A Systematic Review and Meta-Analysis of Depression and Protein–Energy Wasting in Kidney Disease

Introduction: Depression comorbid with chronic disease may be mediated by inflammation. We sought to characterize relationships between inflammatory biomarkers and depressive symptoms in patients with chronic kidney disease and end-stage kidney disease. Methods: A systematic literature search was conducted by 2 authors up to March 19, 2019, for studies of patients with chronic kidney disease or end-stage kidney disease evaluating circulating inflammatory biomarkers associated with depression of chronic disease: albumin, C-reactive protein (CRP), high-sensitivity CRP, interleukin-6 (IL-6), tumor necrosis factor-α, and interleukin-1. Standardized mean differences in biomarkers between individuals with and without depression were computed and analyzed using mixed effects models. Correlations between biomarkers and the severity of depressive symptoms were computed. Results: Thirty-four studies (5652 participants) compared biomarkers between depressed and nondepressed individuals. Individuals with depression had lower albumin levels (standardized mean difference, −0.37; 95% confidence interval [CI], −0.61 to −0.13), higher CRP levels (standardized mean difference, 0.76; 95% CI, 0.16–1.37), and higher IL-6 levels (standardized mean difference, 0.42; 95% CI, 0.21–0.63). Studies were heterogeneous for albumin, CRP, high-sensitivity CRP, and tumor necrosis factor-α. Twenty-three studies (3047 participants) investigated correlations between biomarkers and depressive symptoms. The severity of depressive symptoms correlated with albumin (Z = −0.25; 95% CI, −0.36 to −0.14), high-sensitivity CRP (Z = 0.28; 95% CI, 0.13–0.43), and IL-6 (Z = 0.34; 95% CI, 0.18–0.49). There was heterogeneity across studies of IL-6. Only 6 studies (321 participants) investigated the effect of antidepressant treatment on inflammatory biomarkers, which was insufficient to combine in meta-analysis. Conclusion: Lower albumin and higher IL-6 were associated with both the presence and severity of depression, CRP with the presence of depression, and high-sensitivity CRP with the severity of depressive symptoms. The effect of interventions to lower inflammation in patients with kidney disease and depression deserves investigation.