Psychosocial Aspects of Kidney Transplantation and Living Kidney Donation

The Waitlist

The vast majority of patients with ESRD will not go on to receive a kidney transplant. The details of the transplant evaluation process are discussed later in this chapter. Less than 20% of dialysis-dependent patients are on the transplant waitlist. Conversely, of patients on the kidney transplant waitlist, close to 80% are dependent on maintenance dialysis, leaving approximately 20% who are not yet dialysis dependent.

In the US before 2004, wait time for kidney transplantation did not begin until a patient was listed for transplant. In recognizing that patients who did not have the benefit of early referral for transplant evaluation might then be subjected unnecessarily to prolonged time to await transplant (i.e., longer periods of maintenance dialysis leading to higher risk of waitlist mortality), an Organ Procurement and Transplantation Network (OPTN)-sponsored alternative allocation system was adopted. This was essentially a “variance” within what became the new kidney allocation system (KAS), which was implemented as of 2014. This variance allows a patient’s wait time to begin (retroactively in some cases by the time of referral for transplant evaluation) at the time they first initiated dialysis (or once listed if not yet dialysis dependent). The response to using this variance has been generally positive. Implementation overall of the new KAS since 2014 has resulted in an increase in the number of transplants in younger candidates, those highly sensitized, Black and Hispanic candidates, and patients who have been dialysis dependent for at least 5 years. Notably, there was a decrease in the number of transplanted kidneys with a kidney donor profile index (KDPI) above 85% (a continuous scale used to estimate the expected survival of a deceased donor kidney), raising concern for graft survival. However, long-term graft survival will need to be monitored, whereas early graft survival appears to be unaffected by the new KAS.

Waitlist Mortality

Awaiting transplantation is not without risk. By the end of calendar year 2015, less than 20% of those on the kidney transplant waitlist actually went on to receive a kidney transplant, underscoring the significant discrepancy between the number of patients in need of transplantation and those who are fortunate enough to receive a donor kidney. Furthermore, of 31,672 people removed from the kidney transplant waitlist in 2015, only 17,611 actually underwent transplantation. Close to 5000 patients died while awaiting transplantation and another 4154 (13.1%) were removed because of deterioration in their health. The average wait time to transplant can range anywhere from less than 1 year (25.8% of patients wait listed) to greater than 5 years (15.7%), with the majority of patients (58.5%) waiting between 1 and 5 years to be transplanted. The median wait time to transplant equals 3.6 years and varies greatly depending on the geographic region where a patient is listed. Although the mortality rate for patients on dialysis and awaiting transplantation has declined significantly (by 27%) since 2004, the expected remaining life span once on replacement therapy was approximately 8 years for patients ages 40 to 44 years, and approximately 4.5 years for individuals 60 to 64 years of age. For patients starting hemodialysis, all-cause mortality peaks at the second month of treatment and decreases thereafter, whereas patients beginning peritoneal dialysis experience a gradual increase in mortality risk within the first 12 months of treatment. It is postulated that this group may see a delayed mortality risk given they are typically a select group, often younger, and likely to have undergone more extensive pre-ESRD planning.

Given this inherent risk, the outlook for patients awaiting transplant while on dialysis can appear quite bleak from the perspective of the patient and family members. In our clinical experience, dialysis patients are acutely aware of the mortality risk associated with living on dialysis. Patients are exposed to medical emergencies on the dialysis unit for fellow dialysis patients, and can be affected profoundly when they observe that a patient has not returned for treatment. In our pretransplant psychosocial evaluations, prospective kidney transplant candidates frequently share their concerns regarding both the physical and psychosocial burdens of being dialysis dependent. For example, one prospective candidate reported that his initial nonadherence with dialysis sessions stemmed from having witnessed another patient suffer medical complications while dialyzing and ultimately never returned for treatment. He shared having to overcome a significant degree of fear to improve his own adherence. Many young patients interviewed have shared how out of place they feel when surrounded by older adult patients and how demoralized they feel to be reliant upon machinery. In contrast, an older transplant candidate expressed her desire for transplant eligibility, while taking the perspective of “how wonderful it is,” that a machine exists that can help keep her alive with a reasonable quality of life (QOL).

Waitlist Physical Quality Of Life

In addition to the mortality risk, patients are at risk for a multitude of physical degradations to their health and, in turn, ultimately QOL while on dialysis. High symptom burden and related conditions can lead to hospitalization for patients dependent on dialysis. For example, a group at Mount Sinai recently looked at common reasons for hospital admission and readmissions for patients on peritoneal dialysis, based on the National Readmission Database (NRD) for 2013. The NRD is a database that includes discharge data (approximately 14 million discharges per year) spanning 21 geographically dispersed states as of 2013 and accounting for nearly 50% of hospitalizations in the US. The leading reasons for initial hospitalization of dialysis-dependent patients included, in descending frequency, implant/catheter complications (23.22%), hypertension, septicemia, diabetes, fluid and electrolyte disorder, peritonitis, congestive heart failure, pneumonia, and acute myocardial infarction. Patients were most frequently readmitted secondary to myocardial infarction, surgical complications, and diabetes, respectively. Independent predictors of readmissions included age (35–49), female gender, comorbidities including liver and peripheral vascular disease, and depression.

In the case of hemodialysis, type of access (arteriovenous fistula, tunneled catheter, or arteriovenous graft) can have a major effect on a patient’s QOL. In a recent study of 77 hemodialysis patients in the Pittsburgh, Pennsylvania area, those with arteriovenous (AV) fistula were more satisfied with their access, compared with those with other types of access noted. Factors that predicted dissatisfaction with access included being on dialysis for less than 1 year, more frequent access-related hospitalizations, and having arteriovenous graft (AVG) access. Greater satisfaction with AV fistula is likely because it provides adequate blood flow and typically lasts longer and has a lower rate of complication than other types of access. As of 2014, close to 65% of prevalent dialysis patients were using an AV fistula for their access. A recent meta-analysis comparing QOL across renal replacement therapies indicated that HRQOL (as assessed with the Medical Outcomes Study Short Form 36-Item Health Survey [SF-36]) was higher for transplanted patients than for dialysis patients (with the exception of the mental health dimension). Surprisingly, there were no statistical differences in QOL between hemodialysis versus peritoneal dialysis. It is important to note that the SF-36 is a generic quality of life instrument, and not specifically designed for dialysis patients. Consequently, it may have been insufficiently sensitive to some important QOL differences between hemodialysis and peritoneal dialysis.

Uremic pruritus is another common problem for patients on hemodialysis, which has been associated in the past with depression, lower QOL, and mortality. A recent international review of 35,452 hemodialysis patients in 17 countries from the Dialysis Outcomes and Practice Patterns Study (DOPPS) examined the prevalence of pruritus, between 1996 and 2015. Although the number of patients who endorsed being “very much” or “extremely bothered by” itching decreased over time by 2015 (28%–18%), those who endorsed being “nearly always” or “always bothered” by itching cited it having a major effect on both their work and social life. It was also found that 17% of patients did not report their symptoms to medical staff, and nearly 70% of medical directors in dialysis units underestimated the prevalence of pruritus for their patients.

Hypothyroidism is another highly prevalent issue in hemodialysis patients and is seen as a risk factor for impaired QOL and depressive symptoms. Higher serum thyrotropin levels have been associated with impaired HRQOL across multiple domains including energy/fatigue, pain, and physical function.

Common physical symptoms from which dialysis patients suffer include fatigue, pain, muscle cramping, sleep disturbance, and sexual dysfunction, affecting at least 50% of patients on dialysis. A primary and disruptive complaint for patients on maintenance dialysis is fatigue, which appears to be driven by a variety of factors for patients with ESRD. Fatigue is a common and often debilitating symptom for patients with chronic kidney disease (CKD), with prevalence rates varying between 42% to 89% of patients with ESRD. In fact, “feeling tired” or “lack of energy” and “trouble staying asleep” were identified within the top five most prevalent symptoms reported by patients in a previous study comparing symptom burden for patients with ESRD on maintenance dialysis versus CKD.

Based on anecdotal clinical experience in assessing pretransplant candidates, fatigue after dialysis sessions significantly shapes the remainder of a patient’s day. Many patients report having to go home to sleep for several hours after their dialysis treatments, and many cite having to pace their activity based on their dialysis schedule. This can cause significant relationship strain with families who have difficulty understanding the patient’s physical experience while on maintenance dialysis and their associated energy limitations.

Behavioral Risk Factors on The Waitlist

In addition to poor QOL on the waitlist, an increasing number of patients may be delisted for medical or behavioral concerns, with nearly one-third of patients delisted in 2007. Because of the elevated risk of waitlist mortality and adverse medical outcomes, a number of investigators have examined behavioral risk factors among waitlisted patients, including physical activity, dietary adherence, and weight management. In addition to the possibility of removal from the waitlist, poorer behavioral compliance has been associated with a greater likelihood of cardiovascular events and mortality before transplantation, underscoring the importance of self-management behaviors that optimize behavioral risk factor modification.

Consistent with the trends observed in the larger US population, rates of obesity, physical inactivity, and poor dietary compliance have risen among transplant candidates over the past 2 decades. Moreover, because these factors all confer greater risk of kidney failure, a higher proportion of individuals who ultimately require kidney transplantation exhibited these behavioral risk factors before they manifested kidney disease. Although estimates vary, the proportion of waitlisted patients with obesity is likely at least 25%. Estimates of physical inactivity and, as a corollary, poor physical fitness are comparably high, with the majority of dialysis-dependent, waitlisted patients exhibiting low levels of physical activity and greater risk of subsequent cardiovascular disease (CVD) events.

Interestingly, emerging data suggest that more refined metrics of body composition provide more accurate prognostication for clinical events. For example, recent studies have demonstrated that waist-to-hip ratio is more predictive of CVD events and mortality relative to BMI. Sarcopenia is a well-recognized chronic condition that is prevalent in patients with CKD, and is defined by a generalized loss of skeletal muscle mass with associated reduced strength or physical performance. There is likely a complex interplay between accelerated protein catabolism induced by metabolic acidosis, proinflammatory cytokines, uremia, and the actual process of dialyzing leading to loss of lean muscle mass that sets the stage for sarcopenia in ESRD. Although findings are mixed regarding associations between sarcopenia and increased risk for mortality, slower gait speed and low muscle strength have been found to be significantly associated with mortality for patients on maintenance dialysis. This underscores the importance of interventions in pretransplant candidate populations for targeting poor muscle strength and lack of physical activity that may be associated with and compounded by complaints of fatigue.

A patient’s functional status appears in part to predict the likelihood of undergoing transplantation once waitlisted. A recent retrospective cohort study of waitlisted patients examined functional status (as assessed by the physical functioning scale of the Medical Outcomes Study 36-Item Short Form Health Survey) from the United Network of Organ Sharing (UNOS) registry data, related to inactivation versus transplantation. Patients in the lowest quartile of physical functioning score were more likely to be inactivated and less likely to undergo transplantation. Although patients with lower physical functioning scores were associated with a decreased 3-year survival posttransplant, patients with lower physical function still lived longer with transplantation compared with dialysis. This predictive importance of physical functioning underscores the importance of developing interventions aimed to improve the overall functionality of kidney transplant candidates.

Anecdotally, at our center a decline in functional status often leads to a patient’s delisting. Intervening to maintain and improve physical function can be challenging. Given that waitlisted patients are often geographically distant from the transplant center, it is difficult to implement interventions to promote regular exercise, particularly when patients may be struggling with physical fatigue and/or depression that may negatively affect their motivation to engage in increased physical activity.

A recent review was conducted by Stanford University and the Veterans Affairs Palo Alto Health Care System of key randomized controlled trials aimed at comparing exercise versus regular care in dialysis-dependent patients, with physical function as a primary outcome. The most common interventions were found to be “intradialytic” exercise, which was delivered during dialysis treatment. This was followed by in-center aerobic exercise delivered on nondialysis days, and in-home exercise regimens, respectively. Interestingly, none of these interventional trials were specifically focused on kidney transplant candidates. This is likely due to the logistical challenges in tailoring/coordinating intervention efforts between transplant teams, dialysis treatment centers, and managing nephrologists. Instead, studies regarding exercise and physical rehabilitation in transplant recipients have primarily been performed by transplant centers post transplantation. As such, researchers proposed the value and clinical benefits in transplant centers establishing “prehabilitation” programming to target the functional decline and muscle wasting seen in patients awaiting transplantation.

Targeting Fitness: Proposed Intervention

Pretransplant exercise programming could translate to positive changes in transplant candidates’ overall HRQOL. In fact, targeting patients with specific exercise interventions during the waitlist period pretransplantation may help break what is potentially a vicious cycle of affective, physical, and medical consequences for the patient waiting on maintenance dialysis ( Fig. 40.1 ).

Cheng and colleagues recently proposed a new treatment paradigm for kidney transplant programs, which includes prehabilitation for kidney transplantation. Several benefits to engaging patients in prehabilitation versus rehabilitation (after transplantation) include intervening early on to affect both frailty and cardiopulmonary fitness, particularly given these are associated with posttransplant morbidity/mortality, and utilization of healthcare services. It is also recognized that physical activity declines within the first year after transplant, and thus unfortunately high rates of attrition are seen in posttransplant exercise programs. Additionally, researchers highlight the fact that patients are often most motivated to engage in healthy behavior change to improve their health as directed by transplant teams while they are awaiting transplantation. Logistics, such as when and how transplant teams will integrate assessment of physical function into their workflow, as well as the type of exercise intervention (e.g., intradialytic or home-based with the use of an electronic portal for communication with the team) to be implemented are important considerations for the feasibility of such programming. Researchers identify using the 6-minute walk and the sit-stand-sit tests as part of their transplant center’s physical function assessments, given they can be incorporated easily into a nurse coordinator’s workflow. This physical function assessment has been incorporated into a program they designed called TRAC (Transplant Readiness Assessment Clinic), which is designed to reassess readiness for transplant once patients are nearing transplantation (based on average wait times at their center). This type of programming has the potential to be mirrored at other transplant centers to improve patient care.

Waitlist Unemployment

In addition to the myriad physical challenges faced by dialysis-dependent patients on the kidney transplant waitlist, dialysis also imposes significant practical obstacles. Hemodialysis sessions typically require patients to travel to dialysis centers 3 days per week, for sessions lasting up to 3 to 4 hours at a time. Patients undergoing peritoneal dialysis must adjust to daily intervention for varied durations of time. These treatments clearly interrupt daily routines and work schedules for those who are able or attempting to maintain employment, despite challenges with their medical condition.

Muehrer and colleagues recently conducted a retrospective review of factors affecting patient employment at the time of dialysis initiation, using data from the United States Renal Data System (USRDS) database (1992–2003). The review included 102,104 patients who were of working age and employed (part- or full-time) 6 months before the initiation of dialysis. A patient was identified as “unable to maintain employment” when they noted a change in their employment status (e.g., from full- to part-time, or to another status altogether, such as retired, student, or homemaker) at the initiation of dialysis. Results revealed that 71% of patients were “unemployed” upon initiation of dialysis treatment, compared with the roughly 10% unemployed in the general population within the US in 2010 (at the time of this review). Several factors were identified that correlated to risk of unemployment in patients initiating dialysis. Individuals who were 55 years and older, nonwhite, and Hispanic were less likely to maintain their previous level of employment. Additionally, the cause of ESRD also appeared to be predictive of loss of employment, in that patients with diabetes or hypertension were less likely to maintain their same level of employment compared with patients with glomerulonephritis, cystic kidney diseases, or other urologic disease. Perhaps not surprisingly, patients who successfully maintained the same level of employment in the 6 months before kidney failure were more likely to select peritoneal dialysis as their initial mode of treatment. This is likely given that peritoneal dialysis allows for some flexibility in one’s treatment schedule, although sessions are typically more days per week compared with in-center hemodialysis. Despite this, peritoneal dialysis as a treatment mode accounted for only 17.5% of patients initiating dialysis in the sample. Given that the majority of patients start on and remain dependent on center-based hemodialysis, loss of employment or a significant change in work status remains a particular threat to financial stability and QOL for patients on dialysis.

Loss of employment can have a profound effect on a patient’s self-identify, as was the case for a middle-aged transplant candidate who had worked to support her family since the young age of 16. Without the ability to work and to provide for her family, she felt completely lost. This significant loss contributed to depression and a growing resentment toward her spouse whom she felt did not understand how dialysis dependence affected her self-worth. Ultimately, this led to their separation and a need for complete review of her social support system for transplantation, because her husband had been her identified primary caregiver.

Waitlist Emotional Quality of Life

The wait period before transplantation involves many emotional adjustments as patients undergo changes to their day-to-day routines, upsets to their family roles/dynamics, and with the associated physical dependency on a machine to dialyze. Depression is likely one of the most studied consequences of dialysis, particularly as it relates to QOL and increased morbidity and mortality. Prevalence rates of depression in patients who are dialysis-dependent vary between 22.8% and 44.8%, based on the method of screening/evaluation. In a recent prospective study of risk factors for readmission in maintenance dialysis patients recruited at the University of North Carolina, 37.7% of patients suffered a 30-day hospital readmission. Notably, readmitted patients were more likely to have a positive screen for depression, poor social support, and lower health literacy based on self-rated health screening instruments; even after adjusting for a variety of clinical features and admission-related factors. Depression in dialysis patients has also been examined in relation to other clinical factors, such as anxiety, sleep disturbance, and fatigue.

Specifically, dialysis-related anxiety has been correlated with severity of both anxiety and depression (as assessed with the Beck Anxiety Inventory [BAI], and the Beck Depression Inventory [BDI]) in a recent cross-sectional study of 246 maintenance hemodialysis patients. Notably, 32% to 51% of these patients endorsed anxiety in the following situations: (1) when presenting for dialysis, (2) hearing alarms, (3) being connected to equipment by a new provider, or (4) the presence of emergency personnel on the dialysis unit.

Depression and sleep disturbance are often interrelated. Disturbed sleep affects nearly 60% of patients on hemodialysis. Patients who meet the diagnostic threshold for depression have been found to endorse significantly more disruption in the quality of their sleep, daytime fatigue, and issues with restless leg syndrome compared with patients endorsing minimal/less depressive symptoms. Interestingly, one recent correlational study found that whereas dialysis shift was not significantly related to sleep quality and depression, poor sleep quality was significantly associated with phosphorus level, reliance on sedatives, diabetes, rural residency, unemployment, illiteracy, female gender, and patient age.

Targeting Depression: Proposed Interventions

Despite the prevalence of depression in ESRD and in patients on maintenance dialysis awaiting transplantation, there is limited evidence to guide optimal treatment and management. Until early 2017, there were only two systemic reviews: (1) looking at antidepressant treatment, and (2) psychosocial interventions for depression. Astonishingly, the systemic review in 2009 of psychosocial interventions resulted in no identified randomized, controlled trials comparing psychosocial intervention with control intervention or no intervention in depressed patients on dialysis.

Quite recently, Friedli and colleagues conducted a randomized controlled feasibility trial examining sertraline versus placebo in patients with major depression on dialysis. Depression was initially screened for using the Beck Depression Inventory-II (BDI-II); those scoring ≥16 and not already being treated were invited to undergo a diagnostic interview to confirm a diagnosis of major depressive disorder. Those meeting criteria for depression were then randomized into two groups (sertraline vs. placebo). Although recruitment began with 709 participants, ultimately only 30 were randomized. Initially 32.6% had elevated BDI-II scores; however, 29% were already receiving treatment and thus were excluded. Of those referred for diagnostic interview, a total of 37 participants were diagnosed with major depression. Over a 6-month period, dropout rates were greater in the sertraline group because of adverse events (one death secondary to cardiac arrest; three dropouts due to nausea, headaches/dizziness, insomnia, concern about side effects, and sweating/palpitations) within the first 2 to 3 months, for a total of seven participants. Two participants withdrew in the placebo group (decided against taking additional medications, participation). Ultimately, depression scores improved significantly in both treatment groups; however, there were no statistical differences between the two groups. Primary challenges with recruitment (approximately 38% of participants eligible for interview declined to participate) and the resultant small sample size were identified limitations of the study and any conclusive findings. Ideas to help inform future randomized trials included a shorter follow-up period and possibly including participants already on pharmacologic management of their depression to increase sample size.

Our transplant center’s medical psychology group is available to provide cognitive behavioral therapy (CBT) for patients both pre- and posttransplantation. However, because patients are often only reevaluated by the transplant team once per year after initial approval for listing, regular follow-up with patients is logistically a challenge. This can be further compounded by a patient’s geographic distance from the center that may make frequent follow-up prohibitive. Therefore screening patients for psychosocial concerns and assisting with alternative local behavioral health referrals is often the best form of intervention that is feasible.

Psychotherapeutic interventions such as CBT, problem-solving therapy, and telephone-adapted mindfulness-based stress reduction show promise for targeting depression and anxiety, while enhancing QOL for patients awaiting transplantation. Specifically, an ongoing clinical trial comparing sertraline versus CBT for ESRD patients with depression (ASCEND) will be the first large-scale multicenter randomized controlled trial to evaluate the efficacy of pharmacologic versus nonpharmacologic treatment of depression in hemodialysis patients. Based on the future findings of this trial, patients on dialysis may finally have access to more optimal, evidence-based treatments for depression, thereby enhancing their overall QOL while awaiting kidney transplantation.