Abstract
Introduction
Frailty and cognitive function are often measured during kidney transplant evaluation. However, patient perspectives on the ethical considerations of this practice are unclear.
Research Question
What are patient perspectives on the use of aging metrics in kidney transplant decision-making?
Design
One hundred participants who were evaluated for kidney transplantation and were enrolled in an ongoing prospective cohort study (response rate = 61.3%) were surveyed. Participants were informed of the definitions of frailty and cognitive impairment and then asked survey questions regarding the use of these measures of aging to determine kidney transplant candidacy.
Results
Participants (75.6%) thought it was unfair to prevent older adults from receiving a kidney transplant based on age, but there was less agreement on whether it was fair to deny frail (46.5%) and cognitively impaired (45.9%) patients from accessing kidney transplantation. Compared to older participants, younger participants had 5.36-times (95%CI:1.94-14.81) the odds of choosing a hypothetical younger, frail patient to list for kidney transplantation than an older, non-frail patient; they also had 3.56-times (95%CI:1.33-9.56) the odds of choosing the hypothetical frail patient with social support rather than a non-frail patient without social support. Participants disagreed on the use of patient age as a listing criterion; 19.5% ranked it as the fairest and 28.7% as the least fair.
Conclusion
The patient views highlighted in this study are an important step toward developing ethical guidelines to ensure fair use of frailty, cognitive function, and chronological age for kidney transplant decision-making.
Introduction
There is a profound organ shortage in the United States that has led to decreased access to kidney transplantation, particularly for older (age ≥ 65 years) patients. 1 Though the Kidney Allocation System improved access to organ transplantation overall, access to kidney transplantation for older candidates decreased by 24.0%. 2 Transplant centers often rely on patient age as well as clinical and social factors to determine eligibility. This narrow focus on chronologic age has resulted in 11% of ideal older candidates who would have identified a live donor being denied access to a kidney transplant. 3 Assessing physiologic age by measuring frailty and cognitive function, rather than relying solely on chronological age, during the evaluation may be one approach to improve decision-making.
Frailty, decreased physiologic reserve resulting in increased vulnerability to various health stressors, 4 is common in candidates; among older candidates, 16.4% are frail. 5 Frailty is measured at the transplant evaluation in approximately 69.0% of U.S. transplant centers, 6 to aid in waitlist decision-making and post-transplant risk stratification. 7 Candidates who were frail at admission experience worse post-transplant outcomes, including longer hospital stay, delirium, higher risk of immunosuppression intolerance, and mortality.8–12 Recipients who were frail are more likely to improve their frailty status by 3 months post-transplant. 13
Cognitive impairment, the decreased performance of mental abilities like learning, thinking, and problem solving, was found to be common in candidates, with up to 22.0% of candidates experiencing global cognitive impairment and 7.7% experiencing severe cognitive impairment. 14 Cognitive impairment was associated with an increased risk of hospitalizations and mortality as well as lower health-related quality of life.15–18 Like frailty status, cognitive performance improved 3 months post-transplant on average. 19
Currently, there are ethical guidelines in place to prevent age from being used as a sole criterion for transplant decision-making; however, they do not consider a patient's frailty and cognitive function as measures of physiologic aging. 20 Transplant centers are seeking a more nuanced approach to using these measures to ensure that the optimal candidates are gaining access to kidney transplantation while not denying access to older candidates. 6 Elicitation of patient perspectives on the use of these assessment criteria for transplant decision-making is necessary because patients are key stakeholders in the listing process 21 and their perspectives on just allocation are essential. 22 Yet, efforts to date have only focused on expert opinions on the use of frailty and cognition in transplant decision-making. 23
The goal of this study was to identify patient values to support the creation of ethical guidelines regarding the use of frailty and cognitive function during the transplant evaluation.
Design/Methods
Study Design
The study design was a survey of participants of an on-going cohort study. One hundred participants who were enrolled in a prospective cohort study at kidney transplant evaluation were subsequently surveyed about the use of frailty, cognitive impairment, and age in transplant decision-making for this study. Participants either elected to complete the survey online after they consented electronically or completed the survey over the phone after they consented orally. There was no incentive for the participants in this study.
The clinical and research activities being reported were approved by the Institutional Review Boards and were consistent with the Declaration of Helsinki and the Declaration of Istanbul as outlined in the Declaration of Istanbul on Organ Trafficking and Transplant Tourism.
Setting
This study took place at an urban transplant center in the eastern United States. Participants completed the survey either by phone or email.
Population
The target population of this study was U.S. patients who were evaluated for kidney transplantation. Compared to all patients listed in the US during the study period, the patients listed at this transplant center were more likely to be Black (45.1% vs 28.8%); however, female patients (38.4% vs 38.1%) and older patients (27.4% vs 20.2%) were similarly represented. The center did not have an absolute age cut-off for listing.
Sampling
This was a convenience sample study of patients from the transplant center who were enrolled in a cohort study and evaluated between January 2019 and November 2021. Cohort study inclusion criteria included: (1) ability to speak English and (2) 18 years of age or older. There were no exclusion criteria in this study.
Data Collection and Procedure
Survey Design
Questions and responses were derived using themes identified from a previous study that assessed transplant candidates’ attitudes and beliefs about the use of frailty and cognitive function. 24 The questions were reviewed by experts in frailty and cognition along with a bioethicist and a statistician. The final survey instrument consisted of 12 questions that covered 4 areas: (1) waitlisting and transplanting of frail patients, (2) waitlisting and transplanting of cognitively impaired patients, (3) hypothetical case scenarios, and (4) ranking transplant decision-making factors in consideration for transplant candidacy (Available upon request).
Demographics and Medical History
Participant demographics and medical history were already obtained by the ongoing prospective cohort study. These included age, sex, race, highest completed years of school, dialysis type, frailty status, and cognitive function at transplant evaluation. Participants who were ≥65 years were defined as older.3,25 Frailty was measured using the physical frailty phenotype (PFP) and participants who had a score of 3 or higher were categorized as frail. 4 Of the 100 participants, 55 did not have frailty scores due to the pause on in-person research during the COVID-19 pandemic; this limited the ability to directly measure 2 components of PFP (walk speed and grip strength). Additionally, global cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). 26 Participants who had a score of lower than 26 on the MoCA were categorized as cognitively impaired. 26
Survey Questionnaire Components
Before starting the survey, participants were informed of the definitions of frailty and cognitive impairment. They were also told that: (1) receiving a transplant could improve frailty status and/or cognitive status, (2) older patients were more likely to be frail and cognitively impaired, and (3) people who are frail or cognitive impaired are at risk for worse post-transplant outcomes.8–19 Prior to questions relating to social support, participants were informed of the definition of social support. Participants were asked questions regarding their opinion of the use of age, frailty, and cognitive function during the decision-making phase for transplantation (Survey and definitions are available upon request).
Waitlisting and Transplanting of Frail and Cognitively Impaired Patients
Participants were asked how much they agreed using the 5-point Likert scale (possible responses: strongly disagree, disagree, neutral, agree, or strongly agree) with the statements: (1) “it is fair to ensure that more frail patients get transplanted first,” (2) “it was fair to prevent patients from being waitlisted because they were frail,” and (3) “transplant centers should be responsible for helping frail patients improve their health status before being considered for the transplant waitlist.” These questions were then repeated with the phrase patients with cognitive decline substituted for frail patients.
Waitlisting Older-Age Patients
Participants were asked how much they agreed with the statement: “it was fair to prevent older patients from being waitlisted for a transplant due to their age.” If they disagreed, then they were asked follow-up questions regarding whether it was fair to prevent an older patient from being waitlisted for a transplant if they were also frail, cognitively impaired, or both frail and cognitively impaired.
Hypothetical Case Scenarios
Participants were asked to imagine themselves as a member of the transplant team and decide which of 2 patients should be put on the transplant waiting list in 4 different scenarios. The first scenario asked participants to decide between a 70-year-old who is not frail or a 40-year-old who is frail. The second scenario asked participants to decide between a 70-year-old without cognitive impairment and a 40-year-old with cognitive impairment. The third scenario asked participants to decide between a non-frail patient with no social support and a frail patient with social support. The last scenario asked participants to decide between a patient with no cognitive impairment and no social support and a patient with cognitive impairment and social support.
Transplant Decision-Making Factor Rankings
Participants were asked to rank the items that they believed were fair for the transplant team to consider from most fair (number 1) to least fair (number 8): older age, frailty, cognitive impairment, lack of social support, medication non-adherence, history of drug use, other medical issues, and current unhealthy lifestyle. These items were chosen by geriatric transplant experts who identified important factors to consider before waitlisting candidates for kidney transplantation in a previous Delphi study. 23
Data Analysis
Ordered logistic regression was used to quantify the associations between the participant's own frailty, cognitive status, and age with their responses (strongly disagree to strongly agree) to questions related to waitlisting. Additionally, logistic regression was used to quantify the association between participant's aging measures and which candidate they chose to waitlist in the hypothetical scenarios after adjusting for race, sex, and education status. Means were calculated for ranking of transplant decision-making waitlist factors as well as the percentage distributions of ranking. Logistic regression models tested whether the participants’ age, frailty, or cognitive status was associated with the way they ranked the related decision-making factors including age, frailty, and cognitive status. Analyses were calculated using Stata 16.1 (Stata Corp, College Station, Texas).
Results
Demographics and Medical History
A total of 100 participants completed the survey with a response rate of 61.3% (Figure 1). Among the participants with a median age of 63 years (Interquartile Range: 51, 71), 34.0% had been listed for transplant within 1 year of evaluation, 44.0% were female, 47.0% were older, 50.0% were Black, and 70.0% had a high school diploma or higher educational attainment. Furthermore, 17.0% were cognitively impaired and 13.0% were frail (Table 1).
Flowchart of participant recruitment by phone or email from a multi-center prospective cohort study who were evaluated for a kidney transplant between January 2019 to November 2021.
Characteristics of Participants Who Provided Opinions on the Use of Frailty, Cognition and Age in Kidney Transplant Decision-Making.
Participants who were less than or equal to 65 years old were categorized as younger.
Global cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Participants who had a score of lower than 26 on the MoCA were categorized as cognitively impaired.
Frailty was measured using the Physical Frailty Phenotype (PFP). Participants who had a score of 3 or higher using the PFP were categorized as frail. Frailty scores were not available for all participants due to data collection issues during COVID-19.
Waitlist and Transplant Decision-Making for Frail and Cognitively Impaired Patients
Forty-seven-point five percent of participants agreed or strongly agreed that it was fair to ensure that frail patients should get transplanted first. Additionally, 46.5% of participants disagreed that it was fair to prevent patients from being waitlisted for a transplant and accessing kidney transplantation because they were frail. Seventy-five-point seven percent of participants agreed or strongly agreed that the transplant centers should be responsible for helping frail patients improve their health status before they were considered for the transplant waitlist (Figure 2).
Participant opinions on the use of frailty, cognition, and age for kidney transplant decision-making.
For cognitive impairment, 31.6% of participants agreed or strongly agreed, and 40.8% of participants were neutral on whether it was fair to ensure that patients with cognitive decline get transplanted first. Additionally, 45.9% of participants disagreed that it was fair to prevent patients from being waitlisted for a transplant and accessing kidney transplantation because they were cognitively impaired. Seventy-point seven percent of participants agreed or strongly agreed that the transplant centers should be responsible for helping patients with cognitive impairment improve their health status before they were considered for the transplant waitlist (Figure 2).
Waitlisting Older Patients
Seventy-five-point six percent of participants disagreed or strongly disagreed that it was fair to prevent older patients from being waitlisted for a transplant due to age. Among those who disagreed or strongly disagreed, 65.8% did so if the patient was also frail, 64.6% if the patient was cognitively impaired, and 53.8% if the patient was both frail and cognitively impaired (Figure 2). Younger participants had 2.46-times (95%CI:1.13-5.29, P = 0.02) the odds of agreeing (compared to older participants) that it was fair to prevent older patient from being waitlisted.
Hypothetical Case Scenarios
When asked to pick 1 of 2 hypothetical patients to list, 52.0% of participants chose the older, non-frail patient over the younger, frail patient (Figure 3a). Compared to older participants, younger participants had 5.36-times (95%CI:1.94-14.81, P < 0.001) the odds of choosing the 40-year-old hypothetical patient who was frail.
Participant hypothetical scenario responses on kidney transplant decision-making. Participants (N=100) were asked to choose which hypothetical patient to list between 2 patients that were being evaluated for a kidney transplant.
In the second hypothetical scenario, 59.0% of participants chose to list the older, non-cognitively impaired patient as opposed to the younger, cognitively impaired patient (Figure 3b). There was no significant association between participant's age or cognitive status and their response.
In the third hypothetical scenario, 62.0% of participants chose to list the frail patient with social support as opposed to the non-frail patient with no social support (Figure 3c). Compared to older participants, younger participants had 3.56-times (95% CI:1.33-9.56, P < 0.01) the odds of choosing the frail patient with social support.
In the final hypothetical scenario, 59.0% of participants chose to list the patient with cognitive impairment and social support as opposed to the patient with no cognitive impairment and no social support (Figure 3d). Compared to older participants, younger participants had 2.94 (95% CI:1.14-5.29, P = 0.02) times the odds of choosing the cognitively impaired patient with social support.
Transplant Decision-Making Factor Rankings
Participants ranked other medical issues as the fairest factor and older age as the least fair factor to other decision-making factors including: frailty, cognitive impairment, lack of social support, medication non-adherence, history of drug use, and current unhealthy lifestyle. However, older age was a polarizing factor; 19.5% of participants ranked it as the fairest factor while 28.7% ranked it as the least fair factor (Table 2).
Participant Rankings of Kidney Transplant Decision-making Factors Based on Perceived Fairness.
Participants (N = 100) were asked to rank the 8 different factors that they believed were fair for the transplant team to consider for transplant from most fair (ranked first) to least fair (ranked eighth). Average rankings were calculated for each of the factors and percentages of participants’ rankings were reported.
Discussion
In this survey of 100 patients who participated, 75.6% thought it was unfair to prevent older adults from receiving a transplant based on chronological age but there was less agreement about whether it was unfair to deny frail (46.5%) and cognitively impaired (45.9%) patients from accessing kidney transplantation. The responses to the hypothetical case scenarios suggested that frailty and cognition were just as or even more important than chronological age when asked to choose which patients to include on the waitlist; these responses were influenced by participant age. Yet, older age was also the most polarizing factor with almost half saying that it was either the fairest or least fair decision-making factor. These findings highlight the complexity of patient perspectives in decision-making based on physiologic and chronologic aging.
This study provided important insights from both younger and older patients and has particular relevance given the aging population. The number of older patients receiving a kidney transplant has increased 19-fold in the last 32 years, with older adults now comprising approximately one-fifth of all recipients. 25 With this shift in patient demographics, factors relating to chronological age, and especially physiological age, should be considered at transplant evaluation. 25 Recent literature has found that the benefit of transplantation, compared to the continuation of dialysis with the competing risk of death or delisting, was likely greater for patients younger than 65 years. 27 Risk stratification may be improved once proxies for physiological age are implemented, including frailty and cognitive impairment measurements. This study has provided perspective on patients’ views regarding frailty and cognitive decline with the goal of providing ethically sound transplant care for older adults.
The results highlight patient perspectives regarding the role transplant centers should have in improving patients’ health status. In total, 75.7% of patients agreed or strongly agreed that transplant centers are responsible for helping frail patients improve their health status. Similarly, 70.7% of patients agreed or strongly agreed that transplant centers are responsible for helping cognitively impaired patients improve their cognitive function. Studies have shown both frailty and cognitive decline can be improved through prehabilitation in candidates.28,29 One study demonstrated improvements in frailty status after an 8-week exercise intervention in 19 candidates. 28 Another study found that patients who received intradialytic cognitive training or exercise training maintained their executive function and psychomotor speed compared to patients who received standard of care. 29 While the sample sizes in these studies were small, the results offer promising prospects for enhancing frailty status and cognitive function prior to transplantation. Larger randomized controlled trials are needed to determine the efficacy of prehabilitation among patients evaluated for transplantation 30 ; results from these trials could help justify more financial and logistical support for transplant centers. Patients suggesting that transplant centers should play a central role in improving their health status may suggest that patients are looking for guidance on how to improve their cognition and frailty. This study gives insight into patient perspectives regarding the responsibility patients believe transplant centers should have to improve frailty status and cognitive function prior to kidney transplantation.
In a previous qualitative study, patients followed a precautionary utilitarian approach to these issues and were uncomfortable using single factors such as frailty or cognitive impairment to deny someone access to kidney transplantation. 24 This study expanded on this by also asking patients to prioritize and rank decision-making factors against each other in scenarios where multiple factors are present. Although patients might not understand the nuances of post-transplant care for frail or cognitively impaired patients, their views and feedback are necessary to create ethical guidelines to support the use of frailty and cognitive function for decision-making.
The results of this study also mirrored the beliefs held by clinicians who care for end-stage kidney disease (ESKD) patients as reported in a Delphi study. 23 Experts in ESKD rated frailty, cognitive impairment, and social support as either very important or important to consider in transplant evaluation. They also found that older age, frailty, and cognitive impairment should not prevent a candidate from getting waitlisted. 23 It is crucial that both patients as well transplant clinicians agree on what characteristics are fair to be considered as part of transplant evaluation.
The strengths of this study included the patient's ability to express a variety of opinions and feelings using a Likert scale, to apply their beliefs on aging factors in hypothetical scenarios, and to directly rank different factors including physiological and chronological aging measures that are used in transplant decision-making. Further, the survey questions were formulated using themes from in-depth interviews with candidates. One limitation of this study was that all of the participants were from a single transplant center that may limit the generalizability of the findings; although it is unlikely that center-based practices or differences in patient characteristics, other than age, influence patient response to ethics questions on frailty and cognition. Compared to national kidney transplant waitlist patients, the participants included more underrepresented populations including Black patients (50.0% vs 28.8%), female patients (44.0% vs 38.1%), and older patients (47.0% vs 20.2%). Though this may not be fully representative of the candidate population, the sample still provides valuable insight into the perspectives of patients, particularly those who are often unrepresented in research. Another potential limitation was the effect of similarity bias, where participants might have shown preference for hypothetical candidates who shared the same age, frailty status, and/or cognitive status as themselves. Additionally, some participants did not have frailty scores due to the pause on in-person research during the COVID-19 pandemic.
Conclusions
Patients who have undergone evaluation for transplantation believe it is valuable to consider cognitive impairment, frailty, and age alongside other factors at evaluation but that none should be the sole driving factor in transplant listing decision-making. Notably, there were substantial differences in perspectives regarding specific aging metrics between older and younger participants. Therefore, transplant centers should not use chronological age alone to determine eligibility for transplantation. The patient views highlighted in this study are an important step toward developing ethical guidelines to ensure fair use of frailty and cognitive function for decision-making. Importantly, patients strongly felt transplant centers have an obligation to take an active role in helping patients improve their frailty and cognitive function prior to transplantation.
Footnotes
Data Availability
Data is available upon request from the Senior Author with a proposal that is approved by the study team.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: National Institute on Aging in the form of a bioethics supplement to grant number R01AG055781 (PI: McAdams-DeMarco). Study investigators were funded by the National Institute on Aging, National Institute of Diabetes and Digestive and Kidney Disease, and the National Institute of Allergy and Infectious Diseases: K24AI144954 (PI: Segev), R01AG055781 (PI: McAdams-DeMarco), R01AG077888 (PI: McAdams-DeMarco), K02AG076883 (PI: McAdams-DeMarco), and R01DK114074 (PI: McAdams-DeMarco).
