Background and objectives High serumIL-6 is amajor risk factor for cardiovascular disease (CVD) in the general population. This cytokine is substantially increased in patientswith CKD, but it is still unknownwhether the link between IL-6 and CVD in CKD is causal in nature. Design, setting, participants, & measurements In a cohort of 755 patientswith stages 2–5 CKD, consecutively recruited from 22 nephrology units in southern Italy, this study assessed the relationship of serum IL-6 with history of CVD, as well as with incident cardiovascular (CV) events (mean follow up6SD, 31610 months) and used the functional polymorphism (2174 G/C) in the promoter of the IL-6 gene to investigate whether the link between IL-6 and CV events is causal. Results In adjusted analyses, serum IL-6 above the median value was associated with history of CVD (P,0.001) and predicted the incidence rate of CV events (hazard ratio, 1.66; 95% confidence interval [95% CI], 1.11 to 2.49; P=0.01). Patients homozygous for the risk allele (C) of the2174G/C polymorphismhad higher levels of IL-6 than did those with other genotypes (P=0.04). Homozygous CC patients more frequently had a history of CVD (odds ratio, 2.15; 95%CI, 1.15 to 4.00; P=0.02) as well as a 87%higher rate of incident CV events (hazard ratio, 1.87; 95% CI, 1.02 to 3.44; P=0.04) compared with other genotypes. Conclusions In patients with stages 2–5 CKD, high serum IL-6 is associated with history of CVD and predicts incident CV events. The parallel relationship with history of CVD and incident CV events of the 2174 G/C polymorphismin the IL-6 gene suggests that IL-6may be causally involved in the high CV risk in this population.,
Clinical Journal of the American Society of Nephrology
Department of Internal Medicine

Spoto, B., Mattace Raso, F., Sijbrands, E., Leonardis, D., Testa, A., Pisano, A., … Zoccali, C. (2015). Association of IL-6 and a functional polymorphism in the IL-6 gene with cardiovascular events in patients with CKD. Clinical Journal of the American Society of Nephrology, 10(2), 232–240. doi:10.2215/CJN.07000714