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• W3133359436 abstract "Patients with advanced chronic kidney disease (CKD) experience multiple bothersome symptoms, undermining their quality of life (QOL). With growing attention to the importance of symptom management in advanced CKD, the evidence regarding symptoms is increasing. In this review, we briefly summarize the current evidence of effective pharmacologic and nonpharmacologic interventions to improve symptoms and QOL in patients with advanced CKD, including those on dialysis. We focused on symptoms that are commonly experienced by patients, such as pain, fatigue, sleep disturbances, itching, nausea and vomiting, cognitive impairment, and anxiety and depression. We noted that research in symptom science focused on improving symptom management in CKD is still very limited. In addition to the lack of clinical practice guidelines to address those common symptoms, the major gaps in the current literature include the evidence regarding mechanistic pathways to inform the development of effective symptom management for CKD populations, the evidence to confirm effective pharmacologic interventions in other populations for CKD populations, and research on how to incorporate effective symptom management approaches into clinical care. Although improving mortality remains as an important area in the kidney community, there is an urgent need to focus on improving symptom management to improve QOL in advanced CKD. Patients with advanced chronic kidney disease (CKD) experience multiple bothersome symptoms, undermining their quality of life (QOL). With growing attention to the importance of symptom management in advanced CKD, the evidence regarding symptoms is increasing. In this review, we briefly summarize the current evidence of effective pharmacologic and nonpharmacologic interventions to improve symptoms and QOL in patients with advanced CKD, including those on dialysis. We focused on symptoms that are commonly experienced by patients, such as pain, fatigue, sleep disturbances, itching, nausea and vomiting, cognitive impairment, and anxiety and depression. We noted that research in symptom science focused on improving symptom management in CKD is still very limited. In addition to the lack of clinical practice guidelines to address those common symptoms, the major gaps in the current literature include the evidence regarding mechanistic pathways to inform the development of effective symptom management for CKD populations, the evidence to confirm effective pharmacologic interventions in other populations for CKD populations, and research on how to incorporate effective symptom management approaches into clinical care. Although improving mortality remains as an important area in the kidney community, there is an urgent need to focus on improving symptom management to improve QOL in advanced CKD. Patients with advanced chronic kidney disease (CKD) experience multiple symptoms, such as fatigue, pain, insomnia, depression, and anxiety,1Abdel-Kader K. Unruh M.L. Weisbord S.D. Symptom burden, depression, and quality of life in chronic and end-stage kidney disease.Clin J Am Soc Nephrol. 2009; 4: 1057-1064Crossref PubMed Scopus (251) Google Scholar,2Nixon A.C. Wilkinson T.J. Young H.M.L. et al.Symptom-burden in people living with frailty and chronic kidney disease.BMC Nephrol. 2020; 21: 411Crossref PubMed Scopus (0) Google Scholar often concurrently,3Davison S.N. Jhangri G.S. Johnson J.A. Longitudinal validation of a modified Edmonton symptom assessment system (ESAS) in haemodialysis patients.Nephrol Dial Transplant. 2006; 21: 3189-3195Crossref PubMed Scopus (112) Google Scholar contributing to symptom distress and compromised quality of life (QOL).4Song M.K. Paul S. Ward S.E. et al.One-year linear trajectories of symptoms, physical functioning, cognitive functioning, emotional well-being, and spiritual well-being among patients receiving dialysis.Am J Kidney Dis. 2018; 72: 198-204Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar, 5Almutary H. Bonner A. Douglas C. Which patients with chronic kidney disease have the greatest symptom burden? A comparative study of advanced CKD stage and dialysis modality.J Ren Care. 2016; 42: 73-82Crossref PubMed Scopus (50) Google Scholar, 6Almutary H. Douglas C. Bonner A. Multidimensional symptom clusters: an exploratory factor analysis in advanced chronic kidney disease.J Adv Nurs. 2016; 72: 2389-2400Crossref PubMed Scopus (25) Google Scholar Although reports of the number of symptoms experienced by patients with advanced CKD vary depending on the measurement used, up to a median of 9 symptoms has been reported.7Weisbord S.D. Fried L.F. Arnold R.M. et al.Prevalence, severity, and importance of physical and emotional symptoms in chronic hemodialysis patients.J Am Soc Nephrol. 2005; 16: 2487-2494Crossref PubMed Scopus (320) Google Scholar The symptoms that are most common and/or bothersome among patients with advanced CKD are pain, fatigue, sleep disturbances, muscle cramps, restless legs, itching, nausea and vomiting, cognitive impairment, and anxiety and depression.5Almutary H. Bonner A. Douglas C. Which patients with chronic kidney disease have the greatest symptom burden? A comparative study of advanced CKD stage and dialysis modality.J Ren Care. 2016; 42: 73-82Crossref PubMed Scopus (50) Google Scholar,8Almutary H. Bonner A. Douglas C. Symptom burden in chronic kidney disease: a review of recent literature.J Ren Care. 2013; 39: 140-150Crossref PubMed Scopus (105) Google Scholar Although such symptom experiences (except uremic symptoms) are rather common in many patients with other advanced chronic illnesses (e.g., cancer, congestive heart failure),9Chen E. Nguyen J. Khan L. et al.Symptom clusters in patients with advanced cancer: a reanalysis comparing different statistical methods.J Pain Symptom Manage. 2012; 44: 23-32Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar most symptoms in CKD are poorly understood and managed.10Weisbord S.D. Fried L.F. Mor M.K. et al.Renal provider recognition of symptoms in patients on maintenance hemodialysis.Clin J Am Soc Nephrol. 2007; 2: 960-967Crossref PubMed Scopus (171) Google Scholar,11Claxton R.N. Blackhall L. Weisbord S.D. et al.Undertreatment of symptoms in patients on maintenance hemodialysis.J Pain Symptom Manage. 2010; 39: 211-218Abstract Full Text Full Text PDF PubMed Scopus (84) Google Scholar In part due to a lack of routine symptom assessment, patients on dialysis often resign from communicating their symptoms to care providers and adopt ineffective self-management strategies.12Song M.K. Ward S.E. Hladik G.A. et al.Depressive symptom severity, contributing factors, and self-management among chronic dialysis patients.Hemodial Int. 2016; 20: 286-292Crossref PubMed Google Scholar,13Flythe J.E. Dorough A. Narendra J.H. et al.Perspectives on symptom experiences and symptom reporting among individuals on hemodialysis.Nephrol Dial Transplant. 2018; 33: 1842-1852Crossref PubMed Scopus (18) Google Scholar National and international kidney communities14Davison S.N. Jassal S.V. Supportive care: integration of patient-centered kidney care to manage symptoms and geriatric syndromes.Clin J Am Soc Nephrol. 2016; 11: 1882-1891Crossref PubMed Scopus (30) Google Scholar, 15Davison S.N. Moss A.H. Supportive care: meeting the needs of patients with advanced chronic kidney disease.Clin J Am Soc Nephrol. 2016; 11: 1879-1880Crossref PubMed Scopus (11) Google Scholar, 16Flythe J.E. Hilliard T. Lumby E. et al.Fostering innovation in symptom management among hemodialysis patients: paths forward for insomnia, muscle cramps, and fatigue.Clin J Am Soc Nephrol. 2019; 14: 150-160Crossref PubMed Scopus (17) Google Scholar have advocated for early integration of palliative care into CKD and dialysis care to improve symptom management and QOL, and research on symptom management has increasingly drawn the attention of investigators and care providers. However, as the extent of the applicability of findings from symptom research in other conditions to CKD populations has yet to be confirmed, especially for drug recommendations, a lack of evidence for symptom management for CKD populations persists. The purpose of this narrative review17Green B.N. Johnson C.D. Adams A. Writing narrative literature reviews for peer-reviewed journals: secrets of the trade.J Sports Chiropract Rehabil. 2001; 15: 5‒19Google Scholar,18Slavin R.E. Best evidence synthesis: an intelligent alternative to meta-analysis.J Clin Epidemiol. 1995; 48: 9-18Abstract Full Text PDF PubMed Scopus (618) Google Scholar is to provide a brief summary of current evidence (e.g., reports of clinical trials, systematic reviews of clinical trials, observational studies) regarding effective interventions to address the symptoms most commonly experienced by patients with advanced CKD. In this review, frailty---although a common condition among these patients---was not included as a “symptom” because it is a state of an accumulation of multiple deficits, such as unintended weight loss and weakness,19Fried L.P. Tangen C.M. Walston J. et al.Frailty in older adults: evidence for a phenotype.J Gerontol A Biol Sci Med Sci. 2001; 56: M146-M156Crossref PubMed Google Scholar,20Xue Q.L. The frailty syndrome: definition and natural history.Clin Geriatr Med. 2011; 27: 1-15Abstract Full Text Full Text PDF PubMed Scopus (640) Google Scholar rather than a symptom that is reported by patients. We searched for evidence of both pharmacologic and nonpharmacologic therapies to provide a holistic approach to symptom management. Our review focuses on patients with advanced CKD who are already, or soon will be, on long-term dialysis. We did not review studies of patients undergoing conservative management (without dialysis) because symptom management for those patients is likely more aggressive due to goals of care that directed conservative management in the first place.21Davison S.N. Levin A. Moss A.H. et al.Executive summary of the KDIGO controversies conference on supportive care in chronic kidney disease: developing a roadmap to improving quality care.Kidney Int. 2015; 88: 447-459Abstract Full Text Full Text PDF PubMed Scopus (208) Google Scholar Pain, defined as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage,”22International Association for the Study of PainPain.https://www.iasp-pain.org/publicationsnews/newsdetail.aspx?itemnumber=9218Date: 2019Date accessed: December 10, 2020Google Scholar is reported by up to 70% of patients with advanced CKD and nearly 100% of hospitalized patients with CKD.23Pham P.C. Khaing K. Sievers T.M. et al.2017 Update on pain management in patients with chronic kidney disease.Clin Kidney J. 2017; 10: 688-697Crossref PubMed Scopus (51) Google Scholar The origin of pain for the majority of these patients is musculoskeletal,23Pham P.C. Khaing K. Sievers T.M. et al.2017 Update on pain management in patients with chronic kidney disease.Clin Kidney J. 2017; 10: 688-697Crossref PubMed Scopus (51) Google Scholar and roughly half rate their pain intensity as moderate to severe.24Koncicki H.M. Unruh M. Schell J.O. Pain management in CKD: a guide for nephrology providers.Am J Kidney Dis. 2017; 69: 451-460Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar Undertreated moderate to severe pain adversely affects QOL and can lead to numerous complications, such as stress, anxiety, depression, and overall reduction in life satisfaction.24Koncicki H.M. Unruh M. Schell J.O. Pain management in CKD: a guide for nephrology providers.Am J Kidney Dis. 2017; 69: 451-460Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar, 25Davison S.N. Tupala B. Wasylynuk B.A. et al.Recommendations for the care of patients receiving conservative kidney management.Clin J Am Soc Nephrol. 2019; 14: 626-634Crossref PubMed Scopus (0) Google Scholar, 26Davison S.N. Clinical pharmacology considerations in pain management in patients with advanced kidney failure.Clin J Am Soc Nephrol. 2019; 14: 917-931Crossref PubMed Scopus (33) Google Scholar The first step toward effective pain management is identifying the type of pain through comprehensive assessment. Nociceptive pain occurs through tissue damage and the stimulation of related receptors.23Pham P.C. Khaing K. Sievers T.M. et al.2017 Update on pain management in patients with chronic kidney disease.Clin Kidney J. 2017; 10: 688-697Crossref PubMed Scopus (51) Google Scholar,25Davison S.N. Tupala B. Wasylynuk B.A. et al.Recommendations for the care of patients receiving conservative kidney management.Clin J Am Soc Nephrol. 2019; 14: 626-634Crossref PubMed Scopus (0) Google Scholar Nociceptive pain is often described as sharp, cramping, or dull.25Davison S.N. Tupala B. Wasylynuk B.A. et al.Recommendations for the care of patients receiving conservative kidney management.Clin J Am Soc Nephrol. 2019; 14: 626-634Crossref PubMed Scopus (0) Google Scholar Neuropathic pain results from damage to the nervous system. It is commonly associated with diabetes, amyloid, and viral infections.23Pham P.C. Khaing K. Sievers T.M. et al.2017 Update on pain management in patients with chronic kidney disease.Clin Kidney J. 2017; 10: 688-697Crossref PubMed Scopus (51) Google Scholar,25Davison S.N. Tupala B. Wasylynuk B.A. et al.Recommendations for the care of patients receiving conservative kidney management.Clin J Am Soc Nephrol. 2019; 14: 626-634Crossref PubMed Scopus (0) Google Scholar Neuropathic pain is described as shooting, stabbing, or burning.24Koncicki H.M. Unruh M. Schell J.O. Pain management in CKD: a guide for nephrology providers.Am J Kidney Dis. 2017; 69: 451-460Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar,26Davison S.N. Clinical pharmacology considerations in pain management in patients with advanced kidney failure.Clin J Am Soc Nephrol. 2019; 14: 917-931Crossref PubMed Scopus (33) Google Scholar,27Cohen S.D. Patel S.S. Khetpal P. et al.Pain, sleep disturbance, and quality of life in patients with chronic kidney disease.Clin J Am Soc Nephrol. 2007; 2: 919-925Crossref PubMed Scopus (100) Google Scholar The World Health Organization’s stepwise approach to pain management may be helpful to guide initiation and use of medications.24Koncicki H.M. Unruh M. Schell J.O. Pain management in CKD: a guide for nephrology providers.Am J Kidney Dis. 2017; 69: 451-460Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar The first-line approach to mild nociceptive pain includes using nonopioid analgesics, such as acetaminophen and short-acting nonsteroidal anti-inflammatory drugs (NSAIDs; Table 1).23Pham P.C. Khaing K. Sievers T.M. et al.2017 Update on pain management in patients with chronic kidney disease.Clin Kidney J. 2017; 10: 688-697Crossref PubMed Scopus (51) Google Scholar,24Koncicki H.M. Unruh M. Schell J.O. Pain management in CKD: a guide for nephrology providers.Am J Kidney Dis. 2017; 69: 451-460Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar However, NSAIDs as well as other pharmacologic agents should be used with caution because of altered pharmacokinetics and risk for adverse effects due to the reduction in renal clearance and potential for accumulation of active metabolites. NSAIDs specifically may contribute to the risk of bleeding and cardiovascular events, as well as renal complications in those with residual function.26Davison S.N. Clinical pharmacology considerations in pain management in patients with advanced kidney failure.Clin J Am Soc Nephrol. 2019; 14: 917-931Crossref PubMed Scopus (33) Google ScholarTable 1Summary of pharmacologic and nonpharmacologic approaches for common symptoms in advanced CKDSymptomPharmacologic approachNonpharmacologic approachPain•Topical anesthetics (e.g., lidocaine or diclofenac)24Koncicki H.M. Unruh M. Schell J.O. Pain management in CKD: a guide for nephrology providers.Am J Kidney Dis. 2017; 69: 451-460Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar•Nonopioid analgesics (e.g., acetaminophen) and short-acting nonsteroidal anti-inflammatory drugs23Pham P.C. Khaing K. Sievers T.M. et al.2017 Update on pain management in patients with chronic kidney disease.Clin Kidney J. 2017; 10: 688-697Crossref PubMed Scopus (51) Google Scholar,24Koncicki H.M. Unruh M. Schell J.O. Pain management in CKD: a guide for nephrology providers.Am J Kidney Dis. 2017; 69: 451-460Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar•For moderate pain, weak opioids (e.g., tramadol and oxycodone and hydromorphone)23Pham P.C. Khaing K. Sievers T.M. et al.2017 Update on pain management in patients with chronic kidney disease.Clin Kidney J. 2017; 10: 688-697Crossref PubMed Scopus (51) Google Scholar•For severe pain, higher doses of oxycodone and hydromorphone as well as long-acting agents (e.g., fentanyl, buprenorphine or methadone)24Koncicki H.M. Unruh M. Schell J.O. Pain management in CKD: a guide for nephrology providers.Am J Kidney Dis. 2017; 69: 451-460Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar,25Davison S.N. Tupala B. Wasylynuk B.A. et al.Recommendations for the care of patients receiving conservative kidney management.Clin J Am Soc Nephrol. 2019; 14: 626-634Crossref PubMed Scopus (0) Google Scholar,28Gelfand S.L. Scherer J.S. Koncicki H.M. Kidney supportive care: core curriculum 2020.Am J Kidney Dis. 2020; 75: 793-806Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar•Exercise, massage, and physical therapy27Cohen S.D. Patel S.S. Khetpal P. et al.Pain, sleep disturbance, and quality of life in patients with chronic kidney disease.Clin J Am Soc Nephrol. 2007; 2: 919-925Crossref PubMed Scopus (100) Google ScholarItching•Gabapentin 100 mg/day along with continued assessment of symptom experience and titration by a medical provider31Mettang T. Kremer A.E. Uremic pruritus.Kidney Int. 2015; 87: 685-691Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar, 32Manenti L. Tansinda P. Vaglio A. 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Haloperidol for the treatment of nausea and vomiting in palliative care patients.Cochrane Database Syst Rev. 2015; 11: CD006271Google ScholarNausea and vomiting•For first-line intervention for nausea, ondansetron•For second-line intervention, metoclopramide 2.5 mg every 4 hours as needed if concern for gastroparesis or constipation•For third-line intervention, olanzapine 2.5 mg every 8 hours as needed or haloperidol 0.5 mg every 8 hours as needed•For severe, refractory symptoms, haloperidol dosing can be titrated to 1 mg25Davison S.N. Tupala B. Wasylynuk B.A. et al.Recommendations for the care of patients receiving conservative kidney management.Clin J Am Soc Nephrol. 2019; 14: 626-634Crossref PubMed Scopus (0) Google Scholar•Environmental and dietary modifications as well as complementary and integrative interventions such as massage, guided imagery and music therapy25Davison S.N. Tupala B. 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• W3133359436 created "2021-03-01" @default.
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• W3133359436 date "2021-04-01" @default.
• W3133359436 modified "2023-10-11" @default.
• W3133359436 title "A Narrative Review of Management Strategies for Common Symptoms in Advanced CKD" @default.
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