Osteoprotegerin is a marker of cardiovascular mortality in patients with chronic kidney disease stages 3–5

Marques, Gustavo Lenci; Hayashi, Shirley Yumi; Bjällmark, Anna; Larsson, Matilda; Riella, Miguel C.; Olandoski, Márcia; Lindholm, Bengt; Nascimento, Marcelo Mazza do

doi:10.1038/s41598-021-82072-z

Cited by 24 publications

(21 citation statements)

References 34 publications

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“…Another bone-protective factor, OPG, prevents mineral resorption by inhibiting osteoclast differentiation and activation, but it is associated with greater cardiovascular disease. Consistent with other reports, a study of over 100 patients with CKD showed significantly greater all-cause and cardiovascular mortality in those with higher baseline OPG levels [160]. Since monocyte/macrophages and osteoclasts share common myeloid precursors, attempts have been made to activate RANK signaling in myeloid cells in vivo.…”

Section: Outlook On Therapeutic Targetssupporting

confidence: 77%

Biomolecules Orchestrating Cardiovascular Calcification

2021

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Vascular calcification, once considered a degenerative, end-stage, and inevitable condition, is now recognized as a complex process regulated in a manner similar to skeletal bone at the molecular and cellular levels. Since the initial discovery of bone morphogenetic protein in calcified human atherosclerotic lesions, decades of research have now led to the recognition that the regulatory mechanisms and the biomolecules that control cardiovascular calcification overlap with those controlling skeletal mineralization. In this review, we focus on key biomolecules driving the ectopic calcification in the circulation and their regulation by metabolic, hormonal, and inflammatory stimuli. Although calcium deposits in the vessel wall introduce rupture stress at their edges facing applied tensile stress, they simultaneously reduce rupture stress at the orthogonal edges, leaving the net risk of plaque rupture and consequent cardiac events depending on local material strength. A clinically important consequence of the shared mechanisms between the vascular and bone tissues is that therapeutic agents designed to inhibit vascular calcification may adversely affect skeletal mineralization and vice versa. Thus, it is essential to consider both systems when developing therapeutic strategies.

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Section: Outlook On Therapeutic Targetssupporting

confidence: 77%

Biomolecules Orchestrating Cardiovascular Calcification

2021

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“…35 Accordingly, elevated serum OPG levels were associated with higher all-cause and cardiovascular 5-year mortality risk, independent of age, CVD, diabetes, and inflammatory markers, in patients with CKD stages 3-5. 36 Most of these studies were performed in diabetic patients, and suggest OPG to be a biomarker of CKD progression. 37,38 Our findings were confirmed on mixed population of diabetic and non-diabetic subjects at different CKD stages, therefore bring novel arguments as to the use of OPG as a mortality predicting marker in CKD patients.…”

Section: Discussionmentioning

confidence: 99%

Circulating Osteoprotegerin in Chronic Kidney Disease and All-Cause Mortality

Kamińska¹,

Stopiński²,

Mucha³

et al. 2021

IJGM

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Background: Chronic kidney disease (CKD) is associated with cardiovascular disease (CKD), mineral and bone disorder (CKD-MBD) and high mortality. Bone-related factors such as osteopontin (OPN), osteocalcin (OC), osteoprotegerin (OPG) and fibroblast growth factor 23 (FGF23) were linked to cardiovascular complications of CKD and are expected to have predictive value in CKD patients. Purpose: The aim of this study was to assess the relationship of OPN, OC, OPG and FGF23 to clinical characteristics and to evaluate their ability to predict mortality in patients with different CKD stages. Methods: The following study groups were enrolled: subjects with end-stage renal disease (38 ESRD), CKD stages 3 and 4 (19 CKD3-4) and non-CKD controls (19), respectively. Blood was withdrawn once to perform the measurements and cardiac computed tomography was used to evaluate coronary calcium score (CS). Patients were followed for 5 years for the ascertainment of their all-cause mortality. Results: Serum OPN, OC and OPG concentrations increased significantly along with the progression of renal disease. We found a significant positive correlation among these proteins. Additionally, OPN and OPG were significantly and positively correlated to CS. Serum OPG revealed the strongest correlation to the calcium turnover markers of GFR decline and was significantly associated with an increased risk of death in subjects with CKD3-4 or ESRD (HR 5.8, CI 95%). Conclusion: Single measurement of osteoprotegerin is associated with 5-year all-cause mortality in patients with CKD3-4 or ESRD. We suggest assessing its concentration, preferably in combination with calcium score, to stratify mortality risks in CKD patients.

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“…Despite the debate on the role of circulating OPG in atherosclerotic disease [ 31 ], as an experimental study reported that exogenous OPG treatment lead to endothelial and vascular smooth cell dysfunction by promoting the production of reactive oxygen species, which may underlie vascular injurious effects in conditions such as hypertension [ 32 ], the phenotype of OPG-knockout mice ultimately indicates circulating OPG as a biomarker, rather than a mediator, of atherosclerosis, as OPG-deficient mice develop early onset arterial calcification [ 33 ]. In this context, the association of high serum OPG level with coronary artery calcification [ 15 , 16 ], and cardiovascular [ 17 , 18 ] and all-cause mortality [ 19 , 20 ] in patients with CKD has been suggested. The association between serum OPG level with long-term visit-to-visit BPV presented in this study highlights a novel role of circulating OPG as a biomarker that predict a surrogate of CV events.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies demonstrated that high serum OPG level is associated with the presence [ 15 ] and severity [ 16 ] of coronary artery calcification in patients with CKD. In this regard, elevated circulating OPG level has been proposed as a predictor of cardiovascular [ 17 , 18 ] and all-cause [ 19 , 20 ] mortality in patients with CKD. Serum OPG level is positively associated with peripheral artery disease, arterial stiffness, and arterial calcification in patients with end-stage renal disease [ 21 , 22 , 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

Association of Circulating Osteoprotegerin Level with Blood Pressure Variability in Patients with Chronic Kidney Disease

Suh

Choi

et al. 2021

JCM

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Circulating osteoprotegerin (OPG) is a biomarker for cardiovascular complications that are closely related to chronic kidney disease (CKD). To investigate the association between circulating OPG level with long-term visit-to-visit blood pressure variability (BPV) in patients with pre-dialysis CKD, a total of 1855 subjects with CKD from stage 1 to pre-dialysis stage 5 from a prospective cohort were analyzed. Long-term visit-to-visit BPV was determined by average real variability (ARV), standard deviation (SD), and coefficient of variation (CoV) of systolic and diastolic blood pressure (SBP and DBP). ARV of SBP (Adjusted β coefficient 0.143, 95% confidence interval 0.021 to 0.264) was significantly associated with serum OPG level. Although SD and CoV of SBP were not significantly associated with serum OPG level in multivariate linear regression analyses, restricted cubic spline visualized the linear correlation of serum OPG level with all of ARV, SD, and CoV. The association between serum OPG level and DBP variability was not significant. Subgroup analyses revealed that the association of serum OPG with BPV is more prominent in the subjects with Charlson comorbidity index ≤3 and in the subjects without history of diabetes mellitus. In conclusion, circulating OPG level is potentially associated with long-term visit-to-visit BPV in patients with pre-dialysis CKD.

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Osteoprotegerin is a marker of cardiovascular mortality in patients with chronic kidney disease stages 3–5

Cited by 24 publications

References 34 publications

Biomolecules Orchestrating Cardiovascular Calcification

Biomolecules Orchestrating Cardiovascular Calcification

Circulating Osteoprotegerin in Chronic Kidney Disease and All-Cause Mortality

Association of Circulating Osteoprotegerin Level with Blood Pressure Variability in Patients with Chronic Kidney Disease

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