Association of Symptoms and Collaborative Care Intervention with Systemic Inflammation Biomarkers in ESKD.

KEY POINTS: There were no associations between biomarkers and patient-reported pain, fatigue, and depression in a large ESKD cohort at baseline. Compared with control, the Technology-Assisted stepped Collaborative Care intervention had a short-term impact on reducing inflammatory burden. Treatment modified the association between changes in symptoms and in certain proinflammatory biomarkers (TNF-α and high sensitivity C-reactive protein) over time. BACKGROUND: Patient-reported symptoms are associated with inflammation biomarkers in many chronic diseases. We examined associations of inflammation biomarkers with pain, fatigue, and depression in patients with ESKD and the effects of a Technology-Assisted stepped Collaborative Care (TĀCcare) intervention on these biomarkers. METHODS: In the TĀCcare multisite randomized control trial, data on patient-reported symptoms were collected at baseline and 3 and 6 months. Anti-inflammatory (IL-1 receptor agonist, IL-10), proinflammatory (TNF-α, high sensitivity C-reactive protein, IL-6), and regulatory (IL-2) biomarkers were assayed. Linear mixed-effects modeling was used to examine within-group and between-group differences after adjusting for age, sex, race, and comorbidities. RESULTS: Among the 160 patients (mean age 58±14 years, 55% men, 52% white), there were no significant associations between inflammation biomarkers and pain, fatigue, or depression at baseline. Both intervention and control groups demonstrated reductions in IL-10 and IL-1 receptor agonist over 6 months (β range=−1.22 to −0.40, P range=<0.001–0.02) At 3 months, the treatment group exhibited decreases in TNF-α (β=−0.22, P < 0.001) and IL-2 (β=−0.71, P < 0.001), whereas the control group showed increases in IL-6/IL-10 ratio (β=0.33, P = 0.03). At 6 months, both groups exhibited decreases in IL-2 (β range=−0.66 to −0.57, P < 0.001); the control group showed significant increases in the ratio of IL-6/IL-10 (β=0.75, P < 0.001) and decrease in TNF-α (β=−0.16, P = 0.02). Compared with controls, the treatment group demonstrated significantly decreased IL-2 at 3 months (β=−0.53, P < 0.001). Significant interaction effects of treatment were observed on the association between changes in proinflammatory biomarkers (TNF-α and high sensitivity C-reactive protein) levels and changes in symptom scores from baseline to 6 months. CONCLUSIONS: The TĀCcare intervention had a short-term impact on reducing inflammatory burden in patients with ESKD. More studies are needed to confirm our findings and to determine whether these biomarkers mediate the link between symptoms and disease progression. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT03440853.