Biochemical Associations with Depression, Anxiety, and Stress in Hemodialysis: The Role of Albumin, Calcium, and β₂-Microglobulin According to Gender

Background: Psychological distress is common in hemodialysis patients and is linked to worse clinical outcomes and lower quality of life. Nutritional and inflammatory disturbances may impact emotional well-being. Gender likely acts as a biological and psychosocial modifier. This study examined the link between depression, anxiety, and stress in hemodialysis patients and a broad range of biochemical markers, focusing on gender as a main factor. Methods: A cross-sectional study included 54 adults on maintenance hemodialysis at a hospital in Madrid, Spain. Emotional distress was measured using the DASS-21. Predialysis biochemical markers assessed were β₂-microglobulin, albumin, hemoglobin, hematocrit, phosphorus, potassium, iron, calcium, and vitamin D. Statistical analyses included Spearman correlations, HC3-robust regressions with Gender × Biomarker interactions, false discovery rate correction (q = 0.10), penalized regressions (ridge/LASSO), partial least squares structural equation modeling (PLS-SEM), and mixed-cluster analysis. Results: Women reported higher depression, anxiety, and stress, and had lower albumin, calcium, and vitamin D (p < 0.05). Depression was independently linked to female gender, lower calcium, and the Gender × β₂-microglobulin interaction (adjusted R² = 0.30). In PLS-SEM analysis, a latent global psychological distress measure was directly related to β₂-microglobulin and inversely related to albumin and calcium (R² = 0.47). Nutritional markers partly mediated the gender–distress link. Cluster analysis found three biopsychosocial profiles: metabolically balanced, catabolic–emotional, and resilient–compensated. Conclusions: Gender shapes the relationships among inflammation, nutrition, and psychological distress in hemodialysis. Including gender-sensitive emotional and nutritional assessments in nephrology nursing could foster more personalized and practical care. Findings highlight the value of gender-aware psycho-nutritional screening in dialysis.