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Dissecting Inflammation in ESRD: Do Cytokines and C-Reactive Protein Have a Complementary Prognostic Value for Mortality in Dialysis Patients?

Carmine Zoccali^*,, Giovanni Tripepi and Francesca Mallamaci^*,

^* Nephrology, Hypertension & Renal Transplantation Unit, Ospedali Riuniti, Reggio Calabria, and CNR-IBIM Clinical Epidemiology of Renal Diseases and Hypertension, Calabria, Italy

Address correspondence to: Prof. Carmine Zoccali, Nephrology, Hypertension & Renal Transplantation Unit & CNR-IBIM, Clinical Epidemiology of Renal Diseases and Hypertension, c/o Ki Point Gransial SRL, Via Filippini n. 85, 89100 Reggio Calabria, Italy. Phone: +39-0965-397010; Fax: +39-0965-26879; E-mail: carmine.zoccali{at}tin.it

Because atherogenesis represents a type of chronic inflammation that involves multiple elements of the inflammatory-immune 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.

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Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673