We found that the proportion of MHD patients with depressive symptoms was 36.7%, which is similar to the finding of Palmer et al. [2]. We also evaluated the prognostic value of NLR for depressive symptoms risk factors in MHD patients and revealed that NLR was an independent predictor of depressive symptoms in MHD patients.

NLR has been shown to predict death, myocardial infarction, and coronary artery disease [18,19,20]. Furthermore, numerous epidemiological studies have shown that chronic low-grade inflammation, as measured by NLR, is linked to risk factors such as diabetes mellitus, hypertension, metabolic syndrome, obesity, and hyperlipidemia [21]. In addition, an increased NLR level has been reported to be associated with preoperative depression in patients with gastric cancer [22] and post-stroke depression [13]. NLR may also be a trait marker for suicidal vulnerability in patients with major depression [23]. Gonca et al. [12] found that the NLR level of adolescents with depression is significantly higher than that of healthy controls and is positively correlated with the severity of depression.. In a recent meta-analysis, Mazza et al. [13] found higher NLR levels in patients with major depressive disorder than in healthy controls. In the present study, we found that NLR was an independent predictor of depressive symptoms in MHD patients, which offers new insights and research directions in this area.

NLR is a biomarker that integrates two subtypes of white blood cells (WBCs) that represent two inversely related immune pathways. It is easily calculated using differential WBC counts and is a more stable measurement than individual WBC counts [24]. The association between NLR and depressive symptoms may be explained by several mechanisms. It is well established that both neutrophilia and lymphocytopenia are typical inflammatory responses to various stressful insults. Lymphocytopenia has been confirmed as a marker of poor nutritional condition in MHD patients [25]. Moreover, the prognostic ability of NLR in MHD patients is assumed to rely on the relationship between inflammation and nutritional status [26]. Thus, previous evidence for an association between inflammation [27] and malnutrition [28] and depression in MHD patients may explain the prognostic ability of NLR in predicting depressive symptoms in this population.

Previous studies have demonstrated the role of inflammation in the pathogenesis of depression; for example, inflammation in patients with somatic diseases increases the risk of developing depression. Patients with depression have elevated levels of peripheral and central proinflammatory cytokines, and proinflammatory agents have been shown to facilitate the progression of depressive symptoms [29]. Importantly, the activation of neutrophils can cause oxidative stress by releasing reactive oxygen species, which may contribute to the pathogenesis of depression [30]. Therefore, NLR appears to be a reliable and stable indicator of depressive symptoms in MHD patients.

During inflammation and infection, proinflammatory cytokines may affect erythrocyte maturation by interfering with erythropoietin, which leads to an increase in RDW [31, 32]. Thus, RDW is also considered an inflammatory marker. A population-based cohort study in Iran found that people with severe depressive symptoms had higher RDW than those without depressive symptoms [33]. Demircan et al. [34] reported that RDW and NLR are higher in patients with major depressive disorder than in healthy controls, but these levels decreased in patients following treatment with a selective serotonin reuptake inhibitor. This suggests that RDW and NLR levels are not only useful as biomarkers for diagnosing depression but also for evaluating treatment efficacy. In the present study, we also found that the RDW of MHD patients with mild and moderate/moderately severe depressive symptoms was higher than that of patients with no depressive symptoms. However, the multivariate logistic regression analysis revealed that RDW may not be an independent risk factor for moderate/moderately severe depressive symptoms. We speculate that anemia is a common complication in patients with CKD, especially those on dialysis, in whom the diagnostic value of RDW is not specific. Alb is a common indicator of malnutrition and inflammatory state [35]. We found that the Alb level in MHD patients with moderate/moderately severe depressive symptoms was lower than that in other groups. Moreover, PHQ-9 scores were negatively correlated with Alb level, which is consistent with the report of Huang et al. [36]. Furthermore, Gregg et al. found that low Alb level is associated with progression of depression in a meta-analysis of 34 studies, which included 5652 patients with CKD and ESRD [37]. However, whether depressive symptoms inhibit appetite and lead to malnutrition remains unclear, and the specific mechanisms involved require further study.

Notably, we found that hsCRP was not associated with the PHQ-9 score, which was similar to the report by Joseph et al. who also found no correlation between high hsCRP and increased PHQ-9 score (≥ 10). Given the crossover in symptoms between depression and advanced CKD, it is likely that patients with a more advanced illness who have higher hsCRP values would self-report more depressive symptoms [38]. However, because of missing hsCRP data in 33 patients, we were not able to ascertain the relationship between hsCRP and PHQ-9 score.

Our study has several limitations. First, this was an observational study; therefore, causal relationships between the risk factors and the outcome variable could not be explored. Second, because of the nature of single-center cross-sectional study designs, our study had regional and time limitations. Thus, the results may not accurately reflect the general population. Third, the PHQ-9 is a self-report scale, which assesses depressive symptoms rather than clinical depression. Finally, although we included demographic and laboratory data, we did not assess the impact of socioeconomic and psychological factors.

In summary, we demonstrated that there is a high prevalence of depressive symptoms in MHD patients. NLR, which is an accessible and inexpensive measure, may be a novel biomarker for predicting the presence of depressive symptoms in MHD patients.

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