IL-1β receptor antagonist reduces inflammation in hemodialysis patients

Abstract

Chronic inflammation is highly prevalent in maintenance hemodialysis (MHD) patients and associates with increased mortality. IL-1β, a pro-inflammatory cytokine, is elevated in MHD patients. A balance between IL-1β and its naturally occurring antagonist may determine the inflammatory response and its consequences in this population. We performed a pilot randomized placebo-controlled trial to evaluate the efficacy of the administration of recombinant human IL-1 receptor antagonist (IL-1ra) on biomarkers of inflammation and nutrition in MHD patients with three consecutive high sensitivity C-reactive protein (hsCRP) measurements >5 mg/L. We randomly assigned 22 patients to placebo or IL-1ra (1:1) for 4 weeks; 14 completed the trial. Patients in the IL-1ra arm had a 53% reduction in mean hsCRP compared with 1% in the placebo arm (P = 0.008), a 40% reduction in mean IL-6 levels compared with a 20% increase in the placebo arm (P = 0.03), and a 23% increase in mean prealbumin compared with 6% in the placebo arm (P = NS). In conclusion, the administration of IL-1ra in MHD patients can lower biomarkers of inflammation. Whether IL-1ra administration improves survival in this population requires additional long-term studies.

Figures

Figure 1.

Patient enrollments, randomization, and completion flow diagram.

Figure 2.

Pre- and poststudy levels of hsCRP (mg/dl) and IL-6 (pg/ml) in individual study subjects. hsCRP decreased in all but one individual in the IL-1ra arm, whereas all placebo subjects were either stable or increased their hsCRP. A similar trend was observed for IL-6 levels. *Comparison for the percent change from baseline to 4 weeks for each marker between groups was done using ANCOVA.