Editorial
Assessing Fatigue in the ESRD Patient:
A Step Forward
Fredric O. Finkelstein and Susan H. Finkelstein
P atient-reported outcome measures (PROMs) as a way
of assessing the health-related quality of life (HRQoL)
of patients are now recognized as key outcome measures in
clinical trials evaluating the impact of different renal
replacement therapies for patients with end-stage renal
Related Article, p. 327
disease (ESRD).1-6 Thus, recent studies comparing more
frequent hemodialysis (HD) to conventional HD, home
HD to center HD, extended HD to conventional treatments,
and home peritoneal dialysis to center HD have all incor-
porated PROMs as important outcome measures.1-6
However, when trying to compare these studies and
evaluate the impact of these different therapies on patients,
a major barrier is that in general, there is no standardiza-
tion of PROMs used to assess HRQoL. The use of PROMs in
dialysis facilities in the United States is complicated
because the Centers for Medicare & Medicaid Services
has now mandated that dialysis facilities ask
patients to complete the Kidney Disease Quality of
Life (KDQOL)-36 annually, screen patients for depression
and pain annually, and complete the In-Center Hemodi-
alysis Survey Consumer Assessment of Healthcare Pro-
viders and Systems (ICH-CAHPS) semi-annually. The
utility of these instruments in accurately assessing the
HRQoL of patients and capturing the individual patient’s
experience with renal replacement therapy has been
questioned.7,8
It is now well documented and accepted that the
HRQoL of dialysis patients is compromised, and appro-
priately, there has recently been an increased focus on
devising strategies to improve the HRQoL of these patients.
Among these strategies, alterations in standard dialysis
treatment regimens have been the subject of several recent
studies. A major problem facing the nephrology commu-
nity is how best to document and monitor the HRQoL of
patients with ESRD and understand the impact of changes
in treatment regimens on HRQoL.9-12 Can there be some
agreement as to which PROMs should be included both as
part of clinical care and as research tools? To address this
question, the article in this issue of AJKD by Ju et al13 opens
an important window into our understanding of the
complexity of assessing even one dimension of HRQoL–
fatigue. The authors reviewed 123 articles that looked at
patient-reported symptoms of fatigue and noted that 43
different measures were used. These varied in length and
content and many were not validated. They conclude that
"a standardized and psychometrically robust measure that
captures dimensions of fatigue that are important to
306
patients is needed to estimate and improve this disabling
complication of HD."13(p337) This work is part of the
Standardized Outcomes in Nephrology–Hemodialysis
(SONG-HD) Initiative, the goal of which is to develop
standardized outcome measures to better assess the impact
of modifications of the various treatment regimens.14 The
importance of standardizing a validated assessment for
fatigue is underscored by the observation that fatigue is a
major domain of difficulty for patients with ESRD.15
It is important to recognize that this standardization will
be particularly difficult in terms of PROMs. The use of
PROMs to assess the impact of dialysis treatments on pa-
tients’ perceptions of their care has proved to be chal-
lenging for several reasons.
First, dialysis patients have a multitude of symptoms
that may be associated with their underlying ESRD, as well
as varied comorbid conditions, social situations, financial
stresses, and/or multiple medications that have been pre-
scribed by any one of several health care providers (dialysis
patients, on average, take about 10-12 different medica-
tions per day).15
Second, these symptoms vary over time, often related to
intercurrent medical, social, psychological, and/or family/
marital problems.16,17 For example, a recent study noted
that pain and depression scores on PROMs in a cohort of HD
patients varied widely from month to month.16 Under-
standing the relationship between the treatment regimen
and these fluctuations in patients’ HRQoL is difficult.
Third, the symptoms that patients experience are often
closely interrelated, and assessing one symptom in isola-
tion may therefore be problematic. For example, fatigue,
which the authors note is often a common concern of
dialysis patients, may be related to depression, sleep
disturbance, restless legs, postdialysis recovery time, dial-
ysis treatment duration, pain, hypotension, anemia, and
acute medical and psychosocial events. Furthermore, the
various medications used to treat these myriad symptoms
can certainly contribute to symptoms of fatigue. Thus,
developing a PROM to focus on fatigue will need to
address the impact of these other variables on patients’
reports of symptoms. In addition, some researchers have
argued that PROMs that address multiple domains need to
remain the focus for the complex patient with ESRD, and
the summary scores, such as the physical and mental
composite scores of the 36-Item Short Form Health Survey
(SF-36), may be particularly useful. These summary scores
have proved to be strongly associated with mortality and
hospitalization rates in HD patients.18 Furthermore, they
have been clearly affected by adjustments in the dialysis
treatment regimen.1,2
AJKD Vol 71 | Iss 3 | March 2018
Editorial
Fourth, a key challenge with any PROM is establishing
the validity of the questionnaire. This can be done more
easily with selected PROM domains, such as depression
and sleep. Thus, a diagnosis of clinical or major depression
needs to be established by an interview. Questionnaires
examining depressive symptoms can be validated against
the interview-based diagnosis. This has been done in pa-
tients with ESRD for the Beck Depression Inventory, Center
for Epidemiological Studies-Depression questionnaire, and
Patient Health Questionnaire-9, for which scores of a
certain level are associated with high sensitivity and
specificity for an interview-based diagnosis of depres-
sion.19 However, how do we validate a fatigue question-
naire given the various factors that can contribute to an
individual patient’s report of fatigue-related symptoms?
This may present a barrier limiting our ability to come to a
uniform agreement on how best to screen for fatigue and
may explain why so many instruments have been used in
prior studies, something that has not been true, for
example, of screening for depressive symptoms.19
Last, it is not clear whether standardized questionnaires
will be able to capture each patient’s unique experience with
alterations in treatment regimens. It needs to be recognized
that each patient will experience dialysis uniquely. Will
there be problematic areas for individual patients that will
not be addressed using standard instruments? Different
domains will be important to each individual. Additionally,
areas of importance for an individual may not be captured in
standardized questionnaires. For each individual, it is
important to try to capture his or her unique concerns. This
may best be done by asking each patient to describe his or
her experience in his or her own words, a technique that is
captured well by the Nobel Prize winner neuroscientist Eric
R. Kandel. In his book, The Age of Insight, he observes that we
need to understand that each individual, because of un-
conscious and conscious processes, experiences the same
event differently, uniquely interpreted and reconstructed by
his or her brain.20 Gill and Feinstein underscored this
problem in their classic article “A Critical Appraisal of the
Quality of Quality of Life Measurements,” in which they
caution that “Because quality of life is a uniquely personal
perception…most measurements of quality of life … seem
to aim at the wrong target.”21(p 619)
Aside from the research aspect of coming to a consensus
on how to incorporate PROMs into standardized outcome
measures, it is important to think about how these as-
sessments can be incorporated into clinical practice as a
way of improving the care of patients and their perceptions
of their HRQoL. One of the major challenges is how to
screen patients effectively, recognizing that they have a
wide variety of symptoms and domains of difficulty.15
How many questionnaires can patients complete? How
often will they be willing to complete these question-
naires? Will the questionnaires provide meaningful infor-
mation if the questionnaires are too long or are
administered too frequently? Will the instruments remain
valid over time with repeated use? Perhaps even more
AJKD Vol 71 | Iss 3 | March 2018
importantly, how will the dialysis facility incorporate the
results of the questionnaires into clinical care? The ultimate
goal is to provide the best possible clinical care and
improve patients’ HRQoL. How the dialysis facility ulti-
mately does this remains the real challenge.
The article by Ju et al is certainly a step in the right di-
rection. Fatigue is a major concern of dialysis patients and
whatever the cause, standardizing how fatigue is reported
by patients will enable researchers to investigate various
therapeutic strategies to address this symptom. However,
this is the time for the nephrology community to be cre-
ative and innovative in its approach to effectively using
PROMs to improve the care of patients with ESRD. Other
specialties have demonstrated the value of such creative
approaches. For example, work in oncology has suggested
that the use of electronic reporting of symptoms to health
care providers can improve care by not only reducing
emergency department visits and hospitalizations, but also
by improving clinicians’ and patients’ experiences of health
care.22 The use of computerized adaptive testing in psy-
chiatry has been used to monitor PROMs and has been
shown to be effective in facilitating patient assessments by
adapting questions to patient responses.23 The utility of
such approaches in the care of patients with ESRD certainly
merits further exploration. We need to investigate whether
incorporating such approaches will enable dialysis pro-
viders to better appreciate the unique concerns of their
patients and adapt the care provided to maximize the
HRQoL of the individual patient.
Article Information
Authors’ Full Names and Academic Degrees: Fredric O.
Finkelstein, MD, and Susan H. Finkelstein, MSW.
Authors’ Affiliation: Yale University, New Haven, CT.
Address for Correspondence: Fredric O. Finkelstein, MD, 136
Sherman Ave, New Haven CT 06511. E-mail: fof@comcast.net
Support: None.
Financial Disclosure: The authors declare that they have no
relevant financial interests.
Peer Review: Received September 24, 2017 in response to an
invitation from the journal. Direct editorial input from an Associate
Editor and a Deputy Editor. Accepted in revised form October 18,
2017.
Publication Information: © 2017 by the National Kidney Founda-
tion, Inc. doi: 10.1053/j.ajkd.2017.10.021
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