Psychonephrology

Higher levels of depression are associated with increased all-cause mortality in individuals with chronic kidney disease: A prospective study based on the NHANES database 
Jingui Zhao, Mei Wu, Li Zhang, Xue Han, Jianrong Wu, Chaoban Wang

Abstract:

Background: Chronic kidney disease (CKD) is a progressive condition associated with high mortality rates worldwide. Although depression is common in CKD patients, it is rarely addressed in current management guidelines, possibly due to limited long-term data.

Methods: We analyzed data from the National Health and Nutrition Examination Survey and the National Death Index from 2005 to 2020. CKD patients with complete data on mortality and covariate data were included. Depression was assessed using the PHQ-9 questionnaire, categorizing participants into four groups: four levels (G1 = 0, G2 = 1-3, G3 = 4-9, G4 ≥ 10). A Cox regression model evaluated the relationship between depression levels and all-cause mortality.

Results: Among 4438 CKD patients (mean age 58.28 years, 48 % male), and a dose-response relationship was observed, with increasing depression severity associated with progressively higher mortality risk. After adjusting for key prognostic indicators of CKD, the Cox regression model demonstrated that the high depression group (G4) exhibited a significantly higher risk of death compared to the no depression group (G1) (model 3-G4: HR = 1.69 (1.33, 2.14), P < 0.001). Subgroup analyses further revealed consistent trends across demographics.

Conclusion: Depression is an independent predictor of increased mortality in CKD patients. Even mild depression can adversely affect survival. Identifying and treating depression in CKD patients may improve prognosis, highlighting the need for further research into this relationship.

 Annotation

The finding:  This prospective cohort analysis used data from the National Health and Nutrition Examination Survey and the National Death Index (2005–2020) to investigate whether depression severity predicts all-cause mortality in 4,438 U.S. adults with CKD. Depression was measured using the PHQ-9 and categorized into four severity groups (none, minimal, mild, and moderate to severe). Cox regression models demonstrated a dose–response association between increasing depression severity and higher mortality risk. After adjustment for demographic and key clinical covariates, patients with mild depressive symptoms had a 42% higher risk of all-cause mortality compared with those without depressive symptoms (HR = 1.42, 95% CI 1.18–1.71, p < 0.001), while those in the highest depression severity category had a 69% higher risk (HR = 1.69, 95% CI 1.33–2.14, p < 0.001). Subgroup analyses showed that this association was largely consistent across age, sex, racial/ethnic groups, and other demographic strata, suggesting a generalizable link between depression and mortality in CKD.

 Strength and weaknesses: The study leveraged a large, nationally representative sample, used a validated depression instrument (PHQ‑9), and employed long-term follow-up through linkage to the National Death Index, enhancing the reliability and generalizability of its findings. In terms of limitations, its observational design limited causal inference and may have been influenced by confounders such as past or current depression treatment, socioeconomic status, CKD progression, and access to and engagement with nephrology care. Additionally, depression and CKD status were each measured at a single time point, which may not have fully captured changes in severity over follow-up. Moreover, only all-cause mortality was assessed, limiting insight into specific causes of death. The study may have also been affected by survivor bias, as individuals with severe CKD or severe depression who died before the survey period were not included.

Relevance:  Prior research has shown that depression is common in CKD and is associated with poorer quality of life, faster progression to end-stage kidney disease, and increased cardiovascular morbidity. This study adds to the literature by demonstrating that depression severity is an independent predictor of mortality in patients with CKD, underscoring its relevance to C-L psychiatry. These findings reinforce the critical role of proactive psychiatric assessment and intervention within multidisciplinary medical care. Notably, because even mild depressive symptoms were associated with increased mortality risk, early screening and a lower threshold for treatment, through psychotherapy, non-pharmacologic interventions, pharmacotherapy, or a combination, may be warranted in this population.

Association of depression with all-cause and cardiovascular mortality among maintenance hemodialysis patients in China: a retrospective cohort study 
Shuang Zhang, Xue-Na Wang, Qi-Jun Wu, Ping Xiao, Zhi-Hong Wang, Yan Lu, Hong Liu, Shu-Xin Liu

Abstract:

Background: Depression is not uncommon among patients with end-stage renal disease being treated by hemodialysis (HD). However, the relationship between depression and mortality is inconclusive. This study aims to investigate the above relationship in maintenance hemodialysis (MHD) patients.

Methods: We conducted a retrospective cohort study involving 746 adults who were treated with long-term HD within a single dialysis center. Depression was assessed with the self-reported Patient Health Questionnaire-9 (PHQ-9). Kaplan-Meier survival analysis, multivariable Cox regression models, restricted cubic splines, subgroup and sensitivity analyses were used to assess the relationship between depression and mortality risks.

Results: Among 746 patients (median follow-up: 30.47 months), 211 deaths (28.28 %) occurred, including 149 (19.97 %) cardiovascular deaths. Compared to the non-depression group, the depression was positively associated with all-cause mortality (HR = 1.34, 95 % = 1.01-1.77) and cardiovascular mortality (HR = 1.55, 95 % = 1.11-2.17) after multivariate adjustments. Similarly, we detected a significant positive association when PHQ-9 score was a continuous variable. Besides, the risk of all-cause and cardiovascular mortality in MHD patients increased by 13 % (HR = 1.13, 95 %CI = 1.00-1.27) and by 19 % (HR = 1.19, 95 %CI = 1.03-1.36) for each standard deviation increase in PHQ-9 score, respectively. The findings were robust in all the subgroup and sensitivity analyses. Kaplan-Meier analysis revealed significantly lower cumulative survival in the depression group compared to the non-depression group (p < 0.05). Furthermore, a positive linear dose-response relationship was observed between PHQ-9 scores and the risk of all-cause and cardiovascular mortality (pnon-linearity > 0.05).

Conclusions: Depression is a heterogeneous disorder and may be associated with increased mortality for MHD patients. Future research needs to assess whether early identification and treatment of depression may help to improve quality of life and survival in MHD patients.

Annotation

The finding: In this single center cohort study, an association between depression (ascertained by PHQ-9 score >/= 5 and overall PHQ-9 score) and mortality (all-cause and cardiovascular mortality) for 746 individuals receiving maintenance hemodialysis was demonstrated (all cause: HR = 1.34, 95% CI = 1.01,1.77; cardiovascular: HR = 1.55, 95% CI = 1.11, 2.17), while controlling for a number of potential socioeconomic and medical confounders. The association was robust to a number of sensitivity analyses, including a) exclusion of deaths <6 months after study start and b) adjusting the depression definition to a PHQ-9 cut point of 10 and 15. Overall 211 deaths were recorded, of which 149 were cardiovascular in nature, and a dose-response relationship was observed between PHQ-9 score and mortality (per standard deviation increment in PHQ-9 score: HR = 1.13, 95% CI = 1.00,1.27).

Strength and weaknesses: Due to the retrospective study design, causality cannot be determined. Due to the single-center design, the broader applicability of the findings cannot be assured, though the baseline characteristics are provided and primarily mimic those in the larger hemodialysis population. Strengths include a robust study design, a relatively large cohort size, with a well-designed analytical approach.

Relevance: Individuals receiving maintenance hemodialysis are at elevated risk of mortality, especially cardiovascular mortality, relative to those not receiving hemodialysis, with the 5-year survival rate estimated at 35-40%. Identifying factors associated with survival is of key importance for clinicians caring for individuals receiving hemodialysis, including CL Psychiatrists, so that interventions targeting these factors can be prioritized.