Because atherogenesis represents a type of chronic inflammation that involves multiple elements of the inflammatoryimmune response, the simultaneous prediction power for death of C-reactive protein (CRP) and proinflammatory cytokines (IL-1, IL-6, IL-18, and TNF-␣) was tested in a cohort of 217 patients with ESRD. During the follow-up period (average 41 mo), 112 patients died. In an analysis that was adjusted for other risk factors, the relative risks for death of patients who were exposed to high levels of one, two, three, and four or more inflammation biomarkers were 1.48, 1.64, 2.76, and 3.05 times higher, respectively, than that of patients in the reference category (no inflammation). In this model, the explained variation in mortality that was attributable to overall inflammation burden (؉9.1%) was marginally higher (P ؍ 0.06) than that provided by IL-6 alone (؉6.1%). In an alternative analysis based on the Bayesian approach (receiver operating characteristic curves analysis), the prediction power of the combined inflammatory burden was identical to that provided by the sole IL-6 (0.59 ؎ 0.04 versus 0.59 ؎ 0.04). IL-6 captures almost entirely the prediction power of the overall inflammation burden in patients with ESRD. IL-6 seems to be an almost ideal indicator of the severity of inflammation. The use of this biomarker can be recommended in clinical studies that aim to better the understanding of inflammation or to modify it in this population.J Am Soc Nephrol 17: S169 -S173, 2006. doi: 10.1681/ASN.2006080910 S ubstantial evidence has been accrued that inflammation is a major factor in the high mortality of ESRD, and a variety of experimental and epidemiologic studies coherently indicate that cytokines and other inflammatory proteins are not only conducive to cardiovascular damage in experimental models but also predictive of cardiovascular events in patients with ESRD. We recently reported that IL-6, a key player in the acute-phase response, is the strongest predictor of mortality among inflammation markers and that C-reactive protein (CRP) seems to be the most suitable marker to grade the inflammation status in clinical practice on cost-effectiveness grounds (1). Whereas the predictive power of individual inflammatory proteins now is well established, the important question of whether the overall inflammation burden that is estimated by the combined measurement of these molecules provides additional prognostic information in comparison with the measurement of individual cytokines and acute-phase reactants has not been studied. The issue is relevant because the major cytokines-IL-1, IL-6, IL-18, TNF-␣, and CRP, the pentraxin that is synthesized by the liver under the stimulus of these cytokines-have pleiotropic and redundant actions at least in part reflecting complementary aspects of the inflammatory-immune process (2,3).In the present study, we therefore tested the prediction power for all-cause mortality of overall inflammation burden as estimated by the measurement of plasma concentration of CRP an...