Relationship between serum magnesium level and coronary artery calcification in maintenance hemodialysis patients

Objective To evaluate the relationship between serum magnesium and coronary artery calcification (CAC) and their associated factors. Methods 131 patients with chronic kidney disease on regular hemodialysis (HD) were recruited into this study from December 2014 to December 2015 in our center. Demographic and clinical data of selected patients were collected. Serum fibroblast growth factor 23 (FGF-23) level was quantified by enzyme linked immunosorbent assay(ELISA). Quantification of coronary artery calcification score (CACs) was determined by multi-slice spiral computed tomography (MSCT). The relationships between serum magnesium and FGF-23 level, CACs, demographic and clinical data were investigated. Results Patients were divided into low serum magnesium group, normal serum magnesium group and high serum magnesium group according to their serum magnesium levels. There were significant differences in the distribution of diabetes history, serum phosphorus, serum albumin, serum pre albumin, serum uric acid among these three groups(P＜0.05). A significant positive correlation was confirmed between serum magnesium level and serum albumin, serum pre albumin, serum phosphorus and serum uric acid by Pearson correlation analysis and Spearman correlation analysis (r=0.389, 0.234, 0.200, 0.234, P=0.000, 0.007, 0.022, 0.007, respectively). According to the degree of CAC, all maintenance hemodialysis (MHD) patients were divided into non-calcification group, low calcification group, moderate calcification group and high calcification group, and there were significant differences in the distribution of the age, serum phosphorus, serum magnesium, FGF-23 levels among these groups (P＜0.05) . Spearman correlation analysis showed that CACs was positively correlated with age, FGF-23, serum phosphorus (r=0.309, 0.277, 0.180, P=0.000, 0.001, 0.040, respectively), while negatively correlated with serum magnesium level (r=-0.238, P=0.006) in patients with MHD. The independent risk factors of CACs were aging, high level of FGF-23 in MHD patients by using ordinal logistic regression. However, Hypermagnesemia was a protective factor. Conclusions The history of diabetes, low serum albumin, phosphorus metabolism disorder and CAC are associated with hypomagnesemia in MHD patients. In MHD patients, aging as well as high level of FGF-23 are the risk factors of CAC, and hypermagnesemia is a protective factor of CAC.     

Relationship between gut microbiota and vascular calcification in hemodialysis patients

IntroductionVascular 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.MethodsA 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.ResultsThe 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.ConclusionsOur 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.     

糖尿病与非糖尿病维持性血液透析患者血管钙化的对比研究

目的探讨糖尿病维持性血液透析（MHD）患者血管钙化的影响因素。方法选择我院MHD患者90例,其中糖尿病组21例、非糖尿病组69例。检测2组透析前、后血压、心率、相关血生化指标以及全段甲状旁腺素（iPTH）、1,84-PTH、25一羟一维生素功,比较2组血管钙化情况,探讨糖尿病组患者血管钙化的相关因素。结果与非糖尿病组相比,糖尿病组透析前血肌酐较低,三酰甘油较高,高密度脂蛋白胆固醇较低（P〈0．05）。糖尿病组iPTH达标率高于非糖尿病组,而钙磷乘积低于后者（P〈0．05）。糖尿病组钙化发生率和钙化积分高于非糖尿病组（P〈0．05）。对糖尿病MHD患者,血管钙化积分与糖尿病病程、慢性肾脏病（CKD）病程、透析时间、iPTH、碱性磷酸酶呈正相关（r值分别为0．491、0499、0．652、0．727和0．564,P值均〈0．05）。结论与非糖尿病患者相比,患有糖尿病的MHD患者有较高的血管钙化发生率及较重的血管钙化程度;其中糖尿病病程、CKD病程、透析时间、iPTH、ALP可能参与糖尿病患者血管钙化的发生和发展。     

透析患者肺动脉高压与血管钙化之间的关系分析

目的探讨透析患者肺动脉高压(pulmonary hypertension,PHT)与血管钙化之间的关系,为临床透析患者PHT的预防与治疗提供依据。方法回顾性分析自贡市第一人民医院透析中心病情稳定的患者172例,其中血液透析88例,腹膜透析患者84例。纳入标准:透析时间3个月,病情稳定的规律性透析患者;排除标准:怀孕、艾滋病毒感染者、严重的感染、肝胆疾病、活动性消耗性疾病(如恶性肿瘤或肺结核);急性心肌梗死、心力衰竭、急性脑血管疾病;原发性甲状旁腺疾病,行甲状旁腺切除、手术、创伤和严重营养不良的患者均排除。所有患者使用超声心动图检查提示肺动脉收缩压大于37 mmHg定义为PHT。采用双手及骨盆X片检查评估患者血管钙化情况。结果血液透析患者PHT、的发生率明显高于腹膜透析患者(51.2%比22.7%);透析患者中有PHT的患者的血管钙化严重程度高于无。PHT的透析患者。多因素分析显示血管钙化程度(OR=2.68)、二尖瓣病变(OR=7.79)、血液透析(OR=3.35)、左心房内径增大(OR=11.39)是透析患者发生PHT的独立危险因素。结论血液透析患者PHT的发生率高于腹膜透析患者;透析患者中血管钙化可能是预测患者PHT发生的独立危险因素,预防透析患者血管钙化的发生对减轻透析患者PHT可能有着重要的临床意义。     

Soluble osteopontin and vascular calcification in hemodialysis patients.

BACKGROUND: Vascular calcification often occurs in patients with uremia. As osteopontin (OPN) is not only involved in the physiological but also the pathological calcification of tissues, OPN may be associated with the pathogenesis of aortic calcification in hemodialysis (HD) patients. METHODS: We examined the expression of OPN in atherosclerotic aortas of HD patients. In addition, we performed a prospective longitudinal study by using CT scans to detect aortic calcifications and by measuring the plasma OPN concentration by ELISA in HD patients (20 men, 16 women; mean age 55.2 +/- 21.3 years) and in healthy volunteers (18 men, 17 women; mean age 54.0 +/- 13.2 years). RESULTS: By immunohistochemical staining, OPN was abundantly localized in atherosclerotic plaques of HD patients. The macrophages surrounding the atheromatous plaques were identified as the OPN-expressing cells. We furthermore found that the concentration of soluble plasma OPN was significantly higher in HD patients as compared with the concentrations in age-matched healthy volunteers (837.3 +/- 443.2 vs. 315.1 +/- 117.4 ng/ml, p < 0.01). The OPN concentration was positively correlated with the aortic calcification index in HD patients (r = 0.749, p < 0.01). CONCLUSION: These data suggest that OPN, secreted by macrophages, plays a role in the calcification of atheromatous plaques in HD patients.     

Role of fibroblast growth factor-23 in peripheral vascular calcification in non-diabetic and diabetic hemodialysis patients

INTRODUCTION: Fibroblast growth factor (FGF) 23 is a recently identified circulating factor that regulates phosphate (Pi) metabolism. Since the derangement of Pi control is an important risk factor for vascular calcification, we investigated the importance of plasma FGF-23 in the development of vascular calcification in the aorta and peripheral artery in hemodialysis patients with and without diabetes mellitus (DM). METHODS: Male hemodialysis patients with DM (n=32) and without DM (n=56) were examined. Plasma samples were obtained before the start of dialysis sessions, and the FGF-23 levels were determined by enzyme-linked immunosorbent assay. Roentgenography of the aorta and hand artery was performed, and visible vascular calcification was evaluated by one examiner, who was blinded to the patient characteristics. RESULTS: In the 56 non-DM hemodialysis patients, vascular calcification was found in the hand artery in 5 patients (8.9%) and in the aorta in 23 patients (41.1%). These levels were significantly lower (p<0.05) than in the 32 DM patients, of whom, 19 (59.4%) and 21 (65.6%) had vascular calcification of the hand artery and aorta, respectively. Multiple regression analyses performed separately in the non-DM and DM patients showed that the plasma FGF-23 level, CaxPi product, and body weight are independent factors significantly associated with hand-artery calcification and that diastolic blood pressure is associated with aorta calcification in non-DM patients. In DM patients, the plasma FGF-23 level and hemodialysis duration emerged as independent factors associated with hand-artery calcification and diastolic blood pressure was associated with aorta calcification. The independent association of the plasma FGF-23 level with hand-artery calcification was retained in both non-DM and DM patients when adjusted for the CaxPi product. CONCLUSION: Our findings show that the plasma FGF-23 level is an independent factor negatively associated with peripheral vascular calcification in the hand artery, but not in the aorta, in both male non-DM and DM hemodialysis patients, even when adjusted for the CaxPi product. This study raises the possibility that the plasma FGF-23 level may provide a reliable marker for Moenckeberg's medial calcification in male hemodialysis patients, independent of its regulatory effect on Pi metabolism.     

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

International Urology and Nephrology - Vascular calcification (VC), which is a pathological process of abnormal calcium and phosphorus deposition in blood vessels, valves, heart and other tissues,...     

Significant inverse relationship between serum undercarboxylated osteocalcin and glycemic control in maintenance hemodialysis patients

Summary

Increased levels of serum undercarboxylated osteocalcin, which were associated with bone metabolism markers, correlated inversely with indices of glucose metabolism (plasma glucose, hemoglobin A1C, and glycated albumin) in hemodialysis patients with abnormalities of bone metabolism.

Introduction

Undercarboxylated osteocalcin (ucOC), a possible marker of bone metabolism and one of the osteoblast-specific secreted proteins, has recently been reported to be associated with glucose metabolism. We tested the hypothesis that ucOC levels are associated with indices of glucose metabolism in chronic hemodialysis patients with abnormalities of bone metabolism.

Methods

Serum ucOC, bone alkaline phosphatase (BAP, a bone formation marker), and tartrate-resistant acid phosphatase-5b (TRACP-5b, a bone resorption marker) were measured in 189 maintenance hemodialysis patients (96 diabetics and 93 non-diabetics), and their relationships with glucose metabolism were examined.

Results

ucOC correlated positively with BAP (ρ?=?0.489, p?<?0.0001), TRACP-5b (ρ?=?0.585, p?<?0.0001) and intact parathyroid hormone (iPTH; ρ?=?0.621, p?<?0.0001). Serum ucOC levels in the diabetic patients were lower than those of non-diabetic patients (p?<?0.001), although there were no significant differences in serum BAP or TRACP-5b between diabetic and non-diabetic patients. Serum ucOC correlated negatively with plasma glucose (ρ?=??0.303, p?<?0.0001), hemoglobin A1C (ρ?=??0.214, p?<?0.01), and glycated albumin (ρ?=??0.271, p?<?0.001), although serum BAP or TRACP-5b did not. In multiple linear regression analysis, log [plasma glucose], log [hemoglobin A1C], and log [glycated albumin] were associated significantly with log [ucOC] after adjustment for age, gender, hemodialysis duration, and body mass index but were not associated with log [BAP], log [TRACP-5b], or log [intact PTH].

Conclusion

Increased levels of serum ucOC, which were associated with bone metabolism markers, were inversely associated with indices of glucose metabolism in hemodialysis patients.     

Role of vascular calcification inhibitors in preventing vascular dysfunction and mortality in hemodialysis patients

Cardiovascular events make up the primary cause of death in hemodialysis patients, and the risk for cardiovascular mortality is significantly increased by vascular calcification, a condition observed frequently in this patient population. The mechanisms underlying the pathogenesis of vascular calcification are complex, and many factors facilitate or hinder the development of calcification. In this review, we first summarize the main factors contributing to the pathogenesis of vascular calcification in patients with end‐stage renal disease. We then explore the role of calcification inhibitors in the calcification process, as well as their effect on vascular dysfunction and mortality in hemodialysis patients.     

Modeling the implications of changes in vascular calcification in patients on hemodialysis

BACKGROUND: The Treat-to-Goal Study found that sevelamer slowed the progression of coronary calcification in patients on hemodialysis compared to calcium-based phosphate binders. To understand the implications of this effect for cardiovascular events, risk equations are needed. METHODS: Data on 179 patients on hemodialysis treated at one center in France included biochemical values during the year prior to study entry, patient characteristics, and cardiovascular events over an average of 4 years. As arterial calcification was evaluated ultrasonographically and quantified using a 0 to 4 score, an equation relating this to the electron-beam tomography (EBT)-based calcification score used in the trial was developed and applied to all patients. The estimated scores were then used in survival and Cox proportional hazards analyses of cardiovascular events in relation to the degree of calcification, controlling for other characteristics. RESULTS: Mean age at inclusion was 54 years, dialysis vintage 70 months, average follow-up 49 months; 32% suffered an event. The calcification score, diabetes, C-reactive protein (CRP), diastolic blood pressure, gender, smoking and hypertension are independent predictors of cardiovascular risk. The resulting equation indicates that, relative to a calcification score below 400, the risk of an initial event increases 44% for a score of 600, and more than doubles for a score of 1000. CONCLUSION: In the absence of long-term follow-up studies, these equations permit quantification of the expected long-term clinical consequences of the impact of various phosphate binders on vascular calcification. Together with resource use and cost information, these equations are key inputs for formal cost-effectiveness analyses.     

The association between serum adiponectin levels and nutritional status of hemodialysis patients

Adiponectin plays an important role in the regulation of body weight, insulin sensitivity, lipid metabolism, and the inflammatory response. Adiponectin is elevated in hemodialysis patients. We investigated the association between altered serum adiponectin levels and the nutritional-inflammation status of hemodialysis patients. Forty-four hemodialysis patients (21 men and 23 women; mean age 53.9 ± 9.2 years) were enrolled and 32 healthy volunteers were included as the control group. Serum adiponectin was measured using a commercial radioimmunoassay kit. Serum albumin, cholesterol, triglyceride, high-sensitivity C-reactive protein, urea, creatinine, transferrin, lean body mass, fat mass, body mass index (BMI), the subjective global assessment (SGA) score, and the malnutrition-inflammation score (MIS) were measured in all patients. Adiponectin levels were significantly elevated in the hemodialysis patients compared with the healthy subjects (24.8 ± 10.4 μg/mL and 6.8 ± 4.2 μg/mL, respectively, p < 0.0001). Serum adiponectin correlated positively with SGA (r = 0.47) and MIS (r = 0.38), and negatively with BMI (r = -0.34), triglyceride (r = -0.53), and glucose levels (r = -0.42). Serum adiponectin levels were significantly higher in malnourished patients than in well-nourished patients when assessed with SGA (20.5 ± 10.4 μg/mL and 29.0 ± 8.7 μg/mL, respectively, p = 0.005). In conclusion, serum adiponectin levels reflect the nutritional-inflammation status of hemodialysis patients. Adiponectin may also be associated with insulin resistance, dyslipidemia, and the inflammatory response in these patients.     

维持性血液透析患者血管钙化的发生情况及相关危险因素分析

目的探讨维持性血液透析患者的血管钙化发生情况及相关危险因素分析。方法选择血液透析患者91例,记录相关人口学资料及临床资料,完善实验室检查。分别以X光片（腰椎侧位、双手、骨盆）评价血管钙化情况。结果91例患者中无血管钙化者22例,有不同程度血管钙化者69例;轻度钙化38例（占41．76％）,中度钙化14例（占19．72％）,重度钙化17例（占23．94％）;统计学分析显示2组间年龄、血磷和钙磷乘积有统计学差异（P〈0．05）;单因素分析显示年龄、血磷、钙磷乘积和未服用活性维生素D是血管钙化的危险因素,多因素分析显示年龄、血磷、未服用活性维生素D为血管钙化独立影响因素。结论血管钙化是维持性血液透析患者常见并发症,且发病率较高,高龄、高磷血症、高钙磷乘积及合理使用活性维生素D在钙化发生、发展中有重要作用。     

Relationship between serum uric acid level and vascular injury markers in hemodialysis patients

Purpose

It has been reported that hyperuricemia causes vascular endothelial injury. Most hemodialysis patients present with hyperuricemia and also with vascular injury, resulting in cardiovascular diseases (CVD). However, the association of serum uric acid (sUA) with vascular injury markers in hemodialysis patients remains unclear. This study aimed to investigate this and discuss the mechanism by which uric acid causes vascular injury.

Methods

We enrolled 48 Japanese maintenance hemodialysis patients without any history of CVD. The association between sUA level and three vascular injury markers (reactive hyperemia index [RHI], ankle–brachial index [ABI], and cardio ankle vascular index [CAVI]) was investigated by linear- and logistic regression analyses.

Results

The median natural logarithm RHI (LnRHI) was 0.36. Linear regression analysis revealed a significant positive correlation between sUA level and LnRHI (β?=?0.42, p?=?0.001) in all patients. Moreover, a significant, strongly positive correlation was observed between sUA and LnRHI in patients who were treated with xanthine oxidase inhibitors (XOIs) (β?=?0.75, p?=?0.001). Further, the linear analysis showed a significant negative correlation between sUA level and CAVI in patients who were treated with XOIs (β?=?? 0.52, p?=?0.049). sUA level was not significantly associated with ABI abnormality.

Conclusions

It is possible that a high level of sUA is significantly associated with better vascular endothelial function and condition of vascular tone in hemodialysis patients who were treated with XOIs. The findings suggest a significant paradox between sUA level and vascular endothelial function in hemodialysis patients; however, the opposite has been reported in patients without hemodialysis.

     

可溶性Klotho蛋白对维持性血液透析患者血管硬化的影响

目的 探讨维持性血液透析(maintenance hemodialysis,MHD)患者血管硬化与可溶性Klotho蛋白(serum soluble Klotho,sKL)之间的关系.方法 收集60例MHD患者的临床资料,采用ELISA法检测sKL浓度.检测MHD患者踝一臂脉搏波传导速度(brachial-ankle pulse wave velocity,baPWV)和颈动脉内中膜厚度(intima-media thickness,IMT),以评价MHD患者血管硬化的程度.用Logistic回归分析法分析MHD患者发生血管硬化的危险因素;用Pearson相关分析法分析sKL浓度与baPWV、IMT的相关性.结果 60例MHD患者中,47例患者baPWV≥1 400 cm/s,血管硬化者占78.3％.根据患者血sKL水平分布范围的四分位数分为4组,Ⅰ组sKL＜405 ng/L,Ⅱ组sKL范围为405～624 ng/L,Ⅲ组sKL范围为624～832 ng/L,Ⅳ组sKL＞832 ng/L;各组的baPWV、Max IMT随着sKL水平的降低而升高(P＜0.01);sKL浓度与baPWV呈负相关(r=-0.115,P＜0.01),血清sKL浓度与Max IMT呈负相关(r=-0.224,P＜0.01),差异有统计学意义.Logistic回归分析法分析结果显示,血清sKL浓度降低(OR=2.336,95％ CI 1.153～7.315)和吸烟(OR =4.025,95％ CI 2.305～11.234)是MHD患者血管硬化的独立危险因素.结论 血清sKL浓度下降与血管硬化相关,血清sKL浓度的测定可能有助于血管硬化的诊断.     

骨硬化蛋白与维持性血液透析患者冠状动脉钙化的关系

Objective To evaluate the potential association of serum sclerostin with the development of coronary artery calcifications(CAC)in maintenance hemodialysis (MHD) patients. Methods Ninety-two patients who were on MHD between Jan 2014 and Jan 2015 in the dialysis center were enrolled prospectively. Serum sclerostin was tested. CAC was measured by multi-slice computed tomography (MSCT) scanning, and the CAC score (CACs) was calculated. Logistic regression analysis was used to determine the risk factor of CAC in MHD patients. The diagnostic value of serum sclerostin for CAC was assessed using receiver operator characteristic curve (ROC). Results CAC (Agatston score>100) was present in 65.2% (60/92) patients, the median CAC score was 446 (26, 1 000). The median of serum sclerostin levels was 37.05 (29.99, 49.04) ng/L. The serum sclerostin levels were significantly elevated in the group of CACs＞400 compared to that in the group of CACs＜100 [40.71(36.69, 74.21) ng/L vs 28.16 (25.27, 33.64) ng/L, P＜0.05]. Multivariate logistic regression analysis showed that serum sclerostin level was independent risk factor for CAC (OR=1.292, 95%CI 1.017-1.641, P＜0.05). The area under the ROC curve (AUC) of serum sclerostin for CAC was 0.846 (95%CI 0.717-0.975, P=0.001), sensitivity was 0.826, and specificity was 0.769 for a cutoff value of 35.165 ng/L. Conclusions Serum sclerostin level is associated with CAC. Serum sclerostin level may have a diagnostic value for CAC in MHD patients.     

Association of pulse wave velocity with vascular and valvular calcification in hemodialysis patients

The recent Kidney Disease: Improving Quality Outcomes (KDIGO) recommendations called for an investigation of the relationship between various radiological methods to assess cardiovascular calcification and measures of arterial stiffness. Accordingly, in 131 adult maintenance hemodialysis patients, we investigated the association of aortic pulse wave velocity (PWV) with calcification of cardiac valves on echocardiography, coronary artery, and thoracic aorta calcium on computed tomography and a calcification score of the abdominal aorta obtained on a plain abdominal X-ray. All tests were performed within a week. Mean PWV increased as the severity of coronary artery, thoracic, and abdominal aorta calcium scores increased (each P<0.05). No trend was present for number of valves with calcification. After multivariable adjustment, abdominal aorta X-ray calcium scores remained associated with PWV (P=0.004), whereas the association of PWV with thoracic aorta and coronary artery calcium scores became marginal (P=0.308 and P=0.083, respectively). No association was found between number of calcified valves and PWV. This study demonstrates a strong association between abdominal aorta calcification on plain X-ray and PWV and a borderline association with thoracic aorta and coronary artery calcification. Sudden death and congestive heart failure, two frequent causes of death in hemodialysis, are likely caused by increased arterial stiffness that can be closely predicted by the presence of aortic calcification on plain X-rays.     

Pulmonary vascular calcification in a nocturnal hemodialysis patient

Although vascular calcification in end-stage renal disease (ESRD) is common, metastatic pulmonary calcification (MPC) is an under-recognized complication of ESRD with the majority of individuals being asymptomatic. Similar to calcification in other arterial vascular beds, elevated serum calcium and phosphate appear to be potent risk factors although the exact pathogenesis of MPC remains largely unclear. Nocturnal hemodialysis (NHD) is a form of renal replacement therapy that offers superior control of serum phosphate and uremia compared to conventional (3 times weekly) intermittent hemodialysis and shows promise in delaying the progression of vascular calcification. Here, we report the first case of MPC involving the pulmonary vasculature in a patient treated with nocturnal hemodialysis and discuss the epidemiology, pathogenesis, histology and natural history of MPC.