Vascular Calcification In Hemodialysis Patients Research Articles

Comparative Study Evaluating the Effect of the Administration of Vitamin K1 versus Placebo on Vascular Calcification in Haemodialysis Patients

Abstract Background Cardiovascular calcification is a risk factor and contributor to morbidity and mortality in End stage kidney disease patients. Cardiovascular calcification is most likely due to an imbalance of promoters (e.g. Calcium and phosphate) and inhibitors (e.g. fetuin-A and matrix Gla protein). Aim of the Work We aimed to study the effect of oral vitamin k1 on serum carboxylated Matrix gla protein in patients on maintenance hemodialysis and to study its effect as an important marker of vascular calcification. Patients and Methods This Placebo Controlled clinical trial was conducted for 3 months on 80 adult ESRD patients on regular Hemodialysis randomly allocated into 2 groups of either vitamin K1 versus oral placebo tablet administration for 3 months. Patients in both groups were age and sex matched, study group included 18 (45%) males and 22 (55%) females with mean age ± SD 47.350 ± 14.420 years, while the placebo group included 16 (40%) males and 24 (60%) with mean age ± SD 49.500 ± 14.509 years, with no significant difference between both groups as regard demographic data, access of hemodialysis, and duration of Hemodialysis. Results There was no significant change in bone parameters (serum Ca, PO4 & Ca/PO4 product) after 3 months of vit K1 administration compared to baseline in the study group. Serum phosphorus levels showed a minimal, yet statistically significant decrease after 3 months of placebo administration, this might be attributed to the different doses of PO4 binders in patients of both groups. Consequently, Ca/ PO4 product showed a statistically significant decrease after 3 months of placebo administration (P = 0.002), mostly attributed to the significant decrease in serum phosphorus in the same group over the same period. We observed that serum MGP levels significantly increased after administration of vitamin k1 in study group (P < 0.001) with 78.05% increase. However, a much lower increase, yet statistically significant increase in serum MGP level was noticed in the placebo group (P < 0.001) with 40.60 % increase. There was no statistically significant difference between the two groups according to their risk factors regarding smoking, HTN, HCV, DM, and ISHD. Conclusion We concluded that Oral vitamin K1 therapy significantly increased serum active form of Matrix GLA protein levels among hemodialysis patients with potential decrease in cardiovascular calcification and cardiovascular diseases.

Circulating miR-129-3p in combination with clinical factors predicts vascular calcification in hemodialysis patients.

Vascular calcification (VC) commonly occurs and seriously increases the risk of cardiovascular events and mortality in patients with hemodialysis. For optimizing individual management, we will develop a diagnostic multivariable prediction model for evaluating the probability of VC. The study was conducted in four steps. First, identification of miRNAs regulating osteogenic differentiation of vascular smooth muscle cells (VSMCs) in calcified condition. Second, observing the role of miR-129-3p on VC in vitro and the association between circulating miR-129-3p and VC in hemodialysis patients. Third, collecting all indicators related to VC as candidate variables, screening predictors from the candidate variables by Lasso regression, developing the prediction model by logistic regression and showing it as a nomogram in training cohort. Last, verifying predictive performance of the model in validation cohort. In cell experiments, miR-129-3p was found to attenuate vascular calcification, and in human, serum miR-129-3p exhibited a negative correlation with vascular calcification, suggesting that miR-129-3p could be one of the candidate predictor variables. Regression analysis demonstrated that miR-129-3p, age, dialysis duration and smoking were valid factors to establish the prediction model and nomogram for VC. The area under receiver operating characteristic curve of the model was 0.8698. The calibration curve showed that predicted probability of the model was in good agreement with actual probability and decision curve analysis indicated better net benefit of the model. Furthermore, internal validation through bootstrap process and external validation by another independent cohort confirmed the stability of the model. We build a diagnostic prediction model and present it as an intuitive tool based on miR-129-3p and clinical indicators to evaluate the probability of VC in hemodialysis patients, facilitating risk stratification and effective decision, which may be of great importance for reducing the risk of serious cardiovascular events.

Study of Osteopontin as a Marker of Arteriovenous Shunt Stenosis in Hemodialysis Patients.

Although arteriovenous fistula (AVF) is the recommended access for hemodialysis (HD), it carries a high risk for stenosis. Since osteopontin (OPN) is implicated in the process of vascular calcification in HD patients, OPN may be a marker for AVF stenosis. The present study evaluated OPN as a potential marker of AVF stenosis in HD patients. Diagnosing a stenotic lesion was made by combining B mode with color and pulse wave Doppler imaging. Criteria for diagnosis of stenotic AVF included 50% reduction in diameter in B mode in combination with a 2-3-fold increase of peak systolic velocity compared with the unaffected segment. The present study included 60 HD patients with stenotic AVF and 60 patients with functional AVF. Comparison between the two groups revealed that patients in the former group had significantly higher serum OPN levels [median (IQR): 17.1 (12.1-30.4) vs 5.8 (5.0-10.0) ng/mL, p<0.001]. All patients were classified into those with low (< median) and with high (≥ median) OPN levels. Comparison between these groups revealed that the former group had a significantly lower frequency of stenotic AVF (31.7 vs 68.3%, p<0.001) and a longer time to AVF stenosis [mean (95% CI): 68.4 (54.7-82.1) vs 46.5 (39.6-53.4) months, p=0.001]. OPN levels in HD patients may be useful markers for predicting and detecting AVF stenosis.

Beyond Bones: Examining Vascular Calcification in Hemodialysis Patients and Its Association with Bone and Mineral Metabolism

Beyond Bones: Examining Vascular Calcification in Hemodialysis Patients and Its Association with Bone and Mineral Metabolism

Comparative Study Evaluating the Effect of the Administration of Vitamin K1 versus Placebo on Vascular Calcification in Haemodialysis Patients

Abstract Background Cardiovascular calcification is a risk factor and contributor to morbidity and mortality in End stage kidney disease patients. Patients with chronic kidney disease develop accelerated calcification of the intima, media, heart valves and myocardium as well as the rare condition of calcific uremic arteriolopathy (calciphylaxis). Pathomechanistically, Cardiovascular calcification is most likely due to an imbalance of promoters (e.g. Calcium and phosphate) and inhibitors (e.g. fetuin-A and matrix Gla protein). Objective to study the effect of oral vitamin k1 on serum Matrix gla protein in patients on maintenance hemodialysis and to study its effect as an important marker of vascular calcification. Patients and Methods This Placebo Controlled clinical trial was conducted for 3 months on 80 adult ESRD patients on regular Hemodialysis recruited from Ain shams university Hospitals hemodialysis unit, their age ranged from 18 to 75 years each participant signed informed consent classified into two groups, with the study group containing 40 patients who received Vitamin K1 therapy 5 mg every other day for three months duration and the control placebo group containing 40 patients who received Placebo every other day for three months duration. Results There was no statistically significant difference between the two groups according to their risk factors regarding smoking, HTN, HCV, DM, and ISHD. In this clinical trial only 29 % of patients were diabetic, but their diabetes was well controlled and there was no significant difference between groups regarding incidence of diabetes. There was no significant difference between groups regarding vascular access (AVF, Double lumen tunneled dialysis catheter) and duration of dialysis (P &amp;gt; 0.05). The current study showed that vitamin k1 therapy resulted in no significant effect in comparison to the placebo group on calcium, phosphorus, calcium-phosphorus product and (P = 0.435), (P = 0.142), (P = 0.191) respectively. Age has non-significant effect on MGP level neither in the study group (P = 0.636) before vitamin k1 therapy nor in the placebo group (P = 0.841) and after vitamin k1 therapy in study group (P = 0.605) and placebo group (P = 0.332). Conclusion Different risk factors including Hypertension, Diabetes Mellitus, Smoking, Heart failure, Ischemic heart disease and hepatitis c virus has no significant effect on serum MGP levels neither before nor after therapy in both study and placebo groups.

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.

Randomized Controlled Clinical Trial of the Effect of Treatment with Vitamin K2 on Vascular Calcification in Hemodialysis Patients (Trevasc-HDK)

Vitamin K deficiency among patients on hemodialysis (HD) affects the function of matrix GLA protein (MGP), a potent vitamin K-dependent inhibitor of vascular calcification (VC). We conducted a single-center randomized controlled trial (RCT) on maintenance HD patients to examine if vitamin K2 supplementation can reduce progression of coronary artery calcification (CAC) over an 18-month study period. Patients were randomized to vitamin K2 group receiving menaquinone-7360 μg 3 times/wk or control group. The primary outcome was CAC scores at the end of the study period. The secondary outcomes were aortic valve calcification (AVC), carotid-femoral pulse wave velocity (cfPWV), aortic augmentation index (AIx), dephosphorylated undercarboxylated MGP (dp-ucMGP) levels, major adverse cardiac events (MACE), and vascular access events. Of the 178 patients randomized, follow-up was completed for 138 patients. The CAC scores between the 2 groups were not statistically different at the end of 18 months (relative mean difference [RMD] 0.85, 95% CI 0.55-1.31). The secondary outcomes did not differ significantly in AVC (RMD 0.82, 95% CI 0.34-1.98), cfPWV (absolute mean difference [AMD] 0.55, 95% CI-0.50 to 1.60), and AIx (AMD 0.13, 95% CI-3.55 to 3.80). Supplementation with vitamin K2 did reduce dp-ucMGP levels (AMD-86, 95% CI-854 to-117). The composite outcome of MACE and mortality was not statistically different between the 2 groups (Hazard ratio= 0.98, 95% CI 0.50-1.94). Our study did not demonstrate a beneficial effect of vitamin K2 in reducing progression of VC in this population at the studied dose and duration.

#5745 CORRELATION BETWEEN MATRIX GLA PROTEIN LEVEL AND EFFECT OF VITAMIN K2 THERAPY ON VASCULAR CALCIFICATION IN HEMODIALYSIS PATIENTS

Abstract Background and Aims In hemodialysis patients, vascular calcifications are precocious, frequent, and excessive. The association between the level of vascular calcifications and mortality has been described in dialysis patients. The dephosphorylated and uncarboxylated matrix Gla protein (dp-ucMGP) is an indicator of vitamin K2 status and correlates with markers of vascular calcification. It is activated by γ glutamyl carboxylase that converts inactive matrix Gla protein into an active form, and vitamin K2 is a cofactor of this reaction. The active form of matrix Gla protein is a known inhibitor of arterial wall calcification and plays an essential role in bone turnover. The biological activity of the calcification-inhibitory matrix Gla protein can be achieved by simple administration of oral vitamin K2. Aim To assess the effect of vitamin k2 supplementation on vascular calcification and matrix Gla protein in hemodialysis patients. In addition, we wanted to clarify the role of vitamin k2 as prophylaxis against vascular calcification in hemodialysis patients not suffering from vascular calcifications. Method The study included 112 hemodialysis adult patients not receiving vitamin k antagonists. The study was conducted at the Urology and Nephrology Center, Mansoura University. Patients who suffered from vascular calcification (68 patients) received oral 180 μgr of vitamin K2 every day for one year. Uncarboxylated matrix Gla protein concentrations were quantified using ELISA before administering vitamin k2 and after 12 months of treatment. In addition, we used an abdominal CT scan to assess aortic calcification with Agatston score. The scan was performed at the beginning of the study and after 12 months of follow-up. Patients who did not suffer from vascular calcification (44 patients) were randomly assigned to either receive oral vitamin K2 or no treatment. Uncarboxylated matrix Gla protein concentrations were quantified using ELISA at randomization and 12 months. Aortic calcification was evaluated using Agatston score after an abdominal CT scan that was performed at the beginning and at 12 months of follow-up. Results There was a positive and statistically significant correlation between un-carboxylated matrix Gla protein level and vascular calcification (rs = 0.64, P-value &amp;lt; 0.001). Among patients with vascular calcification, the baseline plasma (dp-ucMGP) significantly decreased by 21.3% after treatment of vitamin k2 for one year. Besides, the median baseline calcium score significantly decreased by 15.1% after 1year of vitamin k2 treatment. On the other hand, patients without vascular calcification had their 1-year matrix GLA protein comparable between the two groups. Despite the reduction of matrix GLA protein in the vitamin k2 naïve group, there was no statistically significant difference. In addition, the calcium score after one year was comparable between both groups. Conclusion Hemodialysis patients are at risk of vascular calcification. There is a positive correlation between (dp-ucMGP) protein and vascular calcification. Supplementation of vitamin K2 is safe and improves the serum markers of its deficiency. Also, vitamin K2 supplementation slows the progression of calcification. On the other hand, there is a lack of strong evidence that vitamin K2 supplementation slows down the calcification progression in dialysis patients. Therefore, we recommend further studies to delineate the efficacy and cost-effectiveness of the drug.

Relationship between gut microbiota and vascular calcification in hemodialysis patients

Introduction Vascular calcification (VC) is an independent risk factor for cardiovascular mortality in end-stage renal disease (ESRD) patients. The pathogenesis of VC is complicated and unclear. Uremic toxins produced by gut microbiota can promote VC. This study aims to identify the differences in gut microbiota between the different VC groups and the main bacteria associated with VC in hemodialysis (HD) patients in an attempt to open up new preventive and therapeutic approaches and define the probable mechanism for VC in HD patients in the future. Methods A total of 73 maintenance HD patients were enrolled in this cross-sectional study. According to the abdominal aortic calcification (AAC) scores, the participants were divided into the high AAC score group and the low AAC score group. High-throughput sequencing of the gut microbiota was performed and the results were evaluated by alpha diversity, beta diversity, species correlation, and model predictive analyses. Results The prevalence of VC was 54.79% (40/73) in the study. The majority of phyla in the two groups were the same, including Firmicutes, Actinobacteriota, Proteobacteria, and Bacteroidota. The microbial diversity in the high AAC score group had a decreasing trend (p = 0.050), and the species abundance was significantly lower (p = 0.044) than that in the low AAC score group. The HD patients with high AAC scores showed an increased abundance of Proteobacteria and decreased abundances of Bacteroidota and Synergistota at the phylum level; increased abundances of Escherichia-Shigella, Ruminococcus_gnavus_group, and Lactobacillus; and decreased abundances of Ruminococcus and Lachnospiraceae_NK4A136_group at the genus level (p<0.05). Escherichia-Shigella and Ruminococcus_gnavus_group were positively correlated with VC, and Ruminococcus, Adlercreutzia, Alistipes, and norank_f__Ruminococcaceae were negatively correlated with VC. Escherichia-Shigella had the greatest influence on VC in HD patients, followed by Ruminococcus and Butyricimonas. Conclusions Our results provide clinical evidence that there was a difference in gut microbiota between the different VC groups in HD patients. Escherichia–Shigella, a lipopolysaccharide (LPS)-producing bacterium, was positively correlated with VC and had the greatest influence on VC. Ruminococcus, a short-chain fatty acid (SCFA)-producing bacterium, was negatively correlated with VC and had the second strongest influence on VC in HD patients. The underlying mechanism is worth studying. These findings hint at a new therapeutic target.

Higher serum trimethylamine-N-oxide levels are associated with increased abdominal aortic calcification in hemodialysis patients

Introduction Vascular calcification (VC) is high prevalent and predicts cardiovascular mortality in dialysis patients. The mechanisms are not known clearly. Trimethylamine-N-oxide (TMAO), a gut-microbiota derivate metabolite, is also associated with cardiovascular outcomes in hemodialysis (HD) patients. This study aims to evaluate serum TMAO levels and establish their relation to VC in HD patients. Methods Serum TMAO concentrations were measured by high-performance liquid chromatography–mass spectrometry. Vascular calcification was evaluated by abdominal aortic calcification (AAC) scores. Taking the AAC score value 5.5 as the cutoff value, the participants were divided into the high AAC score group and the low AAC score group. Results A total of 184 HD patients and 39 healthy controls were enrolled in this cross-sectional study. Serum Ln(TMAO) (the natural logarithm of TMAO) concentrations were significantly higher in HD patients than that of control subjects (1.82 ± 0.62 vs. −1.60 ± 0.77, p < 0.001). Compared with the group with low AAC scores, the HD patients with high AAC scores showed significantly higher serum Ln(TMAO) levels (2.09 ± 0.55 vs. 1.67 ± 0.54, p < 0.001). In the multivariate regression analysis, serum Ln(TMAO), HD vintage, with diabetic mellitus, age and plasma intact parathyroid hormone (iPTH) were independent determinant factors for VC in HD patients. Conclusions Higher serum TMAO levels, older age, longer HD vintage, higher plasma iPTH and with diabetes mellitus were independent risk factors for VC in HD patients. The underlying mechanism deserves further investigations and the finding hints at a new target for the treatment of VC.

Citric acid-based bicarbonate dialysate attenuates aortic arch calcification in maintenance hemodialysis patients: a retrospective observational study.

Progression of aortic calcification is associated with all-cause and cardiovascular mortality in hemodialysis patients. Blood calciprotein particle (CPP) levels are associated with coronary artery calcification and were reported to be inhibited when using citric acid-based bicarbonate dialysate (CD). Therefore, this study aimed to examine the effect of CD on the progression of the aortic arch calcification score (AoACS) and blood CPP levels in hemodialysis patients. A 12-month retrospective observational study of 262 hemodialysis patients was conducted. AoACS was evaluated by calculating the number of calcifications in 16 segments of the aortic arch on chest X-ray (minimum score is 0; maximum score is 16 points). The patients were divided into the following groups according to their baseline AoACS: grade 0, AoACS = 0 points; grade 1, AoACS 1-4 points; grade 2, AoACS 5-8 points; grade 3, AoACS 9 points or higher. Patients on bisphosphonates or warfarin or with AoACS grade 3 were excluded. Progression, defined as ΔAoACS (12-month score - baseline score) > 0 points, was compared between the CD and acetic acid-based bicarbonate dialysate (AD) groups before and after adjusting the background using propensity score matching. The AoACS progression rate was significantly lower in the CD group than in the AD group (before matching: P = 0.020, after matching: P = 0.002). Multivariate logistic regression analysis showed that CD was significantly associated with AoACS progression (odds ratio 0.52, 95% confidence interval 0.29‒0.92, P = 0.025). CD may slow the progression of vascular calcification in hemodialysis patients.

Compensatory elevated serum intermedin levels are associated with increased vascular calcification in hemodialysis patients.

Vascular calcification (VC), which is a pathological process of abnormal calcium and phosphorus deposition in blood vessels, valves, heart and other tissues, is highly prevalent and predicts mortality in dialysis patients. Its mechanisms are complex and unclear. We presume that intermedin (IMD), a kind of small molecule active peptide, may play roles in VC in hemodialysis (HD) patients. This study aims to evaluate serum IMD levels and establish their relation to VC and other parameters in HD patients. A total of 116 patients on maintenance HD treatment and 52 age- and sex-matched healthy controls were enrolled in this study. Serum IMD levels were measured by radioimmunoassay (RIA). VC was evaluated by abdominal aortic calcification scores. Serum IMD levels were significantly lower in HD patients than in controls [24.89 (13.55, 50.24) pg/ml vs. 137.79 (93.21, 201.64) pg/ml, P < 0.0001]. In addition, IMD was negatively correlated with the serum phosphate level (P = 0.036) in HD patients. However, compared with the group whose IMD levels were above the median, patients with IMD levelsless than the median had a lower incidence of VC (P = 0.031). Multivariate logistic regression analyses revealed that serum IMD levels more than 24.89pg/ml (P = 0.014, OR = 0.285), higher serum iPTH levels (P < 0.0001, OR = 1.093) and older age (P = 0.009, OR = 1.003) were significant independent determinant factors for VC in HD patients. The serum IMD levels were significantly lower in HD patients than that in healthy group. In addition to higher PTH levels and older age, compensatory elevated IMD levels may be an independently determinant factor for VC in HD patients. This was the first study about IMD and VC in dialysis patients.

MO789: The Effect of Oral Vitamin K2 Versus K1 on Vascular Calcification in Hemodialysis Patients: A Randomized Controlled Trial

Abstract BACKGROUND AND AIMS Vascular calcification is a common complication of end-stage renal disease and an important cause of cardiovascular diseases and mortality. Vitamin K is essential for the activation of matrix Gla protein (MGP), a powerful inhibitor of tissue calcification. However, there are limited data on the efficacy and safety of different vitamin K forms on vascular calcification in hemodialysis patients, most of whom are essentially vitamin K deficient. METHOD A prospective, randomized, placebo-controlled clinical trial, that included 120 eligible hemodialysis patients who were randomly assigned to one of three equal study groups: vitamin K1 (10 mg phytomenadione thrice-weekly), vitamin K2 (90 ug daily), or placebo for 3 months. Serum MGP, calcium, phosphorus, their product and intact parathyroid hormone (iPTH) levels were all assessed at baseline and at the end of the study. RESULTS MGP levels showed a significant increase in the vitamin K2 group (700%) compared with (78%) and (40%) in vitamin K1 and placebo groups respectively. No change was found in bone profile at 3 months compared with baseline at both of the treatment groups. No correlations between calcium, phosphorous and PTH and MGP levels at baseline or after treatment. None of the treatment group patients experienced any adverse effects. CONCLUSION Vitamin K supplementation was tolerable and effective in improving levels of a potent calcification inhibitor as MGP, with K2 form showing superiority over K1 in their impact on MGP levels among hemodialysis patients.

The Relationship between Serum Sclerostin Levels and Bone Mineral Disorders and Vascular Calcification in Hemodialysis Patients

Background and aim of the study: Sclerostin is produced by osteocytes and has been shown to down-regulate the synthesis of many markers of bone formation by osteogenic cells. The aim of this study to investigate the relationship between serum sclerostin levels and bone mineral disorders and vascular calcification in hemodialysis patients (HD).&#x0D; Methods:This is a cross-sectional study of 70 patients with ESRD on regular HD for at least six months, Theodor Bilharz Research Institute, Giza, Egypt.Twenty-five subjects who matched the ages, genders, and demographics of the study patients were included as a control group.All patients and control groups included in the study underwent a full through history and clinical examination. Serum calcium, phosphorus, alkaline phosphatase and intact PTH (iPTH) levels were measured. Serum sclerostin was measured by an ELISA. Bone Mineral Densitometry Measurements BMD (g/cm2) was determined by dual-energy X-ray absorptiometry (DXA). CT scan was done to detect the presence or absence of vascular calcification and transthoracic echocardiogram to detect the presence or absence of valvular calcification.&#x0D; Results:The mean seumscleostin levels was a statistically significant high in the HD patients when compared with the control group (156.8 ±121.4 Vs.29.38±0.84, p =0.0001 ) and statistically significant high mean ALP in the HD patients when compared with the control group (147.2 ± 94.3 Vs. 38.8 ±23.4, p = 0.0001). The mean BMD was statistically significant low in the HD patients when compared with the controls (0.839±0.086 g/ m2 Vs.1.306 ±0.153 g/ m2, p = 0.0001).The mean seumscleostin levels was statistically significant high in the HD patients with vascular and valvular calcification when compared with HD patients without calcification.Using spearman correlation coefficient analysis, there was statistically significant negative correlations between serum sclerostin levels and iPTH(r=-0.362, p =0.0021), ALP (r=-0.301, p =0.0114), and BMD (r=-0.469, p =0.0278 ), and there was a statistically significant positive correlation between serum sclerostin levels and phosphate(r=0.5829, p =0.0001 ).Independent predictors of BMD in HD patients were determined using multi-variate regression analysis. Sclerostin levels, iPTH, ALP, and age were found to be independent predictors of BMD.&#x0D; Conclusion: High sclerostin levels in patients with ESRD on HD were associated with high risk of vascular and valvularcalcification and were independent predictors of low BMD in such population.

Osteocalcin and vascular calcification in hemodialysis patients: an observational cohort study.

Vascular calcification contributes to morbidity and mortality in patients with ESRD on maintenance hemodialysis. To study the relationship between osteocalcin and vascular calcification. 160 patients with ESRD on maintenance hemodialysis and 60 age-and sex-matched healthy controls were recruited. Serum vitamin K2 and osteocalcin both intact and undercarboxylated were measured. Transthoracic echocardiography was done for valvular calcification and thickening, and carotid duplex was done for carotid intimal medial calcification and thickening. Hemodialysis patients have higher median serum vitamin K2 (p < 0.001), higher undercarboxylated osteocalcin (p < 0.001). Only older age, duration of hypertension, and duration of established cardiovascular disease are associated with carotid media-intimal calcification. Old age is a strong predictor of carotid media intimal thickening. Female sex is associated with a valvular thickening. Functional vitamin K deficiency is present in maintenance hemodialysis patients and serum osteocalcin is not associated with cardiovascular calcification.

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.

Fibroblast Growth Factor 21 Predicts and Promotes Vascular Calcification in Haemodialysis Patients

Background: Cardiovascular disease (CVD) is the leading cause of death in haemodialysis (HD) patients. Vascular calcification (VC) is dramatically accelerated and is strongly associated with CVD events and mortality in HD patients. VC coexists with osteoporosis in many studies. Fibroblast growth factor 21 (FGF21) which is known as an adipocytokine is a new hypoglycemic strategy and is inversely related to bone mineral density. Methods: To evaluate the contribution of FGF21 to VC in HD patients, we detected circulating FGF21 levels and measured the whole thoracic aorta calcification scores (TACS) and calcification scores of the 3 segments of thoracic aorta, including ascending thoracic aorta (ATACS), aortic arch (AoACS), and descending thoracic aorta (DTACS) of our HD patients in this cross-sectional study. In addition, we pre-incubated human aortic endothelial cells (HAECs) with FGF21 in the presence or absence of parathyroid hormone (PTH) in vitro. Results: The median serum FGF21 level in HD patients was 11-fold higher than that in healthy controls. Ln(FGF21) was positively correlated with Ln(TACS+1), Ln(ATACS+1), Ln(AoACS+1), and Ln(DTACS+1), respectively, in HD patients. Serum FGF21 was independently associated with TACS and ATACS, AoACS, and DTACS. FGF21 which was combined with age, calcium, and intact PTH demonstrated a high area under the curve of 0.84 with optimal sensitivity (84%) and specificity (71%) for the prediction of VC in HD patients. Our vitro results showed that FGF21 enhanced the calcification effect of PTH on HAECs by increasing calcium deposition and endothelial-to-mesenchymal transition. Conclusions: Circulating FGF21 was notably higher and was a potential predictor and promoter of VC in HD patients.

The impact of cholecalciferol on markers of vascular calcification in hemodialysis patients: A randomized placebo controlled study

Background and aimVascular calcification is an independent risk factor for cardiovascular diseases and all-cause mortality in end stage renal disease, and particularly in hemodialysis patients. Vitamin D deficiency has been shown to be associated with vascular calcification among this category of patients. Cholecalciferol or vitamin D3; the native inactivated 25-hydroxy vitamin D [25(OH)D], has been proposed to have a good impact on vascular calcification and vitamin D deficiency. However, clinical data is still limited. Methods and resultsA prospective, randomized, placebo-controlled study was carried out to evaluate the effect of oral cholecalciferol on vascular calcification and 25(OH)D levels in hemodialysis patients. A total of sixty eligible hemodialysis patients were randomly assigned to either a treatment group (Oral 200.000IU Cholecalciferol per month) or a placebo group, for 3 months. Serum 25-hydroxy vitamin D (25(OH)D), fetuin-A, fibroblast growth factor (FGF-23), osteoprotegerin (OPG), calcium, phosphorus, their product (CaXP) and intact parathyroid hormone (iPTH) levels, were all assessed at baseline and at the end of the study. ClinicalTrials.gov registration number: NCT03602430. Cholecalciferol significantly increased serum levels of 25(OH)D and fetuin-A in the treatment group (p-value < 0.001), while no significant difference was observed in the placebo group. Cholecalciferol administration showed no effect on either FGF-23 or OPG. None of the treatment group patients experienced any adverse effects. ConclusionCholecalciferol was shown to be an effective, tolerable, inexpensive pharmacotherapeutic option to overcome vitamin D deficiency, with a possible modulating effect on fetuin-A, among hemodialysis patients. ClinicalTrials.gov registration numberNCT03602430.

Relationship between vitamin D receptor gene polymorphism FokI and fetuin A as marker of vascular calcification in Egyptian hemodialysis patients

Background: Vascular calcification is a common complication in end-stage renal disease patients and the leading cause of morbidity and mortality. Aim of the work: The current work aimed to evaluate the possible relationship between vitamin D receptor gene polymorphism FokI with fetuin-A and intact parathormone hormone in Egyptian hemodialysis patients. Patient and Methods: This study is a cross-sectional study including 50 hemodialysis patients attending the hemodialysis unit in Al-Zahra University Hospital and 30 apparently healthy persons as a control group. For all studied subjects, a detailed history was taken, physical examination, carotid intima-media thickness by carotid duplex, echocardiography, Laboratory investigations included serum levels of calcium, phosphorus, iPTH, fetuin, and genotype frequency by PCR Results: There was a highly significant increase in carotid intimal media thickness in the patient group Vs. control group & a highly significant decrease in serum Fetuin-A in the patient's group Vs. control group. There was a significant difference in the genotype distribution of FokI polymorphism among patients and control. There were significant negative relationships between FF genotype and iPTH and a highly significant negative correlation between serum fetuin-A and iPTH in the patient group. Conclusion: Vitamin D receptor gene FokI polymorphism FF genotyping is more frequent in hemodialysis patients who have higher iPTH and lower fetuin-A levels, which could identify the high-risk group susceptible to vascular calcification in hemodialysis patients. Further studies are needed.

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.