Risk Factor For Vascular Calcification Research Articles

Cardiovascular calcification in hemodialysis patients: A Qatar-based prevalence and risk factors study.

Patients with end-stage kidney disease on hemodialysis (HD) have an increased risk of death due to the high prevalence of cardiovascular disease. Vascular calcification (VC) is predictive of cardiovascular disease and mortality. We conducted a study to evaluate the prevalence and risk factors for VC in dialysis patients in Qatar. This is a retrospective nationwide study including all chronic ambulatory dialysis patients in Qatar from 2020 to 2022. We used our national electronic medical record to track demographics, clinical characteristics, comorbidities, laboratory values, and diagnostic data for each patient. Calcifications were assessed by echocardiography (routinely done for all our dialysis population per national protocol), computed tomography, X-ray, and ultrasound. The study protocol was approved by the local medical research ethics committee (MRC-01-20-377). 842 HD patients were included in this study. Vascular calcifications (VC) were prevalent in 52.6% of patients. The main site of VC was Mitral valve calcifications in 55.5% of patients. Patients with VC were significantly older and had more prevalence of diabetes mellitus (p = 0.001 and p = 0.006, respectively). There was no statistically significant difference between patients with calcifications and patients without calcifications regarding serum calcium, phosphorus, and PTH level. In multivariate analysis, age and diabetes significantly increased the risk factor for calcification (95% CI 1.033-1.065, p < 0.0001, and 95% CI 1.128-2.272, p < 0001, respectively). Moreover, higher vitamin D levels and higher doses of IV Alfacalcidol were significant risk factors for calcifications (95% CI 1.005-1.030, p < 0.007, and 95% CI 1.092-1.270, p < 0.0001, respectively). Our study found that vascular calcification was widespread among our dialysis population in Qatar. Implementing the practice of echocardiography in dialysis patients was extremely helpful and the most productive in detecting vascular calcification. Diabetes mellitus almost doubles the risk for vascular calcifications in dialysis patients. These results are beneficial in identifying risk factors for vascular calcification, which can help stratify dialysis patients' risk of cardiovascular disease and optimize prevention efforts.

Analysis of factors influencing vascular calcification in peritoneal dialysis patients and their impact on long-term prognosis

BackgroundThis study aims to investigate the influencing factors of vascular calcification in peritoneal dialysis (PD) patients and its relationship with long-term prognosis.MethodsThis retrospective cohort study included chronic kidney disease patients undergoing peritoneal dialysis at the Peritoneal Dialysis Center of Beijing Luhu Hospital, Capital Medical University, from January 2019 to March 2019. Demographic and clinical laboratory data, including serum sclerostin (SOST), calcium (Ca), phosphate (P), serum albumin (ALB), and intact parathyroid hormone (iPTH) levels, were collected. Abdominal aortic calcification (AAC) was assessed using abdominal lateral X-ray examination to determine the occurrence of vascular calcification, and patients were divided into the AAC group and Non-AAC group based on the results.ResultsA total of 91 patients were included in the study. The AAC group consisted of 46 patients, while the Non-AAC group consisted of 45 patients. The AAC group had significantly older patients compared to the non-AAC group (P < 0.001) and longer dialysis time (P = 0.004). Multivariable logistic regression analysis indicated that risk factors for vascular calcification in PD patients included dialysis time, diabetes, hypertension, and SOST. Kaplan–Meier survival analysis showed that the AAC group had a significantly higher mortality rate than the non-AAC group (χ2 = 35.993, P < 0.001). Multivariable Cox regression analysis revealed that dialysis time, diabetes and AAC were risk factors for all-cause mortality in peritoneal dialysis patients.ConclusionLonger dialysis time, comorbid diabetes, comorbid hypertension, and SOST are risk factors for vascular calcification in PD patients. Additionally, AAC, longer dialysis time, and comorbid diabetes are associated with increased risk of all-cause mortality in peritoneal dialysis patients.

Comparative Analysis of Vascular Calcification Risk Factors in Pre-Hemodialysis and Prevalent Hemodialysis Adult Patients: Insights into Calcification Biomarker Associations and Implications for Intervention Strategies in Chronic Kidney Disease.

This retrospective study aimed to compare risk factors for vascular calcification (VC) between pre-hemodialysis (HD) and prevalent HD adult patients while investigating associations with calcification biomarkers. Baseline data from 30 pre-HD and 85 HD patients were analyzed, including iPTH, vitamin D, FGF 23, fetuin-A, sclerostin, and VC scores (Adragao method). Prevalence of VC was similar in both groups, but HD patients had more frequent VC scores ≥ 6. Pre-HD patients were older, with higher prevalence of hypertension and less frequent use of calcium phosphate binders. Both groups showed similar patterns of hyperphosphatemia, low vitamin D, and iPTH. Fetuin-A and sclerostin levels were higher in pre-HD, while FGF 23 was elevated in HD patients. Higher VC risk in pre-HD patients was associated with male gender, older age, lower fetuin-A and higher sclerostin, lower ferritin, and no vitamin D treatment, while in HD patients with higher sclerostin, FGF 23 and urea, and lower iPTH. Conclusion: Biomarkers could be measurable indicators of biological processes underlying VC in CKD patients that may serve as a potential guide for considering personalized therapeutic approaches. Further studies are needed to elucidate the underlying pathways.

The emerging roles of irisin in vascular calcification.

Vascular calcification is a common accompanying pathological change in many chronic diseases, which is caused by calcium deposition in the blood vessel wall and leads to abnormal blood vessel function. With the progress of medical technology, the diagnosis rate of vascular calcification has explosively increased. However, due to its mechanism's complexity, no effective drug can relieve or even reverse vascular calcification. Irisin is a myogenic cytokine regulating adipose tissue browning, energy metabolism, glucose metabolism, and other physiological processes. Previous studies have shown that irisin could serve as a predictor for vascular calcification, and protect against hypertension, diabetes, chronic kidney disease, and other risk factors for vascular calcification. In terms of mechanism, it improves vascular endothelial dysfunction and phenotypic transformation of vascular smooth muscle cells. All the above evidence suggests that irisin plays a predictive and protective role in vascular calcification. In this review, we summarize the association of irisin to the related risk factors for vascular calcification and mainly explore the role of irisin in vascular calcification.

Establishment and evaluation of a nomogram prediction model for the risk of vascular calcification in stage 5 chronic kidney disease patients

Vascular calcification (VC) is a common complication of chronic kidney disease (CKD) that has a detrimental effect on patients' survival and prognosis. The aim of this study was to develop and validate a practical and reliable prediction model for VC in CKD5 patients. The medical records of 544 CKD5 patients were reviewed retrospectively. Multivariate logistic regression analysis was used to identify the independent risk factors for vascular calcification in patients with CKD5 and then created a nomogram prediction model. The area under the receiver operating characteristic curve (AUC), Hosmer–Lemeshow test, and decision curve analysis (DCA) were used to assess model performance. The patients were split into groups with normal and high serum uric acid levels, and the factors influencing these levels were investigated. Age, BUN, SUA, P and TG were independent risk factors for vascular calcification in CKD5 patients in the modeling group (P < 0.05). In the internal validation, the results of model showed that the AUC was 0.917. No significant divergence between the predicted probability of the nomogram and the actual incidence rate (x2 = 5.406, P = 0.753) was revealed by the calibration plot and HL test, thus confirming that the calibration was satisfactory. The external validation also showed good discrimination (AUC = 0.973). The calibration chart and HL test also demonstrated good consistency. Besides, the correlation analysis of serum uric acid levels in all CKD5 patients revealed that elevated uric acid levels may be related to gender, BUN, P, and TG.

Comparative Study Evaluating the Effect of the Administration of Vitamin K2 versus Placebo on Vascular Calcification in Haemodialysis Patients

Abstract Background Vitamin K deficiency serves as risk factor for vascular calcification in CKD patients. Vitamin K family includes phylloquinone (vitamin K1) and several menaquinones (vitamin K2). Until trials are designed to compare the effects of phylloquinone and menaquinone on CAC and other cardiovascular outcomes, it is not known if one form of vitamin K is superior to any other form of vitamin in terms of cardiovascular health. Objective To evaluate the effect of supplementation of vitamin K2 (menaquinone, MK-7) on circulating levels of calcification regulators and to assess their safety in patients on regular hemodialysis patients. Patients and Methods The study was conducted on 84 ESRD patient on regular Hemodialysis recruited from Ain shams university Hospitals hemodialysis unit, their age ranged from 18 to 75 years This study was conducted from June 2020 to September 2020 in Hemodialysis Unit of Ain Shams University Hospitals, each participant signed informed consent. The study was approved by the Research Ethical Committee of Faculty of Medicine, Ain Shams University in April 2020. Patients were equally divided into two groups: Vitamin K2 group: 42 patients will receive 90 ug per day orally in addition to their standard treatment for 3 months period. Placebo group: 42 patients will receive placebo orally in addition to their standard treatment for 3 months period. Results In our study there was no statistically significant difference between the two groups according to their risk factors regarding smoking, HTN, HCV, DM, and ISHD. In this work only 22.5 % of patients were diabetic in 1st group and 35% were diabetic in placebo group, but their diabetes was well controlled and there was no significant difference between groups regarding incidence of There was no significant difference between groups regarding vascular access (AVF, Permicath) and duration of dialysis this study did not find a significant difference in blood pressure, BMI, serum levels of calcium, phosphorus, hemoglobin%, PTH, between group I and group II at the start of the study and after 3 months. Conclusion The study are that it is a pilot study with a small sample size, no funding was present., also carotid duplex was not done so effect of vitamin k2 administration and rise in serum MGP level on vessels calcification and atherosclerotic changes couldn’t be assessed.

Bone Specific Alkaline Phosphatase and Serum Calcification Propensity Are Not Influenced by Etelcalcetide vs. Alfacalcidol Treatment, and Only Bone Specific Alkaline Phosphatase Is Correlated With Fibroblast Growth Factor 23: Sub-Analysis Results of the ETACAR-HD Study

Secondary hyperparathyroidism in chronic kidney disease poses a major risk factor for vascular calcification and high bone turnover, leading to mineralization defects. The aim was to analyze the effect of active vitamin D and calcimimetic treatment on fibroblast growth factor 23 (FGF23), serum calcification propensity (T50), a surrogate marker of calcification stress and bone specific alkaline phosphatase (BAP) in hemodialysis. This is a subanalysis of a randomized trial comparing etelcalcetide vs. alfacalcidol in 62 hemodialysis patients for 1 year. We compared the change of BAP and serum calcification propensity between the two medications and assessed the influence of FGF23 change over time. We found no significant differences in the change of BAP or serum calcification propensity (T50) levels from baseline to study end between treatment arms (difference in change of marker between treatment with etelcalcetide vs. alfacalcidol: BAP : 2.0 ng/ml [95% CI-1.5,5.4], p = 0.3; T50: –15 min [95% CI –49,19], p = 0.4). Using FGF23 change over time, we could show that BAP levels at study end were associated with FGF23 change (–0.14 [95% CI –0.21, –0.08], p < 0.001). We did not observe the same association between FGF23 change and T50 (effect of FGF23 change on T50: 3.7 [95% CI –5.1, 12], p = 0.4; R2 = 0.07 vs. R2 = 0.06). No significant difference was found in serum calcification propensity (T50) values between treatment arms. FGF23 was not associated with serum calcification propensity (T50), but was negatively correlated with BAP underlying its role in the bone metabolism.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [NCT03182699].

Prevalence and risk factors for vascular calcification based on the ankle-brachial index in the general population: a cross-sectional study

BackgroundTo investigate the prevalence of vascular calcification based on the ankle‐brachial index (ABI) value and analyse the risk factors for vascular calcification in the general population.MethodsA cross-sectional study was conducted to collect clinical, laboratory, and lifestyle data in individuals aged 30–70 recruited from the physical examination centre. The automatic arteriosclerosis detector was used to measure the ABI. Difference tests, correlation analyses, and multivariate logistic regression analyses were performed to identify risk factors for vascular calcification.ResultsThe overall prevalence of vascular calcification was 24.39% in 1033 subjects. The prevalence of vascular calcification in males was much higher than that in females (27.80% vs. 17.49%, P < 0.001). The differences in age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), hypertension, and fatty liver disease were statistically significant in males (P < 0.05). The differences between serum uric acid (UA), total cholesterol (TC), TG, low-density lipoprotein cholesterol (LDL-C), estimated glomerular filtration rate (eGFR), alcohol consumption, exercise, and postmenopausal status were statistically significant in females (P < 0.05). Increased age (odds ratio (OR) = 1.028, 95% confidence interval (CI) 1.008–1.049, P = 0.007), increased BMI (OR = 1.238, 95% CI 1.147–1.337, P < 0.001) and elevated DBP (OR = 2.563, 95% CI 1.262–5.205, P = 0.009) were independent risk factors for vascular calcification in males after adjusting for confounding factors. Increased BMI (OR = 1.159, 95% CI 1.029–1.304, P = 0.015), elevated UA (OR = 1.545, 95% CI 1.077–2.216, P = 0.018), elevated LDL-C (OR = 1.044, 95% CI 1.060–1.027, P < 0.001), and a lack of exercise (OR = 2.402, 95% CI 1.073–5.373, P = 0.033) were independent risk factors for vascular calcification in females.ConclusionsThe prevalence of vascular calcification based on the ABI value is also high in the general population of our centre. Increased age, BMI, and elevated DBP are independent risk factors for vascular calcification in males. Increased BMI, UA, LDL-C, and a lack of exercise are independent risk factors for vascular calcification in females. Attention should be given to strengthening the prevention and control of vascular calcification in the general population.

Narrative review of exosomes: novel players in vascular calcification of chronic kidney disease.

Vascular calcification (VC) has been proved the main pathophysiology basis that results in the cardiovascular disease which become the leading cause of death in patients with chronic kidney disease. The disordered mineral metabolism, hyperphosphatemia, overuse of calcium binders, occurred in the setting of uremia, have become the critical risk factors of vascular calcification in chronic kidney disease, in which the vascular smooth muscle cells undergo differentiation to osteoblast-like cells. The mechanisms involved in vascular calcification are complicated and exosomes, as novel players, are proven to play a vital role in VC and function as initializers for mineral deposition. Exosomal miRNAs play an important role in the regulation of cellular functions in vascular calcification. In this review, we focused on the roles of exosomes during VC, especially on their effects on regulating vascular calcification through initializing mineral deposition as a nidus, transporting microRNAs to the recipient cells and mediating the vascular smooth muscle cells differentiation to osteoblast-like cells.

Epidemiological Research Advances in Vascular Calcification in Diabetes.

Vascular calcification is the transformation of arterial wall mesenchymal cells, particularly smooth muscle cells (SMCs), into osteoblast phenotypes by various pathological factors. Additionally, vascular transformation mediates the abnormal deposition of calcium salts in the vascular wall, such as intimal and media calcification. Various pathological types have been described, such as calcification and valve calcification. The incidence of vascular calcification in patients with diabetes is much higher than that in nondiabetic patients, representing a critical cause of cardiovascular events in patients with diabetes. Because basic research on the clinical transformation of vascular calcification has yet to be conducted, this study systematically expounds on the risk factors for vascular calcification, vascular bed differences, sex differences, ethnic differences, diagnosis, severity assessments, and treatments to facilitate the identification of a new entry point for basic research and subsequent clinical transformation regarding vascular calcification and corresponding clinical evaluation strategies.

Is the Importance of Magnesium in Chronic Kidney Disease Underappreciated?

Magnesium (Mg) is one of the most important cations in the organism, essential for regulating vascular tone, cardiac rhythm, and endothelial functions. In patients with advanced stage chronic kidney disease (CKD) Mg deficit was associated in various studies with vascular calcifications and increased cardiovascular morbidity and mortality. Patients with CKD frequently have hyperparathyroidism, parathormone (PTH) being an important risk factor for vascular calcifications. Increased serum Mg levels inhibit PTH secretion and stimulate left ventricular hypertrophy, while low serum Mg levels stimulate PTH secretion. Correcting Mg de deficiency results in reduced cardiovascular mortality in these patients.

Vascular Calcification in Patients with Early-Stage Chronic Kidney Disease: The Pivotal Role of Estimated Glomerular Filtration Rate

Background: Vascular calcification in advanced chronic kidney disease (CKD) is correlated with uremic toxins and severely impaired calciumphosphate- parathyroid metabolism. The association factors of vascular calcification in early-stage CKD are still unestablished. Objective: To identify the risk factors for vascular calcification in the early-stage CKD, which was the non-target population, different from other previous studies that explored this association in advanced stage CKD. Materials and Methods: The present study was a longitudinal study conducted to examine the risk factors of vascular calcification in CKD stage G2 and G3 patients who had no previous cardiovascular diseases. All parameters including coronary artery calcification (CAC) and abdominal aortic calcification (AAC) at baseline and after twelve months were evaluated. Results: Twenty-two patients without established cardiovascular diseases were included and completed the follow-up period. Mean baseline LDL was 99 mg/dL and no patient received statin. At 12-month, the median CAC score was significantly increased to 266 (126 to 956) versus 282 (198 to 846), (p=0.024]. By multivariable analysis in generalized estimating equations, only estimated glomerular filtration rate (eGFR) was associated with CAC score greater than 400 (aOR 0.92, p=0.041), and AAC score greater than 5 (aOR 0.90, p=0.023). Conclusion: In early-stage CKD, eGFR was associated with vascular calcification. Further studies should explore the potential benefits of delaying CKD progression on vascular calcification in the early-stage CKD patients. Keywords: Chronic kidney disease; Vascular calcification; Coronary artery calcification; Abdominal aortic calcification; Glomerular filtration rate; Renal function

MO572BONE BIOPSY AND MINERAL METABOLISM, CARDIOVASCULAR DISEASE AND PATIENT SURVIVAL IN END-STAGE RENAL PATIENTS

Abstract Background and Aims Chronic kidney disease-mineral and bone disorder (CKD-MBD) is frequent in end-stage renal disease (ESRD) patients, increasing morbid-mortality. The aim of this study was to determine the prevalence and phenotype of bone disease before transplantation; and to correlate FGF23, klotho and sclerostin serum levels with bone histomorphometric parameters and CV disease. The secondary aim was to correlate bone biopsies data with other bone related parameters, as PTH, bone alkaline phosphatase, 25-hidroxivitamin D3, calcitonin, calcium, phosphorus, and magnesium. Method We performed a prospective cohort study of a sample of ESRD patients listed for renal transplant. All patients were submitted to renal transplant and were followed for 12 months. Patient and graft survival were recorded. At inclusion, demographic and clinical data were collected, laboratorial evaluation; bone biopsy and X-ray of the pelvis and hands (Adragão score) were performed. Continuous variables are presented as medians and categorical variables as frequencies. Associations between variables were performed using Wilcoxon rank sum test, Fisher and Kruskal Wallis test. Multivariate analysis was performed using logistic regression. STATA software was used and p &amp;lt; 0.05 was considered statistically significant. Results We included 84 patients. Median age 53.5 (IQ range: 40.5 – 61.5) years, 59 men (70.2%), 65 caucasian (77.4%). The median left ventricular mass index was 108.5 (92 – 129) g/m2, with 32 patients presenting left ventricular hypertrophy and 19 valve calcifications. Median Adragão score was 1 (0 – 2). We diagnosed adynamic bone disease in 15 patients; hyperparathyroid bone disease in 19 patients; osteomalacia in 1 patient and mixed renal osteodystrophy in 3 patients. At the end of 12 months, 4 patients died, 5 had graft failure (non-primary function) and 4 had a cardiovascular event. Sclerostin was found to be a risk factor for low bone volume; whereas low phosphorus, low FGF23 and high bAP risk factors for abnormal mineralization. High turnover was mainly present in patients with high bAP and phosphorus and low sclerostin levels. The presence of valve calcifications was associated with low volume and with low or high turnover disorder. FGF23 appears as an important independent factor for vascular calcifications [as well age (p=0.009), BMI (p=0.02), presence of diabetes (p=0.01)], and for cardiovascular events. Sclerostin emerged as a risk factor for vascular calcifications and lower levels of sclerostin were associated with patient survival at the end of 12 months. Conclusion From the bone-derived hormones, sclerostin and FGF23 seem to act as risk factors for vascular calcifications and worse outcomes.

MO473INTERACTION OF SCLEROSTIN AND OSTEOPROTHERIN IN THE DEVELOPMENT OF VASCULAR CALCIFICATIONS AT STAGE 3-5 OF CHRONIC KIDNEY DISEASE

Abstract Background and Aims: Background and Aims: . Vascular calcification (VC) due to bone-mineral metabolism disorders is a predictor of high cardiovascular mortality in patients with late-stage chronic kidney disease (CKD) . The established bone-vascular axis in CKD, which relates to interactions between changes in the bone and vascular systems that have similar mechanisms, allows bone metabolism inhibitors to act as potential risk factors for VC. Morphogenetic protein osteoprotegerin (OPG) and glycoprotein sclerostin are opposite inhibitors of bone metabolism: OPG inhibits osteoclastogenesis, sclerostin has an inhibitory effect on osteoblastogenesis. Although both proteins are recognized as high-risk factors for remodeling the heart and large arteries in patients with CKD, the mechanisms and possibilities for correcting these changes are not fully clear. of the study was to investigate the mechanisms of the relationship between OPG and sclerostin in the development of cardiovascular complications due to calcification of the aorta and large arteries in the late stages of CKD. Method: Method The cross-sectional study included 105 patients with stage 3-5 CKD [49 men; 64.0 (23.0-76.0)years]. The glomerular filtration rate determined using the CKD-EPI equation was 38.4 (8.6–92.3) ml / min / 1.73 m2. The general clinical examination included assessment of hematopoiesis (hemoglobin, hematocrit, ferritin and transferrin), determination of total protein and albumin levels, cholesterol, electrolytes (sodium, potassium) in the blood, and indicators of nitrogen metabolism (creatinine, urea). Parameters of bone-mineral metabolism – parathyroid hormone (PTH), calcium, phosphorus, alkaline phosphatase of blood serum-were evaluated. The level of morphogenetic protein OPG and glycoprotein sclerostin was determined using commercial ELISA kit from Biomedica (Austria) by enzyme immunoassay. The morphofunctional features of the aorta and large arteries were studied by duplex scanning using the Doppler effect. We determined the peak systolic velocity of blood flow in the aortic arch (Vps-peak systolic velocity) , which indirectly indicates the state of the aortic wall and its lumen. Echocardiography with Doppler imaging was performed on the "ALOKA 4000" device. The LV myocardial mass index (LVMI), LV hypertrophy variants, LV systolic and diastolic function were determined. Results Cardiovascular damage, which manifests itself in the form of various variants of left ventricular hypertrophy, aortic rigidity, arteriosclerosis and vascular calcification, and directly correlated with the severity of renal failure, was detected in 86% of the examined patients with stage 3-5 CKD. The level of OPG and sclerostin in the blood serum increased with the progression of renal failure from the 3rd to the 5th. The main associations with Vps changes were high OPG levels [OR = 2.39 95% confidence interval (95% CI) (1.34–4.86) for levels ranging from 5.98 to 9.26 pmol / L and OR = 5.54 95% CI (2.64–13.5) for levels ≥9.26 pmol / L; P &amp;lt;0.0001] and high sclerostin levels [OR = 2.64 95% CI (1.42–5.16) for levels ranging from 0.744 to 1.211 ng / ml and OR = 3.69 95% CI (1.76–7.31) for a level ≥1.211 ng / ml; P = 0.0001]. Thus, the logistic regression model showed that the risk of aortic calcification was significantly increased when both OPG (≥5.98 pmol / L) and sclerostin (≥0.744 ng / ml) levels were high [ uncorrected model: OR = 11.93 (4.54–25.2); P &amp;lt;0.0001; on the model adjusted for generally recognized cardiovascular disease risk factors: OR= 5.55 (1.43–1914); P = 0.02]. Conclusion The results suggest that bone metabolism inhibitors, OPG and sclerostin, are independently associated with aortic calcification with potential additive effects in patients with stage 3-5 CKD. The risk of vascular calcification was significantly increased when OPG and sclerostin levels were high

Effect of Treating Hyperphosphatemia With Lanthanum Carbonate vs Calcium Carbonate on Cardiovascular Events in Patients With Chronic Kidney Disease Undergoing Hemodialysis

Among patients with hyperphosphatemia undergoing dialysis, it is unclear whether non-calcium-based phosphate binders are more effective than calcium-based binders for reducing cardiovascular events. To determine whether lanthanum carbonate reduces cardiovascular events compared with calcium carbonate in patients with hyperphosphatemia at risk of vascular calcification undergoing hemodialysis. Open-label, randomized, parallel-group clinical trial with blinded end point adjudication performed in 2374 patients with chronic kidney disease from 273 hemodialysis facilities in Japan. Eligible patients had hyperphosphatemia and 1 or more risk factors for vascular calcification (ie, ≥65 years, postmenopausal, diabetes). Enrollment occurred from November 2011 to July 2014; follow-up ended June 2018. Patients were randomized to receive either lanthanum carbonate (n = 1154) or calcium carbonate (n = 1155) and titrated to achieve serum phosphate levels of between 3.5 mg/dL and 6.0 mg/dL. The primary outcome was a composite cardiovascular event (cardiovascular death, nonfatal myocardial infarction or stroke, unstable angina, transient ischemic attack, or hospitalization for heart failure or ventricular arrhythmia). Secondary outcomes included overall survival, secondary hyperparathyroidism-free survival, hip fracture-free survival, and adverse events. Among 2309 randomized patients (median age, 69 years; 40.5% women), 1851 (80.2%) completed the trial. After a median follow-up of 3.16 years, cardiovascular events occurred in 147 of 1063 patients in the lanthanum calcium group and 134 of 1072 patients in the calcium carbonate group (incidence rate, 4.80 vs 4.30 per 100 person-years; difference 0.50 per 100 person-years [95% CI, -0.57 to 1.56]; hazard ratio [HR], 1.11 [95%, CI, 0.88 to 1.41], P = .37). There were no significant differences in all-cause death (difference, 0.43 per 100 person-years [95% CI, -0.63 to 1.49]; HR, 1.10 [95% CI, 0.88 to 1.37]; P = .42) or hip fracture (difference, 0.10 per 100 person-years [95% CI, -0.26 to 0.47]; HR, 1.21 [95% CI, 0.62 to 2.35]; P = .58). The lanthanum carbonate group had an increased risk of cardiovascular death (difference, 0.61 per 100 person-years [95% CI, 0.02 to 1.21]; HR, 1.51 [95% CI, 1.01 to 2.27]; P = .045) and secondary hyperparathyroidism (difference, 1.34 [95% CI, 0.49 to 2.19]; HR, 1.62 [95% CI, 1.19 to 2.20]; P = .002). Adverse events occurred in 282 (25.7%) in the lanthanum carbonate group and 259 (23.4%) in the calcium carbonate groups. Among patients undergoing hemodialysis with hyperphosphatemia and at least 1 vascular calcification risk factor, treatment of hyperphosphatemia with lanthanum carbonate compared with calcium carbonate did not result in a significant difference in composite cardiovascular events. However, the event rate was low, and the findings may not apply to patients at higher risk. ClinicalTrials.gov Identifier: NCT01578200; UMIN Clinical Trial Registry Identifier: UMIN000006815.

Osteocalcin and Abdominal Aortic Calcification in Hemodialysis Patients: An Observational Cross-Sectional Study.

ObjectivesTo investigate the serum level of osteocalcin (OC), also known as bone Gla protein, in maintenance hemodialysis (MHD) patients and its correlation with abdominal aortic calcification (AAC).MethodsFrom July 2017 to February 2020, we enrolled 108 adult MHD patients. Routine fasting blood laboratory tests were performed before the start of the second hemodialysis in a week. Abdominal aortic calcification score (AACs) was assessed within 1 month. Pearson correlation and Logistic regression were used to analyze the data.ResultsThe OC level was 231.56 (25.92,361.33) ng/ml, elevating significantly in this group of MHD patients. It had a positive correlation with serum phosphorus (r = 0.511, P = 0.001), intact parathyroid hormone(iPTH) (r = 0.594, P = 0.0001), fibroblast growth factor 23(FGF23) (r = 0.485, P = 0.003) and a negative correlation with age(r = -0.356, P = 0.039). Based on the AACs, patients were divided into two groups. Serum OC level were higher in patients with AACs≥5 (p=0.032). A multiple logistics regression analysis revealed that age (odds ratio [OR]1.14, P=0.005) and OC(OR=1.10, P=0.008)were risk factors for high AACs(≥5).ConclusionThe study implicated that OC elevated significantly in this group of MHD patients.OC is positively correlated with phosphorus, iPTH, FGF23, and a negative correlation with age. OC was a risk factor for vascular calcification in this study, but this study did not classify osteocalcin as c-OC and unOC. Whether unOC is associated more directly with vascular calcification requires further study.

Predictors of Vascular Calcification in Hemodialysis Patients

Background: The prevalence of both cardiovascular mortality and vascular calcification is much higher in patients with chronic kidney disease (CKD) than in the general population so early detection and intervention of VC may prevent or delay the progression and achieve improved patient outcomes. Objectives: To detect different predictors of vascular calcification in haemodialysis patients. Methods: This was a cross sectional observational study that included 85 patients with end stage renal disease (ESRD) on regular dialysis 47 males and 38 females ranged between 18 and 80 years old selected from Nephrology Unit, Internal Medicine Department, Menoufia University Hospital from April 2019 to May 2020. Serum calcium, phosphorus, alkhaline phosphatase, intact PTH, serum Matrix GLA protein, vitamin D and non-contrast CT for calcium scoring of femoral arteries were performed. Results: There was a significant correlation between age of the patient by years (p value 0.0001), serum calcium (p value 0.0001), phosphate (0.0001), calcium phosphate products (p value 0.0001) and alkhaline phosphatase (0.0001), and vascular calcification score detected by non-contrast CT on femoral arteries and negative correlation between serum Matrix GLA protein p value 0.0001) and the detected calcification score; the lower the MGP level the higher calcification score while there was no correlation between body mass index (BMI) (p value 0.021) intact PTH (p value 0.117), serum vitamin D level (p value 0.643), serum albumin (p value 0.643), serum haemoglobin (p value 0.257) and duration of dialysis (p value 0.260) and the detected score. Serum phosphate and calcium phosphorus product are independent risk factors for vascular calcification severity in haemodialysis patients. Conclusions: serum phosphate, calcium phosphate products are risk factors for vascular calcification while intact PTH vitamin D has no significant role in developing vascular calcification in hemodialysis patients. Matrix GLA protein was inversely correlated with vascular calcification score.

Sevelamer Use, Vitamin K Levels, Vascular Calcifications, and Vertebral Fractures in Hemodialysis Patients: Results from the VIKI Study

Hyperphosphatemia is a risk factor for vascular calcifications (VCs), which are part of the chronic kidney disease-mineral and bone disorders (CKD-MBD). Vitamin K-dependent proteins such as matrix Gla protein (MGP) and bone Gla proteins (BGP, or osteocalcin) can inhibit VCs and regulate bone mineralization. In this analysis of the Vitamin K Italian (VIKI) study, the relationship between vitamin K status, vertebral fractures (VFs) and VCs in 387 hemodialysis (HD) patients with (N = 163; 42.1%) or without N = 224; 57.9%) sevelamer was evaluated. Levels of vitamin K vitamers K1 and K2 or menaquinones (MK; MK4-7), total and undercarboxylated (uc) forms for both BGP and MGP were determined. Although no differences in clinical characteristics were noted, lower levels of MK4 (0.45 versus 0.6 ng/mL, p = .01) and a greater MK4 deficiency was observed in sevelamer-treated patients (13.5% versus 5.4%, p = .005). Multivariate logistic regression revealed that MK4 deficiency was associated with sevelamer use (odds ratio [OR] = 2.64, 95% confidence interval [CI] 1.25-5.58, p = .011) and aortic calcification (OR = 8.04, 95% CI 1.07-60.26, p = .04). In the same logistic model, sevelamer amplified the effect of total BGP levels on the odds of VFs in patients with total BGP <150 μg/L compared with those with total BGP ≥150 μg/L (OR = 3.15, 95% CI 1.46-6.76, p = .003). In contrast, there was no such effect in those untreated (total BGP <150 μg/L versus total BGP ≥150 μg/L: OR = 1.21, 95% CI 0.66-2.23, p = .54]; p = .049 for effect modification by sevelamer). Sevelamer may interfere with MK4 levels in HD patients and interact with low BGP levels to increase bone fractures in CKD patients. © 2020 American Society for Bone and Mineral Research (ASBMR).

Serum Calcification Propensity in Children on Chronic Hemodialysis

Serum Calcification Propensity in Children on Chronic Hemodialysis

P0667FIBROBLAST GROWTH FACTOR 21 PROMOTES AND PREDICTS VASCULAR CALCIFICATION IN HAEMODIALYSIS PATIENTS

Abstract Background and Aims Cardiovascular disease (CVD) is the leading cause of death in hemodialysis (HD) patients. Vascular calcification (VC) is dramatically accelerated and strongly associated with CVD events and mortality in HD patients. This study aimed to achieve 4 objectives using a population-based retrospective cohort of HD patients: (1)quantify the correlation between FGF21 and VC; (2)determine whether FGF21 is a novel risk factor for VC; (3)examine the predictive effect of FGF21 on VC; (4)explore the underlying mechanism of FGF21 in promoting VC, especially focused on the EndMT process, in cultured human aortic endothelial cells (HAECs). Method 802 HD patients were screened, at last 388 HD patients were eligible in the study. Serum FGF21 levels were assessed by ELISA kits. Chest radiographies of HD patients taken by multislice computed tomography were used to measure TACS. HD patients were divided into two groups : low TACS group (&amp;lt; median of TACS) and high TACS group (≧median of TACS). Univariate analyses were performed to compare the differences between two groups. Categorical data were compared using the Chi-square test. Stepwise multivariate linear regression analyses were employed to evaluate variables independently associated with TACS. The ROC curves were performed to calculate the AUC and compare the prognostic value of every independently associated factor or united factor to VC. Additionally HAECs was pretreated with FGF21 in the presence or absence of PTH. The formation of calcium deposits was analysed by Alizarin Red staining (ARS). PCR for the measurement of mRNA of CD31, RUNX2 and FSP1 to evaluate endothelial-to-mesenchymal transition (EndMT) of HAECs. Results Prevalence of VC was 70.1% in this study. Serum FGF21 levels of HD patients were 11-fold higher than controls (median 217 vs. 20 pg/ml). HD patients in the high TACS group had older age, higher FGF21, higher FGF23, longer dialysis vintage, higher incidence of hypertension and higher incidence of CVD (all P&amp;lt;0.05) compared with those in the low TACS group. Ln (FGF21) was positively related with Ln (TACs+1) (r=0.295). ROC curves showed that the AUC of FGF21 for predicting TAC was 0.63 (P&amp;lt;0.01), while FGF21 combined with other independent associated factors like age, calcium and PTH, the AUC markedly increased (AUC=0.84) with optimal sensitivity (82%) and specificity (71%). ARS showed that calcium deposition was observed in cultured HAECs stimulated by PTH alone and even aggravated by PTH+FGF21; however, no calcium deposition was observed in HAECs stimulated by FGF21 alone. Compared with the control, reduced expression of CD31(endothelial cell marker) mRNA in parallel with increased expression of RUNX2(osteoblast marker) mRNA and FSP1(mesenchymal cell marker) mRNA was observed in HAECs stimulated by PTH. However, FGF21 alone had no significant effect on the EndMT process. Notably, stimulation of PTH+FGF21 in HAECs aggravated the effect of PTH alone on EndMT. Conclusion This study is the first to show that serum FGF21 levels were significantly and independently correlated with VC in HD patients. Furthermore, FGF21 combined with PTH, calcium and age can significantly predict VC in HD patients. Additionally FGF21 aggravated the effect of PTH on calcium deposition and EndMT in HAECs. Taken together, our in vivo and in vitro results indicated that FGF21 was a novel predictor and promoter of VC in HD patients.