Mahmut Ilker Yilmaz1, Yalcin Solak2, Mutlu Saglam3, Tuncer Cayci4, Cengizhan Acikel5, Hilmi Umut Unal1, Tayfun Eyileten1, Yusuf Oguz1, Sebahattin Sari3, Juan Jesus Carrero6, Peter Stenvinkel7, Adrian Covic8, Mehmet Kanbay9. 1. Departments of Nephrology. 2. Department of Medicine, Division of Nephrology, Karaman State Hospital, Karaman, Turkey; 3. Radiology. 4. Biochemistry, and. 5. Epidemiology, Gülhane School of Medicine, Ankara, Turkey; 6. Department of Medicine, Division of Renal Medicine andCentres for Molecular Medicine and Gender Medicine, Karolinska Institute, Stockholm, Sweden; 7. Department of Medicine, Division of Renal Medicine and. 8. Nephrology Clinic, Dialysis and Renal Transplant Center, C.I. PARHON University Hospital and Grigore T. Popa University of Medicine, Iasi, Romania; and. 9. Department of Medicine, Division of Nephrology, İstanbul Medeniyet University School of Medicine, Istanbul, Turkey drkanbay@yahoo.com.
Abstract
BACKGROUND AND OBJECTIVES: Cardiovascular disease is the leading cause of death in patients with CKD. IL-10 is considered an antiatherosclerotic cytokine. However, previous studies have failed to observe an association between IL-10 and cardiovascular disease in CKD. This study aimed to evaluate whether serum IL-10 levels were associated with the risk of cardiovascular events in CKD patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Four hundred three patients with stages 1-5 CKD were followed for a mean of 38 (range=2-42) months for fatal and nonfatal cardiovascular events. IL-10 and IL-6 were measured at baseline together with surrogates of endothelial function (flow-mediated dilatation) and proinflammatory markers (high-sensitivity C-reactive protein and pentraxin-3). The association between IL-10 and flow-mediated dilatation through linear regression analyses was evaluated. The association between IL-10 and the risk of cardiovascular events was assessed with Cox regression analysis. RESULTS: IL-10, IL-6, high-sensitivity C-reactive protein, and pentraxin-3 levels were higher among participants with lower eGFR. Both fatal (25 of 200 versus 6 of 203 patients) and combined fatal and nonfatal (106 of 200 versus 23 of 203 patients) cardiovascular events were more common in patients with IL-10 concentration above the median. Flow-mediated dilatation was significantly lower in patients with higher serum IL-10 levels, but IL-10 was not associated with flow-mediated dilatation in multivariate analysis. Kaplan-Meier survival curves showed that patients with IL-10 below the median value (<21.5 pg/ml) had higher cumulative survival compared with patients who had IL-10 levels above the median value (log-rank test, P<0.001). CONCLUSIONS: IL-10 levels increase along with the reduction of kidney function. Higher serum IL-10 levels were associated with the risk of cardiovascular events during follow-up. We speculate that higher IL-10 levels in this context signify an overall proinflammatory milieu.
BACKGROUND AND OBJECTIVES:Cardiovascular disease is the leading cause of death in patients with CKD. IL-10 is considered an antiatherosclerotic cytokine. However, previous studies have failed to observe an association between IL-10 and cardiovascular disease in CKD. This study aimed to evaluate whether serum IL-10 levels were associated with the risk of cardiovascular events in CKD patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Four hundred three patients with stages 1-5 CKD were followed for a mean of 38 (range=2-42) months for fatal and nonfatal cardiovascular events. IL-10 and IL-6 were measured at baseline together with surrogates of endothelial function (flow-mediated dilatation) and proinflammatory markers (high-sensitivity C-reactive protein and pentraxin-3). The association between IL-10 and flow-mediated dilatation through linear regression analyses was evaluated. The association between IL-10 and the risk of cardiovascular events was assessed with Cox regression analysis. RESULTS:IL-10, IL-6, high-sensitivity C-reactive protein, and pentraxin-3 levels were higher among participants with lower eGFR. Both fatal (25 of 200 versus 6 of 203 patients) and combined fatal and nonfatal (106 of 200 versus 23 of 203 patients) cardiovascular events were more common in patients with IL-10 concentration above the median. Flow-mediated dilatation was significantly lower in patients with higher serum IL-10 levels, but IL-10 was not associated with flow-mediated dilatation in multivariate analysis. Kaplan-Meier survival curves showed that patients with IL-10 below the median value (<21.5 pg/ml) had higher cumulative survival compared with patients who had IL-10 levels above the median value (log-rank test, P<0.001). CONCLUSIONS:IL-10 levels increase along with the reduction of kidney function. Higher serum IL-10 levels were associated with the risk of cardiovascular events during follow-up. We speculate that higher IL-10 levels in this context signify an overall proinflammatory milieu.
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