Pain_Management_and_End-of_Life_Care.

Jump to Navigation * St Christopher's Hospice * Department of Health * Help the Hospices ------------------------------------------------- Top of Form Search form Search Bottom of Form contact Text size: -A +A Switch view: * Normal Style SheetA * High Visibility Style SheetA * Home * Current Issue * Past Issues * Article Archives * Editorial Board * About the Journal * Instructions to Authors * External Courses * Log out Patients' experiences of fatigue in the end stages of renal disease Key words: End-of-life care End-stage renal disease Fatigue Symptom burden Clinical review Published: 2011 Vol: 1 No: 2 First published in this online journal Declaration of interests: none Author: Kate Critchley Author profile (accurate when this article was originally published): Kate Critchley is a Clinical Nurse Specialist (Community Palliative Care), St Joseph’s Hospice, Hackney, London, and MSc Student, Department of Palliative Care, Policy and Rehabilitation, King’s College London. Email: k.critchley@stjh.org.uk Download pdf: Patients' experiences of fatigue in the end stages of renal disease The number of patients diagnosed with end-stage renal disease (ESRD) is increasing annually and will continue to rise as a result of the ageing population. Research exploring the symptom burden in ESRD has shown it to be equal to that of the symptom burden experienced by patients with terminal cancer. Fatigue is one of the most prevalent symptoms experienced by ESRD patients. It is very debilitating. The severity of fatigue in ESRD has been found to be associated with loss of physical function, reduced activity levels, sleep disturbance and depression. Causal mechanisms of ESRD-related fatigue are essentially unknown. However, they are thought to be multidimensional, including sociodemographic, physical and psychological factors. This article provides an overview of ESRD and the associated symptom burden. It then concentrates on the symptom of ESRD-related fatigue and discusses current research in relation to its pathophysiology and the effect that it has on patients. Discussion of the management of fatigue in ESRD is outside the remit of the article. Chronic kidney disease (CKD) is progressive loss in renal function over months or years (National Kidney Foundation Kidney Disease Outcome Quality Index (NKF KDOQI), 2002; Zhang and Rothenbacher, 2008). It is associated with a significant symptom burden (Murtagh et al, 2004, 2008a,b; Noble et al, 2010b). When people are in the endstages of renal disease, survival relies on renal-replacement therapy (RRT) such as dialysis and transplantation. Some patients will be dialysed up until death (Noble et al, 2010b). People with end-stage renal disease (ESRD) and other chronic conditions where there is no curative treatment may feel helpless and lacking in control (Tsay, 2004; Mollaoglu, 2009). In ESRD, pain, breathlessness, sleeping problems and fatigue are common symptoms (Solano et al, 2006; Janssen et al, 2008). The end-stage disease trajectory of ESRD will depend on treatment options, underlying renal pathology and the presence of co-morbidities such as cardiovascular disease (Murtagh et al, 2004, 2008b). Therefore, disease and dying trajectories in ESRD are difficult to predict (Murtagh et al, 2004). Little is known about the disease trajectory of people with ESRD managed without dialysis. It may follow a ‘prolonged, dwindling’ path towards death, i.e. a steady decline, or there may be dips in functional ability, frequent hospitalisation and sudden death (Lunney et al, 2003; Murtagh et al, 2004; Noble et al, 2010b). The majority of patients with ESRD feel fatigued (Thomas-Hawkins, 2000; Murtagh et al, 2007a). Fatigue has a negative impact on patients’ quality of life and ability to carry out daily living activities (Mok and Tam, 2001; O’Sullivan and McCarthy, 2007). This article will provide an overview of ESRD and the associated symptom burden. It will then concentrate on fatigue, the related pathophysiology and implications for patients. Literature search strategy The following electronic databases were searched for research and systematic reviews from 1990 to end of 2010: MEDLINE, Embase, British Nursing Index and Archive and the Cochrane Library. The search strategy used free-text words and relevant subject headings to expose the chosen topic. Search terms relating to the condition were ‘end-stage renal disease’ or ‘ESRD’ or ‘end-stage renal failure’ or ‘ESRF’ or ‘chronic kidney failure’ or ‘CKF’ or ‘chronic kidney disease’ or ‘CKD’ or ‘advanced kidney disease’ or ‘AKD’ or ‘dialysis’ or ‘renal-replacement therapy’. Search terms relating to management were ‘palliat*’ (truncated) or ‘end of life’ or ‘symptom control’ or ‘conservative’ or ‘management’ or ‘treatment’. Search terms relating to the symptom of fatigue were ‘fatigue’ or ‘chronic’ or ‘acute’ or ‘pathophysiology’. These three groups of words were then combined. Inclusion criteria were: research papers (e.g. both qualitative and quantitative and systematic reviews); English language articles; all disciplines; haemodialysis and peritoneal dialysis. Exclusion criteria were: children; kidney transplantation; carers/family. Reference lists of included studies were also examined for relevant studies. Chronic and end-stage kidney disease CKD is a complex, chronic disease. It is a progressive loss in kidney or renal function over months or years. An overview of the kidneys’ functions is provided in Figure 1. High-risk factors include hypertension and diabetes, glomerular disease (see below) and having a blood relative with CKD (NKF KDOQI, 2002; Zhang and Rothenbacher, 2008). Patients with CKD who require RRT are considered to have ESRD. ESRD is a worldwide, public health concern (Schieppati and Remuzzi, 2005). Grassmann et al (2005) surveyed 122 countries, accounting for 92% of the world population and 99% of people with ESRD receiving treatment. They found that 1.8 million people were treated for ESRD at the end of 2004. The estimated prevalence of CKD in the US in 2005 was 11% (19.2 million) of the adult population (Schieppati and Remuzzi, 2005). In 2008, 47,525 adult patients were registered as receiving RRT in the UK, a UK prevalence of 774 per million population (Tomson, 2009). However, these figures only accounted for patients with ESRD receiving treatment. Smith et al (2003) have suggested that a further 20% of people with advanced CKD are managed conservatively. National prevalence data are not available for people choosing not to have RRT. The survival of patients with conservatively managed ESRD is unclear. One study found the median overall life expectancy of members of a population (median age 79 years) who had chosen not to undergo dialysis was 1.95 years (Wong et al, 2007). Diagnostic criteria Figure 1. The functions of the kidneys | The kidneys are part of the urinary system and have three major functions, i.e. excretory, regulatory and metabolic. They maintain a relatively constant extracellular environment necessary for cells to function normally. Their functions include the regulation of electrolytes and blood pressure (by maintaining salt and water balance), maintenance of acid-base balance and correction of the balance of body water volume. They are a natural filter of the blood, removing waste products, e.g. urea, creatinine and ammonium, which are diverted to the urinary bladder. The kidneys are also responsible for reabsorption of water, glucose, and amino acids. They produce hormones, including calcitriol (a hormonally active form of vitamin D that increases the level of calcium in the blood) and erythropoietin (a hormone that controls red cell production).Sources: Rose and Rennke (1994), Thomas (2002) | Clinical evidence of possible CKD includes proteinuria, haematuria, a genetic diagnosis of kidney disease (e.g. polycystic kidney disease) or structurally abnormal kidneys (NKF KDOQI, 2002; Bonner et al, 2010). CKD is identified by a blood test for creatinine. (Creatinine is a compound formed by protein metabolism during muscle contraction and is excreted in the urine.) Higher levels of creatinine indicate a falling glomerular filtration rate (GFR) and, as a result, a decreased capability of the kidneys to excrete waste products (NKF KDOQI, 2002). GFR is the volume of fluid filtered from the kidney glomerular capillaries into the Bowman’s capsule per unit of time. It is calculated by measuring the presence in the urine of any chemical, which has a fixed level in the blood. (The Bowman’s capsule is situated around the glomerulus of each nephron of the kidney. It acts as a filter to remove organic wastes, excess inorganic salts and water.) The international classification of CKD, developed by the National Kidney Foundation (NKF KDOQI, 2002) in the US, uses an estimated GFR to measure renal function. There are five stages of CKD (Table 1). CKD has been defined as kidney damage with or without a GFR of less than 60 ml/min/1.73 m² for 3 months or longer. GFR over 90 ml/ min/1.73 m2 is deemed normal unless other evidence of kidney disease is available, in which case CKD stage 1 is present (NKF KDOQI, 2002). ESRD (stage 5) is diagnosed when the GFR is less than 15 ml/min/1.73 m² and RRT (e.g. dialysis or transplantation) is required to prolong life (Department of Health, 2005; Bonner et al, 2010). The low GFR associated with CKD leads to a range of symptoms (Murtagh et al, 2007a; Murphy et al, 2009; Bonner et al, 2010). Symptom burden of ESRD Table 1Stages of kidney disease based on glomerular filtration rate (GFR), a measurement of the kidney’s function | Stage | GFR (ml/min/1.73 m2 ) | Description | 1 | 90+ | Normal kidney function but urine or other abnormalities indicate kidney disease | 2 | 60-89 | Mildly reduced kidney function, urine or other abnormalities point to kidney disease | 3 | 30-59 | Moderately reduced kidney function | 4 | 15-29 | Severely reduced kidney function | 5 | 14 or less | Very severe or end-stage kidney failure | Chronic kidney failure is defined as either kidney damage or GFR <60 ml/min/1.73 m2 for ≥3 months. Kidney damage is defined as pathological abnormalities or markers of damage, including abnormalities in blood or urine tests or imaging studiesSource: National Kidney Foundation Kidney Disease Outcome Quality Index (NKF KDOQI, 2002) | The prevalence of ESRD symptoms has not been widely researched, for both patients undergoing RRT and those who elect not to undergo active treatment (Murtagh et al, 2007b; Noble et al, 2010a). Pain, breathlessness and fatigue are common symptoms among patients with progressive chronic diseases, including renal disease (Solano et al, 2006). Janssen et al (2008) reviewed the daily symptom burden prevalence in patients with end-stage chronic organ failure, in particular congestive heart failure, chronic obstructive pulmonary disease and chronic renal failure. They found a significant symptom burden in these patient groups. The most frequently reported symptoms were fatigue, dyspnoea, insomnia and pain (Janssen et al, 2008). Noble et al (2010a) found high symptom prevalence in a renal population cared for without RRT. The most commonly reported symptoms that impacted on daily living included fatigue, breathlessness, oedema, pruritus, pain, nausea and vomiting. Their findings indicated that symptoms escalate as death approaches, with some symptoms, e.g. fluid overload, lethargy and fatigue, becoming increasingly difficult to manage. Saini et al (2006) compared ESRD patients not receiving dialysis with advanced metastatic cancer patients, to determine ESRD symptom burden and its effect on quality of life. They found that symptom burden and impairment of quality of life were similar in both disease groups. Patients with ESRD undergoing dialysis have been found to experience a high symptom burden, impacting on their health-related quality of life (HRQoL), both mental and physical (Davison and Jhangri, 2010). HRQoL is a multidimensional concept that encompasses physical health, psychological state and social relationships. It is determined by patients’ health status and symptoms and their emotional response to, and the social implications of, their health problems (Leventhal and Colman, 1997). In ESRD, impaired HRQoL has been associated with both fatigue and depression. Senol et al (2010), in a cross-sectional study, aimed to determine which factors affected HRQoL in 156 adult patients receiving peritoneal dialysis. HRQoL, depression, and fatigue were measured using the Short Form-36 (SF-36) health survey, the Beck Depression Inventory, and the Fatigue Severity Scale respectively. Depression and fatigue accounted for 37% of physical HRQoL impairment. Davison and Jhangri (2010) analysed the association between symptom burden and HRQoL in 591 haemodialysis patients. Patients completed the modified Edmonton Symptom Assessment System and the Kidney Dialysis Quality of Life Short Form at baseline and after 6 months. There were no demographic, serological, or dialysis-related predictors for HRQoL or symptom burden. Independent predictors of mental HRQoL were pain, tiredness, lack of wellbeing and depression. Fatigue was one of the independent predictors of physical HRQoL (along with pain, lack of wellbeing and shortness of breath). ESRD-related fatigue The feeling of being ‘fatigued’ is associated with many disorders and treatments (Peuckmann et al, 2010). No universal definition of fatigue is available due to the subjective nature of its experience and the fact that it is an ‘invisible’ symptom (McCann and Boore, 2000; Peuckmann et al, 2010). Unlike in healthy individuals, fatigue in patients with advanced disease is often not relieved by rest (Peuckmann et al, 2010). The fatigue patients experience can be very debilitating. Ream and Richardson (1996) have described it as a subjective, unrelenting, unpleasant symptom incorporating total body feelings, ranging from tiredness to exhaustion. It has been described as tiredness not relieved by sufficient sleep, physical weakness, exhaustion and lack of energy and motivation, all of which interfere with people’s ability to function to their normal ability (Aistars, 1987; Ream and Richardson, 1996; Aaronson et al, 1999; Sharpe and Wilks, 2002; Lee et al, 2007). Physical fatigue is a frequently experienced symptom of ESRD. It has been reported that the majority of patients with ESRD feel low in energy and excessively tired (Thomas-Hawkins, 2000). ESRD-related fatigue has a mean prevalence in the UK renal population of 71% (range 12–97%) (Murtagh et al, 2007b). It is one of the most troubling symptoms in ESRD and has a negative impact on quality of life (Mok and Tam, 2001; O’Sullivan and McCarthy, 2007). Fatigue has also been connected to sleep disorders and poor quality sleep in patients undergoing dialysis (Devins et al, 1993; Sklar et al, 1996). Koyama et al (2010) found that fatigue may be an important predictor for cardiovascular events in ESRD. A total of 788 patients undergoing haemodialysis therapy (506 male, 282 female) were surveyed between October and November 2005, and followed up 26 months later to monitor whether they had suffered fatal or non-fatal cardiovascular events. The questionnaire included eight fatigue-related factors: fatigue itself, anxiety and depression, loss of attention and memory, pain, overwork, autonomic imbalance, sleep problems and infection. A total of 14.7% had fatigue scores higher than twice the standard deviation of the mean for healthy volunteers. Patients exhibited a significantly higher risk for cardiovascular events (P<0.01), independent of common risk factors, such as age, diabetes, cardiovascular history and inflammation and malnutrition (Koyama et al, 2010). Causes of fatigue in ESRD TNFa = tumour necrosis factor alpha (cytokine involved in systemic inflammation)IL-1 = interleukin 1 (pro-inflammatory cytokine)IFNy = interferon type II (immuno-regulator)Figure 2. The pathogenesis of fatigue. Sources: Harris (2008), Jhamb et al (2008), Bossola et al (2009). | Although fatigue is a common symptom in ESRD (McCann and Boore, 2000; Bonner et al, 2008; Mollaoglu, 2009), minimal work has been carried out relating to why it occurs. Physiological, psychological and sociodemographic factors have been suggested as possible causes of ESRD-related fatigue, including abnormal urea and haemoglobin levels, inflammation, depression, sleep disturbances, nutritional deficiencies and haemodialysis (Harris, 2008; Jhamb et al, 2008; Bossola et al, 2009). The pathophysiology of fatigue in ESRD is not fully understood. Figure 2 demonstrates the interrelation of possible causes. Figure 3 presents two predominant pathophysiological causes — inflammation and anaemia. The majority of studies exploring fatigue in ESRD relate to patients receiving dialysis. Bossola et al (2009) explored the association between fatigue and demographic, clinical and laboratory variables in 62 ESRD patients receiving haemodialysis (excluding participants who had conditions elevating inflammatory markers, e.g. human immunodeficiency virus). They found significant correlations between fatigue and serum creatinine, albumin and serum interleukin 6 (IL-6) levels. Age, comorbidities and levels of depression and anxiety were higher in fatigued patients than non-fatigued patients. McCann and Boore (2000) found that fatigue in adult haemodialysis patients was associated with the presence of sleep problems, poor physical health status and depression. However, they found no association between fatigue and biochemical variables. In a later study, Bossola et al (2010) aimed to evaluate whether there was a relationship between anorexia and fatigue in 76 patients (44 male, 32 female) undergoing haemodialysis. They also measured the plasma levels of IL-6 and C-reactive protein (CRP) in patients with or without anorexia and/ or fatigue. Appetite was assessed using the first question of the Hemodialysis Study Appetite questionnaire, fatigue using the vitality scale of the SF-36 and co-morbidities using the Charlson Comorbidity Index. Plasma IL-6 levels (pg/mL) were significantly higher in anorexic and fatigued patients than in those who were not anorexic and fatigued (P<0.001) and anorexic but not fatigued patients (P<0.01). Also, the plasma CRP levels (mg/dL) were significantly higher in anorexic and fatigued patients than non-anorexic and non-fatigued patients, anorexic but non-fatigued patients, and non-anorexic but fatigued patients (P=0.001). It was concluded that the presence of significantly higher levels of plasma IL-6 and CRP and a higher frequency of comorbidities were associated with the presence of both anorexia and fatigue. Effects of fatigue on patients with ESRD The effects of fatigue on patients with ESRD vary in quantity, duration and intensity. Fatigue severity has been directly associated with poor physical function, limitations in physical activity, low levels of vitality and energy, sleep problems and depression (McCann and Boore, 2000; Lee et al, 2007; O’Sullivan and McCarthy, 2007; Bossola et al, 2009). Patients may also experience elevated levels of fatigue immediately after dialysis (Tsay, 2004; Lee et al, 2007). However, the causal mechanisms are not clear. Figure 3. Pathophysiology of inflammation and anaemia in end-stage renal disease, resulting in fatigue | Inflammation: Inflammation appears to be a predominant cause of fatigue in end-stage renal disease (ESRD). Circulating levels of pro-inflammatory cytokines — TNFa (tumour necrosis factor alpha, the cytokine involved in systemic inflammation), IL-1 (interleukin 1, a pro-inflammatory cytokine) and IFNy (interferon type II, an immuno-regulator) — have been investigated in relation to their links with fatigue in chronic conditions. IL-1 and IL-6 (pro- and anti-inflammatory cytokines) have been specifically implicated in rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis and chronic liver disease (Swain, 2000). Cytokines are small proteins involved in cellular communication, inflammatory processes and immuno-modulation. ESRD has been identified as an inflammatory state, during which cytokines are released as part of the acutephase response. The acute-phase response is a group of physiological processes occurring soon after the onset of infection, trauma, inflammatory processes and some malignant conditions, including increase in levels of certain blood proteins, fever, vascular permeability and metabolic/pathological changes. However, the origins of these processes are unknown (Bergström et al, 2000). Current evidence relating to the mechanisms of cytokines indicates they directly activate the nervous system, hypothalamus, pituitary gland and adrenal glands. They have also been related to sleep disorders, depression and anxiety (Jhamb et al, 2008).Anaemia: Anaemia is very common in patients with ESRD, arising, largely, from excessive cytokine production, which depresses erythropoietin production in the kidney and erythropoietin response in the bone marrow (Brown et al, 2007; Silverberg et al, 2010). Erythropoietin is a renal hormone, which stimulates increased red blood cell production in response to decreased oxygen in the tissues. Possible treatment strategies for ESRD-related anaemia include the use of both erythropoiesis-stimulating agents as well as oral and intravenous iron (Keown et al, 2010; Silverberg et al, 2010). Recently, evidence has indicated that cytokines can also cause iron deficiency in renal patients by increasing hepcidin, an iron regulatory peptide produced in the liver (Arabul et al, 2009; Silverberg et al, 2010). Hepcidin reduces gastrointestinal iron absorption and iron release from iron stores located in the macrophages and hepatocytes (Silverberg et al, 2010). Available research has not confirmed whether anaemia causes or contributes to fatigue. Evidence can be contradictory. A number of studies have not found a relationship between haemoglobin (Hb) levels and fatigue (McCann and Boore, 2000; Tsay, 2004; Bonner et al, 2008; Bossola et al, 2009), whereas one study found that participants with low fatigue scores had high Hb levels (Mollaoglu, 2009). | Lee et al (2007) explored, through in-depth, qualitative interviews, how 14 patients (four men and 10 women) being treated in a haemodialysis unit in a hospital in South Taiwan experienced the symptom of fatigue. It was hoped that the findings would help nurses plan fatigue-relieving strategies for this patient population. Ages ranged from 26 to 72 years (mean 52 years). Participants had been receiving haemodialysis for on average 2.6 years. It was found that the fatigue had many dimensions. Ten themes emerged from the interview analysis, which were classified into three domains: physical, affective and cognitive (Table 2). Participants experienced severe physical fatigue following treatment. They also suffered common symptoms associated with uraemia, e.g. increased and irregular heart rate, pain in their back, shoulders and bones, cramp, dizziness and heaviness/numbness in their hands and feet. (In renal failure uraemia is the build up of nitrogenous waste products in the blood.) Such symptoms caused their whole body to feel tired. Participants’ general lack of physical energy meant they could not carry out normal daily activities. The lack of physical strength caused participants to feel trapped by their poor bodily condition. Table 2Lee et al’s (2007) 10 themes relating to fatigue, classified under three domains | Physical fatigue: Habitual fatigue, experiencing uraemic symptoms, suffering from sleeping disturbance, insufficient physical energyAffective fatigue: Detesting long-term treatment, perceiving depression, feeling exhaustedCognitive fatigue: Regretting lost cognition, intentional isolation, coping with fatigue | Affective fatigue was related to emotional reactions to fatigue. Having to undergo an endless process of treatment caused participants to feel overwhelmed, depressed and out of control, which exacerbated their sense of exhaustion. As one participant stated: ‘I can’t stand the tiredness any more. I am going to burn out. It seems that all the energy was gone.’ Another said: ‘...this is terrible, nothing is right. You have to fight against it all the time. I have been thinking of killing myself.’ Participants thought their fatigue was associated with a decrease in cognitive function. They were unable to remember things and had difficulty concentrating. Their lack of energy caused them to lose interest and motivation in their surroundings. They felt increasingly apathetic and isolated from the outside world. Some felt that their cognitive abilities had worsened after they had started haemodialysis. Many experienced sleep disturbance, with some waking every 2 or 3 hours. As one participant said: ‘I just can’t sleep well. Sometimes, I sit all night. But you can’t sleep well that way. I usually woke up after an hour.’ McCann and Boore (2000) analysed fatigue in 39 adult patients with ESRD attending a regional nephrology unit in Ireland two or three times a week for haemodialysis and factors that could be associated with fatigue in renal patients. The areas of fatigue measured were general fatigue, physical fatigue, reduced motivation, reduced activity and mental fatigue. Patients were excluded if they had other conditions associated with fatigue, e.g. rheumatoid arthritis and cancer. The researchers used a structured, selfreport questionnaire and biochemical data from retrospective monthly blood tests, i.e. haemoglobin, ferritin, urea, albumin, phosphate and calcium levels (which are indicators of anaemia, malnutrition, kidney function and dialysis adequacy). Fatigue was measured using: the Multidimensional Fatigue Inventory, a fatigue visual analogue scale (from ‘no tiredness at all’ to ‘complete exhaustion’); and the 4-item vitality scale from the SF-36 health survey (the concept of vitality being considered the opposite to fatigue on a fatigue–vitality continuum). Patients experienced a variety of symptoms, e.g. angina, stomach pain, nausea, headache, shortness of breath, cramps, itch, lack of sleep, joint pain, muscle wasting and weakness. However, they all experienced fatigue, tiredness and low levels of vitality and had a limited physical health status that reduced their ability to perform physical and workrelated activities. No associations were found between fatigue and biochemical and situational variables. A complex pattern of relationships between the physiological and psychological factors was identified as influencing the experience of fatigue in people with ESRD undergoing haemodialysis. Physical health status, sleep, depression and anxiety were significant influencing factors on the experience of fatigue. It was concluded that there is potential for improving patients’ quality of life by minimising the symptoms experienced. Sleep problems are commonly associated with fatigue (Tsay, 2004; O’Sullivan and McCarthy, 2007; Lee et al, 2007; Bossola et al, 2009). It is not known to what extent fatigue causes or contributes to sleep disturbances or whether sleep disturbances influence fatigue. Sleep can be affected by other symptoms of ESRD such as restless leg syndrome, sleep apnoea and itchiness (Tsay, 2004). In Tsay’s (2004) study of 106 patients with ESRD who had been treated with haemodialysis for at least 3 months in Taiwan, 90% stated that they started to feel fatigued after receiving their first haemodialysis treatment and the fatigue persisted over time. The majority thought the haemodialysis was the direct cause of their fatigue and the most effective way of relieving fatigue was sleeping or resting. Bossola et al (2009) found that ESRD patients on haemodialysis with insomnia scored lower (mean of 47.7) on the vitality score (0–100) (<51 represents limitations or disability related to fatigue). Sleep disturbance also emerged as one of the 10 themes identified in Lee et al’s (2007) phenomenological study. Participants felt that their tiredness was directly caused by sleep disturbance. Fatigue is one of the major diagnostic symptoms of depression (American Psychiatric Association, 1994; Pessin et al, 2005; World Health Organization, 2007). Depression and fatigue are closely related and frequently exist in chronic disease (Harris, 2008). Depression has been found to be common in patients in ESRD on haemodialysis (Chen et al, 2010). However, it is often not recognised in terminally ill patients as its symptoms mimic those of advanced disease, e.g. fatigue and sleeping for long periods (Pessin et al, 2005). Depression is associated with severity of symptom burden and quality of life, which are both related to increased morbidity and mortality in patients undergoing dialysis (Weisbord et al, 2005). Chen et al (2010) conducted a cross-sectional study of 200 adult patients with ESRD on haemodialysis in order to understand the relationships between depression, anxiety, fatigue, poor HRQoL and increased suicide risk. Psychological characteristics were assessed using the Mini-International Neuropsychiatric Interview, Hospital Anxiety and Depression Scale, shortform Health-Related Quality of Life Scale, and Chalder Fatigue Scale. Seventy of the 200 patients (35%) had symptoms of depression, with 43 (21.5%) having had suicidal ideation the previous month. Depressed patients had greater levels of fatigue and anxiety, more common suicidal ideation, and poorer quality of life than non-depressed patients. Depression (P<0.001) and anxiety (P<0.001) had a significant direct relationship with suicidal ideation, whereas fatigue and quality of life did not. Another study found that 19 of 39 patients with ESRD undergoing haemodialysis were most likely, or definitely, depressed and 15 patients were likely or definitely suffering from anxiety (McCann and Boore, 2000). The researchers screened all patients using the Hospital Anxiety and Depression Scale and found relationships between depression and five categories of fatigue measured (general fatigue, physical fatigue, reduced activity, mental fatigue and reduced motivation) and between anxiety and two fatigue categories (general fatigue and mental fatigue). A relationship was found to exist between depression, anxiety, fatigue and sleep problems. A complex pattern of relationships between the physiological and psychological factors was identified as influencing the experience of fatigue in people with ESRD undergoing haemodialysis. Depression and anxiety were significant influencing factors on the experience of fatigue. However, the descriptive and cross-sectional nature of the study design meant it was not possible to understand causality, e.g. whether fatigue causes depression or depression causes fatigue. The relationship between fatigue and reduced physical functioning and activity levels has been found in patients with ESRD, regardless of whether or not they are receiving RRT (Brunier and Graydon, 1993; McCann and Boore, 2000; O’Sullivan and McCarthy, 2007; Bonner et al, 2010). However, it is unclear whether fatigue is directly responsible for reduced activity and physical functioning (O’Sullivan and McCarthy, 2007). Patients with advanced ESRD, especially those on long-term dialysis, often suffer from muscle wasting and fatigue (Kosmadakis et al, 2010). Inactivity, muscle wasting and reduced physical functioning are associated with increased mortality in ESRD (Stenvinkel et al, 2002). O’Sullivan and McCarthy (2007) explored the relationship between fatigue and physical functioning in 46 patients with ESRD receiving haemodialysis (average length of time on dialysis 1.87 years). Patients completed the Multi-dimensional Fatigue Inventory, the SF-36 health survey and a demographic questionnaire. People experienced severe limitations in physical functioning and the performance of daily activities and moderate role and social limitations. They felt tired and lacked energy. Some participants told the researchers anecdotally that they often had to sleep for long periods after dialysis. However, others stated that they felt more tired on days when they were not having dialysis. There was a significant moderate negative relationship between general fatigue and physical functioning (P=0.007), indicating that, as physical functioning levels increased, fatigue levels decreased. Lower levels of fatigue were reported with regard to cognitive symptoms of fatigue, e.g. reduced motivation and mental fatigue. Significant relationships were found between overall physical functioning and older age (P=0.021) and employment status (P=0.019). The researchers hypothesised that increased physical functioning associated with employed patients in comparison to patients not working might indicate that increased activity levels improve physical functioning. However, employed patients also had a lower mean age (48.5 years) than unemployed patients (62 years) and there was a nonsignificant trend for the level of fatigue to increase with older age. The cross-sectional nature of the study meant that it was not possible to ascertain whether fatigue was responsible for poorer physical functioning or if decreased physical functioning caused increased fatigue. The other factors that may influence fatigue severity include biochemical processes, adequacy of dialysis treatment, depression, sleep disturbances, co-morbidities, and symptoms such as restless leg syndrome and anaemia. However, research into fatigue and physical functioning in cancer patients indicates that increasing activity levels may result in decreased fatigue levels and improved physical functioning (Windsor et al, 2004; Campbell et al, 2005; Brown et al, 2005). Whatever the cause, reduction in physical functioning can have a negative impact on patients’ psychological wellbeing, quality of life and ability to keep employed (O’Sullivan and McCarthy, 2007). It also prevents patients from doing what they want to do, e.g. socialising, exercising, reading and household chores (Lee et al, 2007; Bonner et al, 2010). Implications for nursing practice This review indicates that clinicians are not assessing ESRD patients routinely for factors that may exacerbate the experience of fatigue, such as depression, sleeping difficulties, biochemical processes and anaemia (McCann and Boore, 2000). Lee et al (2007) have suggested that health professionals may consider fatigue to be an inevitable part of ESRD and therefore ignore it. However, it is essential that health professionals, including nurses, assess and monitor fatigue levels and its possible causes in patients with ESRD. For example, symptoms such as depression and anxiety are not being diagnosed in patients with fatigue in ESRD (McCann and Boore, 2000). If depression and anxiety were recognised and treated, there is a possibility that the fatigue in some patients may be less pronounced or at least better managed. Also, it has been suggested that if ESRD patients could have better quality sleep, they may feel less fatigued (Tsay, 2004; Lee et al, 2007; O’Sullivan and McCarthy, 2007; Bossola et al, 2009). However, it is unclear whether fatigue causes or is the result of sleep disturbances in ESRD (Bossola et al, 2009). Sleep can also be affected by other symptoms of ESRD, e.g. restless leg syndrome and itchiness (Tsay, 2004). Cognitive behavioural therapy (CBT) was found by Chen et al (2008) to reduce the severity of sleeping problems and insomnia in patients undergoing peritoneal dialysis with no active medical or psychiatric history. The researchers concluded that CBT might be an effective non-pharmacological intervention for improving the quality of sleep. However, only a small number of participants (n=24) were included in the study and some participants were concurrently using hypnotics. Therefore, the findings should be interpreted with a degree of caution. Nurses should be assisting ESRD patients to develop energy-conserving and energy-building strategies, e.g. regular mild exercise and pacing physical activity with rest periods (Lee et al, 2007). O’Sullivan and McCarthy’s (2007) finding of a significant relationship between increase in physical activity and decreased fatigue scores, supports evidence indicating that exercise has an anti-inflammatory effect, reducing cytokine levels and levels of fatigue (Jhamb et al, 2008). It also highlights the importance of assessing fatigue and physical functioning ability in the clinical setting. Rehabilitative strategies that aim to reduce fatigue and maximise activity levels need to be encouraged (Bonner et al, 2010). Exercise in patients receiving regular dialysis treatment for ESRD is only offered in a minority of renal units. Therefore, work is needed to increase awareness of the potential benefits of increased physical activity for patients with ESRD (Kosmadakis et al, 2010). Conclusion ESRD has a severe symptom burden, equal to that of terminal cancer. Fatigue is a particularly common symptom in ESRD. It is very debilitating and is associated with loss of physical function, sleep disturbance, depression and anxiety. It has a negative effect on people’s quality of life, psychological and physical wellbeing, and ability to remain employed and socialise. The causal mechanisms of fatigue in ESRD are essentially unknown. They are thought to be multi-dimensional, including sociodemographic, physical and psychological factors. Further research is required to understand the causes of fatigue in ESRD and effective management strategies, including the potential benefits of increased physical activity. Health professionals, including nurses, need to assess and monitor fatigue levels in patients with ESRD. It is also important that they are aware that patients with ESRD may be suffering from depression. As fatigue is acknowledged as a diagnostic indicator of depression, if depression is treated successfully, there is the potential that some patients may become less fatigued. 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