The relationship between IL-10 levels and cardiovascular events in patients with CKD.
OBJECTIVE
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.


METHODS
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.
Departments of Nephrology.
Mahmut Ilker
MI
Yilmaz
Department of Medicine, Division of Nephrology, Karaman State Hospital, Karaman, Turkey;
Yalcin
Y
Solak
Radiology.
Mutlu
M
Saglam
Biochemistry, and.
Tuncer
T
Cayci
Epidemiology, Gülhane School of Medicine, Ankara, Turkey;
Cengizhan
C
Acikel
Departments of Nephrology.
Hilmi Umut
HU
Unal
Departments of Nephrology.
Tayfun
T
Eyileten
Departments of Nephrology.
Yusuf
Y
Oguz
Radiology.
Sebahattin
S
Sari
Department of Medicine, Division of Renal Medicine andCentres for Molecular Medicine and Gender Medicine, Karolinska Institute, Stockholm, Sweden;
Juan Jesus
JJ
Carrero
Department of Medicine, Division of Renal Medicine and.
Peter
P
Stenvinkel
Nephrology Clinic, Dialysis and Renal Transplant Center, C.I. PARHON University Hospital and Grigore T. Popa University of Medicine, Iasi, Romania; and.
Adrian
A
Covic
Department of Medicine, Division of Nephrology, İstanbul Medeniyet University School of Medicine, Istanbul, Turkey drkanbay@yahoo.com.
Mehmet
M
Kanbay
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality / Q000503:physiopathology; D003430:Cross-Sectional Studies; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D016753:Interleukin-10 / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012039:Regional Blood Flow; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications* / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology; D012307:Risk Factors; D000683:Serum Amyloid P-Component / Q000032:analysis; D013997:Time Factors; D015854:Up-Regulation; D014664:Vasodilation; D000099153:Pentraxins
D015415:Biomarkers; D002097:C-Reactive Protein; D018836:Inflammation Mediators; D016753:Interleukin-10; D015850:Interleukin-6; D000683:Serum Amyloid P-Component; D000099153:Pentraxins; C508609:IL10 protein, human; C508600:IL6 protein, human
CKD; IL-10; cardiovascular disease; kidney disease