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IL-18 is involved in vascular injury in end-stage renal disease patients

Background. The role of interleukin (IL)-6 and IL-18 in induction of the inflammatory reaction underlying arteriosclerosis, and protective effect of an anti-inflammatory cytokine IL-10 in this process, have been confirmed by experimental and clinical observations. A systemic inflammatory reaction ma...

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Published in:Nephrology, dialysis, transplantation dialysis, transplantation, 2009-02, Vol.24 (2), p.589-596
Main Authors: Porażko, Tomasz, Kuźniar, Jakub, Kusztal, Mariusz, Kuźniar, Tomasz J., Weyde, Wacław, Kuriata-Kordek, Magdalena, Klinger, Marian
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Language:English
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Summary:Background. The role of interleukin (IL)-6 and IL-18 in induction of the inflammatory reaction underlying arteriosclerosis, and protective effect of an anti-inflammatory cytokine IL-10 in this process, have been confirmed by experimental and clinical observations. A systemic inflammatory reaction marker, C-reactive protein (CRP), is known to be associated with the induction of IL-6 and IL-18 release. The chronic inflammatory state associated with renal insufficiency contributes to acceleration of arteriosclerosis, reflected by decreased elasticity which can be measured with aortal pulse wave velocity (PWV). It is well known that chronic kidney disease (CKD) is associated with the chronic inflammatory process, as evidenced by increase in CRP and IL-6 level. It also results in a drop of fetuin-A concentration which is the calcification inhibitor negatively regulated by inflammation. Part of the derangements associated with the progressive renal failure is also the rise of activated monocyte pool, which among others produces IL-18. The aim of the present study was to evaluate, through measurements of CRP, fetuin-A and aortal pulse wave velocity (aoPWV), whether IL-6 and IL-18 affect the arterial wall of CKD patients as a part of general inflammatory process or locally, through their effect on the arterial lesion development. Materials and methods. The study was performed in a group of 102 patients with stage V CKD (73 treated with haemodialysis and 29 treated with continuous ambulatory peritoneal dialysis) (CKD5 group) and in 30 healthy controls. We measured serum high-sensitivity C-reactive protein (hs-CRP), fetuin-A, IL-6, IL-18, IL-10 (ELISA) and others (haemoglobin level, white blood cell count, serum calcium, phosphate, calcium–phosphate product, albumin, fibrinogen, cholesterol, high-density lipoprotein (HDL), triglycerides and parathormone). ECG-gated carotid and femoral artery waveforms were recorded and analysed. Results. Serum levels of hs-CRP, IL-6, IL-10 and IL-18 were higher and fetuin-A levels were lower in the CKD5 group than in controls [6.4 (0.6–22.3) mg/dl versus 2.5 (0.5–5.2) mg/dl; 8.29 pg/ml (0.96–74.48)] versus 2.78 (7.91–0.77) pg/ml; 6.5 (3.7–29.7) pg/ml versus 4.1 (3.8–7.2) pg/ml; 254.4 (468.8–47.5) pg/ml versus 89.3 (91.3–27.5) pg/ml]. The aoPWV was higher in the CKD5 group patients than in the control group (9.4 ± 1.75 m/s versus 7.76 ± 1.67 m/s; P < 0.05, respectively). Serum fetuin-A level was negatively associated with hs-CRP and
ISSN:0931-0509
1460-2385
DOI:10.1093/ndt/gfn486