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Background: Inflammatory biomarkers are elevated in patients with chronic kidney disease (CKD) and associated with poor outcomes. Major depressive disorder (MDD) is prevalent in CKD and associated with inflammation. No studies investigated the effect of MDD treatment on plasma inflammatory biomarkers in patients with non-dialysis CKD. Methods: In a pre-specified analysis of the randomized, double-blind CKD Antidepressant Sertraline Trial, we investigated whether treatment with sertraline vs. placebo or response to treatment would affect plasma levels of albumin, pre-albumin, interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP), measured at baseline and after 12 weeks of treatment. We also explored whether somatic vs. non-somatic depressive symptoms, measured using the Quick Inventory of Depressive Symptomatology, and quality of life subscales, measured using the Kidney Disease Quality of Life short form, were associated with baseline levels of these inflammatory biomarkers.  Results: Of the 193 participants, mean (SD) age was 58.4 (13) years and 57.5% were black, 42.0% white, and 18.1% Hispanic. Higher baseline hsCRP correlated with somatic depressive symptoms (r=0.205, P=0.010), fatigue (r=0.223, P=0.005), and poorer physical functioning (r=-0.263, P=0.001). There was no change in hsCRP in the sertraline group. HsCRP increased in placebo non-responders from baseline (median [IQR] 3.7 [1.7, 10.0] mg/L) to exit (4.9 [1.8, 8.8], P=0.011). The change from baseline to exit differed between placebo responders (-0.4 [-9.3, 0.2]) vs. non-responders (0.8 [-0.1, 3.9], P=0.008). There were no differences in changes in albumin, pre-albumin, or IL-6 from baseline in any group. Conclusions: Among patients with CKD and MDD, hsCRP correlated with somatic symptoms of depression and fatigue, but not with non-somatic symptoms. Sertraline treatment was not associated with a longitudinal change in hsCRP from baseline regardless of treatment effect on depressive symptoms, but those who failed to respond to placebo had an increase in hsCRP over time. This area deserves further investigation.

Depression and the Effect of Sertraline on Inflammatory Biomarkers in Patients with Nondialysis CKD