplantation. The key risk factors for recurrence include younger age at diagnosis, rapid progression to ESRD (<3 years), race (reduced risk for blacks and Hispanics), and loss of previous allografts owing to recurrence. The medical hallmark of FSGS recurrence is proteinuria, which is usually diagnosed within hours to days after transplantation.Footnote 46, Footnote 47 Factors that are not associated with recurrence include human leukocyte antigen (HLA) mismatch, histologic subtype, time on dialysis, and immunosuppression type.Footnote 48, Footnote 49
Despite progress and improvement in FSGS recurrence comprehension, kidney transplants’ outcomes in patients with FSGS are still inferior to transplants for other causes of kidney disease. To date, novel insights into the pathogenesis of FSGS and its recurrence failed to change the outcomes markedly. Yet, plasmapheresis, high-dose cyclosporine, and rituximab are the most promising therapeutic options.Footnote 50, Footnote 51
In summary, for the majority of FSGS patients, renal transplantation should be contemplated as the treatment of choice. Nevertheless, transplantation’s success rate among these patients may be impaired due to the disease’s common risk of recurrence on the allograft and inferior graft survival rate.Footnote 52
Medication Nonadherence
Nonadherence with medication is an intricate and multifaceted healthcare problem. Adherence is defined as the degree to which patients are capable of following the recommendations for prescribed treatments. Patients may be nonadherent during different treatment stages, whereas the reasons for deviation are diverse and may be intentional or unintentional.Footnote 53 In the realm of transplantation, patient adherence is critical for a positive prognosis. It incorporates a range of behaviors spanning from lifestyle changes to laboratory visits and routine attendance at clinics. Immunosuppressive therapy adherence denotes patients following the recommendations and instructions given by healthcare professionals.Footnote 54, Footnote 55 Since posttransplant adherence with immunosuppression is crucial to the transplant’s success, nonadherence can result in considerable numbers of patients who fail to profit from the optimal benefit of transplantation; it may also be expressed in increased morbidity or even end with mortality.Footnote 56, Footnote 57
Prudential Judgment
Additional measures of efficiency include predictions regarding patient survival, years added to life, or enhancement in life quality. Unlike predictions regarding graft survival, these predictions are left to clinicians’ prudential judgment.Footnote 58, Footnote 59 In other words, these measures are dependent on the discretion of clinicians and transplant centers and are not strictly objective. As a result, the system may be vulnerable to manipulation, affecting its efficiency and the extent to which it is equitable.Footnote 60
When considering efficiency across different allocation policies, it is necessary to select an outcome measure that accurately reflects what the decisionmaker is trying to achieve. Since patients might ultimately benefit more from consideration, which seizes both quantity and quality of life, in the following subsection, we would like to elaborate on two measures that attempt to capture both of these qualities simultaneously.
Measures of Health Improvement
QALY
The QALY has served decades as a recognized health outcome metric.Footnote 61 In general, it is a composite metric that takes into account both morbidity (quality of life) and mortality (survival). Grounded in decision science and expected utility theory,Footnote 62 the QALY is based on the premise that people move through health states in the course of their lives and that each health state has a value ascribed to it. Health is defined as the value-weighted time—life years weighted by their quality—accumulated over the relevant time horizon. The general calculation of a QALY is QALY = Time × Utility.
DALY
The World Health Organization uses the measure of DALY. One DALY can be perceived as one lost year of “healthy” life. The sum of these DALYs across the population, or the burden of disease, can be considered a measurement of the disparity between current health status and an idyllic health situation in which the entire population lives to an advanced age, free of disease, and disability. DALYs for a disease or health condition are calculated as the sum of the years of life lost owing to untimely mortality in the population and the years lost because of disability for individuals living with the health condition or its outcomes.Footnote 63
Since both efficiency and equity are stated objectives of the organ allocation system, and because it is unfeasible to maximize these two outcomes simultaneously, perhaps, researchers should consider building a function, a measure of organ allocation. Namely, similar to DALY, which combines and scales morbidity and mortality, a metric that combines and measures the two outcomes of equity and efficiency should be developed.Footnote 64
Equity Considerations
There are numerous criteria for defining equity in organ allocation, where no approach is objectively superior to its alternatives.Footnote 65 In what follows, we elaborate on some of the factors taken into consideration in efforts to design equitable allocation policies. It is important to note that in Australia and the United States, social utility measurements are excluded from organ allocation ethics. That is, measures of societal benefit, economic productivity, or family cohesion have been ruled out as ethically justified criteria for organ allocation.Footnote 66, Footnote 67 The rationale for this decision is that considering these parameters might generate a slippery slope for decisionmakers and complicate an already delicate process.
Ancestry/Ethnicity
Non-Caucasian patients waiting for deceased-donor kidney transplants are simultaneously underrepresented in the donor pool and overrepresented (compared to the general population) in the ESRD population. This disparity, combined with allocation policies that emphasize HLA matching, leads non-white populations to be disenfranchised. Specifically, compared with Caucasians, non-whites endure longer waiting times before transplantation and are more likely to suffer other implications.Footnote 68 In the United States, for example, the disparity between blacks and whites manifests in the following ways: (a) after kidney transplantation, the graft survival rates among blacks are 10%–20% lower compared with those of any other ethnic group; (b) kidneys from black donors have significantly lower graft survival rates compared with kidneys from other populations, regardless of which ethnic group they are transplanted into; (c) blacks wait two times longer than whites do for kidney transplants; (d) the prevalence of ESRD in blacks is disproportionate to their representation in the population, because of their increased proneness to hypertension and diabetes, which is 2–4 times greater than that of whites; (e) compared with whites, blacks are referred later for kidney transplantation, are wait-listed later, and receive transplants later, irrespective of financial statusFootnote 69, Footnote 70; (f) the emphasis on HLA matching leads to racial inequity in the allocation system: the allocation schema is based on HLA antigens in North American whites,Footnote 71 which have been well defined since the early 1980sFootnote 72; and (g) following transplantation, among patients treated with the immunosuppressive drug tacrolimus, blacks are two times more likely than whites to develop diabetes.Footnote 73
Biases of Healthcare Providers
Several researchers have claimed that blacks and other minorities are victims of institutionalized racism/sexism. Due to their ethnicity or gender, they have unequal, disadvantaged, or inferior access to transplants and the transplant waiting list. The argument stresses that race and gender matter and that these factors determine whether a patient will be referred to a transplant evaluation and affect his/her time on the waiting list.Footnote 74, Footnote 75
Immunological Barriers
Candidates with high levels of panel reactive antibodies (>85%) have a much smaller pool of potential donors than those who are not highly sensitized and, subsequently, wait for prolonged periods for suitable grafts. To this end, pretransplant desensitization programs designed to remove donor-specific HLA antibodies have been proposed to enable transplantation in such individuals. However, these programs suffer from drawbacks in terms of both efficiency and equity. From a utilitarian perspective, this is not the ideal use of limited resources financially (it is a resource-intensive process) and organwise (nonsensitized patients can better utilize the organ). From an equity perspective, it may be considered unfair for sensitized persons to be prioritized.Footnote 76
Geographical Location
Within a specific country, patients located in different geographical regions may experience disparities in their access to transplantation and, particularly, in the ease with which they gain entry to the transplant waiting list and the extent of time spent there.Footnote 77 The combination of organs’ varying degrees of viability and the proximity to the donated organ determines that the mere locale of one’s residence or registration might outweigh medical needs or ethical assertions.Footnote 78 According to Dan Davis and Rebecca Wolitz,Footnote 79 this geographical preference is an elementary feature of current allocation systems design. It is not merely a “mishap” in the logical working of the allocation algorithm. Critics of this approach dispute the legitimacy of geography as a criterion for allocation, claiming that nonmedical criteria should not steer policy any more than a person’s wealth, celebrity, religion, ethnicity, or race should (Donna E. Shalala’s testimony on organ allocation before the U.S. Senate Committee in Davis and WolitzFootnote 80).
Ability to Pay
The principle of equity is challenged by those whose socioeconomic status affords them opportunities to access transplants denied to persons of lesser status. In particular, such individuals may be able to “buy” organs from live donors. Some argue that this situation might be beneficial to wait-list candidates, as every live transplant removes an individual from the waiting list for a deceased donor organ, thus increasing the chances of those remaining in the pool receiving one.Footnote 81, Footnote 82
In the United States, a particularly salient concern is that if an individual has no financial ability to pay for medication, they will be advised against transplantation. Individuals who do receive transplants and subsequently lose their insurance risk rejecting their grafts due to the inability to afford their medications.Footnote 83 These problems contradict the principle of equitable access to transplants.
Preferred Status
Some advocate that, as a matter of reciprocity and fairness, those willing to give organs (e.g., registered organ donors) should be given priority to receive organs, should the need present itself.Footnote 84 Supporters of this principle argue that, in addition to promoting fairness, offering preferred status to registered donors will have an equal attraction to rich and poor alike and might, therefore, mitigate economic disparities in access to organs. Opponents claim that it undermines the altruistic appeal of the act of donating a “gift of life” and, as a result, inhibits donation instead of encouraging it.Footnote 85 This concern would be particularly salient if preferred status were to outweigh other criteria for organ allocation decisions (a policy supported, e.g., by LifeSharers, a private organ donation network that operated for several years in the United States).Footnote 86 Critics (e.g., the United Network for Organ Sharing [UNOS]) suggest that if this factor is instituted as a primary criterion for allocation decisions, the system might go down a “slippery slope” of complicated calculations of prospective candidates’ value and deservingness of treatment.Footnote 87
Blood Group O
Patients with blood group O have fewer ABO-compatible living donorsFootnote 88 compared with patients of other blood groups. At the same time, blood group O donor kidneys are available to candidates of different blood groups. As a result, blood group O patients are disadvantaged in organ allocation systems: they accumulate on the waiting list, endure longer waiting times than other patients, and experience higher death rates. Furthermore, in comparison with patients of different blood groups, candidates with blood group O incline toward inferior long-term life and graft survival and, as a result, are at greater risk of being removed from the waiting list prior to receiving a transplant.Footnote 89 Petra Glander et al.Footnote 90 claim that longer waiting time on dialysis is the factor responsible for blood group O patients’ inferior health status at the time of transplantation, leading to inferior long-term outcomes after transplantation. These observations suggest that blood group O candidates do not receive fair and equal access to transplantation.
Evidently, organ allocation systems worldwide took into consideration several characteristics that presented a challenge to the equity trait and revised their policies accordingly. For instance, in numerous allocation schemes, the categorization of kidneys for transplant is based on the identity of the blood types of the donor and of the recipient (i.e., O → O and B → B).Footnote 91, Footnote 92 Moreover, transplant organizations strive to enhance equity in allocation by significantly increasing transplant opportunities for disadvantaged ethnic minorities and highly sensitized patients.Footnote 93, Footnote 94, Footnote 95
Suggestions
Unfortunately, this review elucidates that there is no consensus on how to develop an organ allocation policy that delivers maximum efficiency while ensuring utmost equity. Although there is a widespread agreement about each ethical guideline’s importance, there is still a strong disagreement about putting all the parameters into practice. Perhaps, Daniel Reidpath et al.Footnote 96 were right, and the question asked should not be what is more vital, a kidney allocation policy that delivers equitable outcomes or one which is medical efficient? Rather, a question that inquires what is more significant to the lay public, organ allocation policy that provides equitable (fairly distributed) outcomes, or an approach that maximizes health gains? Therefore, in line with this perspective, we suggest paving the right path toward a more balanced allocation system depends on a broad and inclusive deliberation system. The inclusion of different stakeholders (e.g., the general public, patients, their families and carers, donor representatives, and healthcare clinicians)Footnote 97 who hold various ideas and viewpoints might yield a fairer and more representative system. In addition, we believe that key stakeholders are most likely to perceive an allocation system as efficient and equitable if the system takes into account those stakeholders’ ideas regarding which criteria yield efficiency and equity.
Following this inclusive line of thought, maybe the trade-off problem should be addressed from a different aspect, for example, recipient choice. Building on prior knowledge and research, we would like to illustrate this point. Xuanming Su and Stefanos ZeniosFootnote 98 argued that to understand the significance candidates attach to outcomes associated with transplant decisions, they should be asked to declare which types of kidneys they would be willing to accept when joining the waiting list, instead of stating their preference when they are offered a kidney (like existing systems). Whereas Jae-Hyeon Ahn and John HornbergerFootnote 99 concluded that engaging candidates in the selection process of optimal donor kidney hold the potential to improve candidates’ quality and duration of life and consequently enhance kidney transplantation programs’ overall efficacy. Amir Elalouf and Uri Yechiali (unpublished data) also state that candidates should be granted the opportunity to evaluate the benefit of accepting the first offered organ and comparing it to the efficacy of waiting for the next one. The authors’ analysis suggests that, compared with other allocation policies such as first come first served or UNOS, the proposed rule offers superior performance in terms of equity (it is the fairest policy for waiting time) and medical efficiency. Hence, the notion that we are trying to portray is that a fairer system requires the public’s involvement in the organ donation and allocation processes by sharing their preferences with decisionmakers. If donated organs are a community resource and are regarded as a national, lifesaving means, guidelines, and principles have to represent and reflect the values and beliefs of the different layers comprising a community.
Summary: Efficiency versus Equity
It is inherently impossible to maximize efficiency (utility) and equity simultaneously; instead, there is a trade-off between the two ethical principles (illustrated in Figure 1). Indeed, addressing any one of the challenges outlined above—including injustice stemming from age, ethnicity, geographical location, socioeconomic status, and so forthFootnote 100—is likely to impair the capacity to address others, thereby creating controversy and potentially inflicting some cost on autonomy, impairing trust, or reducing live donation.Footnote 101, Footnote 102 Thus, a righteous and fair organ allocation process that will satisfy all the community layers is still not in sight. Yet, policymakers generally agree on the criteria that should not be considered in organ allocation decisions, for example, arbitrarily deprioritizing certain groups merely since they are easily identifiable and distinguishable or because of their instrumental or societal value.Footnote 103 Hence, national allocation systems and local policies concerning the evaluation of potential recipients and acceptance of organs are designed to balance the various ethical (efficiency/equity) principles in a standardized and socially acceptable manner.Footnote 104 Table 1 summarizes how the kidney allocation system, which UNOS currently implements, attempts to address each principle.Footnote 105
a Friedewald JJ, Samara CJ, Kasiske BL, Israni AK, Stewart D, Cherikh W, et al. The kidney allocation system. The Surgical Clinics of North America 2013;93(6):1395–406. doi:10.1016/j.suc.2013.08.007. The table was adapted to the current paper.
Abbreviations: ESRD, end-stage renal disease; KDPI, kidney donor profile index.
Acknowledgment
This work was supported by grant 2016/78 from the Israel National Institute for Health Policy Research.