Elevated interleukin-12 and interleukin-18 in chronic kidney disease are not associated with arterial stiffness

Abstract

Background: Chronic kidney disease (CKD) patients are at increased risk of cardiovascular disease (CVD) mortality compared to the general population. Evidence suggests inflammation is important in the pathogenesis of CVD in CKD and inflammatory bio-markers such as C-reactive protein (CRP) and pro-atherogenic cytokines such as interleukin(IL)-6, IL-12 and IL-18 are associated with CVD-related outcomes in the general population and CKD. In the general population, IL-12 and IL-18 are implicated in the pathogenesis of atherosclerosis and are associated with acute CVD events, including mortality. Although IL-12 and IL-18 are increased in CKD, extrapolating an equally important role for these cytokines in the pathogenesis of CVD in CKD remains uncertain. In this study we aim to compare serum levels of pro-atherogenic cytokines in non-dialysis CKD patients and healthy individuals. We will also assess the relationship between these cytokines and arterial stiffness, a surrogate marker of CVD.

Methods: We performed a case-control study examining IL-12, IL-18, aortic pulse wave velocity (PWV) and augmentation index (AIx) in healthy volunteers (n=69) and stage 3-4 (n=70) and stage 5 (n=84) CKD subjects.

Results: IL12 levels were elevated in stage 3-4 (129 pg/mL; IQR 56-222) and stage 5 (125 pg/mL; IQR 45-240) CKD in comparison to healthy controls (65 pg/mL; IQR 5-229). IL18 was elevated in CKD stage 5 (617 pg/mL; IQR 468-793) in comparison to CKD stage 3-4 (417 pg/mL; IQR 288-494) and healthy controls (359 pg/mL; IQR 238-548). In multivariate analysis, only glomerular filtration rate (GFR) remained an independent predictor of IL-18 (p<0.01). Neither IL-12 nor IL-18 were associated with PWV or AIx.

Conclusion: IL-12 and IL-18 are elevated during the earlier stages of CKD but are not associated with arterial stiffness. The association with GFR suggests that IL-18 is largely dependent upon renal clearance.

Keywords: Arterial stiffness; Chronic kidney disease; Interleukin-12; Interleukin-18.