Osteoprotegerin in Chronic Kidney Disease: Associations with Vascular Damage and Cardiovascular Events

Abstract

Vascular injury and dysfunction contribute to cardiovascular disease, the leading cause of death in patients with chronic kidney disease (CKD). Osteoprotegerin (OPG) is a soluble member of the tumor necrosis factor receptor superfamily that has been linked to atherogenesis and endothelial dysfunction. Elevated circulating OPG levels predict future cardiovascular events (CVE). Our aim was to evaluate the determinants of circulating OPG levels, to investigate the relationship between OPG and markers of vascular damage and to test whether OPG improves risk stratification for future CVE beyond traditional and renal-specific risk factors in a CKD population. 291 patients with CKD stage 1-5 not on dialysis were included in the study. In the multivariate analysis, OPG was a significant predictor for flow-mediated dilatation, but not for carotid intima media thickness levels. During follow-up (median 36 months, IQR = 32-42 months), 87 patients had CVE. In the Cox survival analysis, OPG levels were independently associated with CVE even after adjustment for traditional and renal-specific cardiovascular risk factors. The addition of OPG to a model based on commonly used cardiovascular factors significantly improved the reclassification abilities of the model for predicting CVE. We show for the first time that OPG improves risk stratification for CVE in a non-dialysis CKD population, above and beyond a model with established traditional and renal-specific cardiovascular risk factors, including estimated glomerular filtration rate and fibroblast growth factor 23.

Osteoprotegerin and Cardiovascular Events in High‐Risk Populations: Meta‐Analysis of 19 Prospective Studies Involving 27 450 Participants

“…When reviewing the full text of the remaining 283 articles, we excluded a further 264 additional articles, leaving 19 prospective studies17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 eligible for inclusion in the meta‐analysis. Patients were recruited on the basis of having diabetes mellitus in 2 studies, kidney disease in 7 studies, preexisting heart disease in 5 studies, and recent acute coronary syndromes in 5 studies.…”

Proteomic Biomarkers Panel: New Insights in Chronic Kidney Disease

“…OPG is considered a member of the TNF receptor family, considered to be correlated with the vascular dysfunction and further with cardiovascular disease, the common problem encountered in patients with CKD. Yilmaz et al were among the first ones to mention the potential role of OPG in CKD patients stratification for cardiovascular risk, along with eGFR and FGF-23, in a CKD group not undergoing dialysis [ 41 ].…”

Machine learning analysis of serum biomarkers for cardiovascular risk assessment in chronic kidney disease

“…The glycoprotein OPG is a member of the tumour necrosis factor–related family, and part of the receptor activator of nuclear factor-kappaB (RANK)–RANK ligand (RANKL)–OPG network. Higher levels of OPG have been associated with coronary atherosclerosis in several studies [ 30 , 31 ] and in CKD, dialysis and kidney transplant patients it has been further associated with adverse events [ 32–34 ]. These associations were also found with the FG analysis, so both OPN and OPG were predictors included in the final model for cardiovascular risk.…”