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Plasma Interleukin-6 is Associated with
Mortality in Dialysis Patients with CKD
Reference: Barreto DV, Barreto FC, Liabeuf S, et al. Plasma
interleukin-6 is independently associated with mortality in
both hemodialysis and pre-dialysis patients with
chronic renal failure. Kidney International.
2010;77:550–556.
• Cardiovascular disease (CVD) is emerging as the most
common cause of death in hemodialysis patients.
• Interleukin-6 (IL-6) system promotes inflammatory events
through the activation and proliferation of lymphocytes,
differentiation of B cells, leukocyte recruitment and the
induction of the acute phase protein response in the liver.
• Chronic inflammation is increasingly recognized as an
important issue due to its role in CVD.
• Interleukin-6 is a 26 kDa polypeptide secreted from
activated monocytes, macrophages, fibroblasts, adipocytes
and endothelial cells in response to various stimuli, such as
TNF-α, IL-1β, bacterial endotoxins, physical exercise and
oxidative stress.
• In elderly and chronic kidney disease (CKD) patients on
dialysis, plasma IL-6 levels have been shown to be a better
predictor of death than IL-1β, TNF-α, C-reactive protein
(CRP) or albumin levels.
• The distribution of IL-6 levels by CKD stage is depicted in Fig. 1.
• The IL-6 levels tended to rise as CKD progressed with the increase
becoming statistically significant at CKD stages 5 and 5D.
• Patients with plasma IL-6 >2.97 pg/mL were significantly older,
had lower diastolic blood pressure, were less likely to be treated
with statins and angiotensin-converting enzyme (ACE) or
angiotensin II type 1 receptor (ARA-2) inhibitors and were more
likely to suffer from latestage CKD.
• These patients had greater levels of CRP and triglyceride levels,
higher pulse wave velocity (PWV) values and aortic calcification
scores.
• In a multivariate linear regression analysis, only CRP, albumin and
the CKD stage were found to be independently associated with
plasma IL-6 levels.
• Results drawn from multivariate linear regression analysis showed
that only CRP, albumin and the CKD stage were found to be
independently associated with plasma IL-6 levels (see Table 1).
• During the study follow-up which included 125 subjects
who were at different stages of CKD, 38 patients died—
22 from cardiac events, 8 from infectious diseases and
8 from other causes.
• Even after adjusting the various covariates in the Cox
regression analysis, IL-6 plasma level still predicted
overall and cardiovascular mortality (see Table 2).
• When restricting the analysis to stage 2–5 predialysis
CKD patients, plasma IL-6 levels remained a predictor
of overall and cardiovascular mortality, in both crude
analysis and the Cox regression analysis (see Figs. 2A
and B).
Discussion
• Higher plasma IL-6 levels predict the risk of future
myocardial infarction among apparently healthy men
and have been associated with severe congestive heart
failure.
• It also predicts that mortality rate was greater than
three other important biomarkers of inflammation CRP,
TNF-α and albumin assayed in the study cohort.
• Studies evaluating the effect of commonly used drugs
with proven antiinflammatory activities (such as statins
and ACE/ARA-2 inhibitors) on plasma IL-6 levels and
associated outcomes in a CKD setting, particularly in
predialysis patients, are acceptable.
Conclusion
• Dialysis patients constitute a high-risk group for cardiovascular
disease.
• Predialysis CKD patients are also at a greater risk of cardiovascular
disease and the associated morbidity and mortality.
• After stratification for age, race and gender, cardiovascular
mortality is several orders of magnitude higher in dialysis patients
than in the general population.
• A clustering of risk factors renders dialysis patients especially
susceptible to CVD.
• Their morbidity and mortality can be favorably altered by
interventional measures which systematically address and modify
each individual risk factor.
• It is necessary to institute intervention during the course of
progressive renal failure, well before the onset of end-stage renal
disease and the initiation of dialysis.
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