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

• Published in: Clinical journal of the American Society of Nephrology Vol. 3; no. 2; pp. 423 - 430
• Main Authors: Badiou, Stéphanie, Cristol, Jean-Paul, Jaussent, Isabelle, Terrier, Nathalie, Morena, Marion, Maurice, François, Leray-Moragues, Hélène, Rivory, Jean-Pierre, Chalabi, Lofti, Delcourt, Cécile, Canaud, Bernard, Dupuy, Anne-Marie
• Format: Journal Article
• Language: English
• Published: United States American Society of Nephrology 01.03.2008
• Subjects: Aged; Cardiovascular Diseases - blood; Cardiovascular Diseases - epidemiology; Cytokines - blood; Dialysis; Female; Humans; Kidney Failure, Chronic - blood; Kidney Failure, Chronic - mortality; Kidney Failure, Chronic - therapy; Male; Middle Aged; Prognosis; Prospective Studies; Proteomics; Renal Dialysis - mortality
• ISSN: 1555-9041; 1555-905X
• DOI: 10.2215/CJN.02010507

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. 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. 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-gamma) 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). 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.