L Parker Gregg1,2, Thomas Carmody3,4, Dustin Le5, Nina Bharadwaj6, Madhukar H Trivedi4, S Susan Hedayati1. 1. Division of Nephrology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas. 2. Renal Section, Medical Service, Veterans Affairs North Texas Health Care System, Dallas, Texas. 3. Division of Biostatistics, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas. 4. Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas. 5. Department of Medicine, University of Michigan, Ann Arbor, Michigan. 6. Tulane University, New Orleans, Louisiana.
Abstract
Background: Inflammatory biomarkers are elevated in patients with 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 nondialysis CKD. Methods: In a prespecified analysis of the randomized, double-blind CKD Antidepressant Sertraline Trial, we investigated whether treatment with sertraline versus placebo or response to treatment would affect plasma levels of albumin, prealbumin, IL-6, and high-sensitivity C-reactive protein (hsCRP), measured at baseline and after 12 weeks of treatment. We also explored whether somatic versus 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. Results: Of the 193 participants, mean age was 58.4 (SD 13) years and 58% were black, 42% were white, and 18% were Hispanic. Higher baseline hsCRP correlated with somatic depressive symptoms (r=0.21; P=0.01), fatigue (r=0.22; P=0.005), and poorer physical functioning (r=-0.26; P=0.001). There was no change in hsCRP in the sertraline group. hsCRP increased in placebo nonresponders from baseline (median, 3.7 mg/L; interquartile range [IQR], 1.7-10.0 mg/L) to exit (median, 4.9 mg/L; IQR, 1.8-8.8 mg/L; P=0.01). The change from baseline to exit differed between placebo responders (median, -0.4 mg/L; IQR, -9.3 to 0.2 mg/L) and nonresponders (median, 0.8 mg/L; IQR, -0.1 to 3.9 mg/L; P=0.008). There were no differences in changes in albumin, prealbumin, 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 nonsomatic 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. Clinical Trial registry name and registration number: CKD Antidepressant Sertraline Trial (CAST), NCT00946998.
Background: Inflammatory biomarkers are elevated in patients with 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 nondialysis CKD. Methods: In a prespecified analysis of the randomized, double-blind CKD Antidepressant Sertraline Trial, we investigated whether treatment with sertraline versus placebo or response to treatment would affect plasma levels of albumin, prealbumin, IL-6, and high-sensitivity C-reactive protein (hsCRP), measured at baseline and after 12 weeks of treatment. We also explored whether somatic versus 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. Results: Of the 193 participants, mean age was 58.4 (SD 13) years and 58% were black, 42% were white, and 18% were Hispanic. Higher baseline hsCRP correlated with somatic depressive symptoms (r=0.21; P=0.01), fatigue (r=0.22; P=0.005), and poorer physical functioning (r=-0.26; P=0.001). There was no change in hsCRP in the sertraline group. hsCRP increased in placebo nonresponders from baseline (median, 3.7 mg/L; interquartile range [IQR], 1.7-10.0 mg/L) to exit (median, 4.9 mg/L; IQR, 1.8-8.8 mg/L; P=0.01). The change from baseline to exit differed between placebo responders (median, -0.4 mg/L; IQR, -9.3 to 0.2 mg/L) and nonresponders (median, 0.8 mg/L; IQR, -0.1 to 3.9 mg/L; P=0.008). There were no differences in changes in albumin, prealbumin, 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 nonsomatic 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. Clinical Trial registry name and registration number: CKD Antidepressant Sertraline Trial (CAST), NCT00946998.
Authors: S Susan Hedayati; Abu T Minhajuddin; Masoud Afshar; Robert D Toto; Madhukar H Trivedi; A John Rush Journal: JAMA Date: 2010-05-19 Impact factor: 56.272
Authors: E Sherwood Brown; Luis Vigil; David A Khan; Joshua D M Liggin; Thomas J Carmody; A John Rush Journal: Biol Psychiatry Date: 2005-07-05 Impact factor: 13.382
Authors: S Susan Hedayati; Abu T Minhajuddin; Robert D Toto; David W Morris; A John Rush Journal: Am J Kidney Dis Date: 2009-06-03 Impact factor: 8.860
Authors: S Susan Hedayati; L Parker Gregg; Thomas Carmody; Nishank Jain; Marisa Toups; A John Rush; Robert D Toto; Madhukar H Trivedi Journal: JAMA Date: 2017-11-21 Impact factor: 56.272
Authors: Nishank Jain; Madhukar H Trivedi; A John Rush; Thomas Carmody; Benji Kurian; Robert D Toto; Ravindra Sarode; S Susan Hedayati Journal: Contemp Clin Trials Date: 2012-10-22 Impact factor: 2.226