Association of Symptoms and Collaborative Care Intervention (TĀCcare) with Systemic Inflammation Biomarkers in End-Stage Kidney Disease.

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 end-stage kidney disease (ESKD) and the effects of a Technology Assisted stepped Collaborative Care (TĀCcare) intervention on these biomarkers.

Methods: In the TĀCcare multi-site randomized control trial, data on patient-reported symptoms were collected at baseline, 3, and 6 months. Anti-inflammatory [interleukin 1 receptor agonist (IL-1RA), IL-10], pro-inflammatory [tumor necrosis factor alpha (TNF-α), high sensitivity C-reactive protein (hs-CRP), IL-6] and regulatory [IL-2] biomarkers were assayed. Linear mixed-effects modeling was used to examine within- 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 group demonstrated reductions in IL-10 and IL-1RA over 6 months (β range=-1.22 to -0.40, p range=<0.001 to 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 to 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 pro-inflammatory biomarkers (TNF-α and hs-CRP) 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 if these biomarkers mediate the link between symptoms and disease progression.