Inflammation modifies the association of osteoprotegerin with mortality in chronic kidney disease

Abstract

Background: The production and expression of osteoprotegerin (OPG), a bone regulating protein, is regulated by inflammatory cytokines.

Methods: As clinical and experimental studies have implicated OPG in atherogenesis, we investigated serum OPG in relation to inflammation, endothelial dysfunction and oxidative stress markers in 265 chronic kidney disease (CKD) stage 5 patients. Cardiovascular disease (CVD), carotid plaques (n=69) and mortality (5 years) in relation to OPG were also analyzed, and the impact of inflammation on the association of OPG with mortality was evaluated.

Results: OPG correlated positively with circulating surrogate markers of inflammatory, endothelial dysfunction and oxidative stress. Patients with clinical CVD or carotid plaques had higher concentrations of OPG than their respective counterparts. Increased OPG levels per se were related to higher cardiovascular and all-cause mortality even after adjustment for age, sex, C-reactive protein, diabetes mellitus and baseline CVD. Moreover, the presence of inflammation further and independently aggravated the hazard ratios (HR) for both cardiovascular (HR=2.8; 95% confidence interval [95% CI], 1.3-6.4; p=0.01) and all-cause (HR=2.5; 95% CI, 1.4-4.5; p<0.01) mortality.

Conclusions: Elevated OPG levels are associated with surrogate markers of inflammation, endothelial dysfunction, oxidative stress and CVD in CKD patients. Moreover, inflammation and OPG levels seem to have additive effects on survival.