Article

Fine-tuning of the prediction of mortality in hemodialysis patients by use of cytokine proteomic determination.

Biochemistry Laboratory, Lapeyronie University Hospital, 371 Avenue Doyen Gaston Giraud, F34295 Montpellier Cedex 5, France.
Clinical Journal of the American Society of Nephrology (impact factor: 5.23). 04/2008; 3(2):423-30. DOI:10.2215/CJN.02010507 pp.423-30
Source: PubMed

ABSTRACT 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.

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Keywords

12 cytokines
 
150 healthy volunteers
 
4-yr prospective study
 
anti-/proinflammatory cytokine ratio
 
clinical outcome
 
control group
 
control subjects
 
cytokine ratios
 
hazard ratio
 
hemodialysis patients
 
high-sensitivity C-reactive protein levels
 
immune dysfunction
 
Inflammation-induced atherosclerosis
 
lymphocytes T helper subsets cytokine secretion
 
noncardiovascular mortality risk
 
proinflammatory state
 
proteomic biochip system
 
stable hemodialysis
 
strong prediction
 
use cytokine proteomic determination