Fatigue, anxiety, depression and quality of life in kidney transplant recipients, haemodialysis patients, patients with a haematological malignancy and healthy controls

Fatigue, anxiety, depression and quality of life in kidney transplant recipients, haemodialysis... Abstract Background The impact of haemodialysis (HD) and kidney transplantation on quality of life (QoL) is often underestimated due to a lack of comparative studies with other patient groups. Methods We conducted a cross-sectional cohort study in 168 patients including HD patients, kidney transplant recipients (KTR), patients with a haematological malignancy either receiving chemotherapy or in remission and healthy controls. All participants completed the 36-item short form survey of health-related quality of life, the Checklist Individual Strength and the Hospital Anxiety and Depression Scale questionnaire. Results HD patients and haematological patients undergoing chemotherapy were more frequently severely fatigued (53.3% and 50% of cases) compared with KTR (33.3%), haematological patients in remission (23.3%) and healthy controls (12.1%, P < 0.001). There were no significant differences in anxiety rates. HD patients and haematological patients undergoing chemotherapy were most likely to be depressed (33.3% and 25%), compared with 16.7% of KTR, 20% of haematological patients in remission and 8.6% of healthy controls (P = 0.066). KTR reported the largest positive health change (+27%, P < 0.001), but still had a lower overall QoL than healthy controls, comparable to haematological patients in remission. HD and chemotherapy patients reported the lowest QoL scores. Conclusions Fatigue and depression are common in HD patients, resulting in a low QoL, comparable to haematological patients receiving chemotherapy. KTR do better, with scores similar to patients with a haematological malignancy in remission, but still have a lower QoL than healthy controls. haemato-oncology, haemodialysis, kidney transplantation, malignancy, quality of life INTRODUCTION Renal replacement therapy (RRT) has profound effects on quality of life (QoL). Most haemodialysis (HD) patients report a severely impaired QoL [1–3]. Kidney transplant recipients (KTR) generally have a better QoL than HD patients, although this difference may be partially explained by age differences between KTR and HD patients [4]. Fatigue is an especially common disabling symptom, cited by 71% of dialysis patients [3] and 39–59% of KTR [5, 6]. The pathophysiology of fatigue in patients with chronic kidney disease is multifactorial. Chronic inflammation is thought to be an important contributor. End-stage renal disease (ESRD) is a state characterized by elevated circulating levels of pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) [7]. These cytokines trigger hyperresponsiveness of muscle ergoreceptors, which sense work performed by muscles and thus signal fatigue. IL-6 and TNF-α have also been associated with sleep disorders, malnutrition and protein catabolism, which further enhance fatigue. In addition to chronic inflammation, uraemia and anaemia also contribute [8, 9]. Research on the pathophysiology of fatigue in KTR is scarce, but chronic inflammation is again a likely contributor. In addition, kidney function, the number of rejection episodes and donor type were found to be correlated with fatigue scores in KTR [5]. Increased rates of fatigue and other disabling symptoms result in consistently higher rates of depression and anxiety in HD patients and KTR [10–13]. Together, fatigue, depression and anxiety all contribute to poor clinical outcomes. This has been especially well established for depression, with the hazard ratio for mortality ranging from 2.0 for KTR to 2.7 for HD patients [14–17]. Identifying and addressing factors that can alleviate the high rates of fatigue, anxiety and depression in patients with ESRD is an effective yet underutilized strategy to improve clinical outcomes. In order to raise awareness for this subject, we aimed to compare QoL, fatigue, anxiety and depression rates in patients with ESRD versus patients with a haematological malignancy undergoing chemotherapy. We postulated that QoL in HD patients and KTR is comparable to QoL in patients with a haematological malignancy undergoing chemotherapy and patients with a haematological malignancy in remission, respectively. To test this hypothesis, we compared these four groups, as well as a healthy control group, with respect to fatigue, anxiety, depression and QoL scores. MATERIALS AND METHODS Study design We conducted a single-centre cross-sectional cohort study in which we included KTR, HD patients, patients with a haematological malignancy undergoing chemotherapy, patients with a haematological malignancy in remission and healthy controls. All participants had to be at least 18 years of age. Exclusion criteria were active psychiatric or neurologic disease, previously diagnosed chronic fatigue syndrome, liver cirrhosis and an inability to understand the questionnaires. HD patients had to have been treated with HD for at least 6 months and KTR had to have received their kidney transplant at least 1 year ago, with a stable estimated glomerular filtration rate (eGFR) [as measured by the Modification of Diet in Renal Disease (MDRD) equation] of at least 30 mL/min/1.73 m2 without rejection episodes in the past 6 months. Patients with a haematological malignancy were required to have an eGFR of at least 60 mL/min/1.73 m2. Patients in remission had to be in remission for at least 1 year. For patients undergoing chemotherapy, brain metastases were an exclusion criterion. Controls were selected randomly from the general population. They were approached by two researchers at various public places, including a public library, a music school and a Christmas fair. Questionnaires The 36-item short form (SF-36) is a widely used health-related QoL survey [18]. It consists of 36 items that assess eight health concepts: physical functioning, role limitations caused by physical health problems, role limitations caused by emotional problems, social functioning, mental health, vitality, bodily pain and general health perception. Scores range from 0% to 100%, with 100% indicating optimal QoL. The Checklist Individual Strength (CIS) [19] is a validated 20-item self-report questionnaire that captures four dimensions of fatigue: subjective experience of fatigue, reduction in motivation, reduction in activity and reduction in concentration. Each item is scored on a 7-point Likert scale. A score of ≥35 on the CIS subjective experience of fatigue defines severe fatigue. The Hospital Anxiety and Depression Scale (HADS) [20] is an extensively validated scale to assess states of anxiety and depression. It contains two 7-item scales: one for anxiety and one for depression, both with a score range of 0–21. A score of ≥8 on either anxiety or depression indicates a probable anxiety or depressive disorder. Endpoints The primary endpoint of this study is health-related QoL. Secondary outcomes are fatigue, anxiety, and depression prevalence and severity in these groups. Statistical analysis We assumed a power of 0.8, an α of 0.05 and decided to sample healthy controls and patients in a ratio of 2:1. Based on existing literature [18], we assumed the difference in QoL between patients and controls to be around 2/3 SD, implying a group size of 28 patients. Baseline characteristics were compared with analysis of variance (ANOVA), Mann–Whitney U test, Kruskal–Wallis and chi-square tests where applicable. The odds ratios of being severely fatigued or having a probable anxiety or depressive disorder were calculated with logistic regression analyses. Linear regression analysis was used for the analysis of QoL. RESULTS The study was conducted in 168 patients including 30 KTR, 30 HD patients, 20 patients with a haematological malignancy undergoing chemotherapy, 30 patients with a haematological malignancy in remission and 58 healthy controls. The baseline characteristics are described in Table 1. There were no significant differences in age, gender, marital status and education between the groups, but there were a higher percentage of Afro-Caribbean patients in the HD group. In all patient groups, at least 27% of patients had stopped working or were working less due to their illness. Table 1 Baseline characteristics   KTR  HD  Chemo  Remission  Controls  P-value    n = 30  n = 30  n = 20  n = 30  n = 58    Age (years)  56 ± 17  57 ± 13  61 ± 15  51 ± 13  58 ± 11  0.117  Gender (% male)  63  63  40  43  45  0.227  Ethnicity (%)            <0.001   Caucasian  63  23  75  80  98     Afro-Caribbean  23  67  10  17  0     Asian  14  10  5  3  2     Other  0  0  10  0  0    Marital status (%)            0.114   Married/Cohabiting  60  47  81  73  64     Single/Divorced/Widow(er)  40  53  19  27  36    Education (%)            0.083   Primary school  0  0  0  0  0     High school  63  70  35  40  47     Vocational training  30  17  35  33  36     Higher vocational training or university  7  13  30  27  17    Working less due to illness (%)  7  13  10  13  0  0.034  Stopped working due to illness (%)  20  27  25  17  0      KTR  HD  Chemo  Remission  Controls  P-value    n = 30  n = 30  n = 20  n = 30  n = 58    Age (years)  56 ± 17  57 ± 13  61 ± 15  51 ± 13  58 ± 11  0.117  Gender (% male)  63  63  40  43  45  0.227  Ethnicity (%)            <0.001   Caucasian  63  23  75  80  98     Afro-Caribbean  23  67  10  17  0     Asian  14  10  5  3  2     Other  0  0  10  0  0    Marital status (%)            0.114   Married/Cohabiting  60  47  81  73  64     Single/Divorced/Widow(er)  40  53  19  27  36    Education (%)            0.083   Primary school  0  0  0  0  0     High school  63  70  35  40  47     Vocational training  30  17  35  33  36     Higher vocational training or university  7  13  30  27  17    Working less due to illness (%)  7  13  10  13  0  0.034  Stopped working due to illness (%)  20  27  25  17  0    All values represented as percentages or mean  ±  SD. P-values calculated with ANOVA and chi-square test where applicable. Chemo, patients with a haematological malignancy receiving chemotherapy; remission, patients with a haematological malignancy in remission. P-values <0.05 are set in bold. Table 1 Baseline characteristics   KTR  HD  Chemo  Remission  Controls  P-value    n = 30  n = 30  n = 20  n = 30  n = 58    Age (years)  56 ± 17  57 ± 13  61 ± 15  51 ± 13  58 ± 11  0.117  Gender (% male)  63  63  40  43  45  0.227  Ethnicity (%)            <0.001   Caucasian  63  23  75  80  98     Afro-Caribbean  23  67  10  17  0     Asian  14  10  5  3  2     Other  0  0  10  0  0    Marital status (%)            0.114   Married/Cohabiting  60  47  81  73  64     Single/Divorced/Widow(er)  40  53  19  27  36    Education (%)            0.083   Primary school  0  0  0  0  0     High school  63  70  35  40  47     Vocational training  30  17  35  33  36     Higher vocational training or university  7  13  30  27  17    Working less due to illness (%)  7  13  10  13  0  0.034  Stopped working due to illness (%)  20  27  25  17  0      KTR  HD  Chemo  Remission  Controls  P-value    n = 30  n = 30  n = 20  n = 30  n = 58    Age (years)  56 ± 17  57 ± 13  61 ± 15  51 ± 13  58 ± 11  0.117  Gender (% male)  63  63  40  43  45  0.227  Ethnicity (%)            <0.001   Caucasian  63  23  75  80  98     Afro-Caribbean  23  67  10  17  0     Asian  14  10  5  3  2     Other  0  0  10  0  0    Marital status (%)            0.114   Married/Cohabiting  60  47  81  73  64     Single/Divorced/Widow(er)  40  53  19  27  36    Education (%)            0.083   Primary school  0  0  0  0  0     High school  63  70  35  40  47     Vocational training  30  17  35  33  36     Higher vocational training or university  7  13  30  27  17    Working less due to illness (%)  7  13  10  13  0  0.034  Stopped working due to illness (%)  20  27  25  17  0    All values represented as percentages or mean  ±  SD. P-values calculated with ANOVA and chi-square test where applicable. Chemo, patients with a haematological malignancy receiving chemotherapy; remission, patients with a haematological malignancy in remission. P-values <0.05 are set in bold. KTR and HD patients were comparable in terms of underlying renal disease (Table 2). All HD patients were treated with in-centre HD three times a week and had started dialysis 2.9 years ago on average. About one-third of KTR had been transplanted pre-emptively; the others had been treated with HD or peritoneal dialysis for an average period of 4.8 years. A total of 53% of KTR had received a kidney from a living donor, 17% from a donation after brain death (DBD) donor and 30% from a donation after cardiac death (DCD) donor. Their transplantation had been performed around 1.5 years ago, with a mean current MDRD eGFR of 57 mL/min/1.73 m2. Table 2 Disease characteristics of renal patients   KTR  HD  P-value    n = 30  n = 30    Primary kidney disease (%)      0.112   Glomerulonephritis  27  10     ADPKD  13  7     DM  27  13     Hypertension  17  47     Urologic  3  3     Other  13  20    Previous RRT      0.012   Pre-emptive  36  N/A     HD  47  100     Peritoneal dialysis  7  0     Both  10  0     Duration of RRT if not   pre-emptive (years)  4.8 (2.7–5.5)  2.9 (1.9–4.5)    Kidney donor type         Living  53       DBD  17       DCD  30      Time elapsed since  transplantation (years)  1.5 (1.4–2.2)      eGFR (MDRD,  mL/min/1.73 m2)  57 ± 30        KTR  HD  P-value    n = 30  n = 30    Primary kidney disease (%)      0.112   Glomerulonephritis  27  10     ADPKD  13  7     DM  27  13     Hypertension  17  47     Urologic  3  3     Other  13  20    Previous RRT      0.012   Pre-emptive  36  N/A     HD  47  100     Peritoneal dialysis  7  0     Both  10  0     Duration of RRT if not   pre-emptive (years)  4.8 (2.7–5.5)  2.9 (1.9–4.5)    Kidney donor type         Living  53       DBD  17       DCD  30      Time elapsed since  transplantation (years)  1.5 (1.4–2.2)      eGFR (MDRD,  mL/min/1.73 m2)  57 ± 30      All values represented as percentages or median and interquartile range. P-values calculated with chi-square tests. ADPKD, adult polycystic kidney disease; DM, diabetes mellitus. P-values <0.05 are set in bold. Table 2 Disease characteristics of renal patients   KTR  HD  P-value    n = 30  n = 30    Primary kidney disease (%)      0.112   Glomerulonephritis  27  10     ADPKD  13  7     DM  27  13     Hypertension  17  47     Urologic  3  3     Other  13  20    Previous RRT      0.012   Pre-emptive  36  N/A     HD  47  100     Peritoneal dialysis  7  0     Both  10  0     Duration of RRT if not   pre-emptive (years)  4.8 (2.7–5.5)  2.9 (1.9–4.5)    Kidney donor type         Living  53       DBD  17       DCD  30      Time elapsed since  transplantation (years)  1.5 (1.4–2.2)      eGFR (MDRD,  mL/min/1.73 m2)  57 ± 30        KTR  HD  P-value    n = 30  n = 30    Primary kidney disease (%)      0.112   Glomerulonephritis  27  10     ADPKD  13  7     DM  27  13     Hypertension  17  47     Urologic  3  3     Other  13  20    Previous RRT      0.012   Pre-emptive  36  N/A     HD  47  100     Peritoneal dialysis  7  0     Both  10  0     Duration of RRT if not   pre-emptive (years)  4.8 (2.7–5.5)  2.9 (1.9–4.5)    Kidney donor type         Living  53       DBD  17       DCD  30      Time elapsed since  transplantation (years)  1.5 (1.4–2.2)      eGFR (MDRD,  mL/min/1.73 m2)  57 ± 30      All values represented as percentages or median and interquartile range. P-values calculated with chi-square tests. ADPKD, adult polycystic kidney disease; DM, diabetes mellitus. P-values <0.05 are set in bold. Table 3 shows that 40% of patients with a haematological malignancy had lymphoma as underlying disease. The chemotherapy group had a larger proportion of multiple myeloma patients, whereas the proportion of acute leukaemia patients was higher in the remission group. Patients on chemotherapy had been receiving chemotherapy for ∼3 months at the time of study; patients in remission had received their last treatment around 3.2 years ago. Table 3 Disease characteristics of patients with a haematological malignancy   Chemo  Remission  P-value    n = 20  n = 30    Underlying haematological disease      0.011   Lymphoma  40  40     Multiple myeloma  50  13     Acute leukaemia  10  33     Chronic leukaemia  0  14    Time elapsed since start of  treatment (months)  3.0 (1.9–4.6)      Time elapsed since  remission (years)    3.2 (2.2–5.6)      Chemo  Remission  P-value    n = 20  n = 30    Underlying haematological disease      0.011   Lymphoma  40  40     Multiple myeloma  50  13     Acute leukaemia  10  33     Chronic leukaemia  0  14    Time elapsed since start of  treatment (months)  3.0 (1.9–4.6)      Time elapsed since  remission (years)    3.2 (2.2–5.6)    All values represented as percentages or median and interquartile range. P-values calculated with chi-square tests. Chemo, patients with a haematological malignancy receiving chemotherapy; remission, patients with a haematological malignancy in remission. P-values <0.05 are set in bold. Table 3 Disease characteristics of patients with a haematological malignancy   Chemo  Remission  P-value    n = 20  n = 30    Underlying haematological disease      0.011   Lymphoma  40  40     Multiple myeloma  50  13     Acute leukaemia  10  33     Chronic leukaemia  0  14    Time elapsed since start of  treatment (months)  3.0 (1.9–4.6)      Time elapsed since  remission (years)    3.2 (2.2–5.6)      Chemo  Remission  P-value    n = 20  n = 30    Underlying haematological disease      0.011   Lymphoma  40  40     Multiple myeloma  50  13     Acute leukaemia  10  33     Chronic leukaemia  0  14    Time elapsed since start of  treatment (months)  3.0 (1.9–4.6)      Time elapsed since  remission (years)    3.2 (2.2–5.6)    All values represented as percentages or median and interquartile range. P-values calculated with chi-square tests. Chemo, patients with a haematological malignancy receiving chemotherapy; remission, patients with a haematological malignancy in remission. P-values <0.05 are set in bold. Figure 1A shows that the prevalence of severe fatigue was very high in HD patients (53.3%) and patients undergoing chemotherapy (50%). KTR had somewhat lower scores (33.3%), but were still more often fatigued than patients with a haematological malignancy in remission (23.3%) and controls (12.1%). Univariate and multivariate logistic regression analyses also revealed high odds ratios for severe fatigue for HD patients and patients undergoing chemotherapy (9.0 and 8.1 for multivariate analysis, P = 0.001, Table 4). The multivariate analysis corrects for the differences in baseline characteristics of the groups. Table 4 Odds ratios of being severely fatigued compared with controls   Univariate analysis  P-value  Multivariate analysisa  P-value  KTR  3.6  0.021  3.3  0.044  HD  8.3  <0.001  9.0  0.001  Chemo  7.3  0.001  8.1  0.001  Remission  2.2  0.178  2.2  0.199    Univariate analysis  P-value  Multivariate analysisa  P-value  KTR  3.6  0.021  3.3  0.044  HD  8.3  <0.001  9.0  0.001  Chemo  7.3  0.001  8.1  0.001  Remission  2.2  0.178  2.2  0.199  R2= 0.173 resp. 0.239. a Adjusted for age, gender, ethnicity, marital status and education level. Chemo, patients with a haematological malignancy receiving chemotherapy; remission, patients with a haematological malignancy in remission. P-values <0.05 are set in bold. Table 4 Odds ratios of being severely fatigued compared with controls   Univariate analysis  P-value  Multivariate analysisa  P-value  KTR  3.6  0.021  3.3  0.044  HD  8.3  <0.001  9.0  0.001  Chemo  7.3  0.001  8.1  0.001  Remission  2.2  0.178  2.2  0.199    Univariate analysis  P-value  Multivariate analysisa  P-value  KTR  3.6  0.021  3.3  0.044  HD  8.3  <0.001  9.0  0.001  Chemo  7.3  0.001  8.1  0.001  Remission  2.2  0.178  2.2  0.199  R2= 0.173 resp. 0.239. a Adjusted for age, gender, ethnicity, marital status and education level. Chemo, patients with a haematological malignancy receiving chemotherapy; remission, patients with a haematological malignancy in remission. P-values <0.05 are set in bold. FIGURE 1 View largeDownload slide Prevalence of fatigue, anxiety and depression. Percentage of patients who (A) are severely fatigued, (B) have a probable anxiety disorder and (C) have a probable depressive disorder. P-values calculated using chi-square test. Chemo, patients with a haematological malignancy receiving chemotherapy; remission, patients with a haematological malignancy in remission. FIGURE 1 View largeDownload slide Prevalence of fatigue, anxiety and depression. Percentage of patients who (A) are severely fatigued, (B) have a probable anxiety disorder and (C) have a probable depressive disorder. P-values calculated using chi-square test. Chemo, patients with a haematological malignancy receiving chemotherapy; remission, patients with a haematological malignancy in remission. Anxiety rates (Figure 1B) were highest in the HD and remission group, with 26.7% of both groups having a probable anxiety disorder. In univariate analysis, the odds ratios were also highest in both these groups (2.6, P = 0.091), but there were no statistically significant differences between the groups in the multivariate analysis (Table 5). Depression rates (Figure 1C) were high in all groups, but especially so in HD patients, with 33.3% of HD patients having a probable depressive disorder. However, after correction for differences in baseline characteristics, patients undergoing chemotherapy had higher odds for a depressive disorder (3.9 versus 1.6, P = 0.088, Table 6). Table 5 Odds ratios of having a probable anxiety disorder compared with controls   Univariate analysis  P-value  Multivariate analysisa  P-value  KTR  1.8  0.325  0.97  0.959  HD  2.6  0.091  0.80  0.775  Chemo  1.3  0.736  0.85  0.848  Remission  2.6  0.091  1.69  0.401    Univariate analysis  P-value  Multivariate analysisa  P-value  KTR  1.8  0.325  0.97  0.959  HD  2.6  0.091  0.80  0.775  Chemo  1.3  0.736  0.85  0.848  Remission  2.6  0.091  1.69  0.401  R2= 0.041 resp. 0.164. a Adjusted for age, gender, ethnicity, marital status and education level. Chemo, patients with a haematological malignancy receiving chemotherapy; remission, patients with a haematological malignancy in remission. Table 5 Odds ratios of having a probable anxiety disorder compared with controls   Univariate analysis  P-value  Multivariate analysisa  P-value  KTR  1.8  0.325  0.97  0.959  HD  2.6  0.091  0.80  0.775  Chemo  1.3  0.736  0.85  0.848  Remission  2.6  0.091  1.69  0.401    Univariate analysis  P-value  Multivariate analysisa  P-value  KTR  1.8  0.325  0.97  0.959  HD  2.6  0.091  0.80  0.775  Chemo  1.3  0.736  0.85  0.848  Remission  2.6  0.091  1.69  0.401  R2= 0.041 resp. 0.164. a Adjusted for age, gender, ethnicity, marital status and education level. Chemo, patients with a haematological malignancy receiving chemotherapy; remission, patients with a haematological malignancy in remission. Table 6 Odds ratios of having a probable depressive disorder compared with controls   Univariate analysis  P-value  Multivariate analysisa  P-value  KTR  2.1  0.267  1.1  0.906  HD  5.3  0.006  1.6  0.549  Chemo  3.5  0.070  3.9  0.088  Remission  2.7  0.136  2.6  0.198    Univariate analysis  P-value  Multivariate analysisa  P-value  KTR  2.1  0.267  1.1  0.906  HD  5.3  0.006  1.6  0.549  Chemo  3.5  0.070  3.9  0.088  Remission  2.7  0.136  2.6  0.198  R2= 0.083 resp. 0.279. a Adjusted for age, gender, ethnicity, marital status and education level. Chemo, patients with a haematological malignancy receiving chemotherapy; remission, patients with a haematological malignancy in remission. P-values <0.05 are set in bold. Table 6 Odds ratios of having a probable depressive disorder compared with controls   Univariate analysis  P-value  Multivariate analysisa  P-value  KTR  2.1  0.267  1.1  0.906  HD  5.3  0.006  1.6  0.549  Chemo  3.5  0.070  3.9  0.088  Remission  2.7  0.136  2.6  0.198    Univariate analysis  P-value  Multivariate analysisa  P-value  KTR  2.1  0.267  1.1  0.906  HD  5.3  0.006  1.6  0.549  Chemo  3.5  0.070  3.9  0.088  Remission  2.7  0.136  2.6  0.198  R2= 0.083 resp. 0.279. a Adjusted for age, gender, ethnicity, marital status and education level. Chemo, patients with a haematological malignancy receiving chemotherapy; remission, patients with a haematological malignancy in remission. P-values <0.05 are set in bold. Fatigue, anxiety and depression were all strongly correlated with an impaired QoL, with correlation coefficients of 0.44 (anxiety), 0.57 (depression) and 0.58 (fatigue), all P-values<0.001. As can be seen from Figure 2, the QoL of HD patients was lower in all categories and comparable to patients undergoing chemotherapy. KTR and patients with a haematological malignancy in remission did somewhat better, but were still significantly worse off than healthy controls, despite the fact that KTR reported the largest positive health change over the past year (Figure 3). To correct for baseline differences in our study, we also performed a multivariate linear regression analysis of QoL, which indicated that KTR had a 17.5% lower QoL than controls. For HD patients, QoL was 23.4% lower, whereas patients undergoing chemotherapy had a 18.2% lower QoL, and patients with a haematological malignancy in remission a 13.3% lower QoL compared with controls (all P-values<0.01). Non-Caucasians reported a 14.1% lower QoL compared with Caucasian participants (P < 0.001). There were no significant differences in QoL between participants of different age groups, education level or marital status. FIGURE 2 View largeDownload slide SF-36 QoL scores. Chemo, patients with a haematological malignancy receiving chemotherapy; remission, patients with a haematological malignancy in remission. FIGURE 2 View largeDownload slide SF-36 QoL scores. Chemo, patients with a haematological malignancy receiving chemotherapy; remission, patients with a haematological malignancy in remission. FIGURE 3 View largeDownload slide SF-36 mean health change. Mean health change over the course of 1 year. Values have been recoded so that positive values indicate an improvement and negative values indicate a deterioration of QoL, with the minimum and maximum score ranging from −50% to +50%. P-value calculated with Kruskall–Wallis test. Chemo, patients with a haematological malignancy receiving chemotherapy; remission, patients with a haematological malignancy in remission. FIGURE 3 View largeDownload slide SF-36 mean health change. Mean health change over the course of 1 year. Values have been recoded so that positive values indicate an improvement and negative values indicate a deterioration of QoL, with the minimum and maximum score ranging from −50% to +50%. P-value calculated with Kruskall–Wallis test. Chemo, patients with a haematological malignancy receiving chemotherapy; remission, patients with a haematological malignancy in remission. DISCUSSION In this cross-sectional study, we found that QoL in HD patients is severely impaired and comparable to patients with a haematological malignancy undergoing chemotherapy. The main determinant of this impaired QoL is a high prevalence of severe fatigue in both groups, but higher depression rates contribute as well. KTR report the highest positive health change (+27%) over the past year, but their QoL still falls short of healthy controls and is comparable to patients with a haematological malignancy in remission. Limitations of this study include the fact that it is a cross-sectional single-centre study. A longitudinal study could clarify how QoL changes over time as patients make the transition from one type of RRT to another or make the transition from undergoing chemotherapy to being in remission. In addition, there were some differences in the baseline characteristics of the groups. We corrected for these differences in our multivariate analyses, but it is possible that there is residual confounding. Our results are in line with previous studies reporting on fatigue, anxiety, depression and QoL in HD patients and KTR [1–7, 10–13]. The major contribution of our study is that, to our knowledge, we are the first to make a direct comparison of HD patients and KTR with other patients with a chronic disease, in our case patients with a haematological malignancy undergoing chemotherapy and in remission, respectively. By doing so, we have shown that ESRD requiring chronic HD is a condition as severe as a malignancy requiring treatment with chemotherapy, which is generally considered the emperor of all maladies [21]. We hope that this comparison will underscore the severity of ESRD and stimulate further research in this field. AUTHORS’ CONTRIBUTIONS M.S.v.S. wrote the initial draft of the article. D.A.A., F.M.v.d.H. and J.M.R.v.d.T. collected the data. The other authors reviewed the draft of the article, provided expertise for revisions and approved the final version of the article. CONFLICT OF INTEREST STATEMENT The authors of this manuscript declare no conflict of interest. The results presented in this paper have not been published previously in whole or part, except in abstract format. REFERENCES 1 Valderrabano F, Jofre R, Lopez GJM. Quality of life in end-stage renal disease patients. Am J Kidney Dis  2001; 38: 443– 464 Google Scholar CrossRef Search ADS PubMed  2 Purnell TS, Auguste P, Crews DC et al.   Comparison of life participation activities among adults treated by hemodialysis, peritoneal dialysis, and kidney transplantation: a systematic review. Am J Kidney Dis  2013; 62: 953– 973 Google Scholar CrossRef Search ADS PubMed  3 Murtagh FE, Addington-Hall J, Higginson IJ. The prevalence of symptoms in end-stage renal disease: a systematic review. Adv Chronic Kidney Dis  2007; 14: 82– 99 Google Scholar CrossRef Search ADS PubMed  4 Liem YS, Bosch JL, Arends LR et al.   Quality of life assessed with the medical outcomes study short form 36-item health survey of patients on renal replacement therapy: a systematic review and meta-analysis. Value Health  2007; 10: 390– 397 Google Scholar CrossRef Search ADS PubMed  5 Goedendorp MM, Hoitsma AJ, Bloot L et al.   Severe fatigue after kidney transplantation: a highly prevalent, disabling and multifactorial symptom. Transpl Int  2013; 26: 1007– 1015 Google Scholar CrossRef Search ADS PubMed  6 Chan W, Bosch JA, Jones D et al.   Predictors and consequences of fatigue in prevalent kidney transplant recipients. Transplantation  2013; 96: 987– 994 Google Scholar CrossRef Search ADS PubMed  7 Jhamb M, Weisbord SD, Steel JL et al.   Fatigue in patients receiving maintenance dialysis: a review of definitions, measures, and contributing factors. Am J Kidney Dis  2008; 52: 353– 365 Google Scholar CrossRef Search ADS PubMed  8 Johansen KL, Finkelstein FO, Revicki DA et al.   Systematic review of the impact of erythropoiesis-stimulating agents on fatigue in dialysis patients. Nephrol Dial Transplant  2012; 27: 2418– 2425 Google Scholar CrossRef Search ADS PubMed  9 Kaltsatou A, Sakkas GK, Poulianiti KP et al.   Uremic myopathy: is oxidative stress implicated in muscle dysfunction in uremia? Front Physiol  2015; 6: 102 Google Scholar CrossRef Search ADS PubMed  10 Cukor D, Coplan J, Brown C et al.   Anxiety disorders in adults treated by hemodialysis: a single-center study. Am J Kidney Dis  2008; 52: 128– 136 Google Scholar CrossRef Search ADS PubMed  11 Karaminia R, Tavallaii SA, Lorgard-Dezfuli-Nejad M et al.   Anxiety and depression: a comparison between renal transplant recipients and hemodialysis patients. Transplant Proc  2007; 39: 1082– 1084 Google Scholar CrossRef Search ADS PubMed  12 Palmer S, Vecchio M, Craig JC et al.   Prevalence of depression in chronic kidney disease: systematic review and meta-analysis of observational studies. Kidney Int  2013; 84: 179– 191 Google Scholar CrossRef Search ADS PubMed  13 Szeifert L, Molnar MZ, Ambrus C et al.   Symptoms of depression in kidney transplant recipients: a cross-sectional study. Am J Kidney Dis  2010; 55: 132– 140 Google Scholar CrossRef Search ADS PubMed  14 Chilcot J, Davenport A, Wellsted D et al.   An association between depressive symptoms and survival in incident dialysis patients. Nephrol Dial Transplant  2011; 26: 1628– 1634 Google Scholar CrossRef Search ADS PubMed  15 Lopes AA, Bragg J, Young E et al.   Depression as a predictor of mortality and hospitalization among hemodialysis patients in the United States and Europe. Kidney Int  2002; 62: 199– 207 Google Scholar CrossRef Search ADS PubMed  16 Novak M, Molnar MZ, Szeifert L et al.   Depressive symptoms and mortality in patients after kidney transplantation: a prospective prevalent cohort study. Psychosom Med  2010; 72: 527– 534 Google Scholar CrossRef Search ADS PubMed  17 Zelle DM, Dorland HF, Rosmalen JG et al.   Impact of depression on long-term outcome after renal transplantation: a prospective cohort study. Transplantation  2012; 94: 1033– 1040 Google Scholar CrossRef Search ADS PubMed  18 RAND Health. 36-Item Short Form Survey (SF-36). https://www.rand.org/health/surveys_tools/mos/36-item-short-form.html (15 April 2018, date last accessed) 19 Vercoulen JH, Swanink CM, Fennis JF et al.   Dimensional assessment of chronic fatigue syndrome. J Psychosom Res  1994; 38: 383– 392 Google Scholar CrossRef Search ADS PubMed  20 Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand  1983; 67: 361– 370 Google Scholar CrossRef Search ADS PubMed  21 Mukherjee S. The Emperor of All Maladies: A Biography of Cancer . New York, NY: Scribner, 2010 © The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nephrology Dialysis Transplantation Oxford University Press

Fatigue, anxiety, depression and quality of life in kidney transplant recipients, haemodialysis patients, patients with a haematological malignancy and healthy controls

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Oxford University Press
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© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
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0931-0509
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1460-2385
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10.1093/ndt/gfy103
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Abstract

Abstract Background The impact of haemodialysis (HD) and kidney transplantation on quality of life (QoL) is often underestimated due to a lack of comparative studies with other patient groups. Methods We conducted a cross-sectional cohort study in 168 patients including HD patients, kidney transplant recipients (KTR), patients with a haematological malignancy either receiving chemotherapy or in remission and healthy controls. All participants completed the 36-item short form survey of health-related quality of life, the Checklist Individual Strength and the Hospital Anxiety and Depression Scale questionnaire. Results HD patients and haematological patients undergoing chemotherapy were more frequently severely fatigued (53.3% and 50% of cases) compared with KTR (33.3%), haematological patients in remission (23.3%) and healthy controls (12.1%, P < 0.001). There were no significant differences in anxiety rates. HD patients and haematological patients undergoing chemotherapy were most likely to be depressed (33.3% and 25%), compared with 16.7% of KTR, 20% of haematological patients in remission and 8.6% of healthy controls (P = 0.066). KTR reported the largest positive health change (+27%, P < 0.001), but still had a lower overall QoL than healthy controls, comparable to haematological patients in remission. HD and chemotherapy patients reported the lowest QoL scores. Conclusions Fatigue and depression are common in HD patients, resulting in a low QoL, comparable to haematological patients receiving chemotherapy. KTR do better, with scores similar to patients with a haematological malignancy in remission, but still have a lower QoL than healthy controls. haemato-oncology, haemodialysis, kidney transplantation, malignancy, quality of life INTRODUCTION Renal replacement therapy (RRT) has profound effects on quality of life (QoL). Most haemodialysis (HD) patients report a severely impaired QoL [1–3]. Kidney transplant recipients (KTR) generally have a better QoL than HD patients, although this difference may be partially explained by age differences between KTR and HD patients [4]. Fatigue is an especially common disabling symptom, cited by 71% of dialysis patients [3] and 39–59% of KTR [5, 6]. The pathophysiology of fatigue in patients with chronic kidney disease is multifactorial. Chronic inflammation is thought to be an important contributor. End-stage renal disease (ESRD) is a state characterized by elevated circulating levels of pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) [7]. These cytokines trigger hyperresponsiveness of muscle ergoreceptors, which sense work performed by muscles and thus signal fatigue. IL-6 and TNF-α have also been associated with sleep disorders, malnutrition and protein catabolism, which further enhance fatigue. In addition to chronic inflammation, uraemia and anaemia also contribute [8, 9]. Research on the pathophysiology of fatigue in KTR is scarce, but chronic inflammation is again a likely contributor. In addition, kidney function, the number of rejection episodes and donor type were found to be correlated with fatigue scores in KTR [5]. Increased rates of fatigue and other disabling symptoms result in consistently higher rates of depression and anxiety in HD patients and KTR [10–13]. Together, fatigue, depression and anxiety all contribute to poor clinical outcomes. This has been especially well established for depression, with the hazard ratio for mortality ranging from 2.0 for KTR to 2.7 for HD patients [14–17]. Identifying and addressing factors that can alleviate the high rates of fatigue, anxiety and depression in patients with ESRD is an effective yet underutilized strategy to improve clinical outcomes. In order to raise awareness for this subject, we aimed to compare QoL, fatigue, anxiety and depression rates in patients with ESRD versus patients with a haematological malignancy undergoing chemotherapy. We postulated that QoL in HD patients and KTR is comparable to QoL in patients with a haematological malignancy undergoing chemotherapy and patients with a haematological malignancy in remission, respectively. To test this hypothesis, we compared these four groups, as well as a healthy control group, with respect to fatigue, anxiety, depression and QoL scores. MATERIALS AND METHODS Study design We conducted a single-centre cross-sectional cohort study in which we included KTR, HD patients, patients with a haematological malignancy undergoing chemotherapy, patients with a haematological malignancy in remission and healthy controls. All participants had to be at least 18 years of age. Exclusion criteria were active psychiatric or neurologic disease, previously diagnosed chronic fatigue syndrome, liver cirrhosis and an inability to understand the questionnaires. HD patients had to have been treated with HD for at least 6 months and KTR had to have received their kidney transplant at least 1 year ago, with a stable estimated glomerular filtration rate (eGFR) [as measured by the Modification of Diet in Renal Disease (MDRD) equation] of at least 30 mL/min/1.73 m2 without rejection episodes in the past 6 months. Patients with a haematological malignancy were required to have an eGFR of at least 60 mL/min/1.73 m2. Patients in remission had to be in remission for at least 1 year. For patients undergoing chemotherapy, brain metastases were an exclusion criterion. Controls were selected randomly from the general population. They were approached by two researchers at various public places, including a public library, a music school and a Christmas fair. Questionnaires The 36-item short form (SF-36) is a widely used health-related QoL survey [18]. It consists of 36 items that assess eight health concepts: physical functioning, role limitations caused by physical health problems, role limitations caused by emotional problems, social functioning, mental health, vitality, bodily pain and general health perception. Scores range from 0% to 100%, with 100% indicating optimal QoL. The Checklist Individual Strength (CIS) [19] is a validated 20-item self-report questionnaire that captures four dimensions of fatigue: subjective experience of fatigue, reduction in motivation, reduction in activity and reduction in concentration. Each item is scored on a 7-point Likert scale. A score of ≥35 on the CIS subjective experience of fatigue defines severe fatigue. The Hospital Anxiety and Depression Scale (HADS) [20] is an extensively validated scale to assess states of anxiety and depression. It contains two 7-item scales: one for anxiety and one for depression, both with a score range of 0–21. A score of ≥8 on either anxiety or depression indicates a probable anxiety or depressive disorder. Endpoints The primary endpoint of this study is health-related QoL. Secondary outcomes are fatigue, anxiety, and depression prevalence and severity in these groups. Statistical analysis We assumed a power of 0.8, an α of 0.05 and decided to sample healthy controls and patients in a ratio of 2:1. Based on existing literature [18], we assumed the difference in QoL between patients and controls to be around 2/3 SD, implying a group size of 28 patients. Baseline characteristics were compared with analysis of variance (ANOVA), Mann–Whitney U test, Kruskal–Wallis and chi-square tests where applicable. The odds ratios of being severely fatigued or having a probable anxiety or depressive disorder were calculated with logistic regression analyses. Linear regression analysis was used for the analysis of QoL. RESULTS The study was conducted in 168 patients including 30 KTR, 30 HD patients, 20 patients with a haematological malignancy undergoing chemotherapy, 30 patients with a haematological malignancy in remission and 58 healthy controls. The baseline characteristics are described in Table 1. There were no significant differences in age, gender, marital status and education between the groups, but there were a higher percentage of Afro-Caribbean patients in the HD group. In all patient groups, at least 27% of patients had stopped working or were working less due to their illness. Table 1 Baseline characteristics   KTR  HD  Chemo  Remission  Controls  P-value    n = 30  n = 30  n = 20  n = 30  n = 58    Age (years)  56 ± 17  57 ± 13  61 ± 15  51 ± 13  58 ± 11  0.117  Gender (% male)  63  63  40  43  45  0.227  Ethnicity (%)            <0.001   Caucasian  63  23  75  80  98     Afro-Caribbean  23  67  10  17  0     Asian  14  10  5  3  2     Other  0  0  10  0  0    Marital status (%)            0.114   Married/Cohabiting  60  47  81  73  64     Single/Divorced/Widow(er)  40  53  19  27  36    Education (%)            0.083   Primary school  0  0  0  0  0     High school  63  70  35  40  47     Vocational training  30  17  35  33  36     Higher vocational training or university  7  13  30  27  17    Working less due to illness (%)  7  13  10  13  0  0.034  Stopped working due to illness (%)  20  27  25  17  0      KTR  HD  Chemo  Remission  Controls  P-value    n = 30  n = 30  n = 20  n = 30  n = 58    Age (years)  56 ± 17  57 ± 13  61 ± 15  51 ± 13  58 ± 11  0.117  Gender (% male)  63  63  40  43  45  0.227  Ethnicity (%)            <0.001   Caucasian  63  23  75  80  98     Afro-Caribbean  23  67  10  17  0     Asian  14  10  5  3  2     Other  0  0  10  0  0    Marital status (%)            0.114   Married/Cohabiting  60  47  81  73  64     Single/Divorced/Widow(er)  40  53  19  27  36    Education (%)            0.083   Primary school  0  0  0  0  0     High school  63  70  35  40  47     Vocational training  30  17  35  33  36     Higher vocational training or university  7  13  30  27  17    Working less due to illness (%)  7  13  10  13  0  0.034  Stopped working due to illness (%)  20  27  25  17  0    All values represented as percentages or mean  ±  SD. P-values calculated with ANOVA and chi-square test where applicable. Chemo, patients with a haematological malignancy receiving chemotherapy; remission, patients with a haematological malignancy in remission. P-values <0.05 are set in bold. Table 1 Baseline characteristics   KTR  HD  Chemo  Remission  Controls  P-value    n = 30  n = 30  n = 20  n = 30  n = 58    Age (years)  56 ± 17  57 ± 13  61 ± 15  51 ± 13  58 ± 11  0.117  Gender (% male)  63  63  40  43  45  0.227  Ethnicity (%)            <0.001   Caucasian  63  23  75  80  98     Afro-Caribbean  23  67  10  17  0     Asian  14  10  5  3  2     Other  0  0  10  0  0    Marital status (%)            0.114   Married/Cohabiting  60  47  81  73  64     Single/Divorced/Widow(er)  40  53  19  27  36    Education (%)            0.083   Primary school  0  0  0  0  0     High school  63  70  35  40  47     Vocational training  30  17  35  33  36     Higher vocational training or university  7  13  30  27  17    Working less due to illness (%)  7  13  10  13  0  0.034  Stopped working due to illness (%)  20  27  25  17  0      KTR  HD  Chemo  Remission  Controls  P-value    n = 30  n = 30  n = 20  n = 30  n = 58    Age (years)  56 ± 17  57 ± 13  61 ± 15  51 ± 13  58 ± 11  0.117  Gender (% male)  63  63  40  43  45  0.227  Ethnicity (%)            <0.001   Caucasian  63  23  75  80  98     Afro-Caribbean  23  67  10  17  0     Asian  14  10  5  3  2     Other  0  0  10  0  0    Marital status (%)            0.114   Married/Cohabiting  60  47  81  73  64     Single/Divorced/Widow(er)  40  53  19  27  36    Education (%)            0.083   Primary school  0  0  0  0  0     High school  63  70  35  40  47     Vocational training  30  17  35  33  36     Higher vocational training or university  7  13  30  27  17    Working less due to illness (%)  7  13  10  13  0  0.034  Stopped working due to illness (%)  20  27  25  17  0    All values represented as percentages or mean  ±  SD. P-values calculated with ANOVA and chi-square test where applicable. Chemo, patients with a haematological malignancy receiving chemotherapy; remission, patients with a haematological malignancy in remission. P-values <0.05 are set in bold. KTR and HD patients were comparable in terms of underlying renal disease (Table 2). All HD patients were treated with in-centre HD three times a week and had started dialysis 2.9 years ago on average. About one-third of KTR had been transplanted pre-emptively; the others had been treated with HD or peritoneal dialysis for an average period of 4.8 years. A total of 53% of KTR had received a kidney from a living donor, 17% from a donation after brain death (DBD) donor and 30% from a donation after cardiac death (DCD) donor. Their transplantation had been performed around 1.5 years ago, with a mean current MDRD eGFR of 57 mL/min/1.73 m2. Table 2 Disease characteristics of renal patients   KTR  HD  P-value    n = 30  n = 30    Primary kidney disease (%)      0.112   Glomerulonephritis  27  10     ADPKD  13  7     DM  27  13     Hypertension  17  47     Urologic  3  3     Other  13  20    Previous RRT      0.012   Pre-emptive  36  N/A     HD  47  100     Peritoneal dialysis  7  0     Both  10  0     Duration of RRT if not   pre-emptive (years)  4.8 (2.7–5.5)  2.9 (1.9–4.5)    Kidney donor type         Living  53       DBD  17       DCD  30      Time elapsed since  transplantation (years)  1.5 (1.4–2.2)      eGFR (MDRD,  mL/min/1.73 m2)  57 ± 30        KTR  HD  P-value    n = 30  n = 30    Primary kidney disease (%)      0.112   Glomerulonephritis  27  10     ADPKD  13  7     DM  27  13     Hypertension  17  47     Urologic  3  3     Other  13  20    Previous RRT      0.012   Pre-emptive  36  N/A     HD  47  100     Peritoneal dialysis  7  0     Both  10  0     Duration of RRT if not   pre-emptive (years)  4.8 (2.7–5.5)  2.9 (1.9–4.5)    Kidney donor type         Living  53       DBD  17       DCD  30      Time elapsed since  transplantation (years)  1.5 (1.4–2.2)      eGFR (MDRD,  mL/min/1.73 m2)  57 ± 30      All values represented as percentages or median and interquartile range. P-values calculated with chi-square tests. ADPKD, adult polycystic kidney disease; DM, diabetes mellitus. P-values <0.05 are set in bold. Table 2 Disease characteristics of renal patients   KTR  HD  P-value    n = 30  n = 30    Primary kidney disease (%)      0.112   Glomerulonephritis  27  10     ADPKD  13  7     DM  27  13     Hypertension  17  47     Urologic  3  3     Other  13  20    Previous RRT      0.012   Pre-emptive  36  N/A     HD  47  100     Peritoneal dialysis  7  0     Both  10  0     Duration of RRT if not   pre-emptive (years)  4.8 (2.7–5.5)  2.9 (1.9–4.5)    Kidney donor type         Living  53       DBD  17       DCD  30      Time elapsed since  transplantation (years)  1.5 (1.4–2.2)      eGFR (MDRD,  mL/min/1.73 m2)  57 ± 30        KTR  HD  P-value    n = 30  n = 30    Primary kidney disease (%)      0.112   Glomerulonephritis  27  10     ADPKD  13  7     DM  27  13     Hypertension  17  47     Urologic  3  3     Other  13  20    Previous RRT      0.012   Pre-emptive  36  N/A     HD  47  100     Peritoneal dialysis  7  0     Both  10  0     Duration of RRT if not   pre-emptive (years)  4.8 (2.7–5.5)  2.9 (1.9–4.5)    Kidney donor type         Living  53       DBD  17       DCD  30      Time elapsed since  transplantation (years)  1.5 (1.4–2.2)      eGFR (MDRD,  mL/min/1.73 m2)  57 ± 30      All values represented as percentages or median and interquartile range. P-values calculated with chi-square tests. ADPKD, adult polycystic kidney disease; DM, diabetes mellitus. P-values <0.05 are set in bold. Table 3 shows that 40% of patients with a haematological malignancy had lymphoma as underlying disease. The chemotherapy group had a larger proportion of multiple myeloma patients, whereas the proportion of acute leukaemia patients was higher in the remission group. Patients on chemotherapy had been receiving chemotherapy for ∼3 months at the time of study; patients in remission had received their last treatment around 3.2 years ago. Table 3 Disease characteristics of patients with a haematological malignancy   Chemo  Remission  P-value    n = 20  n = 30    Underlying haematological disease      0.011   Lymphoma  40  40     Multiple myeloma  50  13     Acute leukaemia  10  33     Chronic leukaemia  0  14    Time elapsed since start of  treatment (months)  3.0 (1.9–4.6)      Time elapsed since  remission (years)    3.2 (2.2–5.6)      Chemo  Remission  P-value    n = 20  n = 30    Underlying haematological disease      0.011   Lymphoma  40  40     Multiple myeloma  50  13     Acute leukaemia  10  33     Chronic leukaemia  0  14    Time elapsed since start of  treatment (months)  3.0 (1.9–4.6)      Time elapsed since  remission (years)    3.2 (2.2–5.6)    All values represented as percentages or median and interquartile range. P-values calculated with chi-square tests. Chemo, patients with a haematological malignancy receiving chemotherapy; remission, patients with a haematological malignancy in remission. P-values <0.05 are set in bold. Table 3 Disease characteristics of patients with a haematological malignancy   Chemo  Remission  P-value    n = 20  n = 30    Underlying haematological disease      0.011   Lymphoma  40  40     Multiple myeloma  50  13     Acute leukaemia  10  33     Chronic leukaemia  0  14    Time elapsed since start of  treatment (months)  3.0 (1.9–4.6)      Time elapsed since  remission (years)    3.2 (2.2–5.6)      Chemo  Remission  P-value    n = 20  n = 30    Underlying haematological disease      0.011   Lymphoma  40  40     Multiple myeloma  50  13     Acute leukaemia  10  33     Chronic leukaemia  0  14    Time elapsed since start of  treatment (months)  3.0 (1.9–4.6)      Time elapsed since  remission (years)    3.2 (2.2–5.6)    All values represented as percentages or median and interquartile range. P-values calculated with chi-square tests. Chemo, patients with a haematological malignancy receiving chemotherapy; remission, patients with a haematological malignancy in remission. P-values <0.05 are set in bold. Figure 1A shows that the prevalence of severe fatigue was very high in HD patients (53.3%) and patients undergoing chemotherapy (50%). KTR had somewhat lower scores (33.3%), but were still more often fatigued than patients with a haematological malignancy in remission (23.3%) and controls (12.1%). Univariate and multivariate logistic regression analyses also revealed high odds ratios for severe fatigue for HD patients and patients undergoing chemotherapy (9.0 and 8.1 for multivariate analysis, P = 0.001, Table 4). The multivariate analysis corrects for the differences in baseline characteristics of the groups. Table 4 Odds ratios of being severely fatigued compared with controls   Univariate analysis  P-value  Multivariate analysisa  P-value  KTR  3.6  0.021  3.3  0.044  HD  8.3  <0.001  9.0  0.001  Chemo  7.3  0.001  8.1  0.001  Remission  2.2  0.178  2.2  0.199    Univariate analysis  P-value  Multivariate analysisa  P-value  KTR  3.6  0.021  3.3  0.044  HD  8.3  <0.001  9.0  0.001  Chemo  7.3  0.001  8.1  0.001  Remission  2.2  0.178  2.2  0.199  R2= 0.173 resp. 0.239. a Adjusted for age, gender, ethnicity, marital status and education level. Chemo, patients with a haematological malignancy receiving chemotherapy; remission, patients with a haematological malignancy in remission. P-values <0.05 are set in bold. Table 4 Odds ratios of being severely fatigued compared with controls   Univariate analysis  P-value  Multivariate analysisa  P-value  KTR  3.6  0.021  3.3  0.044  HD  8.3  <0.001  9.0  0.001  Chemo  7.3  0.001  8.1  0.001  Remission  2.2  0.178  2.2  0.199    Univariate analysis  P-value  Multivariate analysisa  P-value  KTR  3.6  0.021  3.3  0.044  HD  8.3  <0.001  9.0  0.001  Chemo  7.3  0.001  8.1  0.001  Remission  2.2  0.178  2.2  0.199  R2= 0.173 resp. 0.239. a Adjusted for age, gender, ethnicity, marital status and education level. Chemo, patients with a haematological malignancy receiving chemotherapy; remission, patients with a haematological malignancy in remission. P-values <0.05 are set in bold. FIGURE 1 View largeDownload slide Prevalence of fatigue, anxiety and depression. Percentage of patients who (A) are severely fatigued, (B) have a probable anxiety disorder and (C) have a probable depressive disorder. P-values calculated using chi-square test. Chemo, patients with a haematological malignancy receiving chemotherapy; remission, patients with a haematological malignancy in remission. FIGURE 1 View largeDownload slide Prevalence of fatigue, anxiety and depression. Percentage of patients who (A) are severely fatigued, (B) have a probable anxiety disorder and (C) have a probable depressive disorder. P-values calculated using chi-square test. Chemo, patients with a haematological malignancy receiving chemotherapy; remission, patients with a haematological malignancy in remission. Anxiety rates (Figure 1B) were highest in the HD and remission group, with 26.7% of both groups having a probable anxiety disorder. In univariate analysis, the odds ratios were also highest in both these groups (2.6, P = 0.091), but there were no statistically significant differences between the groups in the multivariate analysis (Table 5). Depression rates (Figure 1C) were high in all groups, but especially so in HD patients, with 33.3% of HD patients having a probable depressive disorder. However, after correction for differences in baseline characteristics, patients undergoing chemotherapy had higher odds for a depressive disorder (3.9 versus 1.6, P = 0.088, Table 6). Table 5 Odds ratios of having a probable anxiety disorder compared with controls   Univariate analysis  P-value  Multivariate analysisa  P-value  KTR  1.8  0.325  0.97  0.959  HD  2.6  0.091  0.80  0.775  Chemo  1.3  0.736  0.85  0.848  Remission  2.6  0.091  1.69  0.401    Univariate analysis  P-value  Multivariate analysisa  P-value  KTR  1.8  0.325  0.97  0.959  HD  2.6  0.091  0.80  0.775  Chemo  1.3  0.736  0.85  0.848  Remission  2.6  0.091  1.69  0.401  R2= 0.041 resp. 0.164. a Adjusted for age, gender, ethnicity, marital status and education level. Chemo, patients with a haematological malignancy receiving chemotherapy; remission, patients with a haematological malignancy in remission. Table 5 Odds ratios of having a probable anxiety disorder compared with controls   Univariate analysis  P-value  Multivariate analysisa  P-value  KTR  1.8  0.325  0.97  0.959  HD  2.6  0.091  0.80  0.775  Chemo  1.3  0.736  0.85  0.848  Remission  2.6  0.091  1.69  0.401    Univariate analysis  P-value  Multivariate analysisa  P-value  KTR  1.8  0.325  0.97  0.959  HD  2.6  0.091  0.80  0.775  Chemo  1.3  0.736  0.85  0.848  Remission  2.6  0.091  1.69  0.401  R2= 0.041 resp. 0.164. a Adjusted for age, gender, ethnicity, marital status and education level. Chemo, patients with a haematological malignancy receiving chemotherapy; remission, patients with a haematological malignancy in remission. Table 6 Odds ratios of having a probable depressive disorder compared with controls   Univariate analysis  P-value  Multivariate analysisa  P-value  KTR  2.1  0.267  1.1  0.906  HD  5.3  0.006  1.6  0.549  Chemo  3.5  0.070  3.9  0.088  Remission  2.7  0.136  2.6  0.198    Univariate analysis  P-value  Multivariate analysisa  P-value  KTR  2.1  0.267  1.1  0.906  HD  5.3  0.006  1.6  0.549  Chemo  3.5  0.070  3.9  0.088  Remission  2.7  0.136  2.6  0.198  R2= 0.083 resp. 0.279. a Adjusted for age, gender, ethnicity, marital status and education level. Chemo, patients with a haematological malignancy receiving chemotherapy; remission, patients with a haematological malignancy in remission. P-values <0.05 are set in bold. Table 6 Odds ratios of having a probable depressive disorder compared with controls   Univariate analysis  P-value  Multivariate analysisa  P-value  KTR  2.1  0.267  1.1  0.906  HD  5.3  0.006  1.6  0.549  Chemo  3.5  0.070  3.9  0.088  Remission  2.7  0.136  2.6  0.198    Univariate analysis  P-value  Multivariate analysisa  P-value  KTR  2.1  0.267  1.1  0.906  HD  5.3  0.006  1.6  0.549  Chemo  3.5  0.070  3.9  0.088  Remission  2.7  0.136  2.6  0.198  R2= 0.083 resp. 0.279. a Adjusted for age, gender, ethnicity, marital status and education level. Chemo, patients with a haematological malignancy receiving chemotherapy; remission, patients with a haematological malignancy in remission. P-values <0.05 are set in bold. Fatigue, anxiety and depression were all strongly correlated with an impaired QoL, with correlation coefficients of 0.44 (anxiety), 0.57 (depression) and 0.58 (fatigue), all P-values<0.001. As can be seen from Figure 2, the QoL of HD patients was lower in all categories and comparable to patients undergoing chemotherapy. KTR and patients with a haematological malignancy in remission did somewhat better, but were still significantly worse off than healthy controls, despite the fact that KTR reported the largest positive health change over the past year (Figure 3). To correct for baseline differences in our study, we also performed a multivariate linear regression analysis of QoL, which indicated that KTR had a 17.5% lower QoL than controls. For HD patients, QoL was 23.4% lower, whereas patients undergoing chemotherapy had a 18.2% lower QoL, and patients with a haematological malignancy in remission a 13.3% lower QoL compared with controls (all P-values<0.01). Non-Caucasians reported a 14.1% lower QoL compared with Caucasian participants (P < 0.001). There were no significant differences in QoL between participants of different age groups, education level or marital status. FIGURE 2 View largeDownload slide SF-36 QoL scores. Chemo, patients with a haematological malignancy receiving chemotherapy; remission, patients with a haematological malignancy in remission. FIGURE 2 View largeDownload slide SF-36 QoL scores. Chemo, patients with a haematological malignancy receiving chemotherapy; remission, patients with a haematological malignancy in remission. FIGURE 3 View largeDownload slide SF-36 mean health change. Mean health change over the course of 1 year. Values have been recoded so that positive values indicate an improvement and negative values indicate a deterioration of QoL, with the minimum and maximum score ranging from −50% to +50%. P-value calculated with Kruskall–Wallis test. Chemo, patients with a haematological malignancy receiving chemotherapy; remission, patients with a haematological malignancy in remission. FIGURE 3 View largeDownload slide SF-36 mean health change. Mean health change over the course of 1 year. Values have been recoded so that positive values indicate an improvement and negative values indicate a deterioration of QoL, with the minimum and maximum score ranging from −50% to +50%. P-value calculated with Kruskall–Wallis test. Chemo, patients with a haematological malignancy receiving chemotherapy; remission, patients with a haematological malignancy in remission. DISCUSSION In this cross-sectional study, we found that QoL in HD patients is severely impaired and comparable to patients with a haematological malignancy undergoing chemotherapy. The main determinant of this impaired QoL is a high prevalence of severe fatigue in both groups, but higher depression rates contribute as well. KTR report the highest positive health change (+27%) over the past year, but their QoL still falls short of healthy controls and is comparable to patients with a haematological malignancy in remission. Limitations of this study include the fact that it is a cross-sectional single-centre study. A longitudinal study could clarify how QoL changes over time as patients make the transition from one type of RRT to another or make the transition from undergoing chemotherapy to being in remission. In addition, there were some differences in the baseline characteristics of the groups. We corrected for these differences in our multivariate analyses, but it is possible that there is residual confounding. Our results are in line with previous studies reporting on fatigue, anxiety, depression and QoL in HD patients and KTR [1–7, 10–13]. The major contribution of our study is that, to our knowledge, we are the first to make a direct comparison of HD patients and KTR with other patients with a chronic disease, in our case patients with a haematological malignancy undergoing chemotherapy and in remission, respectively. By doing so, we have shown that ESRD requiring chronic HD is a condition as severe as a malignancy requiring treatment with chemotherapy, which is generally considered the emperor of all maladies [21]. We hope that this comparison will underscore the severity of ESRD and stimulate further research in this field. AUTHORS’ CONTRIBUTIONS M.S.v.S. wrote the initial draft of the article. D.A.A., F.M.v.d.H. and J.M.R.v.d.T. collected the data. The other authors reviewed the draft of the article, provided expertise for revisions and approved the final version of the article. CONFLICT OF INTEREST STATEMENT The authors of this manuscript declare no conflict of interest. The results presented in this paper have not been published previously in whole or part, except in abstract format. REFERENCES 1 Valderrabano F, Jofre R, Lopez GJM. Quality of life in end-stage renal disease patients. Am J Kidney Dis  2001; 38: 443– 464 Google Scholar CrossRef Search ADS PubMed  2 Purnell TS, Auguste P, Crews DC et al.   Comparison of life participation activities among adults treated by hemodialysis, peritoneal dialysis, and kidney transplantation: a systematic review. Am J Kidney Dis  2013; 62: 953– 973 Google Scholar CrossRef Search ADS PubMed  3 Murtagh FE, Addington-Hall J, Higginson IJ. The prevalence of symptoms in end-stage renal disease: a systematic review. Adv Chronic Kidney Dis  2007; 14: 82– 99 Google Scholar CrossRef Search ADS PubMed  4 Liem YS, Bosch JL, Arends LR et al.   Quality of life assessed with the medical outcomes study short form 36-item health survey of patients on renal replacement therapy: a systematic review and meta-analysis. 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Psychosom Med  2010; 72: 527– 534 Google Scholar CrossRef Search ADS PubMed  17 Zelle DM, Dorland HF, Rosmalen JG et al.   Impact of depression on long-term outcome after renal transplantation: a prospective cohort study. Transplantation  2012; 94: 1033– 1040 Google Scholar CrossRef Search ADS PubMed  18 RAND Health. 36-Item Short Form Survey (SF-36). https://www.rand.org/health/surveys_tools/mos/36-item-short-form.html (15 April 2018, date last accessed) 19 Vercoulen JH, Swanink CM, Fennis JF et al.   Dimensional assessment of chronic fatigue syndrome. J Psychosom Res  1994; 38: 383– 392 Google Scholar CrossRef Search ADS PubMed  20 Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand  1983; 67: 361– 370 Google Scholar CrossRef Search ADS PubMed  21 Mukherjee S. The Emperor of All Maladies: A Biography of Cancer . New York, NY: Scribner, 2010 © The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

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Nephrology Dialysis TransplantationOxford University Press

Published: May 2, 2018

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