Effects of Aldosterone, Osteoprotegerin and Fibroblast Growth Factor-23 and Some Biochemical Markers in Chronic Kidney Disease Patients (Stage II-IV) among Patients with or without Cardiovascular Events
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Chronic Kidney Disease (CKD) is a public health problem and many studies support the link between kidney dysfunction and cardiovascular events. Aldosterone has been shown for decades that a plasma aldosterone concentration is elevated in CKD. Whilst, Osteoprotegerin (OPG), after its capacity to protect bone, also osteoprotegerin is elevated in patients with chronic kidney disease (CKD), where it could predict the deterioration of kidney function, cardiovascular, vascular events and all-cause mortality. On the other hand, fibroblast growth factors (FGFs), in patients with CKD, its levels seem to increase progressively as kidney function worsens. The aim of the present study is to assess the correlations between serum osteoprotegerin, aldosterone and fibroblast growth factor-23 levels in patients with chronic kidney disease stage (II-IV) with and without cardiovascular events.
The study includes fifty-nine patients with chronic kidney disease(CKD) and according to CKD-EPI /Creatinine/ 2009 equation to be allocated as stage II-IV, patients were divided into three groups: Group1 (29 patients) with chronic kidney disease(CKD) stage (II-IV) with cardiovascular events. Group2 (30 patients) with chronic kidney disease stage (II-IV) without cardiovascular event, to be compared with Group 3(23 apparently healthy subjects), age and sex matched to that of patients. Serum obtained from their blood specimens to measure; glucose, urea, creatinine, calcium, phosphate, sodium, potassium, aldosterone, FGF-23, Osteoprotergen.
Data analysis showed that fasting serum glucose levels of CKD patients (with and without CV disorder) had significantly higher values as compared to the controls (76.5% and 29% respectively).
Serum Aldosterone, FGF-23, OPG levels were presented with no significant variation among studied groups with CV events or those without CV events.Chronic Kidney Disease (CKD) is a public health problem and many studies support the link between kidney dysfunction and cardiovascular events. Aldosterone has been shown for decades that a plasma aldosterone concentration is elevated in CKD. Whilst, Osteoprotegerin (OPG), after its capacity to protect bone, also osteoprotegerin is elevated in patients with chronic kidney disease (CKD), where it could predict the deterioration of kidney function, cardiovascular, vascular events and all-cause mortality. On the other hand, fibroblast growth factors (FGFs), in patients with CKD, its levels seem to increase progressively as kidney function worsens. The aim of the present study is to assess the correlations between serum osteoprotegerin, aldosterone and fibroblast growth factor-23 levels in patients with chronic kidney disease stage (II-IV) with and without cardiovascular events.
The study includes fifty-nine patients with chronic kidney disease(CKD) and according to CKD-EPI /Creatinine/ 2009 equation to be allocated as stage II-IV, patients were divided into three groups: Group1 (29 patients) with chronic kidney disease(CKD) stage (II-IV) with cardiovascular events. Group2 (30 patients) with chronic kidney disease stage (II-IV) without cardiovascular event, to be compared with Group 3(23 apparently healthy subjects), age and sex matched to that of patients. Serum obtained from their blood specimens to measure; glucose, urea, creatinine, calcium, phosphate, sodium, potassium, aldosterone, FGF-23, Osteoprotergen.
Data analysis showed that fasting serum glucose levels of CKD patients (with and without CV disorder) had significantly higher values as compared to the controls (76.5% and 29% respectively).
Serum Aldosterone, FGF-23, OPG levels were presented with no significant variation among studied groups with CV events or those without CV events.
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Studies on bones metabolism regulation mechanisms leaded to discovery of RANKL/OPG/RANK signal system (receptor activator of nuclear factor kappaB ligand/osteoprotegerin/receptor activator of nuclear factor kappaB). It was found that beyond bone metabolism regulation Osteoprotegerin (OPG) is involved in some other processes: apoptosis, regulation of immunological system. Data from numerous studies performed in the last years indicate potential association between OPG and cardiovascular pathology. OPG was identified as atherosclerosis marker. Molecular mechanism by which OPG exerts its atherogenic effect is not fully elucidated.
Bone remodeling
RANK Ligand
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Objective To investigate the relationsh ip between the age and the osteoprotegerin by human osteoblast cultured in vitro.Methods 12 cases of adult osteoblast were isolated and cu ltured in vitro.The age ranges from 39 years old to 74 years old.Two groups are divided by their age.Expression of mRNA transcripts of osteoprotegerin were asse ssed by RT-PCR.Results The expression of mRNA transcripts of osteoprotege rin of the younger group(60 years old) was higher than that of the older group (60 years old)(P0.05).Conclusion Osteoprotegerin expression was declined with a ge,and this may contribute to the age-related bone loss.
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BACKGROUND: Recent studies show that osteoprotegerin can inhibit the activity of osteoclast and regulate the process of cartilage reshaping. Osteoprotegerin plays a great role in maintaining the integrity of cartilage tissue of intervertebral disc. OBJECTIVE: To determine the expression of osteoprotegerin in the intervertebral disk of the patients with lumbar disc degeneration (LDD), and then to analyze the relationship between the expression levels of osteoprotegerin and the severity of LDD. METHODS: Sixty-four patients with LDD (LDD group) and twenty-five patients with disc burst fractures (control group) were enrolled in this study. The intervertebral disc tissues were collected after surgery. Then the mRNA expression and protein levels of osteoprotegerin in the intervertebral disk were examined by real-time polymerase chain reaction (PCR). The protein level of osteoprotegerin was determined by ELISA method. The grade of disc degeneration was classified according to MRI findings by Schneiderman’s classification and the association between the levels of osteoprotegerin and the Schneiderman’s grades was analyzed. RESULTS AND CONCLUSION: The mRNA expression and protein levels of osteoprotegerin in the intervertebral disc in LDD group were significantly higher than that in the control group which were tested by real-time PCR method and ELISA method. Unconditional logistic regression analysis revealed that elevated mRNA expression and protein levels of osteoprotegerin were independent risk factors of the presence of LDD. In addition, the mRNA expression and protein levels of osteoprotegerin were both significantly correlated with Schneiderman’s grades (r =0.367, P 0.001 and r =0.412, P 0.001, respectively). Patients with higher Schneiderman’s grade showed relatively higher levels of osteoprotegerin. The levels of osteoprotegerin were significantly elevated in the intervertebral disc of patients with LDD and were significantly associated with the severity of LDD.
Intervertebral Disc
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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.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.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.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%).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.
Osteopontin
Bone remodeling
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Through using the method of immuno-histochemistry,this paper observed the effect of swimming and age increasing on osteoprotegerin of rat.The result showed that the expression of osteoprotegerin tended to increase from adolescence to adult.However,from the later phase of adult to early elder,there was tendency to decrease.Exercise can increase the expression of osteoprotegerin,especially for alternative day's exercise.
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Chronic kidney disease (CKD) has been known to be associated with an increased risk of cardiovascular (CV) mortality and morbidity in Japan. Although traditional risk factors contribute to the development of CV disease in CKD patients, they cannot fully explain the unacceptably high incidence of CV mortality. Recently, non-traditional risk factors, including abnormal mineral metabolism, have been suggested to be involved in the increased risk of CV events. The medical treatment of CKD-mineral bone disorders (CKD-MBD) has been associated with encouraging, but inconsistent, improvement in CV disease complications and patient survival. A better understanding of the biomarkers and mechanisms involved in left ventricular hypertrophy (LVH) and vascular calcification might improve the diagnosis and treatment of the CV disease secondary to CKD-MBD, thus improving patient survival. Recent insights into fibroblast growth factor 23 (FGF23) and its co-receptor, Klotho, have led to marked advancements in the interpretation of data about CKD-MBD and CV damage.
Nephrology
Klotho
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To investigate the expression of receptor activator of nuclear factor-κB (RANK), its ligand RANKL, and osteoprotegerin, and observe the effects of αD3 on their expressions in male rats at different ages.Wistar rats at 6 weeks, 6 months, and 24 months (n=15) were examined for mRNA expressions of RANK/RANKL and osteoprotegerin in the left proximal femur using RT-PCR and for their protein expressions in the right femur using immunohistochemistry. RANK/RANKL and osteoprotegerin expressions were also detected in another 15 rats aged 24 months following intragastric administration of 0.05 µg/kg αD3 (3 times a week for 10 weeks).Compared with 6-week-old rats, 6-month- and 24-month-old rats showed a 6.2-fold and 7.3-fold increase of RANKL mRNA expression, respectively (P<0.05), and osteoprotegerin mRNA levels increased slightly with age. αD3 treatment resulted in significantly increased expression of RANK in 24-month-old rats with a lowered RANKL/osteoprotegerin ratio. RANKL and osteoprotegerin were co-localized in the osteoblasts and chondrocytes. αD3 treatment also caused an increased expression of osteoprotegerin mRNA in 24-month-old rats.The age-related increase of the ratio of RANKL/osteoprotegerin mRNA promotes osteoclast activity and bone turnover. αD3 has favorable effect on osteogenesis and suppress bone absorption in the femur possibly by reducing RANK expression and lowering RANKL/osteoprotegerin ratio.
RANK Ligand
Bone remodeling
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Abstract Osteoprotegerin and osteoprotegerin ligand have recently been identified as novel proteins that inhibit and stimulate, respectively, osteoclast formation. We examined the possibility that osteoprotegerin would inhibit cancer‐induced osteoclastogenesis and cancer growth in bone. An experimental model was used in which osteolytic tumors are known to stimulate osteoclastogenesis and grow in femora of osteoclast‐deficient mice ( op / op ). Osteoprotegerin treatment decreased the number of osteoclasts by 90% (p < 0.0007) at sites of tumor in a dose‐dependent manner and decreased bone tumor area by greater than 90% (p < 0.003). The mechanisms through which osteoprotegerin decreased osteoclast formation in tumor‐bearing animals included (a) an osteoprotegerin‐mediated, systemic reduction in the number of splenic and bone marrow‐residing osteoclast precursor cells. (b) a decrease in the number of osteoclast precursor cells at sites of tumor as detected by cathepsin K and receptor activator of NFkB mRNA expression, and (c) a decrease in osteoprotegerin ligand mRNA at sites of tumor. These findings suggest that osteoprotegerin treatment, in addition to having direct antagonistic effects on endogenous osteoprotegerin ligand, decreases the number of osteoclast precursors and reduces production of osteoprotegerin ligand at sites of osteolytic tumor.
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Background Micro RNA ‐125b (miR‐125b) has been shown to regulate vascular calcification ( VC ), and serum miR‐125b levels are a potential biomarker for estimating the risk of uremic VC status. However, it is unknown whether clinical features, including chronic kidney disease–mineral bone disorder molecules, affect serum miR‐125b levels. Methods and Results Patients receiving chronic dialysis for ≥3 months were recruited from different institutes. Serum miR‐125b and chronic kidney disease–mineral bone disorder effectors, including intact parathyroid hormone, 25‐ OH ‐D, fibroblast growth factor‐23, osteoprotegerin, and fetuin‐A, were quantified. We used multivariate regression analyses to identify factors associated with low serum miR‐125b levels and an area under receiver operating characteristic curve curve to derive optimal cutoffs for factors exhibiting close associations. Further regression analyses evaluated the influence of miR‐125b on VC risk. Among 223 patients receiving chronic dialysis (mean age, 67.3 years; mean years of dialysis, 5.2), 54 (24.2%) had high serum miR‐125b levels. Osteoprotegerin ( P =0.013), fibroblast growth factor‐23 ( P =0.006), and fetuin‐A ( P =0.036) were linearly associated with serum miR‐125b levels. High osteoprotegerin levels independently correlated with high serum miR‐125 levels. Adding serum miR‐125b levels and serum osteoprotegerin levels (≥400 pg/mL) into models estimating the risk of uremic VC increased the area under receiver operating characteristic curve values (for models without miR‐125b/osteoprotegerin, with miR‐125b, and both: 0.74, 0.79, and 0.81, respectively). Conclusions Serum osteoprotegerin levels ≥400 pg/mL and serum miR‐125b levels synergistically increased the accuracy of estimating VC risk among patients receiving chronic dialysis. Taking miR‐125b and osteoprotegerin levels into consideration when estimating VC risk may be recommended.
Osteopontin
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