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American Journal of Kidney Diseases

Assessing Fatigue in the ESRD Patient: A Step Forward

      Related Article, p. 327
      Patient-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 disease (ESRD).
      • Kraus M.A.
      • Fluck R.J.
      • Weinhandl E.D.
      • et al.
      Intensive hemodialysis and health-related quality of life.
      • Garg A.X.
      • Suri S.
      • Eggers P.
      • et al.
      Frequent Hemodialysis Network Trial Investigators
      Patients receiving frequent hemodialysis have better health-related quality of life compared to patients receiving conventional hemodialysis.
      • Finkelstein F.O.
      • Schiller B.
      • Daoui R.
      • et al.
      At-home short daily hemodialysis improves the long-term health-related quality of life.
      • Culleton B.F.
      • Asola M.R.
      The impact of short daily and nocturnal hemodialysis on quality of life, cardiovascular risk and survival.
      • Wu A.W.
      • Fink N.E.
      • Marsh-Manzi J.V.
      • et al.
      Changes in quality of life during hemodialysis and peritoneal dialysis treatment: generic and disease specific measures.
      • Jardine M.J.
      • Zuo L.
      • Gray N.A.
      • et al.
      A trial of extending hemodialysis hours and quality of life.
      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 incorporated PROMs as important outcome measures.
      • Kraus M.A.
      • Fluck R.J.
      • Weinhandl E.D.
      • et al.
      Intensive hemodialysis and health-related quality of life.
      • Garg A.X.
      • Suri S.
      • Eggers P.
      • et al.
      Frequent Hemodialysis Network Trial Investigators
      Patients receiving frequent hemodialysis have better health-related quality of life compared to patients receiving conventional hemodialysis.
      • Finkelstein F.O.
      • Schiller B.
      • Daoui R.
      • et al.
      At-home short daily hemodialysis improves the long-term health-related quality of life.
      • Culleton B.F.
      • Asola M.R.
      The impact of short daily and nocturnal hemodialysis on quality of life, cardiovascular risk and survival.
      • Wu A.W.
      • Fink N.E.
      • Marsh-Manzi J.V.
      • et al.
      Changes in quality of life during hemodialysis and peritoneal dialysis treatment: generic and disease specific measures.
      • Jardine M.J.
      • Zuo L.
      • Gray N.A.
      • et al.
      A trial of extending hemodialysis hours and quality of life.
      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 standardization 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 Hemodialysis Survey Consumer Assessment of Healthcare Providers 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.
      • Finkelstein F.O.
      Performance measures in dialysis facilities: what is the goal?.
      • Kliger A.S.
      Quality measures in dialysis: time for a measured scorecard.
      It is now well documented and accepted that the HRQoL of dialysis patients is compromised, and appropriately, 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 community is how best to document and monitor the HRQoL of patients with ESRD and understand the impact of changes in treatment regimens on HRQoL.
      • Finkelstein F.O.
      • Finkelstein S.H.
      Time to rethink our approach to patient-reported outcome measures for ESRD.
      • Hayes Peipert J.D.
      • Hays R.D.
      Using patient-reported measures in dialysis clinics.
      • Ju A.
      • Tong A.
      Considerations and challenges in selecting patient-reported outcome measures for clinical trials in nephrology.
      • Kurella Tamura M.
      Introduction to patient-reported outcomes perspectives series.
      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 al
      • Ju A.
      • Unruh M.L.
      • Davison S.N.
      • et al.
      Patient-reported outcome measures or fatigue in patients on hemodialysis: a systematic review.
      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 patients is needed to estimate and improve this disabling complication of HD."
      • Ju A.
      • Unruh M.L.
      • Davison S.N.
      • et al.
      Patient-reported outcome measures or fatigue in patients on hemodialysis: a systematic review.
      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.
      • Evangelidis N.
      • Tong A.
      • Manns B.
      • et al.
      Standardized Outcomes in Nephrology–Hemodialysis (SONG-HD) initiative. Developing a set of core outcomes for trials in hemodialysis: an international Delphi survey.
      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.
      • Cabrera V.
      • Hansson J.
      • Kliger A.S.
      • Finkelstein F.O.
      Symptom management of the patient with chronic kidney disease: the role of dialysis.
      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 patients’ perceptions of their care has proved to be challenging 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 prescribed by any one of several health care providers (dialysis patients, on average, take about 10-12 different medications per day).
      • Cabrera V.
      • Hansson J.
      • Kliger A.S.
      • Finkelstein F.O.
      Symptom management of the patient with chronic kidney disease: the role of dialysis.
      Second, these symptoms vary over time, often related to intercurrent medical, social, psychological, and/or family/marital problems.
      • Weisbord S.D.
      • Mor M.K.
      • Green J.A.
      • et al.
      Comparison of symptom management strategies for pain, erectile dysfunction, and depression in patients receiving chronic hemodialysis: a cluster randomized effectiveness trial.
      • Pittman Z.C.
      • John S.G.
      • McIntyre C.W.
      Collection of daily patient reported outcomes is feasible and demonstrates differential patient experience in chronic kidney disease.
      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.
      • Weisbord S.D.
      • Mor M.K.
      • Green J.A.
      • et al.
      Comparison of symptom management strategies for pain, erectile dysfunction, and depression in patients receiving chronic hemodialysis: a cluster randomized effectiveness trial.
      Understanding 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 isolation 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, dialysis 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.
      • Mapes D.
      • Lopes A.A.
      • Satayathum S.
      • et al.
      Health-related quality of life as a predictor of mortality and hospitalization: the Dialysis Outcomes and Practice Patterns Study (DOPPS).
      Furthermore, they have been clearly affected by adjustments in the dialysis treatment regimen.
      • Kraus M.A.
      • Fluck R.J.
      • Weinhandl E.D.
      • et al.
      Intensive hemodialysis and health-related quality of life.
      • Garg A.X.
      • Suri S.
      • Eggers P.
      • et al.
      Frequent Hemodialysis Network Trial Investigators
      Patients receiving frequent hemodialysis have better health-related quality of life compared to patients receiving conventional hemodialysis.
      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 patients 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 depression.
      • Hedayati S.
      • Finkelstein F.O.
      Epidemiology, diagnosis and management of depression in patients with CKD.
      However, how do we validate a fatigue questionnaire 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.
      • Hedayati S.
      • Finkelstein F.O.
      Epidemiology, diagnosis and management of depression in patients with CKD.
      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 unconscious and conscious processes, experiences the same event differently, uniquely interpreted and reconstructed by his or her brain.
      • Kandel E.
      The Age of Insight.
      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.”
      • Gill T.M.
      • Feinstein A.R.
      A critical appraisal of the quality of quality-of-life measurements.
      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 assessments 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.
      • Cabrera V.
      • Hansson J.
      • Kliger A.S.
      • Finkelstein F.O.
      Symptom management of the patient with chronic kidney disease: the role of dialysis.
      How many questionnaires can patients complete? How often will they be willing to complete these questionnaires? Will the questionnaires provide meaningful information if the questionnaires are too long or are administered too frequently? Will the instruments remain valid over time with repeated use? Perhaps even more 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 ultimately does this remains the real challenge.
      The article by Ju et al is certainly a step in the right direction. 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 creative 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.
      • Basch E.
      Patient reported outcomes—harnessing patients’ voices to improve clinical care.
      The use of computerized adaptive testing in psychiatry has been used to monitor PROMs and has been shown to be effective in facilitating patient assessments by adapting questions to patient responses.
      • Gibbons R.D.
      • Weiss D.J.
      • Frank E.
      • Kupfer D.
      Computerized adaptive diagnosis and testing of mental health disorders.
      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 providers to better appreciate the unique concerns of their patients and adapt the care provided to maximize the HRQoL of the individual patient.

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