Marker Of Vascular Calcification Research Articles

Osteoprotegerin and Vascular Dysfunction in Patients with Stage 3 Chronic Kidney Disease and Those without Renal Dysfunction: A Case-Control Study.

Osteoprotegerin (OPG) is a marker of vascular calcification and cardiovascular risk in patients with chronic kidney disease (CKD). This study aimed to compare and correlate OPG values with flow-mediated dilation (FMD) and pulse wave velocity (PWV) measurements in patients in stage 3 CKD and those without renal dysfunction. This case-control study was conducted in a specialized hypertension center in 2022. A total of 79 patients over 18 years of age participated in the study. The case group consisted of 30 patients with moderate renal dysfunction (CKD stage 3) and the control group included 49 individuals with glomerular filtration rate ≥ 60 mL/min/1.73 m2. The significance level adopted in the statistical analysis was 5%. Central pulse pressure (cPP), PWV, and augmentation index (AIx) were higher in patients with renal dysfunction. The serum OPG level positively correlated with peripheral and central systolic blood pressure, cPP, PWV, and AIx. Conversely, the serum OPG did not correlate with FMD. OPG and PWV are possible biomarkers of vascular dysfunction that are altered in patients with moderate renal dysfunction. Despite limitations of this study, including that it was a case-control study conducted at a single center, it has the potential, as a proof of concept, to generate the hypothesis of OPG and PWV as biomarkers of early vascular damage in this population.

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.

#1943 The association of uncarboxylated, non-phosphorylated Matrix Gla protein with arterial stiffness in hemodialysis and peritoneal dialysis patients

Abstract Background and Aims Vitamin K deficiency has been identified as a marker of vascular calcification AND STIFNESS and an independent cardiovascular risk factor in hemodialysis (HD) and peritoneal dialysis (PD) patients, as the most powerful inhibitor of vascular calcification, Matrix Gla Protein requires vitamin K to become activated. However, until to date, it has not yet been clarified whether hepatic or extrahepatic markers of vitamin K status reflect the arterial status of dialysis patients. In this study we aimed to investigate the association of vitamin K deficiency with arterial stiffness in End-Stage Kidney Disease (ESKD) patients. Method In 42 ESKD patients undergoing either HD or PD, we measured plasma levels of the inactive vitamin-K dependent Matrix Gla Protein (dp-ucMGP) and serum levels of prothrombin (PIVKA-II) as markers of extrahepatic and hepatic insufficiency of vitamin K (CARIM Institute, Maastricht, Netherlands). In these patients we determined arterial stiffness parameters (pulse wave velocity-PWV) by the Mobil-O-Graph device (IEM, Stolberg, Germany). Results Serum PIVKA-II was associated with T2D duration (r = −0.38, p = 0.013), phosphorus levels (r = −0.41, p = 0.009) serum albumin (r = −0.33, p = 0.036) Spearman's rho test, and the type of transporter in PD patients (p = 0.039), Kruskal-Wallis test. Plasma dp-ucMGP was associated with PWV (r = 0.51, p = 0.001), peripheral (r = −0.37, p = 0.016) and central diastolic blood pressure (BP) (r = −0.34, p = 0.026) and age (r = 0.41, p = 0.007), Spearman's rho. Patients with T2DM, history of acute myocardial infarction and those receiving warfarin had significantly increased levels of circulating dp-ucMGP (p = 0.036, p = 0.039 and p < 0.0001, respectively, Kruskal-Wallis). Warfarin was associated with a 2.5-fold and a 23-fold increase in dp-ucMGP and PIVKA-II levels, respectively. Stepwise multiple regression analysis showed that PWV (p = 0.001, B = 494, 95% CI: 242-746) was an independent predictor of dp-ucMGP, independent of age, T2T2, history of myocardial infraction and diastolic BP. Conclusion Elevated plasma dp-ucMGP levels (suggesting extrahepatic vitamin K deficiency) were associated with increased arterial stiffness in dialysis patients.

Impact of bisphenol a on the levels of vascular calcification biomarkers in type 2 diabetes mellitus with vascular complications: A case-control study

Bisphenol A (BPA) is an endocrine disruptor present in polycarbonate plastics used in food containers and water bottles that resists insulin action and leads to type 2 diabetes mellitus (T2DM). However, there is scant research on the impact of BPA on T2DM-related vascular complications. Fetuin-A (FTA) and osteoprotegerin (OPG) are crucial markers for vascular calcification, which is the primary risk factor for developing vascular complications. This study aims to link external factor BPA levels with the vascular calcification markers FTA and OPG in diabetic subjects with and without vascular complications. Therefore, 120 study subjects were included and divided as control (n = 30), T2DM with cardiovascular diseases (CVD) (n = 30), T2DM with diabetic nephropathy (DN) (n = 30), and T2DM without vascular complications (n = 30). Serum and urinary FTA, OPG, and BPA levels were measured using an ELISA. FTA (AHSG) and OPG (TNFRSF11B) gene expression were analyzed using qPCR. Both serum (p < 0.001) and urinary BPA (p < 0.001) were found higher in T2DM with CVD and DN than T2DM without vascular complications and control. Also, T2DM with CVD and DN patients had lower serum and urinary FTA protein levels and increased serum and urinary OPG (p < 0.001) levels than T2DM without vascular complications and control. Moreover, FTA (AHSG) gene expression was negatively associated with serum BPA (p < 0.001) and urinary BPA (p < 0.01). Likewise, OPG (TNFRSF11B) gene expression was positively significant with serum BPA (p < 0.001) and urinary BPA (p < 0.01) in the study groups. These findings suggest that elevated blood and urinary BPA levels contribute to the severity of vascular complications in T2DM patients through vascular calcification.

IDF23-0370 The association between BAP levels and other markers of vascular calcification in patients with T2DM

IDF23-0370 The association between BAP levels and other markers of vascular calcification in patients with T2DM

Wnt signaling pathway and sclerostin in the development of atherosclerosis and vascular calcification.

Atherosclerosis is a complex process involving endothelial dysfunction, vascular inflammation, vascular smooth muscle cell (VSMC) proliferation, angiogenesis, and calcification. One of the pathomechanisms of atherosclerosis is the upregulation of Wnt signaling. This study aimed to summarize the current knowledge regarding the role of Wnt signaling and sclerostin in atherosclerosis, vascular calcification, aneurysms, and mortality based on the PubMed database. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendation and identified 160 papers that were included in this systematic review. The published data highlight that the upregulation of Wnt components facilitates the initiation and progression of atherosclerosis, arterial remodeling, VSMCs proliferation and phenotypic transition to the osteoblastic lineage in the arterial wall. This results in protein secretion, cell migration, calcification, fibrosis and aneurysm formation. The transformation of VSMCs into osteoblast-like cells that is observed in atherosclerosis results in sclerostin expression inhibiting the Wnt pathway. Furthermore, it was shown that sclerostin, expressed in atherosclerotic plaques, inhibits aneurysm formation in a mouse model. However, in humans, while the antisclerostin antibody romosozumab inhibits bone resorption, biochemical parameters of endothelial activation and inflammation are not affected, and the incidence of aneurysms is not increased. It was suggested that detecting sclerostin in the calcified aortic atherosclerotic plaques reflects a defense mechanism against Wnt activation and inhibition of atherosclerosis, although this has only been shown in animal models. Moreover, an increased number of vascular cells converted to osteogenic phenotypes results in increased plasma sclerostin concentrations. Therefore, plasma sclerostin derived from bone limits its importance as a global marker of vascular calcification.

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.

#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.

Can Bone-Specific Alkaline Phosphatase be a Marker of Vascular Calcification in Type 2 Diabetes Mellitus?

Alkaline phosphatase (ALP) enzyme has been linked to vascular calcification. Unexplained elevations in serum ALP levels have been reported in patients with type 2 diabetes mellitus (T2DM). We assessed bone-specific alkaline phosphatase (BAP) levels in patients with T2DM who had unexplained ALP elevations and studied the association between BAP and other markers of vascular calcification. Patients with T2DM who had high serum ALP in the absence of known causes of ALP elevation were studied. The control group was T2DM patients with normal ALP. We measured the serum levels of BAP along with the leptin, fetuin-A, and vitamin K2 levels. Ankle-brachial index (ABI) was also measured in both groups. Serum BAP levels were significantly higher in the group with high ALP when compared with the normal ALP group. A significant positive correlation was present between BAP and serum fetuin-A as well as between BAP and Vit K2 levels. There was no correlation between BAP and serum leptin. ABI was comparable between the two groups. Patients with T2DM may have unexplained elevation in ALP due to an increase in BAP. Elevation in BAP may be associated with other markers of vascular calcification suggesting an increased risk of vascular calcification.

Association of Red Blood Cell Distribution Width and Neutrophil-to-Lymphocyte Ratio with Calcification and Cardiovascular Markers in Chronic Kidney Disease.

We aimed to investigate the association between Red Blood Cell Distribution Width (RDW) and Neutrophil-to-Lymphocyte Ratio (NLR), simple, rapidly assessed markers from the complete blood count with vascular calcification (VC)/stiffness and cardiovascular disease (CVD) in chronic kidney disease (CKD). Dephosphorylated, uncarboxylated matrix Gla-protein (dp-ucMGP), and central/peripheral hemodynamics' parameters were measured in 158 CKD patients, including Hemodialysis and Peritoneal Dialysis. Spearman's rho analysis showed that RDW correlated with C-reactive protein (CRP) (r = 0.29, p < 0.001), dp-ucMGP (r = 0.43, p = < 0.0001), central diastolic blood pressure (DBP) (r = -0.19, p = 0.02), and albuminuria (r = -0.17, p = 0.03). NLR correlated with the duration of CVD (r = 0.32, p < 0.001), CRP (r = 0.27, p = 0.01), dp-ucMGP (r = 0.43, p < 0.0001), central DBP (r = -0.32, p < 0.0001) and eGFR (r = -0.25, p = 0.04). In multiple regression models, circulating dp-ucMGP was an independent predictor of RDW (β = 0.001, p = 0.001) and NLR (β = 0.002, p = 0.002). In CKD patients, RDW and NLR are associated with traditional and novel markers of VC and CVD.

Calcium isotopes as a biomarker for vascular calcification in chronic kidney disease.

Calcium balance is abnormal in adults with chronic kidney disease (CKD) and is associated with the development of vascular calcification. It is currently not routine to screen for vascular calcification in CKD patients. In this cross-sectional study, we investigate whether the ratio of naturally occurring calcium (Ca) isotopes, 44Ca and 42Ca, in serum could be used as a noninvasive marker of vascular calcification in CKD. We recruited 78 participants from a tertiary hospital renal center: 28 controls, 9 subjects with mild-moderate CKD, 22 undertaking dialysis and 19 who received a kidney transplant. For each participant, systolic blood pressure, ankle brachial index, pulse wave velocity, and estimated glomerular filtration rate were measured, along with serum markers. Calcium concentrations and isotope ratios were measured in urine and serum. While we found no significant association between urine Ca isotope composition (noted δ44/42Ca) between the different groups, δ44/42Ca values in serum were significantly different between healthy controls, subjects with mild-moderate CKD and those undertaking dialysis (P<0.01). Receiver operative characteristic curve analysis shows that the diagnostic utility of serum δ44/42Ca for detecting medial artery calcification is very good (AUC=0.818, sensitivity 81.8% and specificity 77.3%, P<0.01), and performs better than existing biomarkers. Although our results will need to be verified in prospective studies across different institutions, serum δ44/42Ca has the potential to be used as an early screening test for vascular calcification.

MicroRNA-145 and microRNA-486 are potential serum biomarkers for vascular calcification.

MicroRNAs (miRs) regulate vascular calcification (VC), and their quantification may contribute to suspicion of the presence of VC. The study was performed in four phases. Phase 1: miRs sequencing of rat calcified and non-calcified aortas. Phase 2: miRs with the highest rate of change, plus miR-145 [the most abundant miR in vascular smooth muscle cells (VSMCs)], were validated in aortas and serum from rats with and without VC. Phase 3: the selected miRs were analyzed in epigastric arteries from kidney donors and recipients, and serum samples from general population. Phase 4: VSMCs were exposed to different phosphorus concentrations, and miR-145 and miR-486 were overexpressed to investigate their role in VC. miR-145, miR-122-5p, miR-486 and miR-598-3p decreased in the rat calcified aortas, but only miR-145 and miR-486 were detected in serum. In human epigastric arteries, miR-145 and miR-486 were lower in kidney transplant recipients compared with donors. Both miRs inversely correlated with arterial calcium content and with VC (Kauppila index). In the general population, the severe VC was associated with the lowest serum levels of both miRs. The receiver operating characteristic curve showed that serum miR-145 was a good biomarker of VC. In VSMCs exposed to high phosphorus, calcium content, osteogenic markers (Runx2 and Osterix) increased, and the contractile marker (α-actin), miR-145 and miR-486 decreased. Overexpression of miR-145, and to a lesser extent miR-486, prevented the increase in calcium content induced by high phosphorus, the osteogenic differentiation and the loss of the contractile phenotype. miR-145 and miR-486 regulate the osteogenic differentiation of VSMCs, and their quantification in serum could serve as a marker of VC.

Assesment of relationship between sarcopenia and vascular calcification in patients with severe aortic stenosis

Background and Aims : Sarcopenia is a progressive disorder involving the accelerated loss of muscle mass and function. Sarcopenia becomes more frequent by ageing. Sarcopenia is associated with inflammation and increased risk for coronary artery disease. Sarcopenia may be diagnosed by several techniques including measurement of spinal muscle area in computed tomography (CT) images. We aimed to evaluate relationship between sarcopenia and vascular calcification in patients scheduled for TAVR.Methods: All of the patients who underwent CT for TAVR planning between 2013 and 2020 were screened and skeletal muscle area at L3 vertebrae level was measured. Parameters regarding vascular calcification were also measured from CT images.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Conclusions: Sarcopenia is an important marker of vascular calcification and it may be measured easily from CT images performed for any indication. MAC and all-cause mortality rate during follow-uo are more frequent in patients with sarcopenia. Background and Aims : Sarcopenia is a progressive disorder involving the accelerated loss of muscle mass and function. Sarcopenia becomes more frequent by ageing. Sarcopenia is associated with inflammation and increased risk for coronary artery disease. Sarcopenia may be diagnosed by several techniques including measurement of spinal muscle area in computed tomography (CT) images. We aimed to evaluate relationship between sarcopenia and vascular calcification in patients scheduled for TAVR. Methods: All of the patients who underwent CT for TAVR planning between 2013 and 2020 were screened and skeletal muscle area at L3 vertebrae level was measured. Parameters regarding vascular calcification were also measured from CT images. Conclusions: Sarcopenia is an important marker of vascular calcification and it may be measured easily from CT images performed for any indication. MAC and all-cause mortality rate during follow-uo are more frequent in patients with sarcopenia.

Relationship of abdominal aortic calcification with lumbar vertebral volumetric bone mineral density assessed by quantitative computed tomography in maintenance hemodialysis patients

IntroductionThis cross-sectional study aimed to investigate the relationship between abdominal aortic calcification (AAC), which is a marker of vascular calcification, and volumetric bone mineral density (vBMD) by quantitative computed tomography (QCT) in maintenance hemodialysis (MHD) patients.MethodsAll participants underwent lumbar vertebral vBMD measurement by QCT. Eight cross-sections were extracted sequentially and analyzed by ImageJ software to obtain the ratio of the calcified area to the abdominal aortic area (the calcification ratio). The AAC score was determined by the sum of the calcification ratios. The relationship between AAC and vBMD was analyzed using multivariate logistic regression.ResultsNinety MHD patients (58.89% male) with a mean age of 63.43 (standard deviation [SD] = 13.20) years were included in the study. AAC was present (AAC score > 0) in 93.33% of the patients. The 75th percentile of the AAC score corresponding to 119 was used as the cutoff point between the mild and severe groups. After full adjustment in the logistic model, AAC was found to be inversely associated with vBMD (odds ratio [OR], 0.970; 95% confidence interval [CI], 0.944 to 0.996; P = 0.025), and patients with osteoporosis had a significantly higher risk of severe AAC than those with normal bone mass (OR, 14.498; 95% CI, 1.507 to 139.486; P = 0.021). The independent inverse association was still stable after adjusting for variables measured at different time periods and using different cutoff points of the AAC score.ConclusionThere was an independent inverse association between AAC and vBMD, and osteoporosis was significantly associated with severe AAC in patients with MHD.

Role of Calcium and Phosphate Ionic Product as an Early Marker of Vascular Calcification to Predict Cardiac Risk in Chronic Kidney Disease: A Case-control Study

Introduction: Cardiovascular disease is the most leading cause of death in patients with Chronic Kidney Disease (CKD) and Vascular Calcification (CV) is one of the strongest predictors of cardiovascular risk. CV is a process characterised by thickening and loss of elasticity of muscular arteries walls which occurs in two distinct sites, the intimal associated with atherosclerotic plaques and medial calcification is characterised by vascular stiffening and arteriosclerosis with adverse clinical outcomes leading to cardiovascular mortality. Disturbed mineral metabolism such as increased serum phosphorus and ionic product may be one such risk factor and is emerging as a principle modifier of CV in the CKD subjects. Aim: To determine serum phosphorus and calcium in CKD patients and compare with calcium phosphorus ionic product as an early independent marker of CV in CKD to predict cardiac mortality. Materials and Methods: This was duration based case-control study conducted in Department of Nephrology, Vydehi Institute of Medical Sciences &amp; Research Centre, Karnataka, India. Fifty cases of CKD presented in stage 3,4 and 5 and 50 healthy individuals between the age group 21-78 years were included as controls. Serum levels of Calcium, Phosphorous were analysed in autoanalyser, Ca x P ionic product was calculated, estimated Glomerular Filtration Rate (eGFR) was calculated by Modification of Diet in Renal Disease (MDRD) formula. All measured variables were compared with eGFR and compared between cases and controls. The results were presented as a mean±Standard Deviation (SD) and p-value &lt;0.05 was considered as significant. Results: Mean age of cases were 47.74±11.01 years and 45.66±11.46 years were of controls. Clinically, confirmed CKD was found more in male patients 31 (62) compared to female 19 (38). eGFR (mL/min) cases (14.12±10.72) and (102.97±27.46) in control, Serum Creatinine (mg/dl) were 7.04±5.34 mg/dL in cases which was significantly more compared to control (0.84±0.20 mg/ dL). Serum Calcium (Ca) (mg/dL) 8.11±1.09 mg/dL in cases less compared with control 9.31±0.42 mg/dL, indicating hypocalcaemia. Serum Phosphrous (P) 5.2932±1.83 mg/dL) in CKD suggesting hyperphosphatemia compared to control (3.27±0.54 mg/dL). Calcium Phosphorus Ionic Product was 46.9108±14.77 in cases, elevated in CKD as compared to control (30.46±5.03). Statistically, significant result was found between serum phosphorus and calcium phosphorus ionic product (p&lt;0.05), well compared with eGFR of stage 3, 4 and 5 CKD patients. Conclusion: Hyperphosphatemia and elevated calcium- phosphate ionic product is an early independent marker of calcification to predict cardiovascular risk in late stages of CKD.

Clinical and laboratory markers of calcifying atherosclerosis

Despite the achievements in the detection of calcium deposits in the walls of blood vessels, there is practically no data on the relationship of calcification of the coronary arteries with clinical and laboratory indicators of calcification in the blood, and the mechanisms of this process have not been fully established. The aim of the work was to establish the relationship between the severity of vascular calcification and clinical and laboratory markers of vascular calcification to improve the effectiveness of the diagnosis of diseases of the cardiovascular system and optimize therapy. The data obtained during the study indicate a high prevalence of vascular calcification in patients with atherosclerosis. Estimates of the calcium index and traditional risk factors are not always sufficient to predict cardiovascular complications. Thus, the identification of specific laboratory markers of calcification and predisposition to calcinosis is very relevant at the present time. Studies have shown that atherosclerosis with vascular calcification is combined with the development of chronic systemic inflammation and inflammation of the vascular wall. At the same time, there are elevated levels of C-reactive protein, endothelin, homocysteine, lipid metabolism indicators, and reduced levels of fetuin-A in the blood, which allows us to recommend these laboratory indicators to prevent cardiovascular complications.

Effects of sevelamer carbonate versus calcium acetate on vascular calcification, inflammation, and endothelial dysfunction in chronic kidney disease.

Hyperphosphatemia is present in most patients with end‐stage renal disease (ESRD) and has been associated with increased cardiovascular mortality. Phosphate binders (calcium‐based and calcium free) are the mainstay pharmacologic treatment to lower phosphorus levels in patients with ESRD. We evaluated biochemical markers of vascular calcification, inflammation, and endothelial dysfunction in patients with chronic kidney disease (CKD) treated with sevelamer carbonate (SC) versus calcium acetate (CA). Fifty patients with CKD (stages 3 and 4) were enrolled and assigned to treatment with SC and CA for 12 weeks. At the end of the study the biomarkers of vascular calcification, inflammation, and endothelial dysfunction were analyzed. A significant increase in HDL‐cholesterol was observed with SC but not with CA in patients with CKD. Treatment with SC reduced serum phosphate, calcium phosphate, and FGF‐23 levels and there was no change with CA treatment. The inflammatory markers IL‐8, IFN‐γ, and TNFα decreased with response to both treatments. The levels of IL‐6 significantly increased with CA treatment and no change was observed in the SC treatment group. SC showed favorable effects on anti‐inflammatory and vascular calcification biomarkers compared to CA treatment in patients with CKD stages 3 and 4 with normal phosphorous values.

Biomarkers of vascular calcification: their relationship with diseases of the cardiovascular system and their importance in clinical practice

The literature review highlights the results of the most recent foreign and Russian studies on topical problems of vascular calcification with an emphasis on the relationship between some biochemical markers of vascular calcification (in priority osteoprotegerin and osteopontin) with cardiovascular disease and other associated conditions. Including some provisions of the reviewed studies help to clarify the pathophysiology mechanisms of vascular calcification. And it should also be noted that many aspects of the reviewed studies are directly related to a clinical practice. The purpose of this review is to generalize and systematize current knowledge about the contribution of vascular calcification biochemical markers to vascular tunic pathology, which finally leads to cardiovascular events. To prepare it, the databases PubMed, Google Scholar, ScienceDirect, MDPI, Hindawi, Oxford Academic were used.

FC 092EFFECT OF GEMIGLIPTIN ON BIOMARKERS OF KIDNEY INJURY AND VASCULAR CALCIFICATION IN DIABETIC NEPHROPATHY: A RANDOMIZED CONTROLLED TRIAL

Abstract Background and Aims Dipeptidyl peptidase-4 (DPP-4) inhibitors improve glycemic control and contain pleiotropic actions on kidney injury, albuminuria and vascular inflammation especially in animal models. We plan to evaluate the efficacy of potent DPP4-inhibitors (gemigliptin) in response to these aspects in diabetic nephropathy patients. Method This is a multi-center, prospective, randomized, placebo-controlled trial. A total of 201 participants were enrolled and randomly assigned to gemigliptin 50 mg daily and standard care of diabetes mellitus for 6 months. The changes of coronary calcium score (CAC score), cardio-ankle vascular index (CAVI), estimated glomerular filtration rate (GFR), markers of vascular calcification and markers of tubular renal injury were evaluated at baseline and 6 months. Results Overall 182 patients completed the study. Significantly reductions in hemoglobinA1C level were seen at month 6 with gemigliptin group (-0.67%) vs. control group (-0.15%; P=0.048). Changes of CAC score, CAVI, estimated GFR and proteinuria did not significantly difference in the both groups during 6 months of study. However, biomarkers of vascular calcification including serum bone alkaline phosphatase and biomarkers of kidney injury including urine neutrophil gelatinase-associated lipocalin (NGAL)/Cr and urine liver fatty acid-binding protein (L-FABP)/Cr improved significantly after gemigliptin treatment when compared to the control group. No serious adverse event was found during study. Conclusion Our study shows that gemigliptin has significant benefits on biomarkers of renal tubular injury and vascular calcification in patients with diabetic nephropathy, but gemigliptin does not affect on renal function and coronary calcification compared with control. The larger and longer follow-up will be essential to determine these beneficial effects.

MO796IMPACT OF ACTIVE VITAMIN D AND CALCIUM PREPARATION ON VASCULAR CALCIFICATION MARKERS IN HEMODIALYSIS PATIENTS WITH HYPOCALCEMIA INDUCED BY CALCIMIMETICS

Abstract Background and Aims Recently, we demonstrated the efficacy of etelcalcetide for control of secondary hyperparathyroidism (SHPT) in the DUET trial; a 12-week multicenter, open-label, randomized (1:1:1), parallel-group study treated with etelcalcetide + active vitamin D (Group E+D), etelcalcetide + oral calcium preparation (Group E+Ca), or control groups (Group C) in 124 subjects undergoing maintenance hemodialysis. Moreover, we also showed that active vitamin D was useful in correcting hypocalcemia induced by calcimimetics, but the oral calcium preparation was superior for suppression of hyperphosphatemia. In this post hoc analysis, we evaluated vascular calcification markers, fibroblast growth factor 23 (FGF23) and calciprotein particles (CPPs), in patients using etelcalcetide (n = 77) extracted from the registrants of the DUET trial. Method Serum levels of FGF23 and CPPs were measured at baseline, 6 weeks and 12 weeks after start of the trial. Skewed data (FGF23 and CPPs) were transformed to natural logarithm to achieve normal distribution prior to statistical analysis. The changes in log CPPs and log FGF23 were estimated in a linear mixed model with each treatment group, time point, and interaction of the treatment group and time point as the fixed effects. We compared these changes between treatment the groups using a linear mixed model and also the Tukey-Kramer method to correct for multiplicity. Additionally, we exploratory examined the correlations among changes of FGF23, CPPs and other biomarkers related to bone mineral metabolisms, iPTH, Ca, P, and calcium-phosphate product, tested by Spearman’s rank correlation coefficient. Results The decreases at the 12-week time point after the trial start in log FGF23 were estimated -1.13 pg/mL in Group E+Ca and -0.10 pg/mL in Group E+D in a linear mixed model, respectively. Similarly, the decreases in CPPs were estimated -1.60 AU in Group E+Ca and -0.82 AU in Group E+D, respectively. Changes of both FGF23 (P = 0.017) and CPPs (P &amp;lt; 0.001) in Group E+Ca significantly decreased compared with those in in Group E+D by Tukey-Kramer multiple-comparison test at 12 weeks after the trial start, while both changes in CPPs and FGF23 could not reach the significant differences between two groups at 6 weeks after the trial start (Figure 1). Reductions in FGF23 positively correlated with reductions in calcium (ρ = 0.42, P &amp;lt; 0.01) and phosphate (ρ = 0.48, P &amp;lt; 0.01) at 6 weeks after the trial start, and in calcium (ρ = 0.30, P &amp;lt; 0.01) and phosphate (ρ =0.70, P &amp;lt; 0.01) at 12 weeks after 6 weeks of the trial start), but there was no correlation with reductions in iPTH at any time point. Reductions in CPPs positively correlated with reductions only in phosphate at 6 weeks after the trial start (ρ = 0.47, P &amp;lt; 0.01) and at 12 weeks after 6 weeks of the trial start (ρ = 0.54, P &amp;lt; 0.01). Conclusion In this analysis, vascular calcification markers were significantly decreased in Group E+Ca compared to those in Group E+D. Further studies should be needed, our study suggests that oral calcium preparation may have an advantage against vascular calcification rather than active vitamin D for the correction of hypocalcemia induced by etelcalcetide in hemodialysis patients with SHPT.