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

Abstract

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. nonsomatic 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. 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.

Inflammatory Determinants and Associated Morbidity in Hemodialysis Patients

“…The association observed here between IL-6 levels and the severity of depressive symptomatology confirms that alterations in immune response and inflammation contribute to the development of depressive symptoms in CKD [ 2 , 39 ]. In addition, IL-6 deteriorates the nutritional status [ 8 ], which adversely affects individuals’ mental health.…”

“…The association of high IL-6 levels with the severity of depressive symptomatology indicates that both an impaired immune response and inflammation have a role in the onset and development of depressive symptoms in CKD [ 2 , 39 ]. A meta-analysis of inflammatory biomarkers, including IL-6, in CKD subjects supported the association of such markers with the presence and severity of depressive symptoms [ 40 ].…”

“…It is a leading cause of morbidity and mortality, and this implies a high social burden [ 1 ]. CKD greatly impairs individuals’ quality life, especially in those with the most advanced stages or who are on replacement therapy [ 2 ]. Hemodialysis continues to be the most common form of replacement therapy [ 3 ]; despite its advantages, hemodialysis entails a reduced adherence to treatment, poor eating habits, and low physical activity [ 4 ], which in turn further impair the patient’s physical, functional, metabolic, social, and mental status [ 4 , 5 ].…”

Fatigue in CKD

“…In patients on maintenance hemodialysis, fatigue is associated with elevated inflammatory biomarkers such as IL-6 and high-sensitivity C-reactive protein (37,64,65). In the only study that investigated the associations of fatigue with inflammatory biomarkers in patients with CKD stages 3b–5 and major depressive disorder, fatigue ascertained by the QIDS-SR 16 depression questionnaire was associated with higher plasma high-sensitivity C-reactive protein, but not with IL-6 or prealbumin (42).…”