TY - JOUR
T1 - Depression and the Effect of Sertraline on Inflammatory Biomarkers in Patients with Nondialysis CKD
AU - Gregg, L. Parker
AU - Carmody, Thomas
AU - Le, Dustin
AU - Bharadwaj, Nina
AU - Trivedi, Madhukar H.
AU - Hedayati, S. Susan
N1 - Publisher Copyright:
Copyright © 2020 by the American Society of Nephrology.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - 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 (r0.21; P0.01), fatigue (r0.22; P0.005), and poorer physical functioning (r-0.26; P0.001). 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; P0.01). 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; P0.008). 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.
AB - 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 (r0.21; P0.01), fatigue (r0.22; P0.005), and poorer physical functioning (r-0.26; P0.001). 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; P0.01). 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; P0.008). 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.
KW - C-reactive protein
KW - Chronic Kidney Disease
KW - Sertraline
KW - biomarkers
KW - chronic kidney disease
KW - depression
KW - fatigue
KW - high-sensitivity C-reactive protein
KW - inflammation
KW - interleukin-6
KW - major depressive disorder
KW - medically unexplained symptoms
KW - quality of life
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U2 - 10.34067/KID.0000062020
DO - 10.34067/KID.0000062020
M3 - Article
C2 - 35368605
AN - SCOPUS:85114794531
SN - 2641-7650
VL - 1
SP - 436
EP - 446
JO - Kidney360
JF - Kidney360
IS - 6
ER -