Cardiac Calcification Research Articles

Validation of quantitative aortic valve calcification assessment by photon-counting computed tomography from contrast-enhanced data sets using virtual non-contrast reconstructions

Abstract Background The spectral information of photon-counting computed tomography (PCCT) permits the reconstruction of energy-selective images. Purpose We evaluated two methods for the reconstruction of virtual non-contrast-enhanced images from contrast-enhanced CT angiographic data sets regarding their ability to quantify aortic valve calcification. Results were validated by comparison to non-enhanced computed tomography. Methods A total of 100 subjects with severe aortic valve stenosis who underwent ECG-synchronized cardiac photon-counting CT for diagnostic workup prior to transcatheter aortic valve implantation (TAVI) were included in the current analysis. A standard true non-contrast acquisition was performed for aortic valve calcium quantification in each subject. In addition, two virtual non-enhanced data sets were reconstructed from contrast-enhanced CT angiographic data: a calcium-specific image ("pure calcium scan", PCS) and a virtual non-contrast (VNC) scan by subtraction of iodine. The PCS algorithm separates calcium and iodine in spectral PCCT images, creating a non-calcium mask for denoised spectral input and preserving calcium contrast in final material decomposition. Iodine extraction is achieved by measurement of the iodine content and its differentiation from native soft tissue attenuation. The Agatston Score was assessed in each of the three image data sets using semi-automated software. Results The mean age of the subjects was 78 ± 7 years, 66% were male. Mean EUROSCORE II was 4 ± 4%, mean STS Score for morbidity and mortality was 16 ± 11%. In the true non-contrast scan used for validation, the mean Agatston Score was 3028 ± 1820. The mean Agatston Score obtained from the PCS data set was 3004 ± 2042 and did not differ significantly from true non—contrast image sets (p=0.716). In the VNC data sets, the mean Agatston score was 1726 ± 1288, significantly lower than in the true non-contrast and the PCS data sets (both <0.001). Both, PCS and VNC data showed a significant correlation with true non-contrast scans (correlation coefficient PCS: 0.978, VNC scan: 0.975, both p<0.001). Conclusion In conclusion, the current results show the possibility to reliably quantify the Agatston Score of larger cardiac calcifications in virtual non-contrast data sets – however, there is substantial influence of the algorithm that is used so that validation of new techniques is of key importance.

Prevalence, Clinical Aspects, and Risk Factors of Aortic Stenosis Among Haemodialysis Patients Attending Nephrology Centre of Benghazi

Background: Cardiac valve calcifications (CVC) are common among patients on haemodialysis (HD). The valves most commonly involved are mitral and secondarily aortic valves. In Libya, there is a lack of research in this field. This is the author’s motivation to conduct this study, which has a significant impact on the health status of patients on HD. Objective: To identify aortic valve calcifications (AVC), prevalence of aortic stenosis (AS) in patients on HD, and to determine clinical aspects and risk factors that may lead to the development of AS. Patients and Methods: A cross-sectional study was conducted between May–November 2023 of adult patients on chronic HD who had received haemodialysis for more than 1 year. Patients with previous cardiac surgery, a history of endocarditis, or severe anaemia (haemoglobin <7.5 mg/dL) were excluded. A sample of 48 patients were enrolled in the study, with all patients undergoing clinical, biochemical, and a trans-thoracic echocardiographic evaluation. Results: Patients were aged 31–60 years ±13.2 standard deviation. AS had a prevalence of 6.3%, mitral regurgitation had a prevalence of 33.3%, and CVC was detected in 60.4% of patients on chronic HD, with AVC seen in 52.1% and mitral valve calcification seen in 25%. Patients with AVC were more often females (58.6%). Diabetes was seen in 64.6% of cases, and autosomal polycystic kidney disease was seen in 25%. The authors found that dyspnoea was the most common symptom (66.7%), followed by palpitations (35.4%) and asymptomatic patients (27.1%). Clinically detected AS was observed in three individuals (6.3%). Surprisingly, patients did not exhibit significant differences in age, duration of dialysis, or comorbidities. However, hyperphosphatemia was detected in 56.25% of patients, and hyperparathyroidism was recorded in 64.50%. Conclusion: The study has shown that aortic stenosis is the second most common valvular lesion in patients on chronic HD, preceded by mitral valve regurgitation. However, asymptomatic AVC has the highest prevalence among patients on chronic HD. Hyperphosphatemia and hyperparathyroidism are major risk factors that enhance the calcification of cardiac valves. Value of the Research: Though it is a snapshot study, it addresses an important comorbidity in patients on chronic HD. Namely, prevalence of aortic stenosis, CVCs, and associated risk factors, which had been reported in many regional and global nephrology literature, but the national Libyan literature still lacks such chronic HD patients’ data.

α-Klotho is associated with cardiovascular and all-cause mortality in patients with stage3band 4 chronic kidney disease(CKD): a long-term prospective cohort study.

α-Klotho deficiency may increase cardiovascular risks and worsen survival. We evaluated the association of α-Klotho with cardiovascular and all-cause mortality in pre-dialysis chronic kidney disease (CKD) patients. In this prospective study, 75 non-diabetic CKD stage 3b-4 patients werefollowed-up for a median of 8years. Primary and secondary outcomes were all-cause and cardiovascular mortality, respectively. Human soluble α-Klotho ELISA Assay (IBL-Takara 27,998-96Well), Human Fibroblast Growth Factor-23 ELISA Assay (intact FGF23, Merck Millipore MILLENZ FGF23-32K), and Human Sclerostin ELISA kits (Biomedica, Vienna, BI-20492) were used to measure serum α-Klotho, FGF23 and sclerostin levels in the certified laboratory at the Sechenov University according to the manufacturers' protocols.All patients underwent echocardiography to evaluate left ventricular mass index (LVMI), left ventricular ejection fraction by Simpson method, and cardiac (valve) calcification score by a semi-quantitative point scale. Lateral abdominal radiography by Kauppila method was used to estimate calcificationof the abdominal aorta.Cox multivariate regression and receiver-operating characteristic curve (ROC)-analysis were used to evaluate risk factors for death and their cut-off values. Primary and secondary endpoints were reached in 15 (20%) and 9 (12%) patients, respectively. Median α-Klotho levels in deceased and surviving patients were 344 and 484pg/ml, respectively (p = 0.002). In a multivariate Cox regression model, baseline α-Klotho levels (HR 0.99, 95% CI 0.98-1.00, p = 0.023), aortic calcification (HR 1.18, 95% CI 1.02-1.36, p = 0.029) and left ventricular mass index (LVMI) (HR 1.04, 95% CI 1.00-1.08, p = 0.033) were associated with the primary endpoint, whereas α-Klotho (HR 0.99, 95% CI 0.98-1.00, p = 0.029), aortic calcification (HR 1.23, 95% CI 1.07-1.42, p = 0.003) and LVMI (HR 1.04, 95% CI 1.00-1.08, p = 0.021) were associated with the secondary endpoint. α-Klotho levels had the highest area under the curve (AUC)by ROC analysis, that is, 0.766 (95% CI 0.70-0.82) for the primary endpoint and 0.842 (95% CI 0.79-0.90) for the secondary endpoint with cut-off values of 412pg/ml (HR 3.06, 95% CI 1.36-6.89, p = 0.007) and 368pg/ml (HR 4.84, 95% CI 1.59-14.73, p = 0.005), respectively. In pre-dialysis CKD patients, α-Klotho levels areassociated with all-cause and cardiovascular mortality and may be considered an early prognostic marker.

Association of diabetes with cardiovascular calcification and all-cause mortality in end-stage renal disease in the early stages of hemodialysis: a retrospective cohort study

BackgroundThe main goal of this study was to examine how diabetes, cardiovascular calcification characteristics and other risk factors affect mortality in end-stage renal disease (ESRD) patients in the early stages of hemodialysis.MethodsA total of 285 ESRD patients in the early stages of hemodialysis were enrolled in this research, including 101 patients with diabetes. Survival time was monitored, and general data, biochemical results, cardiac ultrasound calcification of valvular tissue, and thoracic CT calcification of the coronary artery and thoracic aorta were recorded. Subgroup analysis and logistic regression were applied to investigate the association between diabetes and calcification. Cox regression analysis and survival between calcification, diabetes, and all-cause mortality. Additionally, the nomogram model was used to estimate the probability of survival for these individuals, and its performance was evaluated using risk stratification, receiver operating characteristic, decision, and calibration curves.ResultsCardiovascular calcification was found in 81.2% of diabetic patients (82/101) and 33.7% of nondiabetic patients (62/184). Diabetic patients had lower phosphorus, calcium, calcium-phosphorus product, plasma PTH levels and lower albumin levels (p < 0.001). People with diabetes were more likely to have calcification than people without diabetes (OR 5.66, 95% CI 1.96–16.36; p < 0.001). The overall mortality rate was 14.7% (42/285). The risk of death was notably greater in patients with both diabetes and calcification (29.27%, 24/82). Diabetes and calcification, along with other factors, collectively predict the risk of death in these patients. The nomogram model demonstrated excellent discriminatory power (area under the curve (AUC) = 0.975 at 5 years), outstanding calibration at low to high-risk levels and provided the greatest net benefit across a wide range of clinical decision thresholds.ConclusionsIn patients with ESRD during the early period of haemodialysis, diabetes significantly increases the risk of cardiovascular calcification, particularly multisite calcification, which is correlated with a higher mortality rate. The risk scores and nomograms developed in this study can assist clinicians in predicting the risk of death and providing individualised treatment plans to lower mortality rates in the early stages of hemodialysis.

#1624 The association between serum beclin 1 level and the presence of aortic valve calcification among individuals on hemodialysis

Abstract Background and Aims The autophagy pathway, a crucial regulator of cellular health and metabolism, plays a fundamental role in maintaining healthy blood vessel function. Studies have established its critical involvement in endothelial cell stability, vascular smooth muscle cell (VSMC) phenotype control, and VSMC calcium balance. Recent evidence, further, underlines autophagy's direct protective role against vascular calcification. It has been shown that autophagy can modulate different cardiovascular pathologies, including valvular calcification. We aimed to explore the potential link between the protein beclin 1 and heart valve calcification in dialysis patients. Method We compared two groups of 51 haemodialysis patients each, defined by the presence (Group 1) or absence of valve calcification (Group 2) on echocardiograms. Both groups underwent beclin 1 level measurements and other assessments (lipid profile). Cardiac valve calcification was diagnosed through echocardiography by identifying dense echoes exceeding 1 millimeter in thickness on one or more aortic valve cusps. The severity of calcification was then classified into three stages: Mild: Calcification thickness ranged from 1 to 3 millimeters and involved less than 50% of the valve leaflet. Moderate: Calcification thickness exceeded 3 millimeters but still affected less than half of the valve leaflet. Severe: Calcification thickness surpassed 3 millimeters and encompassed more than 50% of the valve leaflet. Results Our analysis demonstrated a statistically significant increase in beclin 1 levels in Group 2 compared to Group 1 (p&amp;lt;0.001), a striking relationship between lower beclin 1 levels and more severe valve calcification. Interestingly, a specific beclin 1 cutoff below 35.5 ng/ml offered the highest accuracy (98% sensitivity and 92% specificity) in predicting valve calcification. Notably, significant differences were found in lipid profiles (Analysis of the lipid profile revealed a striking trend in Group I, with significant elevations in cholesterol, triglycerides, and LDL. Conversely, HDL levels were significantly higher in Group II). and prevalence of heart disease between the groups. Analysis of IHD prevalence across the two groups yielded a striking result. Group 1 displayed a significantly higher proportion of individuals with IHD (17 cases) compared to group 2 (3 cases), with a statistically significant difference (p&amp;lt;0.001). Conclusion Based on these results, it appears promising to integrate serum Beclin 1 measurements into a risk assessment model for the development of heart valve calcification in dialysis patients.

Reversal of complete atrioventricular block in dialysis patients following parathyroidectomy: A case report

BACKGROUND Refractory secondary hyperparathyroidism (SHPT) is a common complication observed in patients with end-stage renal disease and can result in ectopic calcification. Metastatic calcification involving the heart valves and the conduction system can easily lead to arrhythmias, including atrioventricular block. This case report describes a maintenance hemodialysis patient with refractory SHPT resulting in a complete atrioventricular block (CAVB), which was eventually reversed to a first-degree atrioventricular block. CASE SUMMARY We present the case of a 31-year-old Asian female who was receiving maintenance hemodialysis because of lupus nephropathy. She developed SHPT, and an electrocardiogram revealed a first-degree atrioventricular block. Then, she underwent parathyroidectomy (PTX) with autotransplantation. Unfortunately, a few years later, she developed SHPT again, and an electrocardiogram revealed a CAVB. A few years after the second PTX surgery, the calcification of the left atrium and left ventricle improved, and her CAVB was reversed. CONCLUSION This case revealed that metastatic cardiac calcification can result in complete atrioventricular blockage. Following parathyroid surgery, calcification of the cardiac conduction system improved, leading to reversal of the atrioventricular block. It is important for dialysis patients to optimize intact parathyroid hormone therapy and pay attention to calcification metastasis.

Platelet activating factor acetylhydrolase is associated with cardiac valvular calcification in dialysis patients

Abstract Objectives The cardiovascular mortality risk is greatly increased in patients with chronic kidney disease (CKD), especially in dialysis patients, due to atherosclerosis. Platelet activating factor acetylhydrolase (PAF-AH) is an enzyme that hydrolyzes platelet activating factor (PAF). Valvular calcifications and PAF-AH are associated with atherosclerosis. However, little is known about the status of PAF-AH activity and valvular calcification in dialysis patients. Therefore, the aim of this study was to investigate the status of these parameters in CKD patients. Methods This study included 92 chronic renal failure (CRF) (dialysis group), and 86 CKD patients (non-dialysis group). Echocardiography was performed to assess valvular calcification. Results There was no significant difference between the dialysis and CKD groups in terms of PAF-AH activities. However, when comparisons were stratified according to the presence of valve calcification, higher PAF-AH activity and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were evident in patients with calcification compared to those without. Additionally, the CRF group also exhibited elevated PAF-AH and NT-proBNP levels. While elevated NT-proBNP persisted in the CKD group, in contrast, changes in PAF-AH were not significant. Conclusions The results of this study suggest that high PAF-AH and NT-proBNP levels are associated with valvular calcification in dialysis patients. Both biomarkers may be used as a risk factor for calcification. Furthermore, inhibition of PAF-AH activity may be a treatment target to reduce calcification.

The association of peritoneal dialysis and hemodialysis on mitral and aortic valve calcification associated mortality: a meta-analysis

Cardiac valve calcification (CVC), characterized by the accumulation of calcium in the heart valves, is highly prevalent among patients undergoing dialysis. This meta-analysis aimed to provide an updated summary of recent studies on the prognostic value of CVC in patients undergoing dialysis. We conducted a search of PubMed, Embase, and Web of Science to identify observational studies investigating cardiovascular or all-cause mortality associated with CVC in dialysis patients until March 2023. Hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were calculated for the meta-analysis, and the strength and significance of the associations between CVC and mortality outcomes in dialysis patients were assessed. From 6218 initially identified studies, we included 10 critical studies with a total of 3376 dialysis patients in a further meta-analysis. Pooled analyses demonstrated a significant association between CVC and an elevated risk of all-cause and cardiovascular mortality in dialysis patients. In our study, we discovered HRs of 1.592 (95% CI 1.410–1.797) for all-cause mortality and 2.444 (95% CI 1.632–3.659) for cardiovascular mortality. Furthermore, subgroup analysis revealed elevated all-cause mortality among patients with mitral valve calcification (HR 1.572; 95% CI 1.200–2.060) compared to those with aortic valve calcification (HR 1.456; 95% CI 1.105–1.917). Similarly, patients undergoing peritoneal dialysis faced a greater risk for all-cause mortality (HR 2.094; 95% CI 1.374–3.191) than those on hemodialysis (HR 1.553; 95% CI 1.369–1.763). This highlights the possibility of CVC being an independent risk factor for dialysis patients, particularly in relation to mitral valve calcification or peritoneal dialysis.

METABOLICALLY ASSOCIATED FATTY LIVER DISEASE IN PATIENTS WITH VERY HIGH CARDIOVASCULAR RISK: PREVALENCE, CLINICAL SIGNIFICANCE, GENDER DIFFERENCES

Introduction. Recently, metabolically associated fatty liver disease (MAFLD) had been proposed as a new term. Due to increasing prevalence, significant morbidity and hepatic and cardiovascular mortality, the association of MAFLD with cardiovascular diseases is gaining considerable relevance and needs further study. The aim of our study was to determine the proportion of MAFLD among patients with a very high cardiovascular risk, and to elucidate clinical features and gender differences in this cohort. Materials and methods. All patients underwent a comprehensive examination to assess both cardiovascular risk and MAFLD. Hepatic steatosis was diagnosed after liver ultrasonography. Participants who met MAFLD criteria were included into the group 1 (n=77; 32 women, 45 men), other patients were assigned to the group 2 (n=39; 19 women, 20 men). Results. Among patients with very high cardiovascular risk, proportion of MAFLD was 66.7 %. Although mild alanine aminotransferase elevation was much more common among patients with MAFLD (16 women (50.0 %) vs. 2 women (10.5 %) in group 2, P = 0.006; 21 men (46.7 %) vs. 2 men in group 2 (10.0 %), P = 0.005), none of the participants met the criteria for steatohepatitis. Despite, the presence of metabolic disorders in the vast majority of participants, proportion of obesity, metabolic dyslipidaemia, prediabetes and type 2 diabetes were significantly higher in patients with MAFLD. Besides, patients with MAFLD usually met 4 or 5 metabolic syndrome criteria, had higher median values of lipid accumulation product (LAP) and HOMA-IR index, but lower median values of Matsuda index. Significant direct correlations were found between MAFLD and LAP, logarithmic index (TG/HDL-C), and HOMA-IR; negative correlations were observed between MAFLD and insulin sensitivity indices. Women with MAFLD had significantly higher median values of glycated haemoglobin, post-load glucose, fasting insulin levels; there was direct correlation between MAFLD and non-HDL-C. Among women with MAFLD, a history of menopause before 45 years of age had 15 persons (46.9 %) vs. one person (5.3 %) in group 2 (P &lt; 0.002); the median age when ASCVD was diagnosed was 58.5 [53.0; 64.0] years vs. 68.0 [63.0; 69.0] years in group 2 (P = 0.002); cardiac valve calcinosis was detected in 31 women (96.6 %) vs. 9 women (47.4 %) in group 2 (P = 0.0001); the left ventricular myocardial mass (LVM) index was 77.5 [62.1; 86.9] g/m2.7 vs. 64.0 [50.6; 74.0] g/m2.7 in women without MAFLD, 67.0 [55.1; 74.0] g/m2.7 in men with MAFLD, and 63.9 [50.0; 73.5] g/m2.7 in men without MAFLD (Kruskal–Wallis ANOVA P &lt;0.0001; median test P=0.002). The prevalence of smoking and alcohol intake was significantly more common among men (gender differences P &lt;0.0001 and P=0.0001 in group 1; P = 0.0004 and P=0.0023 in group 2 for smoking and alcohol intake, respectively). Men with MAFLD had significantly higher median values of fasting plasma glucose, fasting and post-load insulin levels than men without MAFLD; there was a significant direct correlation between MAFLD and serum TG level. In addition, 11 men with MAFLD (24.4 %) had hypertriglyceridemia &gt;2.3 mmol/l that was not observed among men without MAFLD (P=0.013). The proportion of men with fasting and post-load hyperinsulinemia was much higher in group 1 than in group 2 (28 persons (62.2%) vs. 3 persons (15.0 %), P=0.0005 and 26 persons (57.8%) vs. 2 persons (10.0 %), P = 0.0003, respectively). Conclusions: among patients with a very high cardiovascular risk, the prevalence of MAFLD was significantly higher than in the general population. Concomitant MAFLD was associated with more severe metabolic disorders (i.e., obesity, metabolic dyslipidaemia, hyperglycaemia, insulin resistance), which usually combined. The LAP index is a simple available tool that may be used in routine clinical practice to determine the need for MAFLD screening. Women with MAFLD frequently had early menopause, cardiac valve calcification, and much higher median value of LVM index; direct correlation was observed between MAFLD and non-HDL-C. Men with MAFLD more often had fasting and/or post-load hyperinsulinemia and moderate hypertriglyceridemia.

Serum magnesium level and cardiac valve calcification in hemodialysis patients

IntroductionCardiac valve calcification is closely related to cardiovascular disease. The aim of this study was to investigate the magnesium level and cardiac valve calcification in hemodialysis patients.MethodsA cross-sectional study was conducted in 105 maintenance hemodialysis patients with complete follow-up data from June 2020 to May 2021 in Beijing Tsinghua Changgung Hospital, Tsinghua University. Baseline data, including sex, age, primary disease, liver and kidney function, electrolytes and parathyroid hormone, were recorded. According to their echocardiograms, patients were divided into a cardiac valve calcification group and a noncardiac valve calcification group, and the correlations between valve calcification and clinical data were analyzed.ResultsOf 105 patients under hemodialysis, 60 (56.6%) were male, with an average age of 62.1 ± 13.5 years and a mean dialysis duration of 58.8 ± 45.4 months. The majority of primary renal diseases were diabetic nephropathy (55, 51.9%). Approximately 64.8% of the 105 maintenance hemodialysis patients had cardiac valve calcification, and 35.2% were in the noncardiac valve calcification group. The independent t test and the chi-square test analysis showed that the cardiac valve calcification group had older age, higher smoking rate, diabetes mellitus, lower extremity arterial occlusion, coronary heart disease, and coronary artery calcification ratio but lower parathyroid hormone, serum calcium, serum magnesium, albumin, prealbumin, and high-density lipoprotein cholesterol levels (P < 0.05). Logistic regression analysis showed that age, diabetes mellitus, coronary artery calcification, lower serum magnesium, lower serum calcium, and lower parathyroid hormone levels were associated with valve calcification.ConclusionThe presence of cardiac valve calcification was associated with age, calcium, phosphorus and lower magnesium level. These factors we should pay more attention in clinical practice.

Association of Cardiac Valve Calcification and 1-year Mortality after Lower-extremity Amputation in Diabetic Patients: A Retrospective Study.

Cardiac valve calcification predisposes patients to a higher risk of adverse cardiovascular events. This study aimed to investigate the association between cardiac valve calcification and 1-year mortality in diabetic patients after lower-extremity amputation. This was a retrospective study conducted on the clinical data of diabetic patients who underwent lower-extremity amputation admitted to the Sun Yat-sen Memorial Hospital, Guangzhou, Guangdong, China for diabetic foot ulcers needed lower extremity amputation surgery between July 2017 and March 2021. Detailed preoperative medical assessments were performed and recorded. Cardiac valve calcification was assessed using echocardiography at baseline. Oneyear follow-up assessments were conducted and included clinical visits, hospital record assessments, and telephone reviews to obtain the survival status of patients. Ninety-three diabetic patients participated in the study. The 1-year follow-up mortality rate after amputation was 24.7%. Compared to the survival group, the prevalence of cardiac valve calcification and the Revised Cardiac Risk Index (RCRI) were higher in the mortality group. In the Cox regression analysis, cardiac valvular calcification (HR=3.427, 95% CI=1.125- 10.443, p =0.030) was found to be an independent predictor of all-cause mortality after amputation. In addition, the patients with both aortic valve calcification and mitral annular calcification had a higher all-cause mortality rate (50%). Receiver operator characteristic curve analysis showed a stronger predictive ability when using a combination of calcified valve number and RCRI (AUC=0.786 95%, CI=0.676-0.896, p =0.000). In diabetic patients after lower-extremity amputation, cardiac valve calcification was associated with all-cause mortality during 1-year follow-up. Combination of calcified valve number and RCRI score showed a stronger predictive value for mortality.

The Dietary Fiber Inulin Slows Progression of Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD) in a Rat Model of CKD.

Chronic kidney disease (CKD)-mineral bone disorder (CKD-MBD) leads to fractures and cardiovascular disease. Observational studies suggest beneficial effects of dietary fiber on both bone and cardiovascular outcomes, but the effect of fiber on CKD-MBD is unknown. To determine the effect of fiber on CKD-MBD, we fed the Cy/+ rat with progressive CKD a casein-based diet of 0.7% phosphate with 10% inulin (fermentable fiber) or cellulose (non-fermentable fiber) from 22 weeks to either 30 or 32 weeks of age (~30% and ~15% of normal kidney function; CKD 4 and 5). We assessed CKD-MBD end points of biochemistry, bone quantity and quality, cardiovascular health, and cecal microbiota and serum gut-derived uremic toxins. Results were analyzed by two-way analysis of variance (ANOVA) to evaluate the main effects of CKD stage and inulin, and their interaction. The results showed that in CKD animals, inulin did not alter kidney function but reduced the increase from stage 4 to 5 in serum levels of phosphate and parathyroid hormone, but not fibroblast growth factor-23 (FGF23). Bone turnover and cortical bone parameters were similarly improved but mechanical properties were not altered. Inulin slowed progression of aorta and cardiac calcification, left ventricular mass index, and fibrosis. To understand the mechanism, we assessed intestinal microbiota and found changes in alpha and beta diversity and significant changes in several taxa with inulin, together with a reduction in circulating gut derived uremic toxins such as indoxyl sulfate and short-chain fatty acids. In conclusion, the addition of the fermentable fiber inulin to the diet of CKD rats led to a slowed progression of CKD-MBD without affecting kidney function, likely mediated by changes in the gut microbiota composition and lowered gut-derived uremic toxins. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Identification of a DBA/2 Mouse Sub-strain as a Model for Pseudoxanthoma Elasticum-Like Tissue Calcification.

Ectopic calcification in the cardiovascular system adversely affects life prognosis. DBA/2 mice experience calcification owing to low expression of Abcc6 as observed in pseudoxanthoma elasticum (PXE) patients; however, little is known about its characteristics as a calcification model. In this study, we explore the suitability of a DBA/2 sub-strain as a PXE-like tissue calcification model, and the effect of a bisphosphonate which prevents calcification of soft tissues in hypercalcemic models was evaluated. The incidence of calcification of the heart was compared among several sub-strains and between both sexes of DBA/2 mice. mRNA expression of calcification-related genes was compared with DBA/2 sub-strains and other mouse strains. In addition, progression of calcification and calciprotein particle formation in serum were examined. Among several sub-strains of DBA/2 mice, male DBA/2CrSlc mice showed the most remarkable cardiac calcification. In DBA/2CrSlc mice, expression of the anti-calcifying genes Abcc6, Enpp1 and Spp1 was lower than that in C57BL/6J, and expression of Enpp1 and Spp1 was lower compared with other sub-strains. Calcification was accompanied by accelerated formation of calciprotein particle, which was prevented by daily treatment with bisphosphonate. A model suitable for ectopic calcification was identified by choosing a sub-strain of DBA/2 mice, in which genetic characteristics would contribute to extended calcification.

Moderate Iron Deficiency Does Not Potentiate Renal or Cardiac Calcification and Subsequent Tissue Injury in Mouse Models of CKD

Chronic kidney disease (CKD) is a public health challenge that affects over 26 million Americans and many more worldwide. Many develop renal and cardiac calcification, which promotes arterial wall stiffness. These structural changes of the vasculature contribute to hypertension and heart failure, increasing the risk of premature death. Dysregulated iron homeostasis also occurs in many patients with CKD, and iron deficiency and anemia are common complications that are independently associated with CKD progression, cardiovascular disease and all-cause mortality. Furthermore, lower transferrin saturation (TSAT) levels are independently associated with higher coronary artery calcification scores in CKD patients receiving hemodialysis. However, whether iron deficiency and/or anemia directly contribute to the pathogenesis of calcification in CKD is unknown. We examined the effects of iron deficiency on renal and cardiac calcification, and tissue injury in mouse models of CKD. We used a dietary model of progressive CKD: 8-week-old male C57BL/6J mice were fed for 8 weeks a customized 0.2% adenine-rich diet that was either iron-replete (100 ppm iron; “adenine-IR” group) or iron-deficient (4 ppm iron, “adenine-ID” group). Control mice were fed a diet without adenine, but with matching iron content (iron-replete “CTRL-IR” and iron-deficient “CTRL-ID” groups). Compared to CTRL-IR mice, CTRL-ID mice developed widespread tissue iron deficiency and anemia as expected. Surprisingly, despite 8 weeks of low iron diet which led to lower serum iron and worse anemia, adenine-ID mice had similarly high liver iron as adenine-IR mice, similar expression of transferrin receptor 1 (marker of tissue iron deficiency) in kidney or heart, and similarly elevated liver hepcidin mRNA. This suggests that hepcidin induction in this CKD model likely protected tissues from iron depletion, at least on the time scale of the experiment. Calcification in adenine mice was evident but was similar between adenine-ID and adenine-IR mice, as observed by the comparable expression of calcification markers in kidney and heart ( Runx2, Sox9, Opn). Additionally, markers of kidney function (BUN and serum creatinine), kidney injury ( Kim1, Lcn2) and cardiac injury( Myh7) were also comparable between adenine-ID and adenine-IR mice. Inflammation and fibrosis were increased in kidney and heart of adenine mice in general, but once again similar between adenine-ID and adenine-IR mice (serum IL-6, Tnfa, Tgfb Col1a1). We then employed a genetic model of progressive CKD ‒ constitutive Col4a3 −/−mice (Alport syndrome, life expectancy in this model ~11 weeks of age), and fed male mice either an IR or ID diet for 7 weeks. Diets were started in juvenile mice (4-week-old), a strategy known to exacerbate the effect of ID diet on tissue iron deficiency and anemia. Despite this, Alport-ID and Alport-IR mice still displayed similar liver iron levels and liver hepcidin expression. Alport-IR and -ID groups also had comparable renal and cardiac calcification, injury, inflammation and fibrosis. Altogether, our findings in two different mouse models of CKD indicate that moderate iron deficiency does not potentiate renal or cardiac calcification and subsequent tissue injury. Our data suggest that despite causing hypoferremia and anemia, chronically elevated hepcidin in CKD might delay the development of tissue iron deficiency in the liver, kidney and heart, and potentially protect against deleterious vascular changes and subsequent tissue injury.

Clinical Implication of Consistently Strict Phosphate Control for Coronary and Valvular Calcification in Incident Patients Undergoing Hemodialysis.

Serum phosphate control is crucial for the progression of vascular and valvular calcifications. Strict phosphate control is recently suggested; however, there is a lack of convincing evidence. Therefore, we explored the effects of strict phosphate control on vascular and valvular calcifications in incident patients undergoing hemodialysis. A total of 64 patients undergoing hemodialysis from our previous randomized controlled trial were included in this study. Coronary artery calcification score (CACS) and cardiac valvular calcification score (CVCS) were evaluated using computed tomography and ultrasound cardiography at baseline and 18 months after the initiation of hemodialysis. The absolute changes in CACS (ΔCACS) and CVCS (ΔCVCS) and the percent change in CACS (%ΔCACS) and CVCS (%ΔCVCS) were calculated. Serum phosphate level was measured at 6, 12, and 18 months after the initiation of hemodialysis. Moreover, phosphate control status was evaluated using the area under the curve (AUC) by the amount of time spent with a serum phosphate level of ≥ 4.5 mg/dL and the extent to which this threshold exceeded over the observation period. ΔCACS, %ΔCACS, ΔCVCS, and %ΔCVCS were significantly lower in the low AUC group than in the high AUC group. ΔCACS and %ΔCACS were also significantly lower. ΔCVCS and %ΔCVCS tended to be lower in patients whose serum phosphate level never exceeded 4.5 mg/dL than in those whose serum phosphate level continuously exceeded 4.5 mg/dL. AUC significantly correlated with ΔCACS and ΔCVCS. Consistently strict phosphate control may slow the progression of coronary and valvular calcifications in incident patients undergoing hemodialysis.

The risk factors and predictive model for cardiac valve calcification in patients on maintenance peritoneal dialysis: a single-center retrospective study

Background Cardiovascular calcification includes cardiac valve calcification (CVC) and vascular calcification. We aimed to analyze risk factors for CVC, and construct a predictive model in maintenance peritoneal dialysis (MPD) patients. Methods We retrospectively analyzed MPD patients who began peritoneal dialysis between January 2014 and September 2021. Patients were randomly assigned to the derivation cohort and validation cohort in a 7:3 ratio. The patients in the derivation cohort were divided into the CVC group and non-CVC group. Logistic regression was used to analyze risk factors, then the rms package in R language was used to construct a nomogram model to predict CVC. Results 1,035 MPD patients were included, with the age of 50.0 ± 14.2 years and 632 males (61.1%). Their median follow-up time was 25 (12, 46) months. The new-onset CVC occurred in 128 patients (12.4%). In the derivation cohort, multivariate logistic regression indicated old age, female, high systolic blood pressure (SBP), high calcium-phosphorus product (Ca × P), high Charlson comorbidity index (CCI) and long dialysis time were independent risk factors for CVC (p < 0.05). We constructed a nomogram model for predicting CVC in the derivation cohort, with a C index of 0.845 (95% CI 0.803–0.886). This model was validated with a C index of 0.845 (95%CI 0.781–0.909) in the validation cohort. Conclusion We constructed a nomogram model for CVC in MPD patients, using independent risk factors including age, sex, SBP, Ca × P, CCI and dialysis time. This model achieved high efficiency in CVC prediction.

Predictive value of serum β2-microglobulin in cardiac valve calcification in maintenance hemodialysis patients.

Cardiac valve calcification (CVC) is associated with adverse cardiovascular events. We studied the risk factors of CVC in maintenance hemodialysis (MHD) patients and the value of serum β2-microglobulin (β2-MG) levels in predicting the incidence of CVC. β2-MG is a middle molecular weight toxin. In recent years, researchers found that elevated blood β2-MG was associated with coronary, thoracic, and abdominal aortic calcifications with significant correlations. β2-MG has been emerging as a strong biomarker for cardiovascular mortality in uremic patients but its role in CVC is not well studied. This study looked specifically at CVC occurrence in relation to β2-MG for MHD patients. Patients who underwent MHD for more than 3 months in the First People's Hospital of Nantong City from November 2012 to November 2019 with complete available data were included in the study. The patients were divided into the CVC group and the non-CVC group. The general information and clinical laboratory indicators of the patients were collected in a retrospective manner. We analyzed the risk factors for developing CVC in MHD patients using binary logistic regression method. Receiver operating characteristic (ROC) curves were used to calculate the cut-off value of β2-MG for predicting CVC. The decision tree (DT) method was used to classify and explore the probability of CVC in patients with MHD. The β2-MG in the CVC group was significantly higher than that in the non-CVC group (t=6.750, P<0.001). Multivariate binary logistic regression analysis showed that gender, age, serum β2-MG, and hemodialysis (HD) adequacy (Kt/V urea) were independent risk factors for CVC in MHD patients. ROC analysis showed that a β2-MG value of 25 µg/L was the best cut-off point for predicting CVC in MHD patients. According to binary logistic regression analysis, the β2-MG ≥25 µg/L group was 3.39 times more likely to develop CVC than the β2-MG <25 µg/L group [odds ratio (OR), 3.39; 95% confidence interval (CI), 1.63-7.06; P=0.001]. The DT model determined that serum β2-MG ≥25 µg/L and age >69 years were important determinants for predicting CVC in MHD patients. Serum β2-MG in MHD patients has a positive correlation with the severity and occurrence of CVC.

Síndrome de Sagliker: una nueva entidad, un problema antiguo.

Introduction: Sagliker syndrome, described by Dr. Yahya Sagliker in 2004, constitutes the most advanced state of secondary hyperparathyroidism in chronic kidney disease. Deforming and disabling clinical syndrome that reduces the quality of life and adds psychological disorders to the patient with chronic kidney disease. This study aims to report on a series of eight cases in Mexico and warn about the correct management and follow-up of secondary hyperparathyroidism. Cases: 8 cases are presented with ages between 17 and 35 years, serum parathyroid hormone levels between 1583 and 4715 pg/ml, and alkaline phosphatase levels between 146 and 2065 IU/L. All cases with brown tumors in the maxilla and mandible characteristic of Sagliker syndrome. Evolution: All patients were ingesting calcium and vitamin D analogs at diagnosis or in the last three months. Conclusion: Sagliker syndrome is the most severe and chronic complication of secondary hyperparathyroidism and chronic kidney disease. The significant bone involvement of this syndrome generates a disabling facial and prolonged bone deformity that impacts morbidity, mortality, and mental health. Concomitant with bone alterations, vascular and cardiac calcifications add a crucial cardiovascular risk, so any surgery constitutes a high risk.

Burosumab - new potent treatment for X-linked hypophosphatemia and tumor-induced osteomalacia

Introduction and purpose: Elevated FGF23 in X-linked hypophosphatemia (XLH) and tumor-induced osteomalacia (TIO) leads to systemic hypophosphatemia, several musculoskeletal manifestations and rickets in children. In this review we describe advances in the management of XLH and TIO using burosumab, which is a new therapeutic option approved both for adults and children. A search was conducted using PubMed and Google Scholarship databases. Brief description of the state of knowledge: Patients with XLH and TIO exhibit a similar clinical picture and way of treatment. Although in TIO surgery is the only definitive treatment, some tumors cannot be removed due to their location. In this case oral conventional therapy is used in treating both in TIO and XLH. Another approved treatment option is the use of burosumab, which is a fully humanised FGF23-antibody. This therapy led to normalisation of phosphate homoeostasis and resulted in improvement of bone turnover, fracture healing, subjective pain, and physical function. Compared to conventional, oral therapy burosumab has been shown to be superior for treatment of XLH and TIO.Conclusions: While burosumab appears to improve treatment outcomes, the effects of chronic or lifelong use have yet to be established. Long term follow-up studies would be necessary to assess especially the potential risk of nephrocalcinosis and cardiac calcification.

Influencing factors of cardiac valve calcification (CVC) in patients with chronic kidney disease and the impact of CVC on long-term prognosis: a single-center retrospective study.

To investigate the effect of cardiac valve calcification (CVC) on the prognosis of patients with chronic kidney disease (CKD). A total of 343 CKD patients were retrospectively analyzed, and divided into two groups according to the presence or absence of cardiac valve calcification. All patients were followed until death, loss to follow-up, or the end point of the study (December 2021). The incidence of CVC among the 343 CKD patients was 29.7%, including 21 cases of mitral valve calcification, 63 cases of aortic valve calcification, and 18 cases of mitral valve combined with aortic valve calcification. The incidence of CVC in CKD stages 1-2 was 0.3%, 5.2% in CKD stages 3-4, and 24.2% in CKD stage 5 (P<0.05). Advanced age, higher serum albumin, higher cystatin C and lower uric acid levels were all associated with a higher risk of CVC. After six years of follow-up, 77 patients (22.4%) died. The causes of death were cardiovascular and cerebrovascular diseases in 36 cases (46.7%), infection in 29 cases (37.7%), gastrointestinal bleeding in nine cases (11.7%), and "other" in the remaining three cases (3.9%). A Kaplan Meier survival analysis showed that the overall survival rate of patients with CVC was lower than that of patients without CVC. The incidence of CVC, mainly aortic calcification, is high in patients with CKD. Advanced age, higher serum albumin and higher cystatin C levels were associated with a higher risk of CVC. Hyperuricemia was associated with a lower risk of CVC. The overall survival rate of patients with CVC was lower than that of patients without CVC.