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


METHODS
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-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).


CONCLUSIONS
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.
Badiou
Stéphanie
S
Biochemistry Laboratory, Lapeyronie University Hospital, 371 Avenue Doyen Gaston Giraud, F34295 Montpellier Cedex 5, France.
Cristol
Jean-Paul
JP
Jaussent
Isabelle
I
Terrier
Nathalie
N
Morena
Marion
M
Maurice
François
F
Leray-Moragues
Hélène
H
Rivory
Jean-Pierre
JP
Chalabi
Lofti
L
Delcourt
Cécile
C
Canaud
Bernard
B
Dupuy
Anne-Marie
AM
D000368:Aged; D002318:Cardiovascular Diseases / Q000097:blood* / Q000453:epidemiology*; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000401:mortality* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D040901:Proteomics; D006435:Renal Dialysis / Q000401:mortality*
D016207:Cytokines