Inflammation is implicated in the pathogenesis of cardiovascular disease and protein-energy wasting, which are important contributors to morbidity and mortality of patients with end stage kidney disease. It has been postulated that suppressing inflammation with anti-cytokine therapy may improve inflammation and related outcomes.
ACTION, a parallel group, double-blind, randomized placebo-controlled pilot trial, evaluated the efficacy, safety, and tolerability of anakinra in hemodialysis patients (1). Eighty patients were randomized to receive anakinra or placebo via their hemodialysis circuit, three times weekly for 24 weeks and then followed for an additional 24 weeks. Highly sensitive C-reactive protein (hsCRP), interleukin (IL)-6, IL-10, IL-1β, tumor necrosis factor-α, and white cell count were collected pre-dialysis at two screening visits and at follow-up visits every 4 weeks (1). Anakinra was well tolerated, with similar adverse events in both arms. Notably, there were no infectious complications, despite the fact that anakinra can reduce the ability to control infections and can cause leukopenia. IL-6 levels decreased significantly in the treatment group with no change in the placebo arm. There was also a greater reduction in hsCRP in the anakinra group; however, the decrease was not statistically significant. Because of the short duration of the study, hard endpoints, such as cardiovascular events and changes in weight, were not examined. The ACTION trial suggests that the use of anakinra to reduce inflammation in patients treated by maintenance hemodialysis is safe, well tolerated, and feasible. The small study size and uniform age distribution limit generalizability of the results. None of the enrolled patients received dialysis via catheters, which may contribute to inflammation; thus, further study is necessary.
The findings of the ACTION trial provide a new outlook into the potential for treatment of inflammation with anti-cytokine therapy in patients receiving maintenance hemodialysis. Further study is needed to assess how these findings translate into the clinical setting with expanded endpoints, including cardiovascular disease, infection, and protein energy wasting and their associated morbidity and mortality.
Reference
Dember LM, et al. A randomized controlled pilot trial of anakinra for hemodialysis inflammation. Kidney Int [published online ahead of print July 19, 2022]. doi: 10.1016/j.kint.2022.06.022; https://doi.org/10.1016/j.kint.2022.06.022
