Association of both depressive symptom scores and specific depressive symptoms with all-cause mortality and cardiovascular mortality among participants with chronic kidney disease

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This study aims to investigate the association between both depressive symptom scores and specific depressive symptoms with all-cause and cardiovascular disease (CVD) mortality among participants with chronic kidney disease (CKD). Methods 2981 participants with CKD, aged 18 years old, were enrolled from NHANES from 2007 to 2014. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9). The total PHQ-9 score ranges from 0 to 27, with higher scores indicating greater severity of depressive symptoms. The primary outcomes were all-cause mortality and CVD mortality. Weighted COX regression was used to analyze association of both depressive symptom scores and specific depressive symptoms with all-cause mortality CVD mortality. Results After an average follow-up of 92 months, 932 deaths among 2981 participants with CKD were recorded, of which 332 were CVD deaths. The RCS plot showed a linear relationship between depressive symptom scores and all-cause (nonlinear P -value = 0.346) and CVD mortality (nonlinear P -value = 0.177). After full adjustment for potential confounders, every 1-point increase in depressive symptom score was associated with a 4% and 5.4% increase in all-cause (HR, 1.040; 95% CI, 1.020-1.060; P -value <0.001) and CVD mortality (HR, 1.054; 95% CI, 1.027-1.081; P -value <0.001), respectively. Additionally, 6-items (Uninterested in things, Feeling down, Tiredness, Change of appetite, Change in speed of action, and Suicidal ideation) in the PHQ-9 were independently associated with all-cause mortality. Similarly, 3-items (Uninterested in things, Feeling down, and Tiredness) were significantly associated with CVD mortality. There was no significant interaction between depressive symptom scores and all-cause and CVD mortality in any subgroup (all P -values for interaction > 0.05). Sensitivity analysis also further confirmed the stability of the above results. Conclusions The elevated depressive symptom scores were significantly associated with an increased risk of all-cause and CVD mortality in participants with CKD. Furthermore, 6 specific depressive symptoms were associated with a high risk of all-cause death, and 3 specific depressive symptoms were associated with a high risk of CVD death. depressive symptom scores specific depressive symptoms mortality chronic kidney disease NHANES Figures Figure 1 Figure 2 Introduction Chronic kidney disease (CKD) is a major global health burden, affecting millions of individuals and leading to significant morbidity and mortality (1). Patients with CKD often experience a range of comorbidities, including cardiovascular diseases (CVD) and mental health disorders such as depression (2, 3). Depression is characterized by persistent feelings of sadness, hopelessness, and a lack of interest or pleasure in daily activities, and it is particularly prevalent among individuals with chronic illnesses (4, 5). The interplay between depression and CKD is complex, and emerging evidence suggests that depressive symptoms may significantly impact the prognosis of CKD patients, particularly concerning all-cause and cardiovascular mortality (6-8). The relationship between depressive symptoms and mortality in CKD patients is multifaceted, involving biological, behavioral, and social factors. Depression can lead to physiological changes, such as increased inflammation, autonomic dysfunction, and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, which can exacerbate the progression of CKD and increase the risk of cardiovascular events (4). Furthermore, CKD patients with depression are more likely to engage in unhealthy behaviors, including poor adherence to medical treatments, smoking, physical inactivity, and poor dietary habits (9), which further elevate their risk of mortality. Previous studies have demonstrated that depression is associated with an increased risk of developing CVD and worsens the prognosis of individuals with existing cardiovascular conditions (8, 10). Despite these findings, the specific mechanisms through which depression influences mortality in CKD patients, particularly the contributions of individual depressive symptoms and overall depressive symptom severity, are not fully understood. Understanding the association between specific depressive symptoms and mortality in CKD patients is crucial for developing targeted interventions. Different depressive symptoms, such as insomnia, fatigue, and anhedonia, may have varying impacts on health outcomes. However, most research has focused on overall depressive symptom scores, potentially overlooking the distinct effects of individual symptoms. This gap in the literature highlights the need to investigate the unique contribution of specific symptoms to mortality risk. This study aims to investigate the association between both depressive symptom scores and specific depressive symptoms with all-cause and cardiovascular mortality among participants with CKD. This research has significant public health implications, emphasizing the importance of early detection and comprehensive management of depression to reduce mortality associated with CKD, which help shape future interventions aimed at mitigating the adverse health impacts of depression, ultimately enhancing the quality of life and survival of CKD patients. Materials and Methods Study Population This study utilized data from the National Health and Nutrition Examination Survey (NHANES), a nationally representative survey conducted by the National Center for Health Statistics (NCHS). NHANES employs a complex, multistage probability sampling design to collect information on the health and nutritional status of the U.S. civilian, non-institutionalized population. For this analysis, we included participants aged 20 years and older with CKD, defined as an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m² or albuminuria (urinary albumin-to-creatinine ratio ≥ 30 mg/g) for 3 months or more (11). As shown in Figure 1 , a total of 24678 participants aged 18 years or older were included from four cycles of the NHANES from 2007 to 2014 years, of which 4138 participants have CKD at baseline. Additionally, of the remaining 4138 participants, 493 participants were excluded due to missing values of depressive symptom scores. After further excluding 664 participants at baseline with missing values of the covariates, 2981 participants were finally enrolled. All-cause mortality was 31.26% (932/2981), and cardiovascular mortality was 11.14% (332/2981). All data in the NHANES database are publicly available and free of charge. Importantly, the NHANES protocols were approved by the NCHS Research Ethics Review Board, and written informed consent was obtained from all participants. The study was conducted in accordance with the Declaration of Helsinki. Each participant signed an informed consent. Data for the present study were derived from the NHANES database, so additional ethical approval was not required. Assessment of depressive symptoms Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9), a self-reported instrument for depression on a scale from 0 (not at all) to 3 (nearly every day). The total PHQ-9 score ranges from 0 to 27, with higher scores indicating greater severity of depressive symptoms. PHQ-9 is composed of 9 items: (1) have little interest in doing things; (2) feeling down, depressed, or hopeless; (3) trouble sleeping or sleeping too much; (4) feeling tired or having little energy; (5) poor appetite or overeating; (6) feeling bad about yourself; (7) trouble concentrating on things; (8) moving or speaking slowly or too fast; (9) thought you would be better off dead. To analyze the association between depressive symptom scores and mortality, participants were categorized into three groups based on tertiles of PHQ-9 scores. Additionally, the presence of specific depressive symptoms was analyzed individually. Outcomes Mortality data were obtained from the NHANES Linked Mortality File, which links NHANES participant data with the National Death Index (NDI) records (https://www.cdc.gov/nchs/data-linkage/mortality-public.htm#). The primary outcomes of the present study were all-cause mortality and cardiovascular mortality. All-cause death was ascribed to death from any cause. CVD death was defined using the International Classification of Diseases, Tenth Revision, including death of heart disease (ICD-10 codes: I00-I09, I11, I13, and I20-I51) or death of cerebrovascular disease (ICD-10 codes: I60-I69) (12). Covariates Covariates included demographic variables (age, sex, ethnicity, poverty, and education level), lifestyle factors (smoking status, alcohol consumption), clinical measurements (body mass index (BMI), waist, systolic blood pressure (SBP), diastolic blood pressure (DBP), and comorbidities (history of diabetes, hypertension, and hyperlipidemia). Hypertension was defined as meeting one of the following criteria: (1) a self-reported history of hypertension; (2) SBP≥ 140 mmHg or DBP≥ 90 mmHg measured at baseline; (3) taking antihypertensive medication (13). Diabetes was characterized by hemoglobin ≥ 6.5% or fasting blood glucose ≥ 7.0 mmol/L, a self-reported history of diabetes, or being on anti-diabetic medication (14). Hyperlipidemia was described as one of the following conditions: (1) low-density lipoprotein cholesterol ≥ 130 mg/dL; (2) high-density lipoprotein cholesterol < 40 mg/dL (male) or < 50 mg/dL (female); (3) total cholesterol ≥ 200 mg/dL; (4) triglycerides ≥ 150 mg/dL; (5) use of cholesterol-lowering drugs (15). Detailed data can be found at https://www.cdc.gov/nchs/nhanes/. Statistical analysis The NHANES sampling weights, strata, and primary sampling units were incorporated into all analyses to account for the complex survey design and to produce nationally representative estimates. Descriptive statistics based on the tertiles of depressive symptom scores (Q1: 0-1 scores, Q2: 1-4 scores, and Q3: 4-27 scores) were used to summarize the characteristics of the study population. Continuous variables are expressed as mean ± standard deviation (SD), and the T test and Kruskal-Wallis test were used for group comparison. Categorical variables were expressed as percentages, and the X 2 test was used for comparison between groups. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of both depressive symptom scores and specific depressive symptoms with all-cause and CVD mortality. No variables were adjusted in the crude model. Age, sex, and ethnicity were adjusted in Model 1. Age, sex, ethnicity, poverty, education level, smoking status, drinking status, BMI, SBP, diabetes, hyperlipidemia, and hypertension were adjusted in Model 2. Meanwhile, the dose-response relationship of depressive symptom scores with all-cause and CVD mortality was assessed by restricted cubic spline (RCS) plots. In addition, subgroups based on age (≤65 years old/>65 years old), sex (Male/Female), ethnicity (White/Black/Mexican/and Other), education level (High school diploma), BMI (≤30kg/m 2 />30 kg/m 2 ), smoking status (Never/Former/Current), drinking status (Never/Former/Current), diabetes (No/Yes), hypertension (No/Yes), and hyperlipidemia (No/Yes), were performed to further analyze the association of depressive symptoms scores with all-cause mortality and cardiovascular mortality. Sensitivity analyses were conducted to assess the robustness of the findings: participants who died within 2 years of follow-up were excluded to reduce the possibility of reverse causality (16). All statistical analyses were performed using R studio 4.4.0 version, and a two-sided p-value of less than 0.05 was considered statistically significant, and NHANES sample weights were taken into account when combining and analyzing data. Results The characteristics of the study population in accordance with the tertiles of depressive symptom scores (Q1: 0-1 scores, Q2: 1-4 scores, and Q3: 4-27 scores) were summarized in Table 1 . A significant difference was found in the comparison of other baseline characteristics based on the tertiles of depressive symptom scores, except for ethnicity, SBP, and hyperlipidemia. Specifically, CKD participants with high depressive symptom scores were younger (Q3: 59.84 vs. Q2: 62.05 vs. Q1: 63.64, P -value <0.001) and had a higher proportion of female participants (Q3: 59.98% vs. Q2: 57.20% vs. Q1: 43.96%, P -value <0.001). After an average follow-up of 92 months, a total of 932 deaths were recorded, of which 332 were CVD deaths. The RCS plot showed a linear relationship between the total depressive symptom scores and all-cause (nonlinear P -value = 0.346) and CVD mortality (nonlinear P -value = 0.177) ( Figure 2 ). As shown in Table 2, models 1, 2, and 3 analyzed the association of depressive symptom scores with all-cause and CVD mortality. After full adjustment for potential confounders (Model 3), every 1-point increase in depressive symptom score was associated with a 4% and 5.4% increase in all-cause (HR, 1.040; 95% CI, 1.020-1.060; P -value <0.001) and CVD mortality (HR, 1.054; 95% CI, 1.027-1.081; P -value <0.001), respectively, in CKD participants. Participants were divided into three groups based on the tertiles of the total PHQ-9 score. Model 3 showed that participants in the Q3 group had a significantly higher incidence of all-cause mortality (HR, 1.418; 95% CI, 1.144-1.759; P -value = 0.001) compared to the reference group (Q1). Similar results were found for CVD mortality (HR, 1.613; 95% CI, 1.244-2.091; P -value <0.001). The association of specific depressive symptoms with all-cause and CVD mortality is shown in Table 3 . 6 items in the PHQ-9 were independently associated with all-cause mortality: Uninterested in things (HR, 1.257; 95% CI, 1.137-1.389; P -value <0.001), Feeling down (HR, 1.131; 95% CI, 1.015-1.261; P -value =0.026), Tiredness (HR, 1.251; 95% CI, 1.149-1.362; P -value <0.001), Change of appetite (HR, 1.129; 95% CI, 1.033-1.234; P -value =0.007), Change in speed of action (HR, 1.174; 95% CI, 1.018-1.353; P -value =0.027), Suicidal ideation (HR, 1.411; 95% CI, 1.064-1.870; P -value =0.017). Similarly, 3-items were significantly associated with CVD mortality: Uninterested in things (HR, 1.226; 95% CI, 1.060-1.418; P -value = 0.006), Feeling down (HR, 1.278; 95% CI, 1.085-1.504; P -value = 0.003), and Tiredness (HR, 1.357; 95% CI, 1.208-1.525; P -value 65 years old), sex (Male/Female), ethnicity (White/Black/Mexican/and Other), education level (High school diploma), BMI (≤30kg/m2/>30 kg/m2), smoking status (Never/Former/Current), drinking status (Never/Former/Current), diabetes (No/Yes), hypertension (No/Yes), and hyperlipidemia (No/Yes) were performed to investigate whether the associations between depressive symptom scores and mortality were influenced by potential confounding factors, and the results found that there was no significant interaction between depressive symptom scores and all-cause mortality in any subgroup (all P -values for interaction > 0.05). Similar results also appeared in the relationship between depressive symptom scores and CVD mortality, and the details are shown in Table 4 . In addition, sensitivity analysis was performed after excluding participants who died within 2 years of follow-up. After fully adjusting for potential confounders (Model 3), higher depressive symptom scores still increased all-cause (HR, 1.030; 95% CI, 1.010-1.051; P -value =0.004) and CVD mortality (HR, 1.046; 95% CI, 1.014-1.078; P value =0.004) in a subgroup of 2841 participants. Additionally, 3-items in the PHQ-9 were independently associated with all-cause mortality: Uninterested in things (HR, 1.223; 95% CI, 1.091-1.370; P -value <0.001), Tiredness (HR, 1.221; 95% CI, 1.117-1.334; P -value <0.001), and Change in speed of action (HR, 1.138; 95% CI, 1.000-1.294; P -value = 0.050). Similarly, 3-items were significantly associated with CVD mortality: Uninterested in things (HR, 1.196; 95% CI, 1.013-1.412; P -value = 0.035), Feeling down (HR, 1.240; 95% CI, 1.021-1.506; P -value = 0.030), Tiredness (HR, 1.312; 95% CI, 1.143-1.505; P -value <0.001). Discussion This study investigated the associations of both depressive symptom scores and specific depressive symptoms with all-cause and CVD mortality in participants with CKD. The results showed that higher depressive symptom scores were significantly associated with all-cause and CVD mortality, and every 1-point increase in depressive symptom score was associated with a 4% and 5.4% increase in all-cause (HR, 1.040; 95% CI, 1.020-1.060; P -value <0.001) and CVD mortality (HR, 1.054; 95% CI, 1.027-1.081; P -value <0.001). Additionally, six specific depressive symptoms in the PHQ-9 (Uninterested in things, Feeling down, Tiredness, Change of appetite, Change in speed of action, and Suicidal ideation) were significantly associated with all-cause mortality, and three specific depressive symptoms (Uninterested in things, Feeling down, and Tiredness) were significantly associated with CVD mortality. Our findings further emphasize the importance of screening and managing depressive symptoms in CKD patients. CKD patients are vulnerable to mental health problems due to their complex disease and multiple comorbidities (3, 17). Depression not only increases patients' distress but also may accelerate disease progression and increase death risk through adverse physiological mechanisms (such as inflammatory response, reduced heart rate variability, and lifestyle changes) (18-20). The results of this study may be explained by the following mechanisms: First, depressive symptoms may adversely affect the cardiovascular system by activating chronic inflammatory responses and increasing oxidative stress levels (21, 22). Second, patients with depression are more likely to engage in unhealthy behaviors, such as smoking, drinking, and lack of exercise, which increase the risk of cardiovascular disease (23-25). Finally, depressive symptoms may affect patients' medication compliance and treatment management, further worsening the prognosis of CKD patients (26). Previous studies have confirmed that depression can increase the risk of death in CKD patients. A meta-analysis conducted by Palmer et al. showed that depression can significantly increase the risk of all-cause mortality (RR, 1.59; 95% CI, 1.35-1.87) (27). Similarly, a study conducted by Krittanawong et al. also found that depression not only increases the risk of all-cause mortality (HR 1.43; 95% CI, 1.27-1.60), but also increases the risk of cardiovascular disease mortality (HR 1.44; 95% CI, 1.27-1.63) (28). However, previous studies only considered the impact of depression on patient prognosis. The diagnosis of depression was determined by multiple items on the depression scale (29). Therefore, most previous studies did not study the impact of specific depressive symptoms on the patients’ prognosis. Because individual depressive symptoms vary when depression occurs, treatment may vary. Therefore, the study on the association of specific depressive symptoms with the patients’ prognosis is very necessary. The results of the present study found that every 1-point increase in depressive symptom score was associated with a 4% and 5.4% increase in all-cause (HR, 1.040; 95% CI, 1.020-1.060; P -value <0.001) and CVD mortality (HR, 1.054; 95% CI, 1.027-1.081; P -value <0.001), respectively, in CKD participants. This is consistent with previous results. Importantly, we also found six specific depressive symptoms in the PHQ-9 (Uninterested in things, Feeling down, Tiredness, Change of appetite, Change in speed of action, and Suicidal ideation) were significantly associated with all-cause mortality, and three specific depressive symptoms (Uninterested in things, Feeling down, and Tiredness) were significantly associated with CVD mortality. This may provide new ideas for personalized treatment of patients with depression. Limitations Although this study provides valuable insights, it also has some limitations. First, the observational design precludes the determination of causality. Second, the assessment of depressive symptoms relied on self-report questionnaires, which may be subject to reporting bias. Additionally, the sample was predominantly drawn from NHANES database, limiting the generalizability of the findings. Conclusion The elevated depressive symptom scores were significantly associated with an increased risk of all-cause and CVD mortality in participants with CKD. Furthermore, 6 specific depressive symptoms (Uninterested in things, Feeling down, Tiredness, Change of appetite, Change in speed of action, and Suicidal ideation) were associated with a high risk of all-cause death. Only 3 specific depressive symptoms (uninterested in things, feeling down, and tiredness) were associated with a high risk of CVD death. These findings highlight the importance of screening and managing depressive symptoms in participants with CKD to improve their prognosis. Declarations Data Availability Statement The data supporting the findings of the present paper could be provided by contacting the corresponding author, without reservation. Competing Interests All authors have no competing interests. Clinical trial number Not applicable. Consent for publication Not applicable. Ethics statement The project was approved by the Research Ethics Review Board of the National Center for Health Statistics (Protocol #2005-06 and #2011-17) and was in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines (https://www.cdc.gov/nchs/nhanes/irba98.htm). Informed consent has been obtained from all participants for the NHANES data. Due to the free availability of the NHANES database, the present study does not require additional ethical review and approval. Author contributions Qiao Zhou and Xinyu Tang: Investigation, Methodology, Formal analysis, Conceptualization, and Writing-Original Draft; Haibo Du and Gaojian Chen: Methodology, Software, Validation, Conceptualization, Investigation and Resources; Song Xue and Yahui Chen: Conceptualization, Supervision, and Project administration. References Fletcher BR, Damery S, Aiyegbusi OL, Anderson N, Calvert M, Cockwell P, et al. Symptom burden and health-related quality of life in chronic kidney disease: A global systematic review and meta-analysis. PLoS Med. 2022;19(4):e1003954. Saeed D, Reza T, Shahzad MW, Karim Mandokhail A, Bakht D, Qizilbash FH, et al. Navigating the Crossroads: Understanding the Link Between Chronic Kidney Disease and Cardiovascular Health. Cureus. 2023;15(12):e51362. Adejumo OA, Edeki IR, Sunday Oyedepo D, Falade J, Yisau OE, Ige OO, et al. Global prevalence of depression in chronic kidney disease: a systematic review and meta-analysis. J Nephrol. 2024. Sheikh-Wu SF, Gerber KS, Pinto MD, Downs CA. Mechanisms and Methods to Understand Depressive Symptoms. Issues Ment Health Nurs. 2022;43(5):434-46. Palmer S, Vecchio M, Craig JC, Tonelli M, Johnson DW, Nicolucci A, et al. Prevalence of depression in chronic kidney disease: systematic review and meta-analysis of observational studies. Kidney Int. 2013;84(1):179-91. Young BA, Von Korff M, Heckbert SR, Ludman EJ, Rutter C, Lin EH, et al. Association of major depression and mortality in Stage 5 diabetic chronic kidney disease. Gen Hosp Psychiatry. 2010;32(2):119-24. Hedayati SS, Jiang W, O'Connor CM, Kuchibhatla M, Krishnan KR, Cuffe MS, et al. The association between depression and chronic kidney disease and mortality among patients hospitalized with congestive heart failure. Am J Kidney Dis. 2004;44(2):207-15. Novak M, Mucsi I, Rhee CM, Streja E, Lu JL, Kalantar-Zadeh K, et al. Increased Risk of Incident Chronic Kidney Disease, Cardiovascular Disease, and Mortality in Patients With Diabetes With Comorbid Depression. Diabetes Care. 2016;39(11):1940-7. Liu Q, Bai B, Liu F, Chen Y, Wang Y, Wang H, et al. Long-Term Trends in Risk Factor Management in Respondents with Chronic Kidney Disease in the USA. Am J Nephrol. 2022;53(8-9):614-23. D'Oro A, Patel DH, Wass S, Dolber T, Nasir K, Dobre M, et al. Depression and incident cardiovascular disease among patients with chronic kidney disease. Int J Cardiol Cardiovasc Risk Prev. 2023;18:200199. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int. 2021;100(4s):S1-s276. Brämer GR. International statistical classification of diseases and related health problems. Tenth revision. World health statistics quarterly Rapport trimestriel de statistiques sanitaires mondiales. 1988;41(1):32-6. James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). Jama. 2014;311(5):507-20. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2020. Diabetes care. 2020;43(Suppl 1):S14-s31. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106(25):3143-421. Cao C, Friedenreich CM, Yang L. Association of daily sitting time and leisure-time physical activity with survival among US cancer survivors. JAMA oncology. 2022;8(3):395-403. Aggarwal HK, Jain D, Dabas G, Yadav RK. Prevalence of Depression, Anxiety and Insomnia in Chronic Kidney Disease Patients and their Co-Relation with the Demographic Variables. Pril (Makedon Akad Nauk Umet Odd Med Nauki). 2017;38(2):35-44. Voorend CGN, van Buren M, Berkhout-Byrne NC, Kerckhoffs APM, van Oevelen M, Gussekloo J, et al. Apathy Symptoms, Physical and Cognitive Function, Health-Related Quality of Life, and Mortality in Older Patients With CKD: A Longitudinal Observational Study. Am J Kidney Dis. 2024;83(2):162-72.e1. Pu L, Zou Y, Wu SK, Wang F, Zhang Y, Li GS, et al. Prevalence and associated factors of depressive symptoms among chronic kidney disease patients in China: Results from the Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE). J Psychosom Res. 2020;128:109869. Chiang HH, Guo HR, Livneh H, Lu MC, Yen ML, Tsai TY. Increased risk of progression to dialysis or death in CKD patients with depressive symptoms: A prospective 3-year follow-up cohort study. J Psychosom Res. 2015;79(3):228-32. Helman TJ, Headrick JP, Vider J, Peart JN, Stapelberg NJC. Sex-specific behavioral, neurobiological, and cardiovascular responses to chronic social stress in mice. J Neurosci Res. 2022;100(11):2004-27. Shao J, Chen Y, Gao D, Liu Y, Hu N, Yin L, et al. Ventromedial hypothalamus relays chronic stress inputs and exerts bidirectional regulation on anxiety state and related sympathetic activity. Front Cell Neurosci. 2023;17:1281919. Wang B, Fan Y, Wang X, Zeng X, Zeng S, Jia H, et al. Influence of lifestyle patterns on depression among adults with diabetes: a mediation effect of dietary inflammatory index. BMC Public Health. 2024;24(1):1779. Tang Z, Yang X, Tan W, Ke Y, Kou C, Zhang M, et al. Patterns of unhealthy lifestyle and their associations with depressive and anxiety symptoms among Chinese young adults: A latent class analysis. J Affect Disord. 2024;352:267-77. Wu W, Ma W, Yuan S, Feng A, Li L, Zheng H, et al. Associations of Unhealthy Lifestyle and Nonalcoholic Fatty Liver Disease With Cardiovascular Healthy Outcomes. J Am Heart Assoc. 2023;12(23):e031440. Esquivel-Mendoza JA, Satyanarayana S, Safren S, Rogers BG. Examining the Longitudinal Effects of Insomnia on Depression and Medication Adherence in People Living with HIV. Behav Sleep Med. 2024:1-10. Palmer SC, Vecchio M, Craig JC, Tonelli M, Johnson DW, Nicolucci A, et al. Association between depression and death in people with CKD: a meta-analysis of cohort studies. Am J Kidney Dis. 2013;62(3):493-505. Krittanawong C, Maitra NS, Qadeer YK, Wang Z, Fogg S, Storch EA, et al. Association of Depression and Cardiovascular Disease. Am J Med. 2023;136(9):881-95. Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001;16(9):606-13. Tables Tables 1 to 4 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table1.docx Table 1.Baseline characteristics according to tertiles of depressive symptom scores. Table2.docx Table 2.Association of depressive symptom scores with all-cause mortality and cardiovascular mortality. Table3.docx Table 3. Association of specific depressive symptoms with incidence of all-cause mortality and cardiovascular mortality. Table4.docx Table 4. Association of depressive symptoms scores with all-cause mortality and cardiovascular mortality stratified by different factors. S.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5788878","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":406915542,"identity":"db612e57-bf6a-40f0-9cad-091cf24b042e","order_by":0,"name":"Qiao Zhou","email":"","orcid":"","institution":"Huaian Hospital Affiliated to Yangzhou University (The Fifth People’s Hospital of Huaian)","correspondingAuthor":false,"prefix":"","firstName":"Qiao","middleName":"","lastName":"Zhou","suffix":""},{"id":406915544,"identity":"33e32b69-aaba-4fb3-bd31-93ecdbaaf4ae","order_by":1,"name":"Xinyu Tang","email":"","orcid":"","institution":"Huaian Hospital Affiliated to Yangzhou University (The Fifth People’s Hospital of Huaian)","correspondingAuthor":false,"prefix":"","firstName":"Xinyu","middleName":"","lastName":"Tang","suffix":""},{"id":406915545,"identity":"fc0cfe56-d604-405a-927f-1500748c6398","order_by":2,"name":"Haibo Du","email":"","orcid":"","institution":"Huaian Hospital Affiliated to Yangzhou University (The Fifth People’s Hospital of Huaian)","correspondingAuthor":false,"prefix":"","firstName":"Haibo","middleName":"","lastName":"Du","suffix":""},{"id":406915546,"identity":"b277bceb-750e-4859-8448-5eef6b3f119f","order_by":3,"name":"Gaojian Chen","email":"","orcid":"","institution":"Huaian Hospital Affiliated to Yangzhou University (The Fifth People’s Hospital of Huaian)","correspondingAuthor":false,"prefix":"","firstName":"Gaojian","middleName":"","lastName":"Chen","suffix":""},{"id":406915547,"identity":"782c9e4c-dd0d-4189-ad35-c237d1cbc958","order_by":4,"name":"Song Xue","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3klEQVRIie3PsYrCQBDG8QkDUy2XdgTR7uqtfJ5ZAqkUrCSFYCBHLMTex7C00zRrs2qbMsEXuOuuvO09klx3xf6rr9gf7ACEQv8wmj6vn5KtN+dHUTV+9JM3SFNonI3y2ibaj34ygfksakuM8sv8fdR+4ICPgU0bU5I3jjKTE8TbnXSTqLhquY8JcW9rcxoDu9uxmyAJy4oUwT2tjSPQvOghpDQLISt/1NKUOIAoNWMpUbMnMIwwJVqcFc02YT9U7y3TA1btd7YWHRfVlx+TeLvvJi+pvz0PhUKh0K/9AA5/SkAMg+szAAAAAElFTkSuQmCC","orcid":"","institution":"Huaian Hospital Affiliated to Yangzhou University (The Fifth People’s Hospital of Huaian)","correspondingAuthor":true,"prefix":"","firstName":"Song","middleName":"","lastName":"Xue","suffix":""},{"id":406915548,"identity":"7280a7bf-f2c1-46fe-9dde-19ac5ec9ba51","order_by":5,"name":"Yahui Chen","email":"","orcid":"","institution":"Huaian Hospital Affiliated to Yangzhou University (The Fifth People’s Hospital of Huaian)","correspondingAuthor":false,"prefix":"","firstName":"Yahui","middleName":"","lastName":"Chen","suffix":""}],"badges":[],"createdAt":"2025-01-08 12:08:23","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5788878/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5788878/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":74960934,"identity":"7f26143a-80db-451b-b620-849c80bf479c","added_by":"auto","created_at":"2025-01-28 18:53:00","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":47165,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart. \u003cstrong\u003eAbbreviation:\u003c/strong\u003e CKD, chronic kidney disease; NHANES, National Health and Nutrition Examination Survey.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-5788878/v1/548ac605a8b20a5081ed840a.png"},{"id":74961706,"identity":"89742024-318c-4c0c-a709-d8a512d781e4","added_by":"auto","created_at":"2025-01-28 19:01:01","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":91393,"visible":true,"origin":"","legend":"\u003cp\u003eAdjusted restricted cubic spline curve for association of depressive scores with all-cause mortality (A) and cardiovascular mortality (B). Graphs show HR for all-cause mortality (A) and cardiovascular mortality (B) with solid lines indicating HR, and dashed lines indicating 95% CIs. Data were fitted by Cox proportional hazards regression model with adjusting for age, sex, ethnicity, poverty, education level, smoking status, drinking status, body mass index, systolic blood pressure, diabetes, hyperlipidemia, and hypertension. Abbreviation: HR, hazard ratio; 95% CI, 95% confidence interval.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-5788878/v1/eda661f5f67bb2620246984c.png"},{"id":74962473,"identity":"280b5100-9dea-43b7-9a51-b9f6b6368284","added_by":"auto","created_at":"2025-01-28 19:17:01","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":632575,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5788878/v1/dafcea27-cf04-4b9d-8859-71cbfe6e4e0a.pdf"},{"id":74960935,"identity":"78c17ecf-7e49-4c31-9db2-7a43cae1961e","added_by":"auto","created_at":"2025-01-28 18:53:00","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":21932,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003eBaseline characteristics according to tertiles of depressive symptom scores.\u003c/p\u003e","description":"","filename":"Table1.docx","url":"https://assets-eu.researchsquare.com/files/rs-5788878/v1/e750878da75111bed8d5f237.docx"},{"id":74960936,"identity":"1e43370d-da83-4c26-a3aa-08f4a3d03dab","added_by":"auto","created_at":"2025-01-28 18:53:00","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":18700,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTable 2.\u003c/strong\u003eAssociation of depressive symptom scores with all-cause mortality and cardiovascular mortality.\u003c/p\u003e","description":"","filename":"Table2.docx","url":"https://assets-eu.researchsquare.com/files/rs-5788878/v1/5b2b1547890495606585d307.docx"},{"id":74960939,"identity":"08da65fd-5e68-48f5-b782-23406e56b0b6","added_by":"auto","created_at":"2025-01-28 18:53:01","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":18155,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTable 3. \u003c/strong\u003eAssociation of specific depressive symptoms with incidence of all-cause mortality and cardiovascular mortality.\u003c/p\u003e","description":"","filename":"Table3.docx","url":"https://assets-eu.researchsquare.com/files/rs-5788878/v1/99fd8f78259af4a9f8b04584.docx"},{"id":74960941,"identity":"ef1fd3f3-4c6d-45af-817b-4fba7979a0ac","added_by":"auto","created_at":"2025-01-28 18:53:01","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":20989,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTable 4. \u003c/strong\u003eAssociation of depressive symptoms scores with all-cause mortality and cardiovascular mortality stratified by different factors.\u003c/p\u003e","description":"","filename":"Table4.docx","url":"https://assets-eu.researchsquare.com/files/rs-5788878/v1/524a401e07f77563b8f91021.docx"},{"id":74960940,"identity":"d4cbf65e-14c9-4641-8369-a17f93462344","added_by":"auto","created_at":"2025-01-28 18:53:01","extension":"docx","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":20624,"visible":true,"origin":"","legend":"","description":"","filename":"S.docx","url":"https://assets-eu.researchsquare.com/files/rs-5788878/v1/ef91ef22e84de1491e942e9b.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Association of both depressive symptom scores and specific depressive symptoms with all-cause mortality and cardiovascular mortality among participants with chronic kidney disease","fulltext":[{"header":"Introduction","content":"\u003cp\u003eChronic kidney disease (CKD) is a major global health burden, affecting millions of individuals and leading to significant morbidity and mortality (1). Patients with CKD often experience a range of comorbidities, including cardiovascular diseases (CVD) and mental health disorders such as depression (2, 3). Depression is characterized by persistent feelings of sadness, hopelessness, and a lack of interest or pleasure in daily activities, and it is particularly prevalent among individuals with chronic illnesses (4, 5). The interplay between depression and CKD is complex, and emerging evidence suggests that depressive symptoms may significantly impact the prognosis of CKD patients, particularly concerning all-cause and cardiovascular mortality (6-8).\u003c/p\u003e\n\u003cp\u003eThe relationship between depressive symptoms and mortality in CKD patients is multifaceted, involving biological, behavioral, and social factors. Depression can lead to physiological changes, such as increased inflammation, autonomic dysfunction, and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, which can exacerbate the progression of CKD and increase the risk of cardiovascular events (4). Furthermore, CKD patients with depression are more likely to engage in unhealthy behaviors, including poor adherence to medical treatments, smoking, physical inactivity, and poor dietary habits (9), which further elevate their risk of mortality.\u003c/p\u003e\n\u003cp\u003ePrevious studies have demonstrated that depression is associated with an increased risk of developing CVD and worsens the prognosis of individuals with existing cardiovascular conditions (8, 10). Despite these findings, the specific mechanisms through which depression influences mortality in CKD patients, particularly the contributions of individual depressive symptoms and overall depressive symptom severity, are not fully understood. Understanding the association between specific depressive symptoms and mortality in CKD patients is crucial for developing targeted interventions. Different depressive symptoms, such as insomnia, fatigue, and anhedonia, may have varying impacts on health outcomes. However, most research has focused on overall depressive symptom scores, potentially overlooking the distinct effects of individual symptoms. This gap in the literature highlights the need to investigate the unique contribution of specific symptoms to mortality risk.\u003c/p\u003e\n\u003cp\u003eThis study aims to investigate the association between both depressive symptom scores and specific depressive symptoms with all-cause and cardiovascular mortality among participants with CKD. This research has significant public health implications, emphasizing the importance of early detection and comprehensive management of depression to reduce mortality associated with CKD, which help shape future interventions aimed at mitigating the adverse health impacts of depression, ultimately enhancing the quality of life and survival of CKD patients.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy Population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study utilized data from the National Health and Nutrition Examination Survey (NHANES), a nationally representative survey conducted by the National Center for Health Statistics (NCHS). NHANES employs a complex, multistage probability sampling design to collect information on the health and nutritional status of the U.S. civilian, non-institutionalized population. For this analysis, we included participants aged 20 years and older with CKD, defined as an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m\u0026sup2; or albuminuria (urinary albumin-to-creatinine ratio \u0026ge; 30 mg/g) for 3 months or more (11).\u003c/p\u003e\n\u003cp\u003eAs shown in \u003cstrong\u003eFigure 1\u003c/strong\u003e, a total of 24678 participants aged 18 years or older were included from four cycles of the NHANES from 2007 to 2014 years, of which 4138 participants have CKD at baseline. Additionally, of the remaining 4138 participants, 493 participants were excluded due to missing values of depressive symptom scores. After further excluding 664 participants at baseline with missing values of the covariates, 2981 participants were finally enrolled. All-cause mortality was 31.26% (932/2981), and cardiovascular mortality was 11.14% (332/2981).\u003c/p\u003e\n\u003cp\u003eAll data in the NHANES database are publicly available and free of charge. Importantly, the NHANES protocols were approved by the NCHS Research Ethics Review Board, and written informed consent was obtained from all participants. The study was conducted in accordance with the Declaration of Helsinki. Each participant signed an informed consent. Data for the present study were derived from the NHANES database, so additional ethical approval was not required.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssessment of depressive symptoms\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDepressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9), a self-reported instrument for depression on a scale from 0 (not at all) to 3 (nearly every day). The total PHQ-9 score ranges from 0 to 27, with higher scores indicating greater severity of depressive symptoms. PHQ-9 is composed of 9 items: (1) have little interest in doing things; (2) feeling down, depressed, or hopeless; (3) trouble sleeping or sleeping too much; (4) feeling tired or having little energy; (5) poor appetite or overeating; (6) feeling bad about yourself; (7) trouble concentrating on things; (8) moving or speaking slowly or too fast; (9) thought you would be better off dead.\u0026nbsp;To analyze the association between depressive symptom scores and mortality, participants were categorized into three groups based on tertiles of PHQ-9 scores. Additionally, the presence of specific depressive symptoms was analyzed individually.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOutcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMortality data were obtained from the NHANES Linked Mortality File, which links NHANES participant data with the National Death Index (NDI) records (https://www.cdc.gov/nchs/data-linkage/mortality-public.htm#). The primary outcomes of the present study were all-cause mortality and cardiovascular mortality. All-cause death was ascribed to death from any cause. CVD death was defined using the International Classification of Diseases, Tenth Revision, including death of heart disease (ICD-10 codes: I00-I09, I11, I13, and I20-I51) or death of cerebrovascular disease (ICD-10 codes: I60-I69) (12).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCovariates\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCovariates included demographic variables (age, sex, ethnicity, poverty, and education level), lifestyle factors (smoking status, alcohol consumption), clinical measurements (body mass index (BMI), waist, systolic blood pressure (SBP), diastolic blood pressure (DBP), and comorbidities (history of diabetes, hypertension, and hyperlipidemia). Hypertension was defined as meeting one of the following criteria: (1) a self-reported history of hypertension; (2) SBP\u0026ge; 140 mmHg or DBP\u0026ge; 90 mmHg measured at baseline; (3) taking antihypertensive medication (13). Diabetes was characterized by hemoglobin \u0026ge; 6.5% or fasting blood glucose \u0026ge; 7.0 mmol/L, a self-reported history of diabetes, or being on anti-diabetic medication (14). Hyperlipidemia was described as one of the following conditions: (1) low-density lipoprotein cholesterol \u0026ge; 130 mg/dL; (2) high-density lipoprotein cholesterol \u0026lt; 40 mg/dL (male) or \u0026lt; 50 mg/dL (female); (3) total cholesterol \u0026ge; 200 mg/dL; (4) triglycerides \u0026ge; 150 mg/dL; (5) use of cholesterol-lowering drugs (15).\u0026nbsp;Detailed data can be found at https://www.cdc.gov/nchs/nhanes/.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe NHANES sampling weights, strata, and primary sampling units were incorporated into all analyses to account for the complex survey design and to produce nationally representative estimates. Descriptive statistics based on the tertiles of depressive symptom scores (Q1: 0-1 scores, Q2: 1-4 scores, and Q3: 4-27 scores) were used to summarize the characteristics of the study population. Continuous variables are expressed as mean \u0026plusmn; standard deviation (SD), and the T test and Kruskal-Wallis test were used for group comparison. Categorical variables were expressed as percentages, and the \u003cem\u003eX\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e test was used for comparison between groups.\u003c/p\u003e\n\u003cp\u003eCox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of both depressive symptom scores and specific depressive symptoms with all-cause and CVD mortality. No variables were adjusted in the crude model. Age, sex, and ethnicity were adjusted in Model 1. Age, sex, ethnicity, poverty, education level, smoking status, drinking status, BMI, SBP, diabetes, hyperlipidemia, and hypertension were adjusted in Model 2. Meanwhile, the dose-response relationship of depressive symptom scores with all-cause and CVD mortality was assessed by restricted cubic spline (RCS) plots. In addition, subgroups based on age (\u0026le;65 years old/\u0026gt;65 years old), sex (Male/Female), ethnicity (White/Black/Mexican/and Other), education level (\u0026lt;High school diploma/High school diploma/\u0026gt;High school diploma), BMI (\u0026le;30kg/m\u003csup\u003e2\u003c/sup\u003e/\u0026gt;30 kg/m\u003csup\u003e2\u003c/sup\u003e), smoking status (Never/Former/Current), drinking status (Never/Former/Current), diabetes (No/Yes), hypertension (No/Yes), and hyperlipidemia (No/Yes), were performed to further analyze the association of depressive symptoms scores with all-cause mortality and cardiovascular mortality. Sensitivity analyses were conducted to assess the robustness of the findings: participants who died within 2 years of follow-up were excluded to reduce the possibility of reverse causality (16).\u003c/p\u003e\n\u003cp\u003eAll statistical analyses were performed using R studio 4.4.0 version, and a two-sided p-value of less than 0.05 was considered statistically significant, and NHANES sample weights were taken into account when combining and analyzing data.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe characteristics of the study population\u0026nbsp;in accordance with the tertiles of depressive symptom scores (Q1: 0-1 scores, Q2: 1-4 scores, and Q3: 4-27 scores) were summarized in \u003cstrong\u003eTable 1\u003c/strong\u003e. A significant difference was found in the comparison of other baseline characteristics based on the tertiles of depressive symptom scores, except for ethnicity, SBP, and hyperlipidemia. Specifically, CKD participants with high depressive symptom scores were younger (Q3: 59.84 vs. Q2: 62.05 vs. Q1: 63.64, \u003cem\u003eP\u003c/em\u003e-value \u0026lt;0.001) and had a higher proportion of female participants (Q3: 59.98% vs. Q2: 57.20% vs. Q1: 43.96%, \u003cem\u003eP\u003c/em\u003e-value \u0026lt;0.001).\u003c/p\u003e\n\u003cp\u003eAfter an average follow-up of 92 months, a total of 932 deaths were recorded, of which 332 were CVD deaths. The RCS plot showed a linear relationship between the total depressive symptom scores and all-cause (nonlinear \u003cem\u003eP\u003c/em\u003e-value = 0.346) and CVD mortality (nonlinear \u003cem\u003eP\u003c/em\u003e-value = 0.177) (\u003cstrong\u003eFigure 2\u003c/strong\u003e). As shown in \u003cstrong\u003eTable 2,\u003c/strong\u003e models 1, 2, and 3 analyzed the association of depressive symptom scores with all-cause and CVD mortality. After full adjustment for potential confounders (Model 3), every 1-point increase in depressive symptom score was associated with a 4% and 5.4% increase in all-cause (HR, 1.040; 95% CI, 1.020-1.060; \u003cem\u003eP\u003c/em\u003e-value \u0026lt;0.001) and CVD mortality (HR, 1.054; 95% CI, 1.027-1.081; \u003cem\u003eP\u003c/em\u003e-value \u0026lt;0.001), respectively, in CKD participants. Participants were divided into three groups based on the tertiles of the total PHQ-9 score. Model 3 showed that participants in the Q3 group had a significantly higher incidence of all-cause mortality (HR, 1.418; 95% CI, 1.144-1.759; \u003cem\u003eP\u003c/em\u003e-value = 0.001) compared to the reference group (Q1). Similar results were found for CVD mortality (HR, 1.613; 95% CI, 1.244-2.091; \u003cem\u003eP\u003c/em\u003e-value \u0026lt;0.001).\u003c/p\u003e\n\u003cp\u003eThe association of specific depressive symptoms with all-cause and CVD mortality is shown in \u003cstrong\u003eTable 3\u003c/strong\u003e. 6 items in the PHQ-9 were independently associated with all-cause mortality: Uninterested in things (HR, 1.257; 95% CI, 1.137-1.389; \u003cem\u003eP\u003c/em\u003e-value \u0026lt;0.001), Feeling down (HR, 1.131; 95% CI, 1.015-1.261; \u003cem\u003eP\u003c/em\u003e-value =0.026), Tiredness (HR, 1.251; 95% CI, 1.149-1.362; \u003cem\u003eP\u003c/em\u003e-value \u0026lt;0.001), Change of appetite (HR, 1.129; 95% CI, 1.033-1.234; \u003cem\u003eP\u003c/em\u003e-value =0.007), Change in speed of action (HR, 1.174; 95% CI, 1.018-1.353; \u003cem\u003eP\u003c/em\u003e-value =0.027), Suicidal ideation (HR, 1.411; 95% CI, 1.064-1.870; \u003cem\u003eP\u003c/em\u003e-value =0.017). Similarly, 3-items were significantly associated with CVD mortality: Uninterested in things (HR, 1.226; 95% CI, 1.060-1.418; \u003cem\u003eP\u003c/em\u003e-value = 0.006), Feeling down (HR, 1.278; 95% CI, 1.085-1.504; \u003cem\u003eP\u003c/em\u003e-value = 0.003), and Tiredness (HR, 1.357; 95% CI, 1.208-1.525; \u003cem\u003eP\u003c/em\u003e-value \u0026lt;0.001).\u003c/p\u003e\n\u003cp\u003eThe stratified Cox proportional risk regression analyses based on age (≤65 years old/\u0026gt;65 years old), sex (Male/Female), ethnicity (White/Black/Mexican/and Other), education level (\u0026lt;High school diploma/High school diploma/\u0026gt;High school diploma), BMI (≤30kg/m2/\u0026gt;30 kg/m2), smoking status (Never/Former/Current), drinking status (Never/Former/Current), diabetes (No/Yes), hypertension (No/Yes), and hyperlipidemia (No/Yes) were performed to investigate whether the associations between depressive symptom scores and mortality were influenced by potential confounding factors, and the results found that there was no significant interaction between depressive symptom scores and all-cause mortality in any subgroup (all \u003cem\u003eP\u003c/em\u003e-values for interaction \u0026gt; 0.05). Similar results also appeared in the relationship between depressive symptom scores and CVD mortality, and the details are shown in \u003cstrong\u003eTable 4\u003c/strong\u003e. In addition, sensitivity analysis was performed after excluding participants who died within 2 years of follow-up. After fully adjusting for potential confounders (Model 3), higher depressive symptom scores still increased all-cause (HR,\u0026nbsp;1.030; 95% CI,\u0026nbsp;1.010-1.051; \u003cem\u003eP\u003c/em\u003e-value =0.004) and CVD mortality (HR,\u0026nbsp;1.046; 95% CI,\u0026nbsp;1.014-1.078; \u003cem\u003eP\u003c/em\u003e value =0.004) in a subgroup of 2841 participants. Additionally, 3-items in the PHQ-9 were independently associated with all-cause mortality: Uninterested in things (HR, 1.223; 95% CI, 1.091-1.370; \u003cem\u003eP\u003c/em\u003e-value \u0026lt;0.001), Tiredness (HR, 1.221; 95% CI, 1.117-1.334; \u003cem\u003eP\u003c/em\u003e-value \u0026lt;0.001), and Change in speed of action (HR, 1.138; 95% CI, 1.000-1.294; \u003cem\u003eP\u003c/em\u003e-value = 0.050). Similarly, 3-items were significantly associated with CVD mortality: Uninterested in things (HR, 1.196; 95% CI, 1.013-1.412; \u003cem\u003eP\u003c/em\u003e-value = 0.035), Feeling down (HR, 1.240; 95% CI, 1.021-1.506; \u003cem\u003eP\u003c/em\u003e-value = 0.030), Tiredness (HR, 1.312; 95% CI, 1.143-1.505; \u003cem\u003eP\u003c/em\u003e-value \u0026lt;0.001).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study investigated the associations of both depressive symptom scores and specific depressive symptoms with all-cause and CVD mortality in participants with CKD. The results showed that higher depressive symptom scores were significantly associated with all-cause and CVD mortality, and every 1-point increase in depressive symptom score was associated with a 4% and 5.4% increase in all-cause (HR, 1.040; 95% CI, 1.020-1.060; \u003cem\u003eP\u003c/em\u003e-value \u0026lt;0.001) and CVD mortality (HR, 1.054; 95% CI, 1.027-1.081; \u003cem\u003eP\u003c/em\u003e-value \u0026lt;0.001). Additionally, six specific depressive symptoms in the PHQ-9 (Uninterested in things, Feeling down, Tiredness, Change of appetite, Change in speed of action, and Suicidal ideation) were significantly associated with all-cause mortality, and three specific depressive symptoms (Uninterested in things, Feeling down, and Tiredness) were significantly associated with CVD mortality.\u003c/p\u003e\n\u003cp\u003eOur findings further emphasize the importance of screening and managing depressive symptoms in CKD patients. CKD patients are vulnerable to mental health problems due to their complex disease and multiple comorbidities (3, 17). Depression not only increases patients' distress but also may accelerate disease progression and increase death risk through adverse physiological mechanisms (such as inflammatory response, reduced heart rate variability, and lifestyle changes) (18-20). The results of this study may be explained by the following mechanisms: First, depressive symptoms may adversely affect the cardiovascular system by activating chronic inflammatory responses and increasing oxidative stress levels (21, 22). Second, patients with depression are more likely to engage in unhealthy behaviors, such as smoking, drinking, and lack of exercise, which increase the risk of cardiovascular disease (23-25). Finally, depressive symptoms may affect patients' medication compliance and treatment management, further worsening the prognosis of CKD patients (26).\u003c/p\u003e\n\u003cp\u003ePrevious studies have confirmed that depression can increase the risk of death in CKD patients. A meta-analysis conducted by Palmer et al. showed that depression can significantly increase the risk of all-cause mortality (RR, 1.59; 95% CI, 1.35-1.87) (27). Similarly, a study conducted by Krittanawong et al. also found that depression not only increases the risk of all-cause mortality (HR 1.43; 95% CI, 1.27-1.60), but also increases the risk of cardiovascular disease mortality (HR 1.44; 95% CI, 1.27-1.63) (28). However, previous studies only considered the impact of depression on patient prognosis. The diagnosis of depression was determined by multiple items on the depression scale (29). Therefore, most previous studies did not study the impact of specific depressive symptoms on the patients’ prognosis. Because individual depressive symptoms vary when depression occurs, treatment may vary. Therefore, the study on the association of specific depressive symptoms with the patients’ prognosis is very necessary. The results of the present study found that every 1-point increase in depressive symptom score was associated with a 4% and 5.4% increase in all-cause (HR, 1.040; 95% CI, 1.020-1.060; \u003cem\u003eP\u003c/em\u003e-value \u0026lt;0.001) and CVD mortality (HR, 1.054; 95% CI, 1.027-1.081; \u003cem\u003eP\u003c/em\u003e-value \u0026lt;0.001), respectively, in CKD participants. This is consistent with previous results. Importantly, we also found six specific depressive symptoms in the PHQ-9 (Uninterested in things, Feeling down, Tiredness, Change of appetite, Change in speed of action, and Suicidal ideation) were significantly associated with all-cause mortality, and three specific depressive symptoms (Uninterested in things, Feeling down, and Tiredness) were significantly associated with CVD mortality. This may provide new ideas for personalized treatment of patients with depression.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLimitations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAlthough this study provides valuable insights, it also has some limitations. First, the observational design precludes the determination of causality. Second, the assessment of depressive symptoms relied on self-report questionnaires, which may be subject to reporting bias. Additionally, the sample was predominantly drawn from NHANES database, limiting the generalizability of the findings.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe elevated depressive symptom scores were significantly associated with an increased risk of all-cause and CVD mortality in participants with CKD. Furthermore, 6 specific depressive symptoms (Uninterested in things, Feeling down, Tiredness, Change of appetite, Change in speed of action, and Suicidal ideation) were associated with a high risk of all-cause death. Only 3 specific depressive symptoms (uninterested in things, feeling down, and tiredness) were associated with a high risk of CVD death. These findings highlight the importance of screening and managing depressive symptoms in participants with CKD to improve their prognosis.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data supporting the findings of the present paper could be provided by contacting the corresponding author, without reservation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe project was approved by the Research Ethics Review Board of the National Center for Health Statistics (Protocol #2005-06 and #2011-17) and was in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines (https://www.cdc.gov/nchs/nhanes/irba98.htm). Informed consent has been obtained from all participants for the NHANES data. Due to the free availability of the NHANES database, the present study does not require additional ethical review and approval.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eQiao Zhou and Xinyu Tang: Investigation, Methodology, Formal analysis, Conceptualization, and Writing-Original Draft; Haibo Du and Gaojian Chen: Methodology, Software, Validation, Conceptualization, Investigation and Resources; Song Xue and Yahui Chen: Conceptualization, Supervision, and Project administration.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eFletcher BR, Damery S, Aiyegbusi OL, Anderson N, Calvert M, Cockwell P, et al. Symptom burden and health-related quality of life in chronic kidney disease: A global systematic review and meta-analysis. PLoS Med. 2022;19(4):e1003954.\u003c/li\u003e\n\u003cli\u003eSaeed D, Reza T, Shahzad MW, Karim Mandokhail A, Bakht D, Qizilbash FH, et al. Navigating the Crossroads: Understanding the Link Between Chronic Kidney Disease and Cardiovascular Health. Cureus. 2023;15(12):e51362.\u003c/li\u003e\n\u003cli\u003eAdejumo OA, Edeki IR, Sunday Oyedepo D, Falade J, Yisau OE, Ige OO, et al. Global prevalence of depression in chronic kidney disease: a systematic review and meta-analysis. J Nephrol. 2024.\u003c/li\u003e\n\u003cli\u003eSheikh-Wu SF, Gerber KS, Pinto MD, Downs CA. Mechanisms and Methods to Understand Depressive Symptoms. Issues Ment Health Nurs. 2022;43(5):434-46.\u003c/li\u003e\n\u003cli\u003ePalmer S, Vecchio M, Craig JC, Tonelli M, Johnson DW, Nicolucci A, et al. Prevalence of depression in chronic kidney disease: systematic review and meta-analysis of observational studies. Kidney Int. 2013;84(1):179-91.\u003c/li\u003e\n\u003cli\u003eYoung BA, Von Korff M, Heckbert SR, Ludman EJ, Rutter C, Lin EH, et al. Association of major depression and mortality in Stage 5 diabetic chronic kidney disease. Gen Hosp Psychiatry. 2010;32(2):119-24.\u003c/li\u003e\n\u003cli\u003eHedayati SS, Jiang W, O\u0026apos;Connor CM, Kuchibhatla M, Krishnan KR, Cuffe MS, et al. The association between depression and chronic kidney disease and mortality among patients hospitalized with congestive heart failure. Am J Kidney Dis. 2004;44(2):207-15.\u003c/li\u003e\n\u003cli\u003eNovak M, Mucsi I, Rhee CM, Streja E, Lu JL, Kalantar-Zadeh K, et al. Increased Risk of Incident Chronic Kidney Disease, Cardiovascular Disease, and Mortality in Patients With Diabetes With Comorbid Depression. Diabetes Care. 2016;39(11):1940-7.\u003c/li\u003e\n\u003cli\u003eLiu Q, Bai B, Liu F, Chen Y, Wang Y, Wang H, et al. Long-Term Trends in Risk Factor Management in Respondents with Chronic Kidney Disease in the USA. Am J Nephrol. 2022;53(8-9):614-23.\u003c/li\u003e\n\u003cli\u003eD\u0026apos;Oro A, Patel DH, Wass S, Dolber T, Nasir K, Dobre M, et al. Depression and incident cardiovascular disease among patients with chronic kidney disease. Int J Cardiol Cardiovasc Risk Prev. 2023;18:200199.\u003c/li\u003e\n\u003cli\u003eKDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int. 2021;100(4s):S1-s276.\u003c/li\u003e\n\u003cli\u003eBr\u0026auml;mer GR. International statistical classification of diseases and related health problems. Tenth revision. World health statistics quarterly Rapport trimestriel de statistiques sanitaires mondiales. 1988;41(1):32-6.\u003c/li\u003e\n\u003cli\u003eJames PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). Jama. 2014;311(5):507-20.\u003c/li\u003e\n\u003cli\u003eClassification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2020. Diabetes care. 2020;43(Suppl 1):S14-s31.\u003c/li\u003e\n\u003cli\u003eThird Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106(25):3143-421.\u003c/li\u003e\n\u003cli\u003eCao C, Friedenreich CM, Yang L. Association of daily sitting time and leisure-time physical activity with survival among US cancer survivors. JAMA oncology. 2022;8(3):395-403.\u003c/li\u003e\n\u003cli\u003eAggarwal HK, Jain D, Dabas G, Yadav RK. Prevalence of Depression, Anxiety and Insomnia in Chronic Kidney Disease Patients and their Co-Relation with the Demographic Variables. Pril (Makedon Akad Nauk Umet Odd Med Nauki). 2017;38(2):35-44.\u003c/li\u003e\n\u003cli\u003eVoorend CGN, van Buren M, Berkhout-Byrne NC, Kerckhoffs APM, van Oevelen M, Gussekloo J, et al. Apathy Symptoms, Physical and Cognitive Function, Health-Related Quality of Life, and Mortality in Older Patients With CKD: A Longitudinal Observational Study. Am J Kidney Dis. 2024;83(2):162-72.e1.\u003c/li\u003e\n\u003cli\u003ePu L, Zou Y, Wu SK, Wang F, Zhang Y, Li GS, et al. Prevalence and associated factors of depressive symptoms among chronic kidney disease patients in China: Results from the Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE). J Psychosom Res. 2020;128:109869.\u003c/li\u003e\n\u003cli\u003eChiang HH, Guo HR, Livneh H, Lu MC, Yen ML, Tsai TY. Increased risk of progression to dialysis or death in CKD patients with depressive symptoms: A prospective 3-year follow-up cohort study. J Psychosom Res. 2015;79(3):228-32.\u003c/li\u003e\n\u003cli\u003eHelman TJ, Headrick JP, Vider J, Peart JN, Stapelberg NJC. Sex-specific behavioral, neurobiological, and cardiovascular responses to chronic social stress in mice. J Neurosci Res. 2022;100(11):2004-27.\u003c/li\u003e\n\u003cli\u003eShao J, Chen Y, Gao D, Liu Y, Hu N, Yin L, et al. Ventromedial hypothalamus relays chronic stress inputs and exerts bidirectional regulation on anxiety state and related sympathetic activity. Front Cell Neurosci. 2023;17:1281919.\u003c/li\u003e\n\u003cli\u003eWang B, Fan Y, Wang X, Zeng X, Zeng S, Jia H, et al. Influence of lifestyle patterns on depression among adults with diabetes: a mediation effect of dietary inflammatory index. BMC Public Health. 2024;24(1):1779.\u003c/li\u003e\n\u003cli\u003eTang Z, Yang X, Tan W, Ke Y, Kou C, Zhang M, et al. Patterns of unhealthy lifestyle and their associations with depressive and anxiety symptoms among Chinese young adults: A latent class analysis. J Affect Disord. 2024;352:267-77.\u003c/li\u003e\n\u003cli\u003eWu W, Ma W, Yuan S, Feng A, Li L, Zheng H, et al. Associations of Unhealthy Lifestyle and Nonalcoholic Fatty Liver Disease With Cardiovascular Healthy Outcomes. J Am Heart Assoc. 2023;12(23):e031440.\u003c/li\u003e\n\u003cli\u003eEsquivel-Mendoza JA, Satyanarayana S, Safren S, Rogers BG. Examining the Longitudinal Effects of Insomnia on Depression and Medication Adherence in People Living with HIV. Behav Sleep Med. 2024:1-10.\u003c/li\u003e\n\u003cli\u003ePalmer SC, Vecchio M, Craig JC, Tonelli M, Johnson DW, Nicolucci A, et al. Association between depression and death in people with CKD: a meta-analysis of cohort studies. Am J Kidney Dis. 2013;62(3):493-505.\u003c/li\u003e\n\u003cli\u003eKrittanawong C, Maitra NS, Qadeer YK, Wang Z, Fogg S, Storch EA, et al. Association of Depression and Cardiovascular Disease. Am J Med. 2023;136(9):881-95.\u003c/li\u003e\n\u003cli\u003eKroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001;16(9):606-13.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 4 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"depressive symptom scores, specific depressive symptoms, mortality, chronic kidney disease, NHANES","lastPublishedDoi":"10.21203/rs.3.rs-5788878/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5788878/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMost research has focused on overall depressive symptom scores, potentially overlooking the distinct effects of individual symptoms. This study aims to investigate the association between both depressive symptom scores and specific depressive symptoms with all-cause and cardiovascular disease (CVD) mortality among participants with chronic kidney disease (CKD).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e2981 participants with CKD, aged 18 years old, were enrolled from NHANES from 2007 to 2014. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9). The total PHQ-9 score ranges from 0 to 27, with higher scores indicating greater severity of depressive symptoms. The primary outcomes were all-cause mortality and CVD mortality. Weighted \u003cem\u003eCOX \u003c/em\u003eregression was used to analyze association of both depressive symptom scores and specific depressive symptoms with all-cause mortality CVD mortality.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAfter an average follow-up of 92 months, 932 deaths among 2981 participants with CKD were recorded, of which 332 were CVD deaths. The RCS plot showed a linear relationship between depressive symptom scores and all-cause (nonlinear \u003cem\u003eP\u003c/em\u003e-value = 0.346) and CVD mortality (nonlinear \u003cem\u003eP\u003c/em\u003e-value = 0.177). After full adjustment for potential confounders, every 1-point increase in depressive symptom score was associated with a 4% and 5.4% increase in all-cause (HR, 1.040; 95% CI, 1.020-1.060; \u003cem\u003eP\u003c/em\u003e-value \u0026lt;0.001) and CVD mortality (HR, 1.054; 95% CI, 1.027-1.081; \u003cem\u003eP\u003c/em\u003e-value \u0026lt;0.001), respectively. Additionally, 6-items (Uninterested in things, Feeling down, Tiredness, Change of appetite, Change in speed of action, and Suicidal ideation) in the PHQ-9 were independently associated with all-cause mortality. Similarly, 3-items (Uninterested in things, Feeling down, and Tiredness) were significantly associated with CVD mortality. There was no significant interaction between depressive symptom scores and all-cause and CVD mortality in any subgroup (all \u003cem\u003eP\u003c/em\u003e-values for interaction \u0026gt; 0.05). Sensitivity analysis also further confirmed the stability of the above results.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe elevated depressive symptom scores were significantly associated with an increased risk of all-cause and CVD mortality in participants with CKD. Furthermore, 6 specific depressive symptoms were associated with a high risk of all-cause death, and 3 specific depressive symptoms were associated with a high risk of CVD death.\u003c/p\u003e","manuscriptTitle":"Association of both depressive symptom scores and specific depressive symptoms with all-cause mortality and cardiovascular mortality among participants with chronic kidney disease","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-28 18:52:54","doi":"10.21203/rs.3.rs-5788878/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5022defe-d827-4025-90ce-2dee99ddd81f","owner":[],"postedDate":"January 28th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-02-10T11:38:29+00:00","versionOfRecord":[],"versionCreatedAt":"2025-01-28 18:52:54","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5788878","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5788878","identity":"rs-5788878","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}