Psychosocial Aspects of Chronic Disease: ESRD as a ...

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Psychosocial Aspects of Chronic Disease: ESRD as a
Paradigmatic Illness

Daniel Cukor,* Scott D. Cohen,† Rolf A. Peterson,† and Paul L. Kimmel†

*Department of Psychiatry and Behavioral Sciences, SUNY Downstate Medical Center, Brooklyn, New York; and
†Division of Renal Diseases and Hypertension, Department of Medicine, George Washington University, Washington, DC

ABSTRACT renal (HPA) axis. Stress mediators are
Psychosocial issues are an understudied yet important concern in the overall health thought to potentially have both pro-
of hemodialysis (HD) patients. Stress is a concomitant of chronic illness and its tective and maladaptive consequences,
treatment, and may have meaningful influences on psychological and medical depending on their peak intensity and
outcomes. This article reviews the influences of psychopathology, social support, the temporal associations of the re-
family issues, dialysis unit culture, and socioeconomic status on patients treated sponse. A further refinement of the
with center HD. Depressive affect and decreased perception of social support have idea of stress includes the ability to
been linked with mortality in several studies of ESRD patients. Decreased marital achieve stability through change, or
satisfaction, disturbances in family dynamics, and lower socioeconomic status (SES) “allostasis”.14,15 The construct of al-
have been associated with poorer health outcomes and can affect patients’ per- lostasis was first developed in an effort
ception of social support and depressive affect. Chronically ill ESRD patients who to understand the physiological basis
undergo treatment with constant interaction and observation by medical staff are for disparate patterns of morbidity and
potentially an ideal group for evaluation of the effects of stress and psychosocial mortality unexplained by SES, access
factors on outcomes in those with chronic disease, as well as an excellent patient issues, or lifestyle choices.16 McEwen
population for intervention to reduce morbidity and mortality. These interactions and Stellar17 proposed the construct of
between potentially modifiable psychosocial risk factors for disease and medical allostatic load to convey the cumula-
aspects of illness form a paradigm for the study of interventions related to tive impact of progressive physiologi-
adjustment to chronic illness in the ESRD population. cal wear and tear that could predispose
biologic organisms to disease. Interest-
J Am Soc Nephrol 18: 3042–3055, 2007. doi: 10.1681/ASN.2007030345 ingly, the factors that comprise the Al-
lostatic Index are weighted toward risk
Remarkable advances in the understand- our understanding of the interaction of factors for cardiovascular disease (such
ing and treatment of ESRD have been psychological factors with medical out- as systolic BP, cortisol and catechol-
achieved over the last 20 yr. However, comes. The notion of “stress” serves to amine excretion, the waist/hip ratio,
most of the investigations have focused provide a research context for the study glycosylated hemoglobin, and the ratio
on medical factors, many of which are of such interactions. of serum HDL to total serum choles-
fixed features. Over recent years, there terol concentration).15 McEwen15,18
has been increasing attention given to the The concept of stress has resisted suggested several response patterns
individual characteristics of patients definition since it was first introduced that are indicative of excessive wear
with an emphasis placed on understand- in the 1930s by Hans Selye,13 but the and tear: 1) a response pattern with ex-
ing the effects the patients’ social situa- word has since permeated the popular
tion, perceptions and responses to the ill- cultural idiom. Stress may be thought Published online ahead of print. Publication date
ness, their physicians and healthcare of as a disruption in the physical con- available at www.jasn.org.
providers, their spouses and families, dition, environment, or psychosocial
and their SES have on outcomes. Al- setting of an organism.14 The concept Address correspondence to: Dr. Paul Kimmel, De-
though this area of “psychonephrology”1 of stress has been operationalized partment of Medicine, George Washington Univer-
has been a subject of research for many through the notion of “stress media- sity, 2150 Pennsylvania Avenue NW, Washington,
years, recent work in patients with2,3 and tors,” typically hormones that affect or DC 20037. Phone: 202-741-2283; Fax: 202-741-
without renal disease4–12 has advanced are produced by the central nervous 2285; E-mail: [email protected]
system or hypothalamic-pituitary-ad-
Copyright © 2007 by the American Society of
Nephrology

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cessive and repeated insults over time, Illness effects
2) a pattern where the organism is un-
able to habituate to stressful stimuli, 3) Family dynamics
a pattern that is activated but remains
at a heightened level of activation with- Culture Dietary constraints
out sufficient recovery to baseline sta- Time restrictions
tus, and 4) a pattern where the primary
mechanisms are inadequate to the Personality STRESSORS Functional limitations
challenge, resulting in the activation of Patient Financial constraints
compensatory mechanisms. These four Changes in employment
response patterns may lead to variable
end-organ responses that may charac- Psychological Relationships with staff
terize patients with chronic illness, and functioning Role change
in particular ESRD.
Support Change in
The ability of stress mediators to re- sexual function
turn to baseline is a particularly salient
issue for patients with renal dysfunction. Medication effects
Because peptide and steroid hormones
undergo metabolism by the kidney and Awareness of
often circulate at levels higher than in pa- impending death
tients without renal disease,19–21 the pa-
tient with chronic kidney disease (CKD) Figure 1. Patient characteristics and stressors that may affect perceived stress in HD
can be considered to exist in an internal patients.
biochemical milieu that is similar to a
chronic stress response. rated by Engel23 to encompass many lev- Table 1. Selected psychosocial
els that may interact to determine health parameters in chronic disease
People’s variability in their percep- status. Some of these stratifications in-
tion of “stress” is critical, because out- clude individual demographic data (age, Individual psychological variables
comes may be quite variable in patients ethnicity, gender), physiological mea- psychopathology
with similar allostatic loads.15 Therefore, sures (e.g., body mass index, cardiovas- personality
age, gender, presence of comorbid ill- cular, immunologic and conditioning illness perception
ness, developmental history, and genetic status), psychological and behavioral pa-
heterogeneity may be associated with rameters (distress, personality factors, Behavioral compliance variables
different outcomes, but personality, health-promoting or -damaging habits), nutrition
mood, habits and behaviors (such as diet, and social or environmental factors (oc- exercise
level of exercise, use of tobacco, alcohol cupational imperatives, level of social sleep
and regulated substances, and spiritual- support, access to health care, residential medication
ity and religious observance) may play characteristics, and SES). Psychological attendance at treatment sessions
roles in modifying disposition of allo- and social parameters (Table 1) might
static load as well. In particular, some of include personality factors, affect, and Social variables
the stressors in the life of a dialysis pa- perceptions of distress, well-being, or ill- social support
tient may cause modifications to the pa- ness, whereas social measures include family/dyad/other
tients’ status in a variety of marital, fa- marital satisfaction, satisfaction with religion
milial, and occupational and societal health care, compliance with the dialysis occupation
contexts (Figure 1). However, to fully ap- regimen, and level, number, and quality residence
preciate the dynamic nature of these de- of interactions with dialysis personnel race/ethnicity
mands one must also understand the pa- socioeconomic status
tient’s perspective on his or her ability to
cope with these stressors. The person’s and staff. ESRD patients exist in a com-
personality, psychological functioning, plex network encompassing, at the min-
resources, and even cultural beliefs may
all affect the perception of the ability to
respond successfully to a challenge (Fig-
ure 1).

Anderson and Armstead22 advanced
the biopsychosocial model first elabo-

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Social therapy (RRT) and BDI scores in our
status studies.34,35 We did not detect differences
between mean BDI scores in incident
Insurance Friends Religion and prevalent hemodialysis popula-
company tions.36 Using US administrative data, we
Partner/ showed that hospitalization for depres-
spouse sion in ESRD patients treated with dialy-
sis was a late event, occurring more fre-
Employer PATIENT Physician quently in patients treated for more than
2 yr rather than an early characteristic of
Economic Close Family Dialysis the response to RRT.25 Lopes et al. found
status friends provider a trend toward greater prevalence of de-
pression, measured using subsets of Kid-
Dialysis ney Disease Quality of Life questions, in
staff patients treated for ESRD for Ͼ1 yr.37 In
a recent study, Hedayati et al.38 used the
Ethnicity Residence Veterans Administration database to
identify 1588 male HD patients. The
Figure 2. Psychosocial parameters: Spheres of influence. physician-diagnosed rate of depression
was 14.7%. Over the course of 2 yr, a di-
imum, family, physicians, dialysis staff, alcohol use in 163 urban HD patients, agnosis of depression was associated with
clinic personnel, hospitals, and dialysis 27.6% were found to have troublesome more hospitalizations and increased du-
and insurance companies (Figure 2). use of alcohol.27 ration of hospitalization but not with
This paper updates the literature on the overall mortality when variation in de-
mechanisms and impact of these psycho- DEPRESSION mographic and medical factors was con-
social influences on HD patients, first trolled.38
outlined in 2001.24 The assessment of depression is compli-
cated by the considerable overlap of de- Depression possibly affects medical
PSYCHOPATHOLOGY pressive and uremic symptoms.2,3,28,29 outcomes in ESRD patients through
However, the Beck Depression Inventory modification of immunologic and
In a review of hospitalization data from (BDI),30 a measure of depressive symp- stress responses, impact on nutritional
US Medicare ESRD patients who were tomatology, has been shown to be a valid status, and/or reduction of compliance
treated with dialysis in 1993, the most measure of depressive affect in HD pop- with, or access to, prescribed dialysis
common psychiatric disorders in the ulations.3,26,28,31–33 A BDI cut-off score of and medical regimens2,3,28,34 (Figure
population were depression and affective 14 to 16 appears to best approximate a 3). Recent studies2,3,24,39,40 have de-
disorders (26%), organic brain syn- psychiatric diagnosis of major depressive scribed preliminary data regarding
dromes and dementia (26%), schizo- disorder in HD patients.3,26,31–33 The these mechanisms in patients with and
phrenia and other psychoses (22%), and prevalence of a current depressive disor- without renal disease.41,42
drug and alcohol abuse (15%).25 In our der in HD patients is estimated at 20% to
Brooklyn data, 19% of urban HD pa- 30% if all depressive disorders are in- Immunologic Response
tients had an active substance abuse di- cluded.3 The “cytokine theory of depression”43
agnosis and 10% had a diagnosis of psy- posits that proinflammatory cytokines,
chosis.26 In an in-depth analysis of There was no correlation between
time since initiation of renal replacement POOR COMPLIANCE
Dietary

Dialysis prescription

DEPRESSION PROGRESSIVE CKD

ALLOSTATIC
DYSREGULATION
Cytokine changes
Stress modulators

Figure 3. Potential mechanism of vicious
cycle between depression and ESRD.

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acting as neuromodulators, mediate the ers of malnutrition in a group of 295 pri- damental, potentially confounding med-
behavioral and neurochemical features marily black patients,71 other studies ical and demographic factors (reviewed
of depression.44–49 There are several sug- have demonstrated such links.72,73 Di- by Kimmel2,24). Several more recent
gested mechanisms that might underlie versity in the study samples or treatment studies had been unable to detect associ-
this effect.50,51 One suggestion is that cy- conditions may explain these disparate ations between depression and mortality
tokine-induced hyperactivity of the HPA findings. In an interesting but method- in HD patients.2,24,28,71,95–97 However, in
axis causes interference in the negative ologically flawed study, Friend et al. a large multinational sample, ESRD pa-
feedback of circulating corticosteroids.52 showed that depression preceded the de- tients treated with hemodialysis who
This dysregulation may also lower the crease in serum albumin concentration were classified as depressed and those
availability of tryptophan by reducing in dialysis patients, implying that depres- who reported frequent depressive affect
levels of its precursor, 5-hydoxy- sion causes malnutrition and not the re- had higher risk of mortality, withdrawal
tryptamine (5-HT), an essential compo- verse.74 There has also been increasing from therapy, and hospitalization.37 The
nent of neurocellular function. Addi- evidence for a molecular mechanism for nontraditional assessment of depression
tionally, there is evidence that inflamma- the cachexia that occurs in CKD pa- used in this study make these results dif-
tory biomarkers such as C-reactive tients.75,76 Levels of TNF-␣, a cytokine ficult to interpret. Nevertheless, the re-
protein are dysregulated and predict out- associated with cachexia, and cortisol, a sults seem to indicate a robust relation-
come in general53,54 and in ESRD pa- stress hormone associated with depres- ship between depressive affect and
tients.55–59 We55,60 and others56 –59 sion and dysregulated carbohydrate me- medical sequelae in contemporary HD
showed cytokine levels were elevated in tabolism, as well as other such mediators patients around the world.71 Although
HD patients, and proinflammatory cyto- have also been shown to be elevated in we were able to detect associations be-
kines were associated with mortality. In ESRD patients treated with HD.55,77,78 tween perception of increased burden of
subanalyses, increased cytokines were as- illness and mortality, and between per-
sociated with increased depressive af- Treatment Compliance ception of a high level of perceived social
fect.60 Stenvinkel et al.61 identified spe- Studies have indicated a relationship be- support and improved survival,71 the
cific immunologic factors such as TNF-␣ tween depressive affect and both labora- baseline level of depressive affect proved
and IL-6 that alter the cytokine network tory and behavioral markers of poor not to be a risk factor for increased mor-
in uremia in ESRD patients. The chronic compliance in dialysis patients.79,80 De- tality in our population of almost 300
proinflammatory state intrinsic to ESRD creased behavioral compliance with the HD patients. More recently, we per-
is related to the higher than expected dialysis prescription correlated with in- formed longitudinal assessments of our
rates of cardiovascular disease and other creased depressive affect in prevalent HD study population to evaluate BDI scores
medical causes of increased mortality in patients.24,40,71,72,81 Decreased compli- obtained up to six times (mean 2.9) over
this population.55,62–65 ance with HD prescription has also been a period of 20 mo to 5 yr. The scores were
associated with poor medical outcomes used as time varying covariates in Cox
There is increasing literature to sup- and increased mortality.71,79,80,82,83 regression models of patient mortality.35
port an association between depression An increased level of depressive affect
and risk factors for cardiovascular dis- Depression and Mortality over time was associated with increased
ease in patients without kidney disease.66 Depression has been associated with in- mortality risk, even when analyses con-
Stress levels have modulating influences creased mortality in the general medical trolled for medical parameters.35 We
on the autonomic nervous system, which population.84–88 Gallo et al. performed a concluded that models incorporating
can lead to coronary vessel vasoconstric- randomized controlled trial to study the multiple assessments of depression more
tion, tachyarrhythmias, and other ad- effect of a depression intervention in accurately predict outcome while still ac-
verse cardiac events.66 In addition, in- twenty general medicine clinics from the counting for patients’ medical and nutri-
creased depressive affect has been Northeastern United States. They found tional status. The effect of timing of as-
associated with the production of vari- a decrease in 5-yr mortality rates in the sessments, baseline conditions, and
ous inflammatory cytokines including group randomized to the depression in- averaging depressive affect over time
IL-6 and C-reactive protein in some tervention.89 could prove critical when outcomes are
studies.67–69 Inflammation is known to assessed. Recently, Boulware and col-
play a key role in the generation and pro- A connection between depression and leagues generated similar results when
gression of atherosclerosis.66,67,70 De- mortality in ESRD patients has been dif- they evaluated baseline and longitudinal
pression is also associated with enhanced ficult to demonstrate. Some studies90–93 data from the Choices for Healthy Out-
platelet aggregation via alterations in se- and our own work94 initially indicated comes in Caring for End-Stage Renal
rotonin and catecholamine pathways.66 that depression was associated with mor- Disease (CHOICE) study, a large cohort
tality in this patient population. These of incident patients starting peritoneal
Malnutrition studies, however, often compared means dialysis and hemodialysis.98 Boulware et
Although we were unable to detect an as- between groups of deceased and surviv- al. determined that levels of depressive
sociation between depression and mark- ing patients without accounting for fun-

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affect at the beginning of the study were is 84% higher than in the general popu- relaxation over a 6-wk course reduced
not associated with increased overall lation.99 Alcohol dependence and hospi- both state and trait anxiety and im-
mortality. However, similar to our find- talization for substance abuse and men- proved QOL.113
ings, using several different time-depen- tal illness were strongly associated with
dent analyses, the investigators demon- subsequent suicide in the ESRD popula- Patients with depression and anxiety,
strated that persistently higher levels of tion.99 This recent study shows defini- or depression and another psychiatric di-
depressive affect over time were associ- tively that populations that withdraw agnosis, may represent a population at
ated with increased risk of death and car- from treatment and those that actively particular risk. Comorbid (so-called
diovascular events in both adjusted and commit suicide represent different “compound”) depression has been asso-
unadjusted analyses. From the currently clinical entities, highlighting that sui- ciated with more profound physiological
available evidence, it is not clear whether cide is associated with alcohol and drug abnormalities and treatment resis-
depression has a direct causal role in dependency and the presence of mental tance.34,114
poor outcomes associated with ESRD or illness.99 The complex relationship be-
if depression is merely a marker of in- tween depression, suicide, and with- Treatment
creased disease comorbidity and illness drawal from treatment needs further Few studies have focused on the treat-
severity. clarification. ment of depression and anxiety disorders
in ESRD patients. Treatment options in-
Withdrawal from Dialysis ANXIETY cluding psychotherapy, cognitive behav-
Estimates indicate that approximately ioral therapy, and pharmacologic agents
20% of US dialysis patients voluntarily In comparison to depression, anxiety are similar to those used in the general
choose to discontinue ESRD thera- disorders have received little clinical at- patient population.24,115–118 However,
py.24,99–104 Interestingly, black patients tention in the ESRD population. Most treatment of psychological disease in the
are much less likely to withdraw from studies rely exclusively on self-report ESRD population presents unique chal-
care than white patients across all ag- scales as a broad measure of anxious dis- lenges. Careful consideration of dose ad-
es.24,100 Age, medical complications, and tress.107–109 Some of our unpublished justments for level of GFR and dialysis
failure to thrive are commonly associ- data suggest that there is poor agreement schedule must be addressed each time
ated with the decision to withdraw from between self-report measures of anxiety medical therapy is being considered.
ESRD therapy.24,100,101 A recent study and a formal anxiety diagnosis in an ur-
found that depression was a predictor of ban HD population. Other studies have The challenges of treating depression
the decision to withdraw from dialy- used structured clinical interviews to in ESRD patients should not serve to
sis.105 Despite the high rate of withdrawal provide a formal anxiety disorder diag- limit use of appropriate therapy. Depres-
from dialysis, the extent to which it nosis. One study found a 30% rate of sion may be undertreated in ESRD pa-
should be considered a suicide equiva- anxiety disorders in HD patients using tients. Watnick et al. reported that just
lent is unclear and controversial.24,102,104 the Primary Care Evaluation of Mental 16% of HD patients with depression
It is known that ESRD patients have the Disorders (PRIME-MD) as a diagnostic were receiving treatment.119 Ameliorat-
potential to commit suicide with relative tool.110 By comparison, the same ing the symptoms of depression is im-
ease through noncompliance, and, in PRIME-MD questionnaire was given to portant because it may improve other
fact, an early study reported rates of sui- 2316 general medical patients, and a 19% adverse outcomes associated with ESRD,
cide to be 100 to 400 times higher in di- prevalence of anxiety disorders was including poor nutritional status and
alysis patients compared with the general found.111 Our work in Brooklyn demon- treatment compliance. This may in turn
population.106 Another study of pre- strated a 27% prevalence of anxiety dis- affect survival.2,3,34,120,121
dominately white patients from Minne- orders using the Structured Clinical In-
sota found suicide rates of ESRD patients terview for the DSM-IV (SCID).26 The Pharmacologic options to treat depres-
to be 0.2%, approximately 15 times impact of high levels of anxiety or an sion include selective serotonin reuptake
greater than that of the general popu- anxiety diagnosis on outcomes is also inhibitors (SSRIs), as well as the newer se-
lation.101 However, true suicidal behav- unclear. Anxiety’s negative impact on lective serotonin and norepinephrine re-
ior and ideation might be more diffi- quality of life (QOL) and disability across uptake inhibitors.24,34,115,122–125 Other
cult to differentiate in this popula- multiple illnesses has been demon- agents such as tricyclic antidepressants,
tion.24,34,103,105 The early findings might strated, but its specific effect in ESRD has monoamine oxidase inhibitors, and St.
have been a result of evaluating white not been studied.112 One study from John’s wort should be avoided if possible
populations at high risk in an era of rela- Turkey found that depression but not because of potential exacerbation of
tively primitive dialytic delivery tech- anxiety correlated with interdialytic common adverse events in dialysis pa-
niques. More recent studies show suicide weight gain.110 Another Turkish study tients, including drug– drug interac-
to be less prevalent in contemporary found that teaching progressive muscle tions, arrhythmias, and orthostatic hy-
ESRD populations,24,99 although the rate potension.24,115,122,125 Patients who
receive these antidepressant medica-
tions should be closely monitored for
development of a prolonged corrected

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QT interval.126,127 If this complication nephrine reuptake inhibitor venlafax- differences in mortality of dialysis pa-
occurs, the antidepressant medication ine.150–154 In clinical practice, anxiety tients between units24,162 or among na-
should be discontinued. may coexist with depression.26 Addi- tional populations,24 perhaps as a result
tional studies are needed to determine of differences in compliance.2,28,79 Al-
There have been limited studies eval- the specific efficacy of these agents for though the relationships between social
uating the efficacy of SSRIs in ESRD pa- treatment of anxiety in ESRD as well as support, social integration, and health
tients.128–131 SSRIs should be favored general medical patients.155 Close con- are robust, the mechanisms underlying
over other antidepressant medication sultation with mental health profession- the linkages have not been clearly delin-
options because of their relatively limited als is always advised before the prescrip- eated.24,71,156,163 Suggested mediators for
side effect profiles, as well as their favor- tion of any psychotropic agents, improved health resulting from more de-
able potential to reduce the symptoms of particularly if ESRD patients display any veloped social support and integration
orthostatic hypotension, a potentially complicated clinical symptoms suggest- include better access to and utilization of
debilitating problem for patients with ing suicidal ideation or mania.115 health care, better compliance, and bet-
ESRD treated with hemodialysis.24,115,132 ter “stress buffering” through improved
A strategy is to reduce the initial starting SOCIAL SUPPORT psychological, neuroendocrine, nutri-
dose of SSRIs by one third.115,125,133 tional, or immunologic function-
Social support refers to a social network’s ing.156,161,163,164
An important adverse event associ- provision of psychological and material
ated with SSRIs that should be consid- resources intended to benefit an individ- Several studies have shown an associ-
ered before prescribing these agents ual’s ability to cope with stress.24,156–158 It ation between survival and perception of
is the potential to increase the risk of ma- is often divided into three types: instru- social support in ESRD patients of differ-
nia in bipolar disorder patients who mental, informational, and emotion- ent ethnic backgrounds.71,95,160,161,165–167
are improperly diagnosed with depres- al.157 Instrumental support involves the McClellan et al. showed, in a prospective
sion.115,134–137 Initial administration of provision of material aid (e.g., financial study, that a QOL measure, which in-
SSRIs may also be associated with an in- assistance). Informational support refers cluded social support, predicted survival
creased risk of suicide during the initial to the provision of helpful information of HD patients.166 Christensen et al.
period of administration; however, this (e.g., guidance). Finally, emotional sup- showed family cohesion, as a social sup-
issue remains controversial.138–140 SSRIs port involves the expression of empathy port indicator measured by the Family
may also exacerbate nausea and bleed- and provides opportunities for emo- Environment Scale, predicted survival in
ing, two common uremic symp- tional expression. Another relevant con- HD patients.95 The effects of medical and
toms.115,121,141–147 cept is social integration, defined as par- treatment parameters such as nutritional
ticipation in a broad range of social status, delivery and intensity of dialysis,
There have been no randomized clin- relationships.158 It includes a behavioral and patient compliance were not con-
ical trials assessing the efficacy of psycho- component, active engagement in a wide trolled in these studies, however. Mc-
therapy for treating depression in this range of social activities or relationships, Clellan and colleagues further showed
population,120,148 but there is some clin- and a cognitive component, a sense of patients’ assessment of level of giving so-
ical evidence that these interventions communality and identification with cial support predicted improved survival
might be effective.149 Optimal treatment one’s social roles.158 in HD patients.167 The relationship of so-
of depressive disorders in ESRD patients, cial support to other medical and psy-
therefore, may involve medical treat- Social support and integration are chosocial parameters, and functional
ment, psychotherapy, or their combina- now acknowledged as important factors status in particular, was not assessed.
tion. in adjustment to chronic and acute ill- Most previous studies also did not in-
ness.24,71,95,156 –161 For example, one clude longitudinal reappraisals of psy-
The treatment options for anxiety dis- study of social integration in healthy par- chological or compliance parameters.
orders are similar. Like antidepressants, ticipants demonstrated that the diversity We showed increased perception of so-
adjustment of anxiolytic dose for level of of one’s social network protected against cial support, measured by the Multidi-
GFR is needed when these agents are pre- developing the common cold after expo- mensional Scale of Perceived Social Sup-
scribed.125 Older treatment options for sure to the virus.159 Social support has port, predicted survival even when
anxiety were limited to barbiturates and been broadly and consistently linked to variation in age, severity of comorbid ill-
benzodiazepines. However, their unfa- improved health outcomes in a variety of ness, level of serum albumin, dialysis
vorable side effect profiles, particularly chronic illnesses in numerous studies in- membrane type, and study site were con-
in patients with hepatic or renal failure, dependent of geographic settings, SES, trolled.71
have led to the use of newer psychotropic and ethnic backgrounds.156 In fact, dif-
agents including buspirone, a partial ag- ferences in social support between High levels of social support have
onist of cerebral serotonin 5-HT 1A re- groups has been suggested to underlie been associated with increased utiliza-
ceptors.125,150–154 Antidepressant agents tion of medical services (reviewed by
may also have a role in therapy for anxi- Kimmel et al.71, Cohen et al.161, and Patel
ety, including SSRIs such as paroxetine
and the newer serotonin and norepi-

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et al.168). Social support may affect com- MARITAL AND FAMILIAL ISSUES More than half of couples including a
pliance of ESRD patients treated with patient with ESRD had evidence of mar-
HD,24,71,79,157,161,168 although the find- The intimacy of a relationship with a life ital disruption.182 Chowanec and
ings have been variable, in part depen- partner may be intense and complex. Binik187 showed dialysis patients and
dent on the parameters assessed in differ- Such relationships may have positive as- spouses had strong links between psy-
ent populations. Support from family pects, such as associations with greater chological distress and perceptions of
and caregivers correlated with a compos- perceived social support, or negative marital strain. Twenty percent of spouses
ite compliance measure in HD patients ones, perhaps associated with hostility. of dialysis patients had “significant de-
in an urban population (reviewed by Marital stability, satisfaction, and per- pressive symptoms” in a Canadian
Kimmel et al.71). Several studies have ceptions of hostility have been associated study.187 Spouses’ level of distress was
suggested that perception of social sup- with differential health outcomes in the not correlated with level of patient func-
port was associated with increased com- general population.60,174–178 Unhappily tion or depression. Social support re-
pliance.71,79,160,161,169 In a study of HD married individuals report poorer health ceived from the patient and social and
patients in Utah, patients who perceived than do happily married or divorced financial stressors experienced by the
high family support had lower levels of people with similar demographic and spouse accounted for a large proportion
interdialytic weight gain and better bio- health characteristics. Marital quality has of spouse perceptions. Another study
chemical compliance measures.160 Leg- predicted length of stay after bypass sur- suggested women caregivers of ESRD pa-
gat et al., in a large study performed using gery for women, but not for men.179 De- tients perceived good QOL and no evi-
data from the United States Renal Data clines in reported marital satisfaction dence of burden, but these two parame-
System, found patients living with some- have been associated with subsequent ters were correlated.191 Lowry and
one, rather than living alone, were less poorer health evaluations. One fascinat- Atcherson found lower levels of anxiety,
likely to shorten HD treatments.83 There ing study180 found that couples’ blister depression, and marital problems in a
was, however, no association of house- wounds healed more slowly and local cy- group of carefully screened home dialysis
hold composition with attendance, in- tokine production (IL-6, TNF-␣, and spouse partners in Iowa than others re-
terdialytic weight gain, or level of serum IL-1) was lower at wound sites after mar- ported,192 although the reasons underly-
phosphate. Moreover, other studies ei- ital conflicts than after social support in- ing differences between this study and
ther could not establish relationships be- teractions. Kiecolt-Glaser and colleagues others are unclear and may relate to se-
tween measures of social support from also found that hostile couples produced lection bias. Berkman, Katz, and Weiss-
family and friends and compliance mea- relatively larger increases in plasma IL-6 man found that, although there was a
sures of HD patients, and such studies and TNF-␣ values the morning after a high prevalence of sexual dysfunction in
have also failed to show a correlation be- conflict than after a social support inter- home dialysis patients, marital and social
tween greater perception of social sup- action compared with couples without adjustment scores were comparable to
port and compliance.71 conflict.180 Marital conflict may affect those of the general population.193 Mo-
perceptions of illness and interfere with guilner, Bauman, and De-Nour found a
Indices of social support correlated the ability of a patient to comply with the correlation between patient and spouse
with level of depressive symptoms, per- complex regimen entailed by RRT. BDI scores.194 We found that spousal lev-
ception of illness effects, and satisfaction els of depression correlated with extent
with life in our studies.24,35,36,168–171 One The development of a chronic ill- of HD patients’ depressive affect, and the
recent ESRD study found that optimism ness in a couple may place strain on greater the level of social support the
was a mediating influence between social usual marital roles. Spouses can be- spouse reported, the less strain they iden-
support and depression.172 Another re- come caregivers and may experience tified in the marriage.186
cent study173 highlighted the need to ac- depression and/or hostility. There also
count for the role of individual differ- might be changes in the patient’s abil- Marital conflict has been associated
ences in the relationship between ity to work, forcing a further shift in the with endocrinological and immunologic
support and depression. The investiga- individual’s roles within the dyad. In changes in women, but not men, in sub-
tors found that greater social support addition, the spouse may be the object jects without renal disease.195 A study of
among individuals high in the personal- of the patients’ negative emotions. Fi- 68 Israeli prevalent HD patients and their
ity trait of “agreeableness” was associated nally, sexual dysfunction can change spouses revealed high levels of distress
with a decrease in depressive symptoms the dynamics of the relationship.181,182 compared with normative groups and
over time, whereas support had little ef- Few studies exist on spousal or family high correlations between distress scores
fect on depression change for individuals relations in ESRD patients, and almost of spouses.184 Married female patients
low in “agreeableness.” Social support none focus on outcomes.182–190 Most had less anxiety than married male pa-
may affect psychological, medical, and studies performed within families of tients. However, male spouses had
biochemical factors in other unknown HD patients have assessed compari- higher levels of distress than female
ways to engender better health out- sons of members of dyads or families spouses. Giving and receipt of social sup-
comes.71,156,168,169 on psychosocial tests. port within a marriage may also change

3048 Journal of the American Society of Nephrology J Am Soc Nephrol 18: 3042–3055, 2007

www.jasn.org SPECIAL ARTICLE

during the ESRD life cycle. In Canadian had significantly increased risk of mor- unknown and should also be explored
couples including a patient with ESRD, tality, but once again the findings were further. It is clear that the culture of the
women patients felt that family support driven solely by the effects in the group of dialysis unit and the connectedness the
declined after the onset of illness, but no women.196 patient feels to the dialysis staff are im-
change in perceived support was noted portant factors and may mediate differ-
by male ESRD patients.185 These data suggest that black women ential outcomes in dialysis programs
with ESRD treated with HD functioning with similar patient populations. Specif-
We studied the relationships between in complex households or in difficult ically, the role of dialysis providers, par-
medical factors, neuro-endocrinological marital situations may be at particular ticularly physicians, may impact HD pa-
and immunologic factors, and outcome risk. This risk may relate to their gender tients’ compliance.
in a subset of 174 male and female HD roles or expectations regarding family
patients functioning in dyadic relation- duties in people with limited economic SOCIOECONOMIC AND
ships.60 Dyadic satisfaction scores were resources and/or diminished social sup- CULTURAL ISSUES
comparable to those of normative popu- port in such settings.24,168 Because previ-
lations, although the women had more ous studies have suggested stress and in- SES has been shown to have a signifi-
negative assessments of their marriages flammatory responses, and depressive cant impact on the incidence and treat-
than the men. Interestingly, a different symptoms are greater in women than ment of ESRD.199,200 Norris and Ag-
pattern of interactions for men and men,195 perhaps these factors mediate odoa201 have developed a model
women was noted. For women, higher outcomes for women more than men highlighting how socioeconomic fac-
levels of depressive affect and increased with ESRD. tors such as low income, poor educa-
perception of the burden of illness corre- tion, residence in low-income areas,
lated with increased severity of illness, UNIT CULTURE and poor access to health care are
and greater circulating levels of IL-1 and strong predictors of the development
␤-endorphin. Marital satisfaction and Given the amount of time most HD pa- of ESRD. Not enough study has been
conflict scores correlated with medical tients spend at their dialysis site, it is rea- given to the notion that differential
risk factors, psychosocial parameters, sonable to speculate that their relation- quality of physician care may charac-
and circulating IL-1 and ␤-endorphin ships within the dialysis unit play an terize programs in different neighbor-
levels, but again, only in the women in important role in determining adjust- hoods. The relationships between race,
the study. Finally, neurologic, immuno- ment and outcomes, but there are few SES, and ESRD outcomes are quite
logic, and marital indices predicted dif- data available on these issues. One study complex and may result from their syn-
ferential survival in the study group, but showed that unmeasured dialysis unit ergistic combination.24,202 Few studies
the dyadic indices were associated with characteristics predicted survival better have assessed the relationship between
outcome only in the women. It appears than the characteristics predicted by dif- survival and SES in the ESRD popula-
that strong negative emotion, such as ferences in case-mix.162 We have demon- tion. Dialysis Outcomes and Practice
perception of dyadic conflict, may be a strated that dialysis unit staff exhibit sus- Pattern Study (DOPPS) data have sug-
particularly important stressor in tained characteristics over time in spite gested that higher SES was associated
women HD patients, activating physio- of the high turnover of individual em- with improved survival, regardless of
logical and neuroendocrinological path- ployees, suggesting that a particular “cul- race.203 A startling finding is the differ-
ways. ture” typifies each dialysis unit.197 To un- ential survival of black patients com-
derstand the relationship between pared with whites in the United States
To expand our understanding of fa- patients’ feelings about the dialysis staff ESRD program100,199,202 because in al-
milial support beyond the dyad, we sur- and outcomes, we surveyed HD patients most all cases higher SES is associated
veyed a prevalent population of almost regarding their level of satisfaction with with improved survival in chronic ill-
500 black HD patients. We defined fam- their nurses, technicians, and nephrolo- nesses.204 Rodriguez et al. recently
ily composition in terms of size and gists. Patients’ increased satisfaction with found higher mortality rates among
structure, with a simple household de- staff and their perception that staff cared white and black dialysis patients living
fined as one in which the patient lived about them correlated with better dietary in areas with zip codes that were pre-
alone or only with a spouse or partner, compliance. Interestingly, patients’ in- dominately composed of blacks. They
and a complex household as being char- creased satisfaction with physicians, but also found lower rates of transplanta-
acterized by patients living with various not nursing or technical personnel, cor- tion in communities that were made up
combinations of relatives and nonrela- related with improved attendance and of a majority of blacks.205 In a prelimi-
tives, often in multigenerational groups. greater total time compliance with the nary investigation,206 we found a para-
After an approximately 3-yr observation dialysis prescription.198 doxical association in which minority
period, Cox regression analyses revealed patients living in areas with higher in-
only age and household structure The impact of social work groups on
emerged as associated with survival. Pa- the unit or organized social activities are
tients who lived in complex households

J Am Soc Nephrol 18: 3042–3055, 2007 Psychosocial Aspects of Chronic Disease 3049

SPECIAL ARTICLE www.jasn.org

equality of distribution of income in and attempt to make their way through make the connections between psycho-
the United States had poorer out- life in the context of their intimate rela- social and biological variables.
comes. These findings are tentative and tionships, families, social networks,
the underlying reasons are unclear, but treatment programs, and cultures. They ACKNOWLEDGMENTS
they may reflect different allocation of must cope with the demands of their oc-
resources between groups in the same cupations, the changes in their life roles, Dr. Cohen is supported by a research fellow-
residential area, differential access to and the challenges and opportunities ship from the National Kidney Foundation
health care and services, discordance that life exposes them to while balancing
between viewpoints of physicians and the restrictions that life on HD entails. As DISCLOSURES
patients, or the effects of discrimina- opposed to the mostly invariant biologi-
tion.207 Another factor to consider is cal factors, psychosocial factors are a po- None.
the interplay of the ethnicities of the tential target for successful interven-
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