Serum osteoprotegerin in prevalent hemodialysis patients: associations with mortality, atherosclerosis and cardiac function

Abstract

BackgroundTo assess whether serum osteoprotegerin (OPG) and/or fetuin-A predict mortality and cardiovascular (CV) morbidity and mortality in hemodialysis patients.MethodsMulticenter, observational, prospective study that included 220 hemodialysis patients followed up for up to 6 years. Serum OPG and fetuin-A levels were measured at baseline and their possible association with clinical characteristics, CV risk biomarkers, carotid ultrasonographic findings, as well as their association with overall and CV mortality and CV events were assessed.ResultsDuring a mean follow-up of 3.22 ± 1.91 years, there were 74 deaths (33.6%) and 86 new cardiovascular events. In the Kaplan-Meier survival analysis, the highest tertile of OPG levels was associated with higher overall mortality (p = 0.005), as well as a higher, although non-significant, incidence of CV events and CV mortality. In contrast, fetuin-A levels did not predict any of these events. OPG levels were directly associated with age, the Charlson comorbidity index (CCI), prevalent cardiovascular disease, carotid intima-media thickness, adiponectin, troponin-I and brain natriuretic peptide (BNP). OPG showed a negative correlation with left ventricular ejection fraction (LVEF) and phosphate levels. In the multivariate Cox proportional hazard analysis, all-cause mortality was associated with the highest tertile of OPG (HR:1.957, p = 0.018), age (HR:1.031, p = 0.036), smoking history (HR:2.122, p = 0.005), the CCI (HR:1.254, p = 0.004), troponin-I (HR:3.894, p = 0.042), IL-18 (HR:1.061, p < 0.001) and albumin levels (HR:0.886, p < 0.001). In the bootstrapping Cox regression analysis, the best cut-off value of OPG associated with mortality was 17.69 pmol/L (95%CI: 5.1–18.02).ConclusionsOPG, but not fetuin-A levels, are independently associated with overall mortality, as well as clinical and subclinical atherosclerosis and cardiac function, in prevalent hemodialysis patients.Electronic supplementary materialThe online version of this article (10.1186/s12882-017-0701-8) contains supplementary material, which is available to authorized users.

Cardiovascular disease in dialysis patients

“…Collado et al [ 40 ] tried to assess whether serum OPG and/or fetuin-A predict mortality and CV morbidity and mortality in HD patients, as well as their association with atherosclerosis and/or vascular calcification and with cardiac structure and function. The presence of carotid atherosclerotic disease, defined by a pathological intima-media thickness and/or presence of carotid plaques with stenosis or calcified atherosclerotic plaques was associated with higher OPG levels but not with fetuin-A levels.…”

Circulating Osteoprotegerin Levels Independently Predict All-cause Mortality in Patients with Chronic Kidney Disease: a Meta-analysis

“…1 ). Seven studies 24, 26-28, 30-32 were included in a qualitative meta-analysis to assess the association of the circulating OPG level, as a categorical variable, with all-cause mortality. Seven studies 8-10, 15, 25, 27, 29 were included in a quantitative meta-analysis to assess the association of a 1 pmol/L increase in the circulating OPG level with all-cause mortality.…”

“…Seven studies 24, 26-28, 30-32, which included a total of 1,934 patients, reported the adjusted HR of all-cause mortality for the highest OPG level group compared with the lower OPG level group. According to the qualitative meta-analysis, patients with the highest OPG levels had a significantly higher risk of all-cause mortality (adjusted HR, 1.88; 95% CI, 1.45 - 2.44) compared with patients with lower OPG levels, and low heterogeneity ( I ² = 25.7%, P = 0.233) was found among studies ( Fig.…”

“…Of the 7 included studies, 2 compared the high and low OPG levels according to the median value 24, 30, 3 compared the 3 rd tertile of the OPG level to the 1 st tertile 26-28, and 1 compared the 4 th tertile of the OPG level to the 1 st tertile 31. The 6 studies mentioned above set the lowest OPG level as the reference to assess the association between the highest OPG level and all-cause mortality.…”

Association between serum osteoprotegerin level and mortality in kidney transplant recipients ‐ a prospective observational cohort study

“…Serum OPG levels are elevated in patients with CKD and end-stage kidney disease, potentially in response to the strongly pro-calcific milieu [8,14]. Studies in dialyzed and nondialyzed patients with CKD have found that, like the general population, high serum OPG levels are associated with vascular calcification and all-cause and cardiovascular mortality [7,[15][16][17][18]. Short-term studies have found that serum OPG declines immediately after KT [19,20].…”