Key WordsDialysis, Kidney Transplantation, Living Kidney Donation, Psychosocial function, Quality of Life
End-stage renal disease (ESRD) is a physically, psychologically, and financially devastating condition that affects more than 661,000 people in the US alone. Maintenance dialysis, necessary for survival for patients with ESRD, is associated with numerous side effects and considerable disruption to all aspects of health-related quality of life (HRQOL). Kidney transplantation is the treatment of choice for qualifying patients with ESRD because is it associated with reduced mortality and morbidity, and superior HRQOL. However, kidney transplantation entails a rigorous evaluation, typically requires prolonged wait times, surgery, and lifelong adherence to a complex immunosuppressive medication regimen, and it is associated with its own threats to mortality and HRQOL.
This chapter explores psychosocial aspects of kidney transplantation. The chapter is divided into three sections: Pretransplant Dialysis, Kidney Transplantation, and Living Kidney Donation. This chapter draws heavily on data from randomized clinical trials, systematic reviews, and consensus statements. We also seek to bring these data to life by including our own anecdotal experiences as transplant psychologists. When relevant, we emphasize interventions that can moderate the negative effects of dialysis, kidney transplantation, and living kidney donation on HRQOL.
Functioning kidneys are necessary for survival. Although kidney transplantation is the treatment of choice for most patients with ESRD, the vast majority of ESRD patients will require maintenance dialysis to survive to transplantation. Of the 661,000 patients in the US with kidney failure, approximately 70% (468,000) are dependent on maintenance dialysis for survival. The majority of these patients (as of 2014) were receiving hemodialysis therapy (63.1%), with another 6.9% receiving peritoneal dialysis (29.6% had a functioning kidney transplant). Maintenance dialysis while awaiting transplantation creates ongoing medical, psychological, and financial burden to patients and their families.
In 2015 the number of adult patients listed and awaiting transplantation in the US decreased from 99,120 to 97,680 throughout the year. This was related to a number of factors, including a combination of a decrease in the number of new listings and inactive candidates, an increase in the number of candidates removed secondary to worsening medical condition(s), and an increase in the number of patients transplanted).
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.
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.
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.
Although kidney transplantation is clearly the optimal treatment for ESRD, only a small percentage of patients who are dialysis-dependent are actively listed and awaiting transplant. Dialysis is associated with a variety of physical and emotional consequences affecting QOL for both patients and their families. Wait times can be long and arduous, with increasing morbidity and mortality as waitlist time increases; thereby potentially adding to the threat of delisting once finally approved. Thus identifying interventions to address both the physiologic and psychological needs of transplant candidates is essential to helping patients maintain their functionality while waiting for a donor organ. There is a need for evidence-based treatments that are feasible to implement by transplant centers, particularly to address emotional factors such as depression in kidney transplant candidates. By better targeting the psychological factors associated with maintenance dialysis, we may help patients break the cycle of their emotional experience negatively affecting a variety of physiologic aspects of their health.
Kidney transplantation remains one of the most common treatment practices among individuals with advanced renal failure necessitating dialysis, with more than 19,000 renal transplants performed in 2016. After transplantation, patients are expected to effectively manage a complex medical regimen, including lifelong immunosuppressive treatment, routine laboratory draws to assess for signs of graft failure (rejection), and adhere to lifestyle recommendations (e.g., diet and exercise) to maximize long-term transplant outcomes. Accordingly, psychological functioning is an important component of both the transplant evaluation and effective adjustment after transplantation, because even subclinical levels of nonadherence have been associated with substantially increased risk of long-term rejection and graft loss. In addition, long-term self-management is difficult to maintain for many patients, underscoring the importance of motivational factors and coping styles in this population.
Kidney Transplantation and Quality of Life
Although perhaps the primary reason for seeking renal transplantation is to improve survival and obviate dialysis treatment, many patients are equally motivated by the possibility of improving QOL. Many dialysis patients, for example, note that many social aspects known to effect QOL are impaired before transplant, including loss of freedom and personal control, as well as pessimism regarding a normal return of function.
The majority of extant studies have demonstrated that renal transplant recipients experience large improvements on metrics of HRQOL, including general health, physical functioning, etc. Not all patients experience the same level of improvements, however, and not surprisingly patients who experience early posttransplant complications report lesser gains in physical and mental health outcomes, as well as greater anxiety and sleep disturbances. In addition to improving after transplant, HRQOL has previously been associated with mortality risk, although this association may be explained by comorbid depressive symptoms. In addition, not all domains of QOL show comparable improvements after transplant and even domains that show improvement appear to stagnate 1 to 2 years posttransplant, with concerns regarding stability of graft functioning and ability to return to work explaining a substantial portion of the variance in QOL outcomes.
In our clinical experience, many patients report anxiety and rumination regarding impending rejection episodes (i.e., waiting for the other shoe to drop), which often leads to disengagement from work and social activities. In addition, many individuals in the US must choose carefully when looking for employment opportunities, because too much work can cause them to lose disability health insurance benefits.
Kidney Transplant Evaluation
Patients wishing to pursue transplantation undergo rigorous assessment to determine their eligibility to receive a new kidney, either from a live or deceased donor. Although requisite medical criteria are typically prioritized, psychosocial functioning is also assessed before transplantation, and patients must meet a minimal standard demonstrating their ability to manage a complex medical regimen. Psychosocial evaluation of pretransplant candidates is complex and varies across centers, but conventionally includes the following domains of function (current and/or historical): social support, psychiatric function and treatment, substance use, cognitive status, educational and employment history, and medical compliance. Although functioning may vary across domains, typically patients are mandated to demonstrate adequate social support, freedom from current substance abuse, and adequate medical compliance. For example, previous consensus documents have generally advocated for the assessment of treatment compliance, mental health history (including cognitive status), substance use, and social support.
In our own practice these domains are also prioritized, with additional assessments of coping styles, knowledge regarding transplantation to establish informed consent, and behavioral health compliance (in addition to compliance with specific treatment recommendations). For example, because many individuals are required to lose weight for the first time to meet eligibility requirements for transplantation, assessments also include an evaluation of prior weight loss attempts, screening for potential weight-related behavioral disorders (e.g., eating disorders), and ability to tolerate psychological aspects of physical activity modification.
In addition to ensuring that minimum standards are met before listing, the overarching goals of pretransplant psychosocial evaluations are to assist in guiding patients toward comprehensive treatment plans that would allow them to become eligible for transplantation and to optimize their functioning on the waitlist. For example, patients with unstable psychiatric function may be recommended to initiate care with a local psychiatrist or other mental health practitioner. Similarly, patients with an extensive and/or recent history of substance use may be required to engage in relapse prevention counseling or other structured substance use program to mitigate the possibility of relapse after transplant. As noted later in this chapter, one concern of particular relevance among renal transplant candidates is the ability to cope effectively on the transplant waitlist, given the long wait times experienced in this population, typically lasting 5 to 6 years. Indeed, a substantial subset of waitlisted patients are delisted when they fail to continue to meet listing requirements.
Coping on The Waitlist
Patients on the waitlist for kidney transplantation are often listed for 5 to 6 years before transplantation in the case of a deceased donor. During this time patients typically continue dialysis, but must maintain eligibility for transplantation despite the exceedingly long length of wait. For many patients, this necessitates effective coping strategies to mitigate the effect of fatigue, poor QOL, and a burdensome treatment schedule required by dialysis before receiving their transplant. As reviewed elsewhere in this chapter, rates of depression are high among individuals with ESRD receiving dialysis (up to one-third), and many nonvegetative symptoms of depression are known sequelae from renal failure, including fatigue, cognitive deficits, decreased appetite, insomnia, and loss of libido. In addition to symptoms more directly attributable to the physiologic aspects of treatment, ESRD is associated with an array of social stressors, including disruption of family roles and social identity, changes in lifestyle, and impairments in personal control over many aspects of one’s life. Because dialysis treatment often lasts for 3 to 4 hours several times per week, patients often need to reorganize their entire weekly schedules to facilitate participation in this life-saving treatment. Not surprisingly, several studies have shown that higher internal locus of control is associated with lower depression among renal transplant candidates. Several studies have attempted to quantify the degree of disruption associated with dialysis, demonstrating that greater perceived illness intrusiveness was associated with greater emotional distress.
An area of increasing interest is the potential role of targeting modifiable risk factors after transplantation as a way of improving posttransplant clinical outcomes. Although kidney graft survival is substantially longer compared with other solid-organ transplant groups (e.g., lung, heart, and liver), long-term kidney allograft survival has stagnated over the past 20 years despite improvements to other aspects of care. Indeed, the health and QOL benefits of kidney transplantation have been well-described. Compared with remaining on dialysis, transplantation is associated with reduced risk of cardiovascular events, morbidity, and mortality, with benefits increasing over time. Despite these improvements, transplantation and chronic immunosuppressive therapy are associated with numerous complications requiring complex coping behaviors to effectively manage.
After transplantation, the majority of patients experience large improvements in QOL relative to their counterparts continuing in dialysis. For example, in a systematic review and meta-analysis of QOL in CKD, Wyld and colleagues found that transplantation was associated with large QOL improvements across an array of utility-based assessment techniques. Similarly, Landreneau and colleagues reported large benefits in HRQOL among transplant recipients compared with those in hemodialysis, as did Tonelli and colleagues, who found that the vast majority of available studies reported benefits after transplantation. Although the majority of patients receiving renal transplantation exhibit improved HRQOL, many patients continue to experience impairments in other domains of functioning after transplant. For example, although HRQOL in the Landreneau study were large, improvements in psychological QOL outcomes after kidney transplantation were much smaller and heterogeneous, suggesting that these benefits are inconsistent. In addition to the importance of QOL benefits in their own right, evidence increasingly suggests that impairments in QOL may provide unique insight into which patients may have greater risk of long-term adverse clinical outcomes, because QOL appears to predict mortality independently of other medical risk factors.
One of the most common untoward psychosocial outcomes is depression, occurring in approximately 25% of patients after kidney transplant. Although the precise prevalence is unknown and dependent on assessment methodology, point estimates of 22%, 25%, or as high as 46% have been reported for elevated depressive symptoms and distress among posttransplant patients. In an analysis of nearly 48,000 Medicare claims, one study reported a cumulative yearly depression incidence of 5%, 7%, and 9% during the first 3 years after transplantation. Although numerous factors have been associated with increased risk of depression after transplant, clinical status appears to be associated across numerous studies, with markers of eGFR, creatinine clearance, and proteinuria all seemingly worse in depressed versus nondepressed patients.
The presence of depressive symptoms after renal transplantation has been associated with impaired QOL and a greater risk of adverse graft outcomes and mortality. In one of the largest studies to examine depressive symptoms and subsequent mortality, Dew and colleagues conducted a meta-analytic review examining depression and anxiety as risk factors for morbidity and mortality after solid-organ transplantation. Although the study included multiple transplant organ groups and aggregated data from more than 50,000 participants, the vast majority of those included were kidney transplant recipients ( n = 49,515). Over a median follow-up of 5.8 years, the authors found that the presence of depression was associated with a 65% greater risk of mortality and death-censored graft loss (risk ratio = 1.65) and that this association was stronger in studies that accounted for potential confounders. In contrast, anxiety was not consistently associated with adverse transplant outcomes and neither depression nor anxiety was predictive of posttransplant morbidity. There are several plausible mechanisms linking depression to worse posttransplant outcomes, ranging from poorer behavioral compliance, immunologic and inflammatory sequelae, and nutritional factors. For example, numerous studies have demonstrated that greater depressive symptoms are predictive of poorer medication adherence and may be improved through adherence and self-management interventions.
Coping Styles and Personality Factors
An emerging body of evidence suggests that differences in coping styles play an important role in predicting QOL outcomes. For example, patients reporting higher levels of problem-solving coping and lower levels of avoidance also report higher levels of QOL after kidney transplant. These results have been replicated elsewhere, with posttransplant patients who used more evasive, emotive, or fatalistic coping demonstrating lower self-efficacy. Similarly, individuals exhibiting higher levels of neuroticism and distress also, not surprisingly, report worse QOL, Although few studies have examined behavioral risk markers, preliminary data suggest that avoidant coping styles may be predictive of medication adherence, underscoring the importance of understanding coping styles in this population. For example, a recent evidence-based review of pretransplant risk factors for posttransplant nonadherence found that lower levels of conscientiousness assessed before transplant were associated subsequent adherence behaviors, whereas more traditional psychosocial risk factors, such as depression and anxiety, were not consistently associated.
An emerging body of evidence suggests that self-efficacy and self-management are critical components of coping successfully with posttransplant care. Despite a broad literature basis in other patient populations, self-management abilities have received relatively little attention among kidney recipients. Self-management is likely a critical component of long-term adaptation to transplant care, because numerous studies have demonstrated that dispositional coping styles interact dynamically with patients’ medical course to determine psychological outcomes. For example, Liu and colleagues found that treatment-related factors, such as complexity of medical regimen and greater pain, were associated with a greater likelihood of disengagement coping styles and lower QOL. Not surprisingly, prospective studies have demonstrated that QOL changes track closely with transitions in care, such that QOL typically improves after transplantation and, among a subset of patients, worsens precipitously in the setting of transplant failure. Intriguingly, measures of illness perception are also strongly correlated with alterations in QOL, suggesting an important role for coping styles in “riding the waves” of posttransplant medical care. Interestingly, coping styles may provide more predictive data compared with other established behavioral risk markers, such as social support. In a systematic review and meta-analysis, Ladin and colleagues found that in higher-quality studies social support was weakly associated with posttransplant outcomes, including medication adherence or other markers of “transplant success.” In addition, coping styles have been associated with differential likelihood of returning to work, disability status, and engagement in leisure activities. Not surprisingly, recent review papers have noted psychosocial changes in CKD as an important and understudied area for future research prioritization.
Physical Activity After Renal Transplantation
In addition to medication compliance, one of the most important long-term health behaviors determining clinical outcomes among renal transplant recipients (RTRs) is engagement in physical activity. Indeed, many RTRs continue to experience greater disability after transplant, despite improvements relative to dialysis, and less than half of RTRs return to full employment. Despite their improved outcomes relative to dialysis patients, RTRs nevertheless have a 4- to 6-fold higher risk of cardiovascular mortality compared with the general population. This greater risk is primarily attributed to CVD risk factors, including hypertension, dyslipidemia, and metabolic dysregulation, but may also be enhanced in patients treated with chronic immunosuppressive therapy. Accordingly, one of the primary behavioral factors conferring increased risk of mortality is physical activity, with additional risk associated with posttransplant obesity, fluid intake, and other modifiable health behaviors.
Multiple longitudinal studies have shown that RTRs are relatively sedentary, with only 25% achieving activity recommendations by 1 year after transplant. In one study, pedometer-measured physical activity was shown to increase when assessed at 3, 6, and 12 months postoperatively. Nevertheless, only a subset of patients met activity recommendations, and body mass index (BMI) increased steadily over time, as did fat percentage, suggesting that lower physical activity precipitated further metabolic dysfunction and worse cardiovascular health. Not surprisingly, lower levels of physical activity have been associated with substantially elevated risk of RTR mortality. For example, previous cohort studies have demonstrated that RTRs engaging in higher levels of physical activity have all-cause and CVD mortality rates approximately 25% to 50% lower compared with their sedentary counterparts. This association was independent of age and other demographic factors and appeared to be driven by an increased incidence of metabolic syndrome.
The importance of psychological factors in predicting long-term physical activity and other compliance behaviors cannot be overstated. For example, Gordon and colleagues demonstrated that self-efficacy was a significant determinant of physical activity and fluid intake, in addition to other social factors such as insurance and marital status. Several investigators have examined pedometer-based interventions to increase physical activity in RTRs, demonstrating that a substantial subset of patients will adhere to physical activity recommendations when monitored. In addition, individuals adhering to the intervention showed improved metabolic profiles compared with their sedentary counterparts. Nevertheless, behavioral activity recommendations have been noted as an area lacking critical input to guide RTRs.
Targeting Sedentary Behavior: An Intervention
Despite the available data, RTRs appear to have the ability to engage effectively in physical activity, and psychological factors play an important role in influencing physical activity participation. For example, RTRs who engage in less physical activity report a higher number of perceived barriers relative to their active counterparts. Similarly, a recent study by Zelle and colleagues found that a subset of RTRs were much less likely to engage in regular physical activity because of a fear of movement. This subset of patients comprised individuals with a history of significant posttransplant clinical event, such as myocardial infarction, transient ischemic attack, or cerebrovascular accident.
Despite the frequency of sedentary behavior and the importance of maintaining physical activity in RTRs, few randomized trials have been conducted after kidney transplant. One of the most recent trials by Lorenz and colleagues examined the effect of a pedometer-based intervention on physical activity and metabolic functioning after transplant. The authors examined the effect of giving all patients transplanted during a 14-month period a pedometer and an exercise prescription, compared with historical controls from the preceding year. Results suggested that simply providing patients with a means of monitoring activity and a prescription for exercise increased physical activity levels. Moreover, patients in the experimental condition demonstrated greater blood pressure reductions compared with controls (systolic blood pressure [SBP] change −7.5 vs. −2.8; posttreatment SBP = 122 vs. 126). Examination of predictors of physical activity adherence demonstrated that patients with a prior history of kidney transplant, diabetes, and smokers were much less likely to maintain physical activity recommendations. In addition, sensitivity analyses in a subset of patients who maintained adherence demonstrated that these individuals had greater weight reductions by 4 months posttransplant, but did not differ on other important metabolic parameters.
In summary, sedentary behavior is common after kidney transplantation and associated with greater risk of adverse clinical outcomes. In addition, preliminary evidence from available interventional studies suggests that physical activity can be improved through relatively parsimonious treatment strategies, providing an important and understudied area for possible intervention. In addition to the direct effects of physical activity, behavioral factors contributing to poorer metabolic function, such as dietary indiscretion, could also provide plausible treatment targets for future trials among kidney transplant recipients.