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  • br Address correspondence to Manisha


    Address correspondence to: Manisha Jhamb, MD, MPH, Renal-Electrolyte Division, University of Pittsburgh School 
    Accepted for publication: December 5, 2018.
    2018 The Authors. Published by Elsevier Inc. on behalf of American 0885-3924/$ - see front matter Academy of Hospice and Palliative Medicine. This is an open access article under the CC BY-NC-ND license (
    Patients with chronic kidney disease (CKD) and end-stage kidney disease (ESKD) experience high mortality, substantial symptom burdens, and poor quality of life (QoL).1 The symptom burden in pa-tients with ESKD may even be similar to that of advanced cancer patients.2,3 Yet, symptom recognition and management in CKD and ESRD by nephrology providers remains suboptimal.4
    For cancer patients, pain, fatigue, and depression were the most common and debilitating symptoms identified in the National Institute of Health State-of-Science Consensus statement.5 This led the Institute of Medicine and several national oncological societies (e.g., American Society for Clinical Oncology, Amer-ican College of Surgeons) to recommend screening and treatment guidelines for these symptoms in cancer patients.6 Only recently, the Kidney Disease Improving Global Outcomes Controversies Conference on Sup-portive Care in 2015 advocated for SPDP of symp-tom assessment and management in routine CKD care.7
    Fatigue is the most common symptom reported by pa-tients with advanced CKD/ESKD and cancer, with a reported prevalence of up to 100%.2,8 Fatigue substan-tially impacts QoL in both patient populations.8,9 Fa-tigue is one of the most highly prioritized symptoms for which treatment is desired among kidney disease pa-tients and clinicians.10,11 However, its treatment in CKD/ ESKD remains challenging due to the patient-specific manifestations, multifactorial etiology, and incompletely understood pathophysiology.8,12 Among cancer pa-tients, symptom cluster research has identified that fa-tigue often coexists with other symptoms such as pain, emotional distress, sleep dysfunction, and depression.13 This has led to the development of cancer-related fatigue management guidelines by the National Comprehensive Cancer Network and the Fatigue Coalition that empha-size a shift of focus from treating fatigue alone to addressing multiple symptoms.14 We hypothesized that symptom clusters also exist among kidney disease pa-tients, given the high burden of pain and depressive symptoms in Late period of phage development population.1 Symptom cluster research in nephrology has been limited to a handful of studies that have been focused on ESKD patients and mostly included non-US cohorts.15e18 Characterizing symptom clusters in CKD and ESKD patients is a key step to under-standing underlying mechanisms and accelerating the development of targeted symptom interventions, as recommended by the National Institute of Health (NIH) 2017 workshop on ‘‘Advancing Symptom Science through Symptom Cluster Research.’’.19 In addition, comparing symptom cluster phenotypes and their pre-dictors across chronic conditions may help identify potentially modifiable risk factors (such as hemoglobin, albumin, cytokines, and hormonal mediators) and 
    inform the development of specific, individualized inter-ventions to improve patient-centered outcomes.19
    The aim of our study was to characterize and compare symptoms (fatigue, pain, and depressive symptoms) and symptom cluster phenotypes among advanced CKD, ESKD, and advanced gastrointestinal (GI) cancer patients (i.e., a group of malignancies associated with very high symptom burden and poor QoL).20 We will also examine potential demographic and disease-specific predictors of symptom clusters among the three patient groups.
    Study Population
    The present study is a post hoc analysis of data collected as part of prospective studies of kidney disease and cancer patients. As part of a larger, prospective cohort study of sleep and QoL in adult, English-speaking patients with CKD Stage 4e5 or ESKD (K23DK66006; R01DK77785), we assessed patients’ fa-tigue, pain, and depressive symptoms.21 Between March 2004 and December 2008, patients were approached during routine nephrology clinic visits, dialysis clinic visits, or initial kidney transplant evaluations at the University of Pittsburgh. This cohort also included pa-tients enrolled in an ancillary Frequent Hemodialysis Network Trials study (FHN; NCT00264758). Exclusions included age less than 18 years and presence of severe active medical or psychiatric illness as has been previ-ously described. Because the main focus of our present study was fatigue, only those patients who completed the fatigue questionnaire (see below) at baseline were included (82 CKD Stage 4e5 and 149 ESKD).