Psychological Factors AffectingEnd-Stage Renal Disease

A Review

JAMES L. LEVENSON, M.D.SUSAN GLOCHESKI, M.D.

This review summarizes recent systematic research literature regarding psychologicalfactors as they affect chronic renal disease. Special attention is devoted to depression.quality oflife. noncompliance. outcome studies. withdrawal from dialysis. and directionsfor future research.

T here has been extensive interest in the psy­chosocial and psychiatric aspects of dialysis

and transplantation paralleling the evolution oftreabnent approaches to end-stage renal disease(ESRD).'-3 In this paper we review the recentsystematic research literature regarding the influ­ence of psychological factors on the course ofchronic renal disease. Topics covered include theprevalence of psychiatric disorders (affectivedisorders) in ESRD patients and comparison ofpsychosocial quality of life in ESRD patientsreceiving different treabnent modalities (hemo­dialysis, peritoneal dialysis. renal transplanta­tion. and home vs. center dialysis). Systematicstudies of psychological factors affecting out­come in ESRD have focused on depression ornoncompliance. We also address the issues ofwithdrawal from dialysis. mechanisms mediatingthe effects of psychological factors. and direc­tions for future research.

METHODS

A Medline literature review was performed cov­ering 1984-1990. supplemented by a GratefulMed review in 199 I. Manual index searches ofmajor journals in the fields of nephrology and

382

consultation-liaison psychiatry also were per­formed (Kidney International. Clinical Nephrol­ogy. Nephron. American Journal of KidneyDisease. Dialysis and Transplantation. Trans­plantation. Psychosomatics. PsychosomaticMedicine). In addition. standard references werereviewed. 1-4 We included only those studies thatutilized assessment measures of established va­lidity. We did not impose strict criteria of ade­quate sample size and adequate control for biasand confounding factors (e.g.• disease severity)because too small a number of studies wouldhave qualified.

PREYALENCE OFPSYCHIATRIC MORBIDITY

Essentially all of the systematic research on theprevalence ofpsychopathology in ESRD patientshas focused on depression. Early research

Received April I. 1991; revised June 17. 1991; acceptedJune 25. 1991. From the Depanments of Psychiatry andMedicine, Medical College of Virginia. Virginia Common­wealth University. Richmond. Address reprint requests to Dr.Levenson. Box 268. MCV Station, Richmond. VA 23298.

Copyright © 1991 The Academy of PsychosomaticMedicine.

PSYCHOSOMATICS

Levenson and Glocheski

This article by Drs. Levenson and Glocheski is thefourth in a series ofcritical review articles that arebeing wriuen as part of the process of examiningthe category "Psychological Factors AffectingPhysical Condition" for possible revisions in DSM­IV. Emphasis in conducting these reviews is placedon examining the existing scientific evidence forrelationships between psychological and behav­ioral factors as influences on the onset. exacerba­tion. and outcome of medical illness. This specialseries is edited by Alan Stoudemire. MD .• who alsois serving as the chair ofthe subcommillee examin­ing PFAPC for DSM-IV. As part of this series andthe DSM-IV revision process. the editors welcomethe responses and suggestions ofinterested readers.

showed widely varying rates of depression indialysis patients. from O%S to 100%.6 One expla­nation for this discrepancy lies in differences inthe definitions and criteria used for depression.For example. in ESRD patients on dialysis. Smithet at.7 found that theproportion of de­pressed patients was47% by the Beck De­pression Inventory.10% by the MultipleAffect AdjectiveChecklist. and 5% byDSM-Ill criteria.Hinrichsen et a1.8

evaluated in-centerhemodialysis pa­tients with the Sched­ule for AffectiveDisorders and Schi­zophrenia and identi­fied 17.7% meetingcriteria for minor de­pression and 6.5%meeting criteria for major depression as definedby Research Diagnostic Criteria (ROC).

In a group of hemodialysis and peritonealdialysis patients. all of whom had been treated forat least 3 months. Craven et at.9 found that 8.1 %met DSM-I11 criteria for major depression andthat 6.1 % met criteria for dysthymic disorder.Lowry and Atcherson 10 evaluated patients whowere just beginning home-based dialysis andfound that 18% met DSM-III criteria for depres­sion. All ofthese prevalence rates are higher thanthose found in community-based samples (suchas the Epidemiologic Catchment Area study). butmost do not appear higher than rates generallyfound in patients with other chronic medicalillnesses. I I

There are a number of serious difficulties incomparing these studies to each other or in gen­eralizing from them. Some focused on a singlemodality and site of treatment (e.g.• in-centerhemodialysis). while others used mixed groups.This makes interpretation difficult because dif­ferences in psychosocial adjustment have beendemonstrated between patients receiving dif-

VOLUME 32· NUMBER 4· FALL 1991

ferent modalities of treatment for ESRD (seebelow). Some studies measured the point pre­valence of psychiatric disorders. while othersassessed lifetime history. Some investigators as­sessed patients early in the course of dialysis.

others much later. andsome made no at­tempt to standardizewhen the patient wasstudied in relation tothe onset of dialysis.Such lack of stan­dardization can createprevalence-incidence(Neyman) bias. 12 It isalso well recognizedby nephrologists andpsychiatrists that psy­chological adjust­ment substantiallyvaries over the courseof ESRD treatment. 13

Differences in demo-graphics (e.g.• race.

sex. age) as well as in location (e.g.• academicmedical center vs. community based. urban vs.rural) should be noted. but such factors are notalways well described.

There are additional problems that have notbeen adequately addressed in studies of the prev­alence of depression in ESRD. Somatic symp­toms are strongly associated with depressedaffect in dialysis patients. 14 but the direction ofcausality remains unclear. Uremia itselfproducesirritability. decreased appetite. insomnia. de­pressed sensorium. apathy. fatigue. and poorcon­centration. Dialyzed patients vary in the degreeto which uremia is successfully corrected. There­fore. some depressive symptoms in the ESRDpopulation may represent incompletely treateduremia rather than depression. IS Furthermore.ESRD patients as a group have many other con­ditions that may mimic depressive states or causeorganic mood disorders. including anemia. elec­trolyte disturbances. and underlying systemicdisease (e.g.• systemic lupus erythematosus). Pa­tients may also take medications with depressiveside effects. including antihypertensives. cortico-

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steroids, antiinflammatory agents, metoclopra­mide, and sedative-hypnotics. Some studies haveaddressed these potential confounding factors bymodifying structured diagnostic instruments todiscount somatic symptoms attributable to med­ical illness or to drugs, for example.8

QUALITY OF LIFE: WHICHTREATMENT IS BEST?

A numberofstudies have compared psychosocialquality of life with dialysis vs. renal transplanta­tion. Evans et at. 16 found that 79% of transplantrecipients functioned psychosocially at nearlynormal levels, compared to 470/0-59% ofdialysispatients. Transplant recipients had better qualityof life than dialysis patients on both objective andsubjective measures. All of the differences inquality of life persisted after the patient case mixwas controlled for differences in demographicsand medical characteristics. Petrie et at. 17 foundthat dialysis patients showed more morbidity onthe General Health Questionnaire (GHQ) (main­ly loss ofemotional control and depression) com­pared to transplant patients and healthy controls.Australian 18 and German 19 reports also have con­firmed better quality of life in renal transplanta­tion. On the other hand, Kalman et at.20 found nodifference in psychiatric morbidity between dial­ysis and transplant patients, even though in theirstudy the former were older and medically moreill. In a recent comparison of 31 transplant recip­ients and 31 dialysis patients matched for dur­ation of treatment, age, education, and familystatus, psychological adjustment was similar inthe two groupS.21 Finally, we should note thatsuch studies usually do not address the effects oftransplant failure, which may result in the worstquality of life.22

Investigators also have compared the qualityof life between patients receiving different dial­ysis modalities. Wolcott et a1.23 found that con­tinuous ambulatory peritoneal dialysis (CAPO)patients had better quality of life and better cog­nitive functioning than hemodialysis patients,with the differences explained neither medicallynor demographically. Others have found little orno difference in psychosocial outcomes between

384

hemodialysis and CAPO patients. 16.24 Compari­son of hemodialysis or CAPO at a hospital vs.dialysis at home has shown treatment at home toappear psychosocially superior, but the magni­tude of difference has varied. 16.24

These quality of life studies have method­ological limitations that hinder comparison andinterpretation. A fundamental problem is thatESRO patients are never randomized to receivea particular form of dialysis or transplantation;indeed, bias in treatment assignment is well rec­ognized.2s.26 Thus, any outcome differences maybe related to pretreatment differences in medical,psychosocial, rehabilitative, or demographiccharacteristics. The most recent studies have at­tempted to correct for this statistically, but itcannot be entirely corrected. This point is exem­plified in a study of 459 ESRO patients thatincluded four modalities of treatment (in-centerhemodialysis, CAPO, related transplant, and ca­daver transplant).27 Differences in quality of lifewere demonstrated, but when the investigatorsadjusted for demographics, primary cause ofESRD, and comorbid illness, they found a reduc­tion in the significance of differences among thefour treatment modalities, as well as a change inthe quality of life rank order.

PSYCHOLOGICAL FACTORSAND OUTCOME STUDIES

There are a number ofpotential measures that canbe studied in ESRD, including survival, ade­quacy of dialysis and dietary compliance (asassessed by blood urea nitrogen, creatinine, po­tassium, phosphate, interdialytic weight gain,blood pressure, and other tests), and complica­tions (bone disease, access problems, infection,pericarditis, and other disorders). Functional out­come measures include various indices ofqualityof life, health care utilization, employment, andfamily stability.

Depression

A Canadian research group28-30 studied therelationship between psychosocial factors andsurvival in 285 home hemodialysis patients.

PSYCHOSOMATICS

They found that depression (on the Basic Person­ality Inventory) was a better predictorof(shorter)survival than was age or a composite physiolog­ical index that included 19 chemical and clinicalvariables.28 Numan et al.31 found that depressivesymptoms (on the Depression Adjective CheckList) were associated with higher mortality andmore frequent hospitalization in 53 hemodialysispatients, who had been on dialysis from zero to150 months. Ziarnik et al.32 studied 47 in-centerhemodialysis patients and found that those whodied within the first year were more likely to havebeen depressed (on a Minnesota Multiphasic Per­sonality Inventory administered prior to begin­ning hemodialysis) than those who survivedlonger. Shulman et al. 33 examined mortality at 10years follow-up in 64 center and home dialysispatients and found that age and depressive symp­toms (on the Beck Depression Inventory) werebetter predictors of survival than medical vari­ables.

A fundamental weakness of most of thesestudies is that no attempt is made to measureand/or to control for disease severity, so the find­ings simply could be the result of patients whoare more ill being more likely to get depressed.Disease severity is a common confounding factorin studies of psychopathology in the medicallyill. 12 A number of general measures of diseaseseverity are available,34 and a measure developedspecifically for ESRD, which has good reliabilityand validity, has been reported recently.35

Other studies have not supported the rela­tionship between depression and decreased sur­vival time in ESRD. Devins et al.36 studied amixed group of 97 patients (hemodialysis,CAPD, transplant) and found no effects of de­pression on survival. Indeed, in their study thosepatients who described their lives as happy over­all had the shortest survival times, leaving theauthors to speculate about denial. In a study of78hemodialysis and CAPD patients over age 70,Husebye et al. 37 also found no relationship be­tween depressive symptoms (Likert Scale) andsurvival.

No published studies were found examiningrelationships between psychological factors andoutcome in renal transplantation, with the excep-

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Levenson and Glocheski

tion of studies that were too small to providemeaningful findings. 38 Fortunately, large, long­term studies are underway.39 Psychosocial inter­vention outcome studies in ESRD mostly havebeen nonrandomized and uncontrolled or poorlycontrolled. In a naturalistic, nonrandomized de­sign, Friend et al.4O investigated the effects ofparticipation in a support group by dialysis pa­tients compared to controls. They found that sup­port-group participants lived longer thannonparticipants, even after controlling for 13psychosocial and physiological covariates. Thisstudy must be interpreted cautiously in view ofthe nonrandomized design as well as the lack ofrecords indicating when patients joined the groupand how long they attended.

Compliance

Studies of compliance in dialysis patientshave many of the same methodological problemsas those focusing on depression. Particularlyproblematic has been the question of how todefine and measure noncompliance. Some stud­ies have used patients' reports and/or physicians'and nurses' impressions, while others have usedchart review of interdialytic weight gain andblood chemistry changes. Manley and Sweeney41have argued that the cutoffs that have been setimpressionistically and used to define compli­ance have tended to inflate the amount of esti­mated noncompliance.

Cummings et al.42 examined which psycho­social factors have the greatest effect on compli­ance. They found that patients' beliefs about theefficacy of, and barriers to, compliance behavior,as well as reported family problems, were con­sistent predictors of the degree of compliance.However, this finding held more consistently forsubjective rather than objective compliance. In awell-designed study of the effects of family pro­cess variables on the survival of center hemodi­alysis patients, Reiss et al.43 examined 23 familiesin a family study laboratory setting. In contrast toexpectations, high scores on family problemsolving, as well as on measures of accomplish­ment and intactness (including intelligence, in­come, and occupational status), predicted early

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death rather than survival. Patient noncompli­ance accounted for most of the association be­tween the family variables and survival. Whilethe relationship found in this study between non­compliance and survival is consistent with otherwork, the association ofnoncompliance and earlydeath with indicators of higher family function­ing is so contrary to clinical experience that thefindings should be interpreted with skepticism,particularly considering the small sample size.Overall, while the effects of noncompliance ondialysis patients' outcomes are well recognizedby clinicians, they remain insufficiently empiri­cally characterized.

WITHDRAWAL FROM DIALYSIS

Psychiatric consultation may be requested whenlong-term dialysis patients wish to discontinuetreatment. Our comments here will be limited toempirical studies; readers are referred elsewherefor discussion ofclinical,44liaison,45 and ethical46

issues. Neu and Kjellstrand47 quantified with-

TABLE 1. Potential confounding factors in end­stage renal disease

Factors That May Affect Course of IllnessBlood pressure controlDegree of uremiaInterdialytic weight gainComplianceCalciUm/phosphorus metabolismCoexisting systemic disease (e.g.• diabetes mellitus.

peripheral vascular disease. coronary artery disease)Etiology of renal diseaseDuration of illness at the time of studyAnemiaPruritisChronic painMedication side effects (e.g.• antihypenensives)

Common Adverse EventsAccess infectionAccess malfunctionGraft rejection

Treatment ModalityHemodialysisHemofiltrationPeritoneal dialysisTransplantation

Site of TreatmentIn centerHome

386

drawal from dialysis in a sample of 1,766 ESRDpatients who entered a dialysis program between1966 and 1983. Dialysis was discontinued in 9%,accounting for 22% of all deaths. Half of thepatients withdrawn were incompetent, requiringsurrogate decision making. The authors assertedthat only 3 of the 155 withdrawals from dialysisrepresented suicide, but this may be an underes­timate because no psychiatric evaluation was re­ported. Similar smaller studies have appearedfrom Canada48 and the Netherlands.49 Early stud­ies that had pointed to a very high rate of suicidein dialysis patients overestimated suicide preva­lence by not distinguishing rational treatmentwithdrawal from suicide. The true rate of suicidein dialysis has not been established systemati­cally; nor has there been careful attention to thepsychological factors that may affect the decisionto withdraw from treatment.

MECHANISMS MEDIATINGTHE EFFECTS OF

PSYCHOLOGICAL FACTORS

The current state of research allows only forspeculation on how psychological factors mightassert influence over outcome in ESRD. We willrestrict our comments to the potential influencesof depression. Depression has been shown toaffect immune function, although the clinical sig­nificance ofthese effects is not yet clear.so It is atleast possible that depression-induced immun­ologic changes might lead to increased infectionsin dialysis and transplant patients. A much lesstheoretical explanation, and one familiar to clini­cians, is that depressed ESRD patients seem morelikely to evidence poor self-care, noncompliance(dietary, medication, dialysis), and poor medicalfollow-up. Depression may be associated withpoor social support in ESRD patients,51 which hasits own adverse impact on medical outcome,although this relationship has not been clearlyestablished in ESRD.52 Depression has been as­sociated in other populations with increased useof analgesics, which in tum have been demon­strated to have a role in the etiology and exacer­bation of chronic renal failure.53

.54 Depression isassociated with smoking, alcoholism, and other

PSYCHOSOMATICS

fonns of substance abuse that are themselvesmajor causes of increased morbidity and mortal­ity. Depression may adversely impact outcome inESRD by serving as a risk factor for other medi­cal comorbidity, e.g., myocardial infarctionSS orreduced aerobic capacity.56 Finally, it is possiblethat adverse effects ofdepression in patients withchronic renal failure are nonspecific because de­pression may be independently associated withincreased mortality in the population at large.57

FUTURE RESEARCH

Psychonephrology is an exciting frontier forresearch exploring the effects of psychologicalfactors on physical conditions, and much ground­breaking work has been accomplished. Furtherresearch with careful attention to methodology isneeded to demonstrate and quantify more clearlythe effects of psychological factors on renal dis­ease. While it would be impossible to control allpotential confounding factors (Table I), futureresearchers should make greater attempts to con­trol for differences in demographics, treatmentmodality, time point in treatment, primary causeof renal failure, other medical and psychiatriccomorbidities, smoking, substance abuse, medi-

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