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.

The Stability of Type D Personality in Dialysis Patients.

PURPOSE: Type D personality has been identified as an independent risk factor for survival in cardiovascular disease (CVD) patients. As CVD is present in about 50% of dialysis patients, it is of clinical interest to assess the prevalence of type D personality, the association with depressive and anxiety symptoms, and stability of type D personality in dialysis patients. METHODS: Data was used from two consecutive measurements of the DIVERS study, a prospective cohort study among chronic dialysis patients in the Netherlands. Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and the Type D Scale-14 (DS14) were used to assess depressive and anxiety symptoms and type D personality, respectively. The association of type D personality was assessed with analysis of variance F test. Stability of type D personality, depressive, and anxiety symptoms were determined by calculating Cohen's κ, and by determining the positive agreement. RESULTS: In total, 349 patients were included of which 249 patients had two measurement points. The prevalence of type D personality was 21% and type D personality was associated with depressive and anxiety symptoms (P < 0.01). Over a 6-month period, Cohen's κ was 0.52, 0.56, and 0.61 for type D personality, depressive, and anxiety symptoms, respectively. Sixty-one, 73, and 73% had a stable type-D personality, depressive, and anxiety symptoms, respectively. CONCLUSION: The presence of type D personality varies over time in dialysis patients. Therefore, type D personality is possibly more a state instead of a trait phenomenon.

The role of tryptophan degradation in the association between inflammatory markers and depressive symptoms in chronic dialysis patients.

BACKGROUND: Among chronic dialysis patients, associations have been found between inflammatory markers and depressive symptoms. In this population, no studies have examined the mechanism linking the association between inflammatory markers and depressive symptoms. We examined whether the association between inflammatory markers and depressive symptoms is mediated by tryptophan (TRP) degradation along the kynurenine (KYN) pathway. METHODS: The data are part of an observational, prospective cohort study in five urban dialysis centres in The Netherlands. Depressive symptoms were determined with the Beck Depression Inventory. Peripheral blood was collected before dialysis to measure inflammatory markers [high sensitivity C-reactive protein (HsCRP), interleukin (IL)-1ß, IL-6, IL-10 and tumour necrosis factor-α (TNF-α)], TRP, KYN and 3-hydroxykynurenine. The KYN/TRP ratio was used as a measure of TRP degradation. The association between inflammatory markers and depressive symptoms was determined using linear regression analysis and adjusted for the KYN/TRP ratio. RESULTS: In total, 490 chronic dialysis patients were included. HsCRP [ ß = 3.8; confidence interval (CI): 1.0-6.6], IL-6 ( ß = 9.1; CI: 4.0-14.1) and TNF-α ( ß = 1.3; CI: 0.9-1.7) were associated with the KYN/TRP ratio. We found significant associations between HsCRP ( ß = 0.8; CI: 0.3-1.3) and IL-6 ( ß = 1.2; CI: 0.3-2.2) levels and depressive symptoms. However, this association was not attenuated after adjustment for the KYN/TRP ratio. Also, no significant associations were found between the KYN/TRP ratio and depressive symptoms. CONCLUSION: The association between inflammatory markers and depressive symptoms in chronic dialysis patients was not mediated by TRP degradation along the KYN pathway.

Short-Form 12 or Short-Form 36 to measure quality-of-life changes in dialysis patients?

BACKGROUND: Short-Form 36 (SF-36) is a self-report health-related quality-of-life (HRQOL) questionnaire, widely used in dialysis patients. It consists of physical and mental component scores (PCS/MCS), ranging from 0 to 100. To improve efficiency, the Short-Form 12 (SF-12) was developed to reproduce PCS and MCS. We assessed the ability of SF-12 versus SF-36 to detect change over time, and the association of SF-12 versus SF-36 with short-term and long-term mortality in dialysis patients. METHODS: Patients were selected from the Netherlands Cooperative Study on the Adequacy of Dialysis (N = 1379), a prospective follow-up study among incident dialysis patients (62.1% HD) who completed SF-36 measurements every 6 months. Changes in scores of SF-12 versus SF-36 were compared with intra-class correlation coefficients (ICCs). Subsequently, Bland-Altman plots were used to assess limits of agreement. Relationship with mortality was assessed with Cox models with and without a time-dependent variable, adjusted for age, sex, ethnicity, comorbidity and dialysis modality at baseline. RESULTS: ICC for change in scores was 0.90 for MCS and 0.84 for PCS. Mean difference was -0.1 and 0.2, respectively, and limits of agreement were -8.3 to 8.4 for MCS change in scores and -8.8 to 9.2 for PCS. Adjusted hazard ratio's for mortality per 5 units increment were 0.87 (95% CI: 0.84-0.91) for MCS12, 0.87 (95% CI: 0.84-0.90) for MCS36, 0.79 (95% CI: 0.76-0.83) for PCS12 and 0.75 (95% CI: 0.71-0.78) for PCS36. CONCLUSIONS: SF-12 can be used to detect change in HRQOL in cohort studies on dialysis patients. SF-12 and SF-36 were similarly associated with short-term and long-term mortality. However, the wide limits of agreement indicate that SF-12 and SF-36 can give different scores on the individual level, suggesting that for individual purposes SF-36 instead of SF-12 should be used.

Association of depressive and anxiety symptoms with adverse events in Dutch chronic kidney disease patients: a prospective cohort study.

BACKGROUND: Depressive symptoms have been reported to be associated with adverse clinical outcome in patients with chronic kidney disease (CKD) not on dialysis. This association has not been examined in Europe. Anxiety and depressive symptoms often co-occur. However, as yet there are no data concerning a possible association of anxiety symptoms with adverse clinical outcome. We examined the association of depressive and anxiety symptoms with adverse clinical outcome in Dutch CKD patients not on dialysis. METHODS: In this 3-year follow-up prospective cohort study, CKD patients not on dialysis with an estimated glomerular filtration rate (eGFR) ≤ 35 ml/min/1.73 m(2) from an urban teaching hospital were selected. Symptoms of depression and anxiety were evaluated using the Beck Depression Inventory (BDI) and the Beck Anxiety Inventory (BAI). Cox proportional hazards models were used to calculate hazard ratio's (HRs) with a composite event of death, initiation of dialysis, and hospitalization as outcome. HRs were adjusted for age, gender, diabetes, cardiovascular disease and eGFR. RESULTS: Of 100 included CKD patients depressive and anxiety symptoms were present in 34 and 31 %, respectively. Adjusted HRs for the composite event for patients with depressive and anxiety symptoms were 2.0 (95 % confidence interval (CI) 1.2-3.5) and 1.6 (95 % CI 0.9-2.7), respectively. Twenty three patients had both depressive and anxiety symptoms of whom adjusted HRs were 2.2 (95 % CI 1.2-4.0) for a composite event. CONCLUSIONS: Depressive and anxiety symptoms are common in patients with CKD in The Netherlands. Depressive symptoms are associated with an increased risk of poor clinical outcome. Anxiety symptoms show a trend for an increased risk of poor clinical outcome. There seems to be no additive effect of anxiety symptoms in addition to depressive symptoms with regard to poor clinical outcome.

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.

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.

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.

Depressive and Anxiety Symptoms in Dutch Immigrant and Native Dialysis Patients.

Due to continuing migration there is more interest in the mental health status of immigrants. The aim of this study is to determine the prevalence of depressive/anxiety symptoms in immigrant and native dialysis patients, and to explore if patient characteristics can explain differences. The Beck depression inventory and the beck anxiety inventory were used. Differences between native and immigrant patients were explored using logistic regression models adjusted for patient characteristics. The prevalence of depressive symptoms was 35% for 245 native patients and 50% for 249 immigrant patients. The prevalence of anxiety symptoms was 35% for native patients and 50% for immigrant patients. In addition, the prevalence for co-morbid depressive and anxiety symptoms was 20% for native patients and 32% for immigrant patients. Crude ORs for depressive/anxiety symptoms for immigrant patients versus native patients were 1.8 (1.2-2.5) and 1.7 (1.2-2.5), respectively. After adjustment for patient characteristics ORs remained the same. Clinicians should be aware that immigrant dialysis patients are more prone to develop depressive and anxiety symptoms. Cultural factors might play a role and should therefore be assessed in future research.

The association of acculturation and depressive and anxiety symptoms in immigrant chronic dialysis patients.

OBJECTIVE: Among immigrant chronic dialysis patients, depressive and anxiety symptoms are common. We aimed to examine the association of acculturation, i.e. the adaptation of immigrants to a new cultural context, and depressive and anxiety symptoms in immigrant chronic dialysis patients. METHODS: The DIVERS study is a prospective cohort study in five urban dialysis centers in the Netherlands. The association of five aspects of acculturation ("Skills", "Social integration", "Traditions", "Values and norms" and "Loss") and the presence of depressive and anxiety symptoms was determined using linear regression analyses, both univariate and multivariate. RESULTS: A total of 249 immigrant chronic dialysis patients were included in the study. The overall prevalence of depressive and anxiety symptoms was 51% and 47%, respectively. "Skills" and "Loss" were significantly associated with the presence of depressive and anxiety symptoms, respectively ("Skills" ß=0.34, CI: 0.11-0.58, and "Loss" ß=0.19, CI: 0.01-0.37; "Skills" ß=0.49, CI: 0.25-0.73, and "Loss" ß=0.33, CI: 0.13-0.53). The associations were comparable after adjustment. No significant associations were found between the other subscales and depressive and anxiety symptoms. CONCLUSION: This study demonstrates that less skills for living in the Dutch society and more feelings of loss are associated with the presence of both depressive and anxiety symptoms in immigrant chronic dialysis patients.