Potential role for interleukin‐1 in the cardio‐renal syndrome

Abstract

Chronic kidney disease (CKD) affects 30–50% of all patients with heart failure (HF) and is a potent risk factor for cardiovascular death and HF hospitalization.1 The correlation of inflammatory markers, such as C-reactive protein (CRP) and interleukin-6 (IL-6), to the severity of both kidney2 and heart3 dysfunction suggests that inflammation may contribute to the pathogenesis of CKD in HF and provides rationale for identifying potential mediators of cardio-renal inflammation. Based upon experimental animal and cellular models, we postulated that interleukin-1 (IL-1), a master regulator of the inflammatory response, could be one such mediator.4 In this post-hoc analysis of the REDHART study (n = 52),5 we compared the antiinflammatory effects of 2 weeks of anakinra 100 mg daily or placebo within the subgroup who had estimated glomerular filtration rate (eGFR) between 30 and 60 mL/min/1.73 m2 (n = 22, 42%). In brief, REDHART was a 2:1 randomized, double-blind, placebo-controlled clinical trial that compared placebo against 2 or 12 weeks of anakinra, recombinant human IL-1 receptor antagonist, in patients with systolic HF and CRP ≥ 2 mg/L who were enrolled within 2 weeks of discharge from HF hospitalization. We measured systemic inflammation using CRP, an established surrogate of IL-1 activity, myeloperoxidase (MPO) activity and neutrophil count. Continuous and categorical variables were summarized as median (interquartile range) and number (percentage), respectively. Between-group differences in baseline characteristics were compared with the Mann–Whitney U test for continuous variables and Fisher’s exact test for categorical variables. All analyses were performed in the on-treatment population of patients who completed 2 weeks of blinded treatment. Within-group treatment response changes were tested for statistical significance with the Wilcoxon signed-rank test and between-group changes with an analysis Figure 1 Effects of anakinra on C-reactive protein in patients with heart failure and chronic kidney disease. Anakinra reduced C-reactive protein in patients with heart failure and chronic kidney disease compared to placebo (P= 0.004 for between-group comparison).