Dissecting Inflammation in ESRD

Abstract

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...

Association of IL-6 and a Functional Polymorphism in the IL-6 Gene with Cardiovascular Events in Patients with CKD

“…Systemic inflammation is common in these patients, particularly those with stage 5 CKD undergoing dialysis (13,14). In line with studies in the general population (5,15), IL-6, a major proinflammatory cytokine, is an established strong predictor of adverse clinical outcomes in patients with stage 5D CKD (16)(17)(18)(19)(20). However, the relationship between IL-6 and CVD at earlier CKD stages was investigated in just one relatively small study by Barreto et al (21), which was based on a limited number of CV events (just 22 events).…”

“…Furthermore, the observation of a parallel increase in IL-6 and CRP in our study is in keeping with the notion that IL-6 drives the synthesis of CRP. High IL-6 has been solidly associated with mortality in patients with stage 5 CKD who are being maintained on long-term dialysis (16)(17)(18)(19)(20).…”

Comparison Analysis of Nutritional Scores for Serial Monitoring of Nutritional Status in Hemodialysis Patients

“…Of interest, the observations that both MIS and GNRI change with time are strongly associated with longitudinal changes of IL-6 levels in our cohort. Because IL-6 is the best indicator of an inflammatory response (26), this in turn represents a powerful predictor of mortality in the maintenance hemodialysis population (27)(28)(29) and this finding can be considered as an additional strength for both scores.…”

Clinical Predictors of Decline in Nutritional Parameters over Time in ESRD

“…Several factors contribute to systemic inflammation in hemodialysis patients, such as bioincompatibility of dialyzers, dialysate contamination, vascular access-related complications, uremia, and intercurrent clinical events (2,3). Many studies reported that systemic inflammation and protein energy wasting measured once relate to mortality in ESRD patients (1,4,5). Yet few studies reported longitudinal changes in these parameters.…”