Serum Osteoprotegerin Levels Related With Cardiovascular Risk Factors in Chronic Kidney Disease

Demir, Pinar; Erdenen, Füsun; Aral, Hale; Emre, Turker; Köse, Şennur; Altunoğlu, Esma; Dolgun, Anıl; İnal, Berrin Berçik; Türkmen, Aydın

doi:10.1002/jcla.21941

Cited by 14 publications

(12 citation statements)

References 40 publications

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“…Moreover, Avila et al showed that OPG was associated with more severe arterial calcification in PD patients [13]. Studies had shown that OPG levels could be modulated by inflammatory cytokines, and the presence and severity of PAD were correlated with inflammation [10,11,17,20]. In a multicenter prospective study, high-sensitivity CRP was significantly associated with abnormal ABI levels, revealing that inflammation played a role in the PAD pathogenesis [17].…”

Section: Discussionmentioning

confidence: 99%

“…Likewise, diabetic patients who had higher OPG levels had approximately one-to twofold increased risk of PAD occurrence and severity, independent of traditional risk factors [8,9]. Moreover, patients with CKD who had higher OPG levels had more advanced renal disease and more pronounced vascular injury, CAD, DM, or all-cause mortality [10,11]. In patients with PAD, the serum OPG level was inversely correlated with ABI and positively correlated with severity grade of PAD, which could be modulated by inflammation [25].…”

Section: Discussionmentioning

confidence: 99%

“…Together, these factors could explain the higher risk of PAD in PD patients. Evidence had shown that patients on HD had non-significant higher levels of OPG than those on PD but patients on both modalities had higher levels than CKD or control patients and the OPG level was significantly correlated with inflammatory markers, such as interleukin-6, albumin, and CRP [10,11]. Moreover, Avila et al showed that OPG was associated with more severe arterial calcification in PD patients [13].…”

Section: Discussionmentioning

confidence: 99%

“…In patients with DM, the serum OPG level could be a predictor for the presence and severity of PAD measured using ABI or color Doppler ultrasonic imaging after adjusting the traditional CV risk factors [8,9]. In patients with chronic kidney disease (CKD), the serum OPG level progressively elevates as the renal function deteriorates, positively correlates with inflammatory markers and intimal-media thickness of carotid arteries, and is most importantly associated with survival [10,11]. In addition, the OPG level was significantly correlated with PAD after renal transplantation [12] and was considered as the strongest predictor of arterial calcification progression in patients on PD [13].…”

Section: Introductionmentioning

confidence: 99%

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Serum osteoprotegerin level is positively associated with peripheral artery disease in patients with peritoneal dialysis

et al. 2020

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Osteoprotegerin (OPG) is a potential biomarker of cardiovascular disease complications and severity. Peripheral arterial disease (PAD) is associated with an increased risk of death in patients on peritoneal dialysis (PD). Therefore, this study aimed to evaluate the relationship between serum OPG levels and PAD by measuring the ankle-brachial index (ABI) of patients on PD. A commercial enzyme-linked immunosorbent assay kit was used to measure OPG values. Left or right ABI values of <0.9 were categorized as the low ABI group. Among 70 patients on PD, 13 (18.6%) were categorized in the low ABI group. Patients in the low ABI group had higher prevalence of diabetes mellitus (p ¼ .044) and higher serum C-reactive protein (CRP) (p < .001) and OPG levels (p < .001) but lower creatinine (p ¼ .013) and peritoneal Kt/V (p ¼ .048) levels than those in the normal ABI group. Results of multivariable logistic regression analysis revealed that OPG [adjusted odds ratio (aOR) 1.027, 95% confidence interval (CI) 1.010-1.045, p ¼ .002] and CRP (aOR 1.102, 95% CI 1.006-1.207, p ¼ .037) levels were independent predictors of PAD in patients on PD. OPG can also be used to predict PAD development with the area under the receiver operating characteristic curve of 0.823 (95% CI: 0.714-0.904, p < .001) in patients on PD. Therefore, serum OPG and CRP levels can be considered as risk factors for PAD development in patients on PD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Serum osteoprotegerin level is positively associated with peripheral artery disease in patients with peritoneal dialysis

et al. 2020

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“…Researches in vitro, and in animal models show that OPG inhibits vascular calcification [72,130,146]. Paradoxically, clinical researches have shown that OPG serum levels is increased in patients with progressive cardiovascular disease [151], correlates with presence and severity of coronary artery disease, is associated with left ventricular hypertrophy and C-reactive protein, is increased in chronic haemodialysis patients [147,152], in type 2 diabetic patients with microvascular complications, and in heart failure after acute myocardial infarction. This has led to an interesting debate about potential role of OPG as a vascular disease biomarker.…”

Section: Opg and Vascular Diseasementioning

confidence: 99%

Vascular Calcification, Atherosclerosis and Bone Loss (Osteoporosis): New Pathophysiological Mechanisms and Future Perspectives for Pharmacological Therapy

2016

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Vascular calcification or ectopic mineralization in blood vessels is an active, cell-regulated process, increasingly recognized as a general cardiovascular risk factor. Ectopic artery mineralization is frequently accompanied by decreased bone mineral density or disturbed bone turnover and development of the osteoporosis. The latest data support the correlation of osteoporosis and atherosclerosis, indicating the parallel progression of two tissue destruction processes with increased fatal and nonfatal coronary events, as well as a higher fracture risk. Patients with osteoporosis, have a higher risk of cardiovascular diseases than subjects with normal bone. Many proteins responsible for bone formation and resorption have been identified in the arterial wall. Vascular calcification includes mostly osteogenic and, to a lesser extent chondrogenic differentiation of osteoblasts and osteoclast-like cells. It has been shown that many of the regulators of bone formation and resorption some bone structural proteins, such as osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL) are also expressed in the atherosclerotic plaque. When RANKL binds to RANK, osteoclasts are activated and bone resorption occurs and processes of vascular calcification become also activated. OPG, protein homologue to receptor activator of nuclear factor-κB (RANK), can bind to RANKL, blocking the binding of RANKL to RANK, that results in inhibition of differentiation of preosteoclasts to mature osteoclasts, lower osteoclast capacity for resorption of bone mineral matrix, and development vascular calcification. The latest data supports that cathepsin K, a cysteine protease, can efficiently degrade type I and II collagen, both of which are major matrix components of the bone and atherosclerotic plaque. These findings further underscore the potential of cathepsin K as a target for novel molecules to treat osteoporosis and atherosclerosis. Thus, the discovery of the cytokine RANKL-RANK-OPG system and significant role of the cathepsin K in the process of bone remodeling, vascular calcification and atherosclerosis has made progress in understanding the mechanisms of disease development and possibly to develop new dual therapies. New therapies for osteoporosis and atherosclerosis that may potentially improve or augment existing treatments include the recently approved anti-receptor activator of NF-κB-ligand monoclonal antibody fms (denosumab) and the cathepsin K inhibitor odanacatib, presently in the late stage of clinical development.

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Osteoprotegerin and RANKL-RANK-OPG-TRAIL signalling axis in heart failure and other cardiovascular diseases

et al. 2021

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Osteoprotegerin (OPG) is a glycoprotein involved in the regulation of bone remodelling. OPG regulates osteoclast activity by blocking the interaction between the receptor activator of nuclear factor kappa B (RANK) and its ligand (RANKL). More and more studies confirm the relationship between OPG and cardiovascular diseases. Numerous studies have confirmed that a high plasma concentration of OPG and a low concentration of tumour necrosis factor–related apoptosis inducing ligand (TRAIL) together with a high OPG/TRAIL ratio are predictors of poor prognosis in patients with myocardial infarction. A high plasma OPG concentration and a high ratio of OPG/TRAIL in the acute myocardial infarction are a prognostic indicator of adverse left ventricular remodelling and of the development of heart failure. Ever more data indicates the participation of OPG in the regulation of the function of vascular endothelial cells and the initiation of the atherosclerotic process in the arteries. Additionally, it has been shown that TRAIL has a protective effect on blood vessels and exerts an anti-atherosclerotic effect. The mechanisms of action of both OPG and TRAIL within the cells of the vascular wall are complex and remain largely unclear. However, these mechanisms of action as well as their interaction in the local vascular environment are of great interest to researchers. This article presents the current state of knowledge on the mechanisms of action of OPG and TRAIL in the circulatory system and their role in cardiovascular diseases. Understanding these mechanisms may allow their use as a therapeutic target in cardiovascular diseases in the future.

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Serum Osteoprotegerin Levels Related With Cardiovascular Risk Factors in Chronic Kidney Disease

Cited by 14 publications

References 40 publications

Serum osteoprotegerin level is positively associated with peripheral artery disease in patients with peritoneal dialysis

Serum osteoprotegerin level is positively associated with peripheral artery disease in patients with peritoneal dialysis

Vascular Calcification, Atherosclerosis and Bone Loss (Osteoporosis): New Pathophysiological Mechanisms and Future Perspectives for Pharmacological Therapy

Osteoprotegerin and RANKL-RANK-OPG-TRAIL signalling axis in heart failure and other cardiovascular diseases

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