Received May 15, 2007
Accepted on December 5, 2007

ORIGINAL ARTICLES

Fine-Tuning of the Prediction of Mortality in Hemodialysis Patients by Use of Cytokine Proteomic Determination

Stéphanie Badiou ^*, Jean-Paul Cristol ^*1, Isabelle Jaussent , Nathalie Terrier ^*, Marion Morena ^*, François Maurice , Hélène Leray-Moragues ^||, Jean-Pierre Rivory , Lofti Chalabi , Cécile Delcourt ^¶, Bernard Canaud ^||, and Anne-Marie Dupuy ^*

*CHU Montpellier, Laboratoire de Biochimie, Hôpital Lapeyronie, Université Montpellier I, INSERM, U888, Centre d’Hémodialyse Languedoc Méditerranée, and ||CHU Montpellier, Service de Néphrologie, Dialyse et Soins Intensifs, Montpellier, and ¶INSERM, U593, and Université Victor Segalen Bordeaux 2, Bordeaux, France

¹ To whom correspondence should be addressed. E-mail: jp-cristol{at}chu-montpellier.fr.

	Abstract

Background and objectives: Inflammation-induced atherosclerosis and enhanced susceptibility to infection are linked to immune dysfunction and account for an important part of mortality in hemodialysis patients. This 4-yr prospective study aimed to use cytokine proteomic determination for predicting cardiovascular and noncardiovascular mortality in hemodialysis patients.

Design, setting, participants, & measurements: Levels of 12 cytokines were measured using a proteomic biochip system in 134 patients who were on stable hemodialysis and compared with a control group of 150 healthy volunteers. Cox proportional hazards regression analysis was used to determine the relationship between cytokine and clinical outcome.

Results: A proinflammatory state characterized by decreased anti-/proinflammatory cytokine ratio was evidenced in hemodialysis patients compared with control subjects. After adjustment for age, gender, smoking, and high-sensitivity C-reactive protein levels, IL-6 and (IL-4+IL-10)/IL-6 ratio were associated with a significant and specific enhanced hazard ratio of cardiovascular mortality (hazard ratio 11.32 [95% confidence interval 2.52 to 50.90; P < 0.01] and hazard ratio 3.14 [95% confidence interval 1.20 to 8.22; P < 0.05], respectively, when comparing the third and first tertiles). It is interesting that (IL-4+IL-6+IL-10)/(IL-2+IFN-) ratio, used as a marker of lymphocytes T helper subsets cytokine secretion, was associated only with noncardiovascular mortality (hazard ratio 4.93; 95% confidence interval 1.03 to 23.65; P < 0.05).

Conclusion: Beyond the strong prediction of cardiovascular mortality by IL-6, determination of cytokine ratios can be useful to identify hemodialysis patients with increased noncardiovascular mortality risk.