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

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.

A combined index of cardiac biomarkers as a risk factor for early cardiovascular mortality in hemodialysis patients

“…Inflammation has been recognized as an important predictor of morbidity and mortality in uremic patients and is strongly associated with cardiovascular disease [8][9][10]. In concordance with previous analyses, we found that high CRP was a risk factor in our dialysis population [13,31,32].…”

“…Modalities of recruitment and followup have been previously described [10,12,13]. Patients free of symptoms or signs of acute inflammatory or infectious diseases were included and were followed up prospectively yearly until 1 January, 2011.…”

“…However, these biomarkers are frequently elevated in ESRF even in asymptomatic patients and could be related to ischemic damages, uremic cardio myopathy and finally poor removal by extrarenal replacement therapy [5][6][7]. Furthermore, it has become clear from epidemiological studies that the proinflammatory state is strongly associated with CVD and poor prognosis in ESRF [8][9][10].…”

Cytokine Removal under Hemodiafiltration with Endogenous Reinfusion in Acute Kidney Injury Secondary to Angioimmunoblastic T-Cell Lymphoma: A Case Report

“…Among others, the Evidence Investigator biochip system (Randox) method allows the simultaneous determination of cytokines, cytokine receptors and growth factors, over five multianalyte arrays. The combination of highly specific antibodies and advanced chemistries enables multiple cytokines and growth factors to be detected simultaneously in a single sample [10]. …”

Polymorphisms of T helper cell cytokine-associated genes and survival of hemodialysis patients – a prospective study

“…Interleukin (IL)-6 and anti−/pro-inflammatory cytokine balance expressed as (IL-4 + IL-10)/IL-6 ratio were associated with an enhanced hazard ratio of cardiovascular mortality in HD patients [2]. Functional imbalance between regulatory T cells and T helper (Th) cells was also found as a contributor to the high incidence of cardiovascular events in this group [3].…”