Interleukin-16 is increased in dialysis patients but is not a cardiovascular risk factor

Abstract

Oxalate, a uremic toxin that accumulates in dialysis patients, is associated with cardiovascular disease. As oxalate crystals can activate immune cells, we tested the hypothesis that plasma oxalate would be associated with cytokine concentrations and cardiovascular outcomes in dialysis patients. In a cohort of 104 US patients with kidney failure requiring dialysis (cohort 1), we measured 21 inflammatory markers. As IL-16 was the only cytokine to correlate with oxalate, we focused further investigations on IL-16. We searched for associations between concentrations of IL-16 and mortality and cardiovascular events in the 4D cohort (1255 patients, cohort 2) and assessed further associations of IL-16 with other uremic toxins in this cohort. IL-16 levels were positively correlated with pOx concentrations (ρ = 0.39 in cohort 1, r = 0.35 in cohort 2) and were elevated in dialysis patients when compared to healthy individuals. No significant association could be found between IL-16 levels and cardiovascular events or mortality in the 4D cohort. We conclude that the cytokine IL-16 correlates with plasma oxalate concentrations and is substantially increased in patients with kidney failure on dialysis. However, no association could be detected between IL-16 concentrations and cardiovascular disease in the 4D cohort.

Keywords: Cardiovascular events; Chronic kidney disease; Cytokines oxalate; Dialysis; Interleukin-16.

Figure 1

Interleukin-16 correlates with plasma oxalate concentrations in patients with kidney failure requiring long-term dialysis (cohort 1). In 104 patients with kidney failure requiring long-term dialysis in the US (cohort 1), plasma oxalate (pOx) concentration, measured by enzymatic assay, and 21 cytokines, measured by a V-PLEX Proinflammatory Panel 1 Human, a V-PLEX Cytokine Panel 1 Human, and an Interleukin(IL)-33-ELISA, were assessed. (A) IL-16 was the only cytokine that correlated with pOx. Scatter plot with regression line (black line). Spearman`s rank test, ρ = 0.39, p < 0.001. (B) The levels of the remaining 20 cytokines did not significantly correlate with pOx concentration. Scatter plots with regression lines and results of the Spearman correlation analysis (Spearman`s rank test; ρ and p-value).