Dialysis withdrawal and symptoms of anxiety and depression: a prospective cohort study.

BACKGROUND: An important aspect of end-of-life decisions in dialysis patients is elective withdrawal from dialysis therapy. Several studies have shown that clinical factors, such as comorbidity, play a role in dialysis withdrawal. The role of symptoms of anxiety and depression is largely unknown. The. METHODS: A prospective multi-center study has been set up to investigate anxiety and depressive symptoms longitudinally in dialysis patients. Anxiety and depressive symptoms were investigated using the Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) as baseline. Adverse events, including dialysis withdrawal and mortality were registered during follow-up. Multivariable cox proportional hazard models were used with anxiety and depression as the independent variable and dialysis withdrawal as the outcome variable. Models included age, sex, ethnicity and a set of clinical comorbidities. RESULTS: A total of 687 patients were included between 2012 and 2017, with a median follow-up of 3.2 years. A total of 48 patients (7%) withdrew from dialysis therapy, and subsequently deceased. Anxiety and depressive symptoms at baseline showed an association with dialysis withdrawal with hazard ratios of 2.31 (1.09-4.88) for anxiety and 2.56 (1.27-5.15) for depressive symptoms, independent of somatic comorbidities. DISCUSSION: Withdrawal from dialysis therapy is associated with anxiety and depressive symptoms. Dialysis patients with more severe depressive and anxiety symptoms were more vulnerable for dialysis withdrawal. Insight in factors that play a role in dialysis withdrawal could aid patients and clinicians making an informed decision and develop clinical guidelines.

[Anaemia]. / Anemie.

The first scientific article on anaemia was published in 1807, marking a tipping point in modern medicine. Despite a vast bulk of literature on this topic, the interpretation of anaemia is not always straight forward. The most common form of anaemia, the iron deficiency anaemia, shares several characteristics with another common form of anaemia, the anaemia of chronic disease, or better: 'inflammatory anaemia'.This article provides the clinician with several factors which could aid in differentiating both forms of anaemia, such as parameters of iron transport, bone marrow investigation as well as atrial with iron supplements. Furthermore, this article discusses iron metabolism and methods of supplementing iron, gives guidance in the use of cut-off values for haemoglobin in the elderly and interpretation of the adequacy of the reticulocyte response. Lastly this article discusses the added value of a manual differentiation to determine the nature of the anaemia.

Validation of Two Screening Tools for Anxiety in Hemodialysis Patients.

BACKGROUND: Symptoms of anxiety are often unrecognized and untreated in dialysis patients. We investigated the diagnostic accuracy of two widely used screening tools for anxiety in hemodialysis patients. METHODS: For this cross-sectional validation study, chronic hemodialysis patients from eight dialysis centers in the Netherlands were included. The Beck Anxiety Inventory (BAI) and Hospital Anxiety and Depression Scale-Anxiety subscale (HADS-A) were validated by the Mini International Neuropsychiatric Inventory (MINI) diagnostic interview. Receiver operating characteristic curves were used to determine the optimal cut-off values. RESULTS: Of 65 participants, 13 (20%) were diagnosed with one or more anxiety disorders on the MINI, of which 5 were included in the analysis. ROC curves showed a good diagnostic accuracy of the BAI and HADS-A. The optimal cut-off value for the BAI was ≥13 (sensitivity 100%, specificity 85%) and for the HADS-A was ≥10 (sensitivity 80%, specificity 100%). CONCLUSIONS: Based on our limited data, both the BAI and the HADS-A seem to be valid screening instruments for anxiety in hemodialysis patients that can be used in routine dialysis care. The HADS-A consists of fewer items and showed fewer false-positive results than the BAI, which might make it more useful in clinical practice.

Depression, anxiety and quality of life of hemodialysis patients before and during the COVID-19 pandemic.

OBJECTIVE: To investigate the impact of the coronavirus pandemic on mental health in hemodialysis patients, we assessed depression, anxiety and quality of life with valid mental health measures before and after the start of the pandemic. METHODS: Data were used from 121 hemodialysis patients from the ongoing prospective multicenter DIVERS-II study. COVID-19 related stress was measured with the Perceived Stress Scale - 10, depression with the Beck Depression Inventory - second edition (BDI-II)), anxiety with the Beck Anxiety Inventory (BAI) and quality of life with the Short Form - 12 (SF-12). Scores during the first and second COVID-19 wave in the Netherlands were compared to data prior to the pandemic with linear mixed models. RESULTS: No significant differences were found in BDI-II, BAI and SF-12 scores between before and during the pandemic. During the first wave, 33% of participants reported COVID-19 related stress and in the second wave 37%. These patients had higher stress levels (mean difference (MD) 4.7 (95%CI 1.5; 8.0), p = 0.005) and BDI-II scores (MD 4.9 (95%CI 0.7; 9.0), p = 0.021) and lower SF-12 mental component summary scores (MD -5.3 (95%CI -9.0, -1.6), p = 0.006) than patients who did not experienced COVID-19 stress. These differences were already present before the pandemic. CONCLUSION: The COVID-19 pandemic does not seem to influence mental health in hemodialysis patients. However, a substantial subgroup of patients with pre-existent mental health problems may be more susceptible to experience COVID-19 related stress.

Symptom dimensions of anxiety and depression in patients receiving peritoneal dialysis compared to haemodialysis.

BACKGROUND: Differences in symptom burden, treatment satisfaction and autonomy between patients receiving peritoneal dialysis and haemodialysis could be reflected by a difference in symptom dimensions of anxiety and depression. The aim of this study is to assess differences in prevalence and symptom dimensions of anxiety and depression between patients receiving peritoneal dialysis and haemodialysis. METHODS: Baseline data from the Depression Related Factors and Outcomes in Dialysis Patients With Various Ethnicities and Races Study were used. Symptoms of anxiety and depression were measured with the Beck Anxiety Inventory and Beck Depression Inventory- second edition. Linear and logistic regression models were used to compare anxiety and depression total scores and somatic and subjective/cognitive symptom dimension scores between patients receiving peritoneal dialysis and haemodialysis, adjusted for potential confounders. RESULTS: In total, 84 patients receiving peritoneal dialysis and 601 patients receiving haemodialysis were included. Clinically significant symptoms of anxiety and depression were present in respectively 22% and 43% of the patients, with no differences between dialysis modality. Both modalities scored high on the somatic symptom dimensions and on individual somatic items. Almost all patients reported symptoms related to loss of energy and sleep. CONCLUSION: No differences in symptom dimensions of anxiety and depression were found between patients receiving peritoneal dialysis and haemodialysis. The high prevalence of somatic symptom dimensions in both groups underscores the possible interaction between somatic and psychiatric symptoms in dialysis patients and the need for early recognition and treatment of symptoms of anxiety and depression regardless of treatment modalities.

Internet-based treatment for depressive symptoms in hemodialysis patients: A cluster randomized controlled trial.

OBJECTIVE: To investigate the effectiveness of a guided internet-based self-help intervention for hemodialysis patients with depressive symptoms. METHOD: Chronic hemodialysis patients from nine Dutch hospitals with a depression score on the Beck Depression Inventory - second edition (BDI-II) of ≥10, were cluster-randomized into a five modules guided internet-based self-help problem solving therapy intervention or a parallel care-as-usual control group. Clusters were based on hemodialysis shift. The primary outcome depression was measured with the BDI-II. Analysis was performed with linear mixed models. RESULTS: A total of 190 hemodialysis patients were cluster-randomized to the intervention (n = 89) or control group (n = 101). Post-intervention measurement was completed by 127 patients (67%) and more than half of the patients (54%) completed the intervention. No significant differences were found on the BDI-II score between the groups (mean difference - 0.1, 95%CI -3.0; 2.7, p = 0.94). Per protocol sensitivity analysis showed comparable results. No significant differences in secondary outcomes were observed between groups. CONCLUSIONS: Guided internet-based self-help problem solving therapy for hemodialysis patients with depressive symptoms does not seem to be effective in reducing these symptoms as compared to usual care. Future research should examine how to best design content and accessibility of an intervention for depressive symptoms in hemodialysis patients. TRIAL REGISTRATION: Dutch Trial Register: Trial NL6648 (NTR6834) (prospectively registered 13th November 2017).

Treatment of current depressive symptoms in dialysis patients: A systematic review and meta-analysis.

OBJECTIVE: Symptoms of depression are highly prevalent and undertreated in dialysis patients. To aid clinicians in offering treatment to patients with depression, we conducted a systematic review and meta-analysis on the treatment of current depressive symptoms in dialysis patients. METHODS: Nine databases were searched on January 8th 2020 for randomized controlled trials on the treatment of depressive symptoms in dialysis patients. In contradiction to previous reviews, we only included studies who selected patients with a score above a defined cut-off for depressive symptoms and used an inactive control group, to investigate the effectiveness of treatments in currently depressed patients. All interventions aimed to treat depressive symptoms were accepted for inclusion. Standardized mean differences were calculated in a random effect meta-analysis. RESULTS: Seventeen studies were included in the systematic review (1640 patients). Nine studies could be included in the meta-analysis. A pooled analysis of 7 studies on psychotherapy showed a standardized mean difference of -0.48 [-0.87; -0.08], with a moderate heterogeneity (I2 = 52%, X2 = 12.56, p = .05). All studies on psychotherapy performed a per protocol analysis and scored high on potential bias. A pooled analysis of two studies on SSRI's showed no statistically significant improvement of depressive symptoms (SMD -0.57 [-6.17; 5.02], I2 = 71%, X2 = 0.2474, p = .06). CONCLUSIONS: Psychotherapy is a promising treatment for currently depressed dialysis patients, although quality of evidence is low. More evidence is needed regarding the efficacy of SSRI's, exercise therapy and dietary supplements in this population. PROSPERO: CRD42018073969.

General distress and symptoms of anxiety and depression: A factor analysis in two cohorts of dialysis patients.

OBJECTIVE: Depression and anxiety often coexist in patients with end-stage-kidney disease. Recently, studies showed that a composite 'general distress score' which combines depression and anxiety symptoms provides a good fit in dialysis and oncology patients. We aim to investigate if the three most frequently used self-report questionnaires to measure depression and anxiety in dialysis patients are sufficiently unidimensional to warrant the use of such a general distress score in two cohorts of dialysis patients. METHODS: This study includes two prospective observational cohorts of dialysis patients (total n = 749) which measured depression and anxiety using Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) and Hospital Anxiety and Depression Scale (HADS). Confirmatory factor analyses was used to investigate both a strictly unidimensional model and a multidimensional bifactor model that includes a general distress, depression and anxiety factor. The comparative fit index (CFI) and The Root Mean Square Error of Approximation (RMSEA) were used as model fit indices. RESULTS: Factor analysis did not show a good fit for a strictly unidimensional general distress factor for both the BDI/BAI and HADS (CFI 0.690 and 0.699, RMSEA 0.079 and 0.125 respectively). The multidimensional model performed better with a moderate fit for the BDI/BAI and HADS (CFI 0.873 and 0.839, RMSEA 0.052 and 0.102). CONCLUSIONS: This data shows that the BDI/BAI and HADS are insufficiently unidimensional to warrant the use of a general distress score in dialysis patients without also investigating anxiety and depression separately. Future research is needed whether the use of a general distress score might be beneficial to identify patients in need of additional (psychological) support.

Symptom dimensions of anxiety and their association with mortality, hospitalization and quality of life in dialysis patients.

OBJECTIVE: Symptoms of anxiety are highly prevalent in dialysis patients and are associated with adverse clinical outcomes. Identifying symptom dimensions may help to understand the pathophysiology, improve screening and guide treatment. Currently, there are no data on symptom dimensions of anxiety in dialysis patients. This study aimed to identify the best fitting dimensional model for anxiety in dialysis patients and assess the association between symptom dimensions of anxiety and adverse clinical outcomes. METHODS: This study is a prospective observational cohort study including patients from 10 urban dialysis centers between 2012 and 2017. Anxiety symptoms were measured using the self-reported questionnaire Beck Anxiety Inventory. Confirmatory factor analysis was used to identify symptom dimensions. The association between dimensions and mortality, hospitalization and quality of life was investigated using stepwise cox, poisson and lineair regression models. Multivariable models included demographic, social, laboratory and clinical variables to adjust for possible confounding. RESULTS: In total 687 chronic dialysis patients were included. A Somatic and Subjective anxiety dimension were identified. Only Somatic anxiety symptoms showed an association with increased risk of hospitalization and mortality (Rate Ratio 1.73 (1.45-2.06) p = .007 and Hazard Ratio 1.65 (1.15-2.37) p = .007 respectively). These associations were independent from somatic comorbidity. All symptom dimensions of anxiety showed an association with Quality of Life. CONCLUSION: This study shows that anxiety is common in chronic dialysis patients and comprises of a somatic, subjective, and a total score. The discrimination between anxiety dimensions can be useful for clinical practice, as they are related to different clinical outcomes.

The (cost) effectiveness of guided internet-based self-help CBT for dialysis patients with symptoms of depression: study protocol of a randomised controlled trial.

BACKGROUND: Only a minority of dialysis patients with depressive symptoms are diagnosed and receive treatment. Depressive symptoms are highly prevalent in this population and are associated with adverse clinical outcomes. Underlying factors for this undertreatment may be the lack of evidence for the safety and effectivity of antidepressant medication, the reluctance of patients to adhere to antidepressant medication, the lack of mental healthcare provision in somatic healthcare environments and end-stage renal disease (ESRD) related physical limitations that complicate face-to-face psychotherapy. Guided Internet-based self-help treatment has demonstrated to be effective for depressive symptoms in other chronic patient populations and may overcome these barriers. The aim of this study is to investigate the (cost) effectiveness of a guided Internet-based self-help intervention for symptoms of depression in dialysis patients. METHODS: This study is a cluster randomized controlled trial (RCT) that investigates the effectiveness of a 5-week Internet-based self-help Problem Solving Therapy (PST) for depressive symptoms in dialysis patients. Depressive symptoms will be measured using the Beck Depression Inventory - second edition (BDI-II), with a cut-off score of ≥10. We aim to include 206 dialysis patients with depressive symptoms who will be cluster randomized to the intervention or the Care as Usual (CAU) control group. Secondary outcomes will include anxiety symptoms, quality of life, economic costs and clinical outcomes, such as inflammatory factors and hair cortisol levels. Assessments will take place at baseline (T0), 2 weeks after intervention (T1) and 6 months (T2), 12 months (T3) and 18 months (T4) after intervention. The control group will be measured at the same time points. Analysis will be based on the intention-to-treat principle. Mixed models will be used to assess the changes within each condition between pre-treatment and post-treatment. DISCUSSION: If demonstrated to be (cost) effective, Internet-based PST will offer new possibilities to treat dialysis patients with depressive symptoms and to improve their quality of care. TRIAL REGISTRATION: Dutch Trial Register: Trial NL6648 (NTR6834) (prospectively registered 13th November 2017).

Dimensions of Depressive Symptoms and Their Association With Mortality, Hospitalization, and Quality of Life in Dialysis Patients: A Cohort Study.

OBJECTIVE: Unraveling specific dimensions of depressive symptoms may help to improve screening and treatment in dialysis patients. We aimed to identify the best-fitting factorial structure for the Beck Depression Inventory-II (BDI) in dialysis patients and to assess the relation of these structure dimensions with quality of life (QoL), hospitalization, and mortality. METHODS: This prospective study included chronic dialysis patients from 10 dialysis centers in five hospitals between 2012 and 2017. Dimensions of depressive symptoms within the BDI were analyzed using confirmatory factor analysis. To investigate the clinical impact of these dimensions, the associations between symptom dimensions and QoL, hospitalization rate, and mortality were investigated using logistic, Poisson, and Cox proportional hazard regression models. Multivariable regression models included demographic, social, and clinical variables. RESULTS: In total, 687 dialysis patients were included. The factor model that included a general and a somatic factor provided the best-fitting structure of the BDI-II. Only the somatic dimension scores were associated with all-cause mortality (hazard ratio of 1.7 [1.2-2.5], p < .007) in the multivariable model. All dimensions were associated with increased hospitalization rate and reduced QoL. CONCLUSIONS: The somatic dimension of the BDI-II in dialysis patients was associated with all-cause mortality, increased hospitalization rate, and reduced QoL. Other dimensions were associated with hospitalization rate and decreased QoL. These findings show that symptom dimensions of depression have differential association with adverse clinical outcomes. Future studies should take symptom dimensions into account when investigating depression-related pathways, screening, and treatment effects in dialysis patients.

Ethnic Differences in the Association of Depressive Symptoms with Clinical Outcome in Dialysis Patients.

BACKGROUND: Studies show mixed results on the association between depressive symptoms and adverse clinical outcomes in patients on dialysis therapy. Ethnicity may play a role in these heterogeneous results. No studies have investigated the interplay between ethnicity and depressive symptoms on clinical outcome in this patient population. This study aims to examine interaction between ethnicity and depressive symptoms on hospitalization and mortality in dialysis patients. METHODS: A multi-ethnic cohort in 10 dialysis centers included 687 dialysis patients between 2012 and 2017, with an average follow-up of 3.2 years. Depressive symptoms were measured using the Beck Depression Inventory. Interaction was assessed by investigating excess risk on an additive scale using both absolute rates and relative risks. Multivariable regression models included demographic, social, and clinical variables. RESULTS: Adverse outcomes are more pronounced in native patients, compared to immigrant patients. The risk for mortality and hospitalization is considerably higher in native patients compared to immigrants. An excess risk on an additive scale indicates the presence of possible causal interaction. CONCLUSIONS: Depressive symptoms are a risk factor for hospitalization and mortality, especially in native dialysis patients. Adverse clinical events associated with depressive symptoms differ among ethnic groups. This differential association could play a role in the conflicting findings in literature. Ethnicity is an important factor when investigating depressive symptoms and clinical outcome in dialysis patients. Future research should focus on the possible mechanisms and pathways involved in these differential associations.

Anxiety Symptoms, Mortality, and Hospitalization in Patients Receiving Maintenance Dialysis: A Cohort Study.

RATIONALE & OBJECTIVE: Anxiety symptoms are common in dialysis patients and have a large impact on quality of life. The association of anxiety symptoms with adverse clinical outcomes in dialysis patients is largely unknown. This study examined the association of anxiety symptoms with hospitalization and mortality in patients receiving maintenance dialysis. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Maintenance dialysis patients treated at 10 dialysis centers in the Netherlands between 2012 and 2016. EXPOSURES: Time-varying symptoms of anxiety and depression using the Beck Anxiety Inventory and Beck Depression Inventory. OUTCOMES: All-cause mortality, 1-year hospitalization rate, and hospital length of stay. ANALYTICAL APPROACH: Cox proportional hazards and Poisson regression models adjusted for sociodemographic and clinical variables. Sensitivity analyses included multiple imputation of missing data and restriction to incident patients only. RESULTS: 687 patients were included, composed of 433 prevalent and 242 incident dialysis patients. Median follow-up time was 3.1 (IQR, 3.0-3.5) years, during which 172 deaths occurred. 22% of patients had anxiety symptoms and 42% had depressive symptoms. Anxiety symptoms were associated with all-cause mortality and 1-year hospitalization rate and length of stay in all multivariable models. Anxiety symptoms showed a clear dose-response relationship with mortality. LIMITATIONS: Depression and anxiety often coexist and share symptoms. The observational design of this study limits inferences about causal mechanisms between anxiety and clinical outcomes. CONCLUSIONS: Anxiety symptoms are independently associated with increased risk for mortality and 1-year hospitalization. Anxiety symptoms are a clinically relevant risk factor for morbidity and mortality in dialysis patients and warrant further research on effective treatment.

Longitudinal Associations Between Inflammation and Depressive Symptoms in Chronic Dialysis Patients.

OBJECTIVE: Patients undergoing chronic dialysis often display sustained elevations of inflammation markers and also have a high prevalence of depressive symptoms. Although multiple studies demonstrated cross-sectional associations between inflammation markers and depressive symptoms in this patient group, longitudinal associations have not been examined. We therefore investigated whether longitudinal associations exist between inflammation markers and depressive symptoms in chronic dialysis patients. METHODS: Data of three consecutive measurements of an observational, prospective cohort study among chronic dialysis patients were used. At baseline, 6-month, and 12-month follow-up, patients completed the Beck Depression Inventory, and inflammation markers (high-sensitivity C-reactive protein [HsCRP], interleukin (IL)-1ß, IL-6, IL-10, and tumor necrosis factor α) were measured. We examined cross-sectional associations between inflammation markers and depressive symptoms using linear regression models. The longitudinal association between inflammation and depressive symptoms was assessed using a linear mixed model analyses. RESULTS: A total of 513 patients were included. Cross-sectional associations were found between HsCRP and depressive symptoms at baseline (ß = 0.9, confidence interval [CI] = 0.4-1.4) and 6-month follow-up (ß = 1.1, CI = 0.3-2.0), and between IL-1ß and depressive symptoms at 6-month follow-up (ß = 1.3, CI = 0.8-1.8) and 12-month follow-up (ß = 1.2, CI = 0.4-1.9). Inflammation makers (HsCRP, IL-6, IL-1ß, IL-10, and tumor necrosis factor α) at baseline were not associated with depressive symptoms at follow-up and vice versa. CONCLUSIONS: We confirmed the presence of cross-sectional associations between inflammation markers and depressive symptoms in chronic dialysis patients, but with our longitudinal data, we found no longitudinal associations. This supports an associative instead of a causal relationship between inflammation and depressive symptoms.

Differences in the association of inflammation and tryptophan with depressive symptoms between white and non-white chronic dialysis patients.

OBJECTIVE: Possibly, different biochemical parameters are involved in the development of depressive symptoms in white and non-white dialysis patients. We examined whether the association between inflammation and depressive symptoms and between tryptophan and depressive symptoms differs between white and non-white dialysis patients and whether the association between inflammation and depressive symptoms is mediated by tryptophan degradation along the kynurenine pathway in both groups. METHOD: Depressive symptoms were measured with the BDI-II. HsCRP, IL-1ß, IL-6, IL-10, and TNFα and tryptophan and its degradation products kynurenine and 3-hydroxykynurenine were measured in 270 white and 220 non-white patients. RESULTS: The presence of depressive symptoms was significantly higher in non-white patients (51%) than in white patients (37%) (P<0.01). Among white patients, HsCRP was significantly associated with depressive symptoms (ß=0.6 (95% CI: 0.1-1.2)). Among non-white patients, significant associations with depressive symptoms were found for both HsCRP (ß=1.0 (95% CI: 0.1-2.0)) and IL-6 (ß=2.6 (95% CI: 0.8-4.4)). Tryptophan levels were only significantly associated with depressive symptoms in non-white patients (ß=-0.3 (95% CI: -0.4--0.1)). Tryptophan degradation along the kynurenine pathway did not mediate the association between inflammatory markers and depressive symptoms in either group. CONCLUSION: Our results indicate that for white and non-white dialysis patients different biochemical parameters are associated with depressive symptoms.