Optimal Phosphate Control Related to Coronary Artery Calcification in Dialysis Patients

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Epicardial Adipose Tissue and Coronary Artery Calcification in Diabetic and Nondiabetic End-Stage Renal Disease Patients

Background/aims: Atherosclerosis, coronary artery calcification, diabetes mellitus, inflammation, endothelial dysfunction, and left ventricular hypertrophy are the most commonly encountered risk factors in the pathogenesis of cardiovascular disease in end-stage renal disease (ESRD) patients. Epicardial adipose tissue (EAT) is the true visceral fat depot of the heart. The relationship between coronary artery disease (CAD) and EAT was shown in healthy subjects and patients with high risk of CAD. To date, there is not enough data about EAT in diabetic and nondiabetic ESRD patients. Therefore, we aimed to investigate the EAT and coronary artery calcification score (CACS) in diabetic and nondiabetic ESRD patients and healthy subjects. Methods: Sixty ESRD patients (17 diabetic, 43 nondiabetic ESRD patients) and 20 healthy subjects were enrolled in the study. EAT and CACS were performed by a 64-slice multidetector computed tomography scanner. Results: There were no differences in age, gender, body mass index, predialysis systolic and diastolic blood pressure levels, biochemical parameters including serum low-density lipoprotein and high-density lipoprotein cholesterol, triglycerides, and C-reactive protein between healthy subjects, diabetic, and nondiabetic ESRD patients. Total CACSs and EAT measurements were significantly higher in diabetic ESRD patients when compared with nondiabetic ESRD patients and healthy subjects. There was statistically significant relationship between EAT and CACS in ESRD patients (p < 0.0001, r = 0.48). Conclusion: In conclusion, we found a significant increase in terms of EAT and CACS in diabetic ESRD patients when compared with nondiabetic ESRD patients and healthy subjects.     

Determinants of Coronary Artery Calcification Progression in Renal Transplant Recipients

Coronary artery calcification (CAC) is associated with increased atherosclerotic burden and cardiovascular events. The objective of this study was to determine the natural history and risk factors associated with CAC progression in a cohort of incident asymptomatic renal transplant recipients with no history of coronary revascularization. Electron-beam computed tomography was performed in 82 subjects at time of transplantation and at least 1 year later. Mean (SD) and median CAC score increased for all subjects from 392.4 (747.9) and 75.8 at time of transplant to 475.3 (873.5), (p = 0.002[log]) and 98.9 (p < 0.001), respectively. Most subjects (89%) with no calcifications remained without calcification. Mean annualized rate (SD) of CAC score change was 52.5 (150) with a median of 0.5. Average yearly percent change was 67.3 (409.6) with a median of 1.4. In multivariate analysis, diastolic blood pressure at 3 months post-transplant, Caucasian race, glomerular filtration rate at 3.0, months post-transplant, body mass index and baseline CAC score were independent predictors of annualized rate of CAC change. There is significant progression of CAC post-renal transplantation in most subjects. Progression is most likely to occur in white patients and is associated with clinical factors such as blood pressure, body mass index, renal function and baseline CAC score.     

Coronary Artery Calcification in Renal Transplant Recipients

Cardiovascular disease is the leading cause of mortality in renal transplant recipients. Although renal transplant recipients frequently undergo cardiac functional tests prior to surgery, coronary atherosclerosis can remain undetected. Coronary artery calcification (CAC), an early marker of atherosclerosis can be quantified using EBCT. The purpose of this study was to determine the extent and characteristics of CAC at the time of renal transplantation. We evaluated 79 consecutive incident asymptomatic renal transplant recipients. Patients were mostly White (62%), male (54%) and had a deceased donor renal transplant (61%). The mean age was 47 (12.1) years. Sixty-five percentage of subjects had CAC. The mean CAC score was 331.5 (562.4) with a median of 43.3. Older age, presence of diabetes, not having a preemptive transplant, deceased donor transplantation and hypercholesterolemia were significantly associated with presence of CAC univariately. Median CAC scores were significantly increased in subjects with diabetes (127.8 vs. 28.9, p=0.05), exposed to dialysis (102.9 vs. 3.7, p<0.001) and deceased donor recipients (169.7 vs. 7.5, p=0.02). Using multiple logistic regression, age and time on dialysis were significantly associated with the presence of CAC at the time of transplant. In summary, CAC is prevalent in patients undergoing kidney transplant. CAC may be a method to identify renal transplant recipients at increased risk for future cardiovascular events.     

Parathyroid hormone and its fragments in children with chronic renal failure

Parathyroid hormone (PTH) immunoradiometric assays (IRMA) exhibit cross-reactivity between 1-84 PTH and long carboxyl-terminal-PTH (C-PTH) molecules. C-PTH antagonizes the biological actions of 1-84 PTH and circulates in excess in chronic renal failure (CRF), partially explaining why supra-physiological PTH levels are recommended to maintain bone turnover. Furthermore, the ratio 1-84 PTH/C-PTH may be related to bone turnover. This study characterizes the 1-84 PTH/C-PTH ratio in children with varying severity of CRF and levels of PTH. Two hundred and forty-one children with CRF, managed with the aim of preventing the development of hyperparathyroidism, had PTH measured by intact IRMA and a new more specific Cyclase-Activating-PTH (CAP) IRMA. C-PTH levels were calculated by subtracting CAP-IRMA from intact IRMA. Fifty-three controls with normal renal function were also recruited. Mean intact IRMA correlated with CAP-IRMA (r=0.98), but was higher (P<0.001). The mean 1-84 PTH/C-PTH ratio was lower than controls in dialysis patients (P=0.022) and those with a glomerular filtration rate <30 ml/min per m² (P=0.033). This ratio was comparable to controls when the PTH level was normal, but was lower with PTH levels outside the normal range (P<0.01). These data suggest that CAP-IRMA gives a more accurate assessment of actual PTH levels than intact IRMA in CRF. Maintenance of normal PTH levels throughout the course of CRF permits the maintenance of a normal 1-84 PTH/C-PTH ratio, the clinical significance of which requires further investigation in children.     

The Value of Computed Tomography-Derived Coronary Artery Calcification Score in Coronary Artery Disease Detection in Asymptomatic Hemodialysis Patients

Background. We evaluated the value of coronary artery calcification (CAC) score in coronary artery disease (CAD) detection in asymptomatic hemodialysis (HD) patients by evaluating the association among CAC score, exercise electrocardiography (EECG), and Thallium-201 dipyridamole scintigraphy. Correlation between aortic pulse wave velocity (PWV) and CAC score was also evaluated. Methods. CAC score was assessed with conventional computed tomography in 40 patients. Thirty patients completed EECG and 25; those with a positive CAC score and/or a positive EECG performed Thallium dipyridamole scintigraphy. Carotid-femoral PWV was assessed in all patients. Results. There was no association among CAC score and EECG or Thallium dipyridamole scintigraphy. In contrast, CAC score was correlated with aortic PWV. Conclusion. The previous results question the role of CAC score in the detection of CAD in asymptomatic HD patients. The correlation between CAC score and aortic PWV raises the possibility that CAC score represents more an indicator of coronary artery medial wall calcification than a marker of CAD.     

Long-Term Effect of Different Dialysate Calcium Concentrations on Parathyroid Hormone Levels in Hemodialysis Patients

The appropriate dialysate calcium concentration (D[Ca]) for hemodialysis (HD) therapy has not yet reached a consensus. We have conducted a prospective control study for five years on the effects of different D[Ca] on serum intact parathyroid hormone (iPTH) levels. Patients were divided into three groups receiving different D[Ca] therapies: the low-Ca (D[Ca]?=?2.5 mEq/L; N?=?96), mid-Ca (D[Ca]?=?3.0 mEq/L; N?=?121), and high-Ca (D[Ca]?=?3.5 mEq/L; N?=?82) groups. After five years' study, only 41 patients in the low-Ca group, 34 in the mid-Ca group, and 32 in the high-Ca group completed the study. The results demonstrated that serum corrected calcium concentrations were significantly lower in the low-Ca group compared with other groups in years 3 and 4, although the products of corrected calcium time phosphate did not show difference between each group.^Δserum alkaline phosphatase (^ΔAlk-p) to baseline levels increased significantly after the fourth year in all three groups (p < 0.05). Serum ^Δ iPTH only increased significantly after the fourth year in the low-Ca group (p < 0.05) but not in the other groups. There were no significant differences in the extent of ^ΔAlk-p and ^ΔiPTH between the groups. Cox proportional methods also showed no difference in cumulative survival between the groups. In conclusion, our results demonstrate that compared with the other two groups of D[Ca], long-term use of D[Ca] of 2.5 mEq/L was associated with relatively lower serum calcium concentration. Perhaps this was related to a greater extent of iPTH concentration elevation after five years.     

In Vitro Parathyroid Hormone Release in Patients with Secondary Hyperparathyroidism

Background: The purpose of this study was to determine the precise endocrim. characteristics of parathyroid function in secondary hyperparathyroidism (sHPT).
Methods: We examined the effects of extracellular ionized calcium (Ca²⁺) varying from 0.5 to 2.0 mM on parathyroid hormone (PTH) release in parathyroid cell suspensions using a mid-regional PTH assay. Cells were obtained from 26 patients with sHPT who were divided into two groups according to the type of hyperplasia they exhibited, either nodular (n=16) or diffuse [n= 10). For compdrison, we also analyzed data from nine patients with primary hyperparathyroidism (pHPT; adenomas).
Results: Significant in vitro suppression of PTH release by Ca²⁺ was observed in the majority of subjects, regardless of the histologic abnormality. The pHPT group exhibited no significant relationship between clinical and in vitro data. In contrast, in the sHPT group (taken as a whole), suppression of PTH release by Ca²⁺ exhibited a plateau at a total serum calcium concentration of 2.5 mmol/L, and a parathyroid gland weight of 2 g.
Conclusions: These findings suggest that there is a curvilinear relationship in sHPT, but not pHPT, between the in vitro calcium sensitivity of parathyroid cells and total serum calcium, as well as gland weight. The in vitro calcium sensitivity in sHPT remains constant when the total serum calcium concentration exceeds 2.5 mmol/L, or when the gland weight exceeds 2 g.     

Secretion of Parathyroid Hormone After Surgical Trauma

Parathyroid hormone was measured in nine patients subjected to surgery under general anaesthesia not involving operative bone trauma. Total calcium concentration, ionized serum calcium and serum albumin was also analyzed pre- and postoperatively. An increase in serum parathyroid hormone was registered postoperatively without any acompanying decrease in ionized serum calcium. the measured changes are at present unexplained, but can be caused by other mechanisms than bone trauma.     

Coronary calcification and its association with mortality in haemodialysis patients

Aim:   Coronary artery calcification (CAC) has been associated with higher mortality in chronic renal disease. The purpose of this study was to assess coronary artery calcium score (CaCs) in haemodialysis patients and to correlate calcium scores with clinical parameters and mortality.
Methods:   A cross-sectional study was conducted in 59 haemodialysis patients. CaCs was assessed by multidetector-row computed tomography and stratified as: CaCs of less than 10 Agatston units (U), no calcification; CaCs of 10–400 U, mild-to-moderate; and CaCs of more than 400 U, severe calcification. The effects of age, haemodialysis duration and biochemical and inflammatory markers on CaCs logarithm were evaluated by multiple linear regression analysis. Cox regression analysis was used to measure the impact of CaCs of more than 400 on 2-year mortality.
Results:   Coronary calcifications were detected in 64.5% of patients, and the median of CaCs was 31.7 U (0–589.7) with a range of 0–5790.0 U. Twenty-one (35.5%) patients had mild-to-moderate and 17 (29%) severe CaCs. Patients with severe CaCs were older and showed a higher prevalence of ischaemic heart disease and a higher body mass index ( P  = 0.04). A trend towards higher C-reactive protein levels was found in patients with severe CaCs. Advanced age was the only variable that influenced CaCs logarithm independently. The effect of severe CaCs on 2-year mortality did not persist after adjustment for other covariates.
Conclusion:   Coronary calcification was highly prevalent in these uraemic patients on chronic haemodialysis. A correlation was evidenced between CaCs and advanced age, but severity of the CAC score did not have an impact on 2-year mortality of this cohort.     

The Relationship between Apelin and Parathyroid Hormone in Hemodialysis Patients

Both apelin and parathyroid hormone (PTH) are endogenous ligands for G-protein-coupled receptors. Apelin acts as a mitogenic agent for osteoblasts, and metabolic bone abnormalities are frequently seen in hemodialysis (HD) patients because of hyperparathyroidism. The aim of this study was to analyze plasma apelin levels in HD patients and to determine whether they are related to PTH concentrations. A total of 23 HD patients [15 men and 8 women, with a mean (SD) age of 54.2 (4.4) years and a mean body mass index (BMI) of 25.0 (4.1) kg/m²] were studied and compared with 15 healthy subjects [6 men and 9 women, with a mean (SD) age of 51.3 (13.6) years and a BMI of 27.0 (4.3) kg/m²]. Plasma apelin-36 was measured using an enzyme immunometric assay method and PTH was measured by ELISA. There was no significant difference in apelin levels between the patients [0.80 (0.6) ng/mL] and the healthy subjects [0.83 (0.23) ng/mL]. There was a positive correlation between apelin and PTH (r = 0.66, p = 0.0001). The patients with PTH >300 pg/mL had significantly higher plasma apelin levels [1.17 (0.7) ng/mL] compared with the patients with PTH <300 pg/mL [0.50 (0.15) ng/mL] (p = 0.003). In conclusion, HD patients with secondary hyperparathyroidism have high plasma apelin levels, which suggest that apelin may protect bone in HD patients by acting as an osteoblastic factor.     

维持性血液透析患者颈动脉钙化相关因素分析

目的：探讨慢性肾衰竭维持性血液透析（MHD）患者颈动脉钙化情况并分析相关因素。方法：对35例MHD患者应用彩色B型超声仪观测双侧颈动脉内膜-中膜厚度（IMT）及钙化情况,同时记录透析龄、收缩压、脉压差,抽血检测血钙、磷、血胆固醇、三酰甘油、白蛋白、C反应蛋白（CRP）、甲状旁腺素,并计算钙磷乘积。结果：35例终末期肾病（ESRD）患者18例（51.4%）存在颈动脉钙化。钙化组IMT值较无钙化组显著增高（P〈0.01）,透析龄、收缩压、脉压差、血磷、钙磷乘积、CRP较无钙化组明显增高（P〈0.05）,而钙化组血浆白蛋白较无钙化组显著降低（P〈0.05）。结论：IMT值、透析龄、血磷、钙磷乘积增高是颈动脉钙化的主要影响因素,收缩压、脉压差、CRP升高和低血浆白蛋白与颈动脉钙化密切相关。MHD患者存在较高的颈动脉钙化率。     

CKD患者冠状动脉钙化的危险因素分析

目的:分析CKD患者冠状动脉钙化与临床指标的相关性,探讨其发生的危险因素。方法:选取473例曾在我院行冠脉CT检查的CKD及非CKD患者,通过收集其生化指标及冠脉CT检查结果,分析CKD患者冠状动脉钙化与临床检查指标的关系。结果:患者冠状动脉钙化积分(CACs)与年龄、尿素氮、肌酐水平、血磷水平和钙磷乘积呈正相关(P<0.05),与肾小球滤过率和血红蛋白呈负相关(P<0.05)。结论:年龄、尿素氮和血磷是患者冠脉发生钙化的独立危险因素,年龄、肌酐水平、肾小球滤过率和血磷水平与冠状动脉钙化严重程度有线性关系。     

Biochemical Indices of Renal Osteodystrophy in Dialysis Patients on the Island of Malta

Objectives: Renal osteodystrophy (ROD) has never been studied on the small Mediterranean island of Malta, which has a largely inbred population. The genetic contribution to the pattern of renal osteodystrophy is being increasingly recognized. We were, thus, interested in studying indices of bone turnover in Maltese end stage renal failure patients. Materials and methods: Sixty unselected patients, representing 65% of all patients undergoing dialysis in the island’s renal unit, were prospectively investigated over a period of 5 months with respect to symptoms, calcium/phosphate chemistry, intact parathyroid hormone (iPTH) and bone alkaline phosphatase (bAP). Bone histomorphometry, which is the gold standard in the diagnosis of ROD, was not within the reach of our small unit. Biochemical markers may not be as sensitive and specific as bone biopsy for individual patient diagnosis of ROD sub-type but they can give a fairly good indication of the spectrum of bone turnover on a population basis. The optimum combination of biochemical marker cut-offs available from studies in the literature was then employed to estimate bone turnover. Results: The following biochemical picture emerged: 42% had iPTH < 79.7 pg/ml (which cut off has a reported specificity of 93.7% for low turnover bone disease), 45% had iPTH > 100 pg/ml and bAP > 10 ng/ml (which combined cut off has a reported specificity of 100% for high turnover bone disease), while 13% could not be classified (ie had intermediate values). Conclusions: Based on biochemical data, the pattern of bone turnover seems to be comparable to the European average. Further indepth study using bone histomorphometry is warranted.     

Association Among Serum Fetuin-A Level, Coronary Artery Calcification, and Bone Mineral Densitometry in Maintenance Hemodialysis Patients

Patients with end‐stage renal disease have a very high prevalance and extent of arterial calcification. A number of studies suggest that similar pathophysiologic mechanisms are responsible for development and progression of calcification of atherosclerotic plaque and bone formation. Fetuin‐A is a potent calcification inhibitor and is expressed in bone, with not‐yet well‐defined functions. The aim of this study was to investigate the relation between bone mineral densitometry parameters, coronary artery calcification, and serum fetuin‐A levels. In a cross‐sectional design, we included 72 maintenance hemodialysis (HD) patients and 30 age‐ and gender‐ matched healthy controls. Serum fetuin‐A levels were studied both in maintenance HD patients and healthy controls. Maintenance HD patients had radius, hip, and lumbar spine bone mineral density (BMD) assessed by dual‐energy X‐ray absorptiometry and coronary artery calcification score (CACS) measured by electron‐beam computed tomography. The associations between site‐specific BMD parameters, CACS, and serum fetuin‐A levels were studied in maintenance HD patients. CACS, mass, and volume of plaques in coronary arteries were significantly higher in patients with a T‐score below ?2.5 than above in the proximal region of the radius, neck and trochanter of the femur, and the lumbar spine. Mean serum fetuin‐A concentration was 0.636 ± 0.118 g/L in maintenance HD patients and it was less than healthy controls (0.829 ± 0.100 g/L, P < 0.0001). CACS, mass, and volume of plaques in coronary arteries correlated significantly with the serum fetuin‐A levels. Moreover, significant positive correlations were shown between the serum fetuin‐A levels, BMD values, and T‐scores of proximal radius, neck, and trochanter of the femur, but not with the lumbar spine. The present study demonstrates an association between serum fetuin‐A levels, coronary artery calcification, and bone mineral densities—except for the lumbar spine, in maintenance HD patients. However, the results should be interpreted with caution because of the cross‐sectional design of the study.     

Comparison of Two Parathyroid Hormone Assays in Hemodialysis Patients

Parathyroid hormone (PTH) determination is essential for the diagnosis of renal osteodystrophy, but differences between the laboratory assays can lead to different therapies. This study compared the new Tosoh ST AIA‐Pack Intact PTH assay (Tosoh Bioscience, San Francisco, CA, USA) with the Elecsys Intact PTH Roche assay (Roche Diagnostics GmbH, Mannheim, Germany), currently considered the gold standard. Nineteen chronic stable hemodialysis patients were enrolled to check PTH levels with the two assays. Median age was 71 years (range 26–84), M/F = 10/9. Blood samples were taken before the start of the same midweek dialysis session. Two blood vacuettes were collected and immediately transported to the central laboratory. The median PTH value was 268 (range 35–901 pg/dL) with the AIA‐Pack versus 184 (range 39–552 pg/dL) with Elecsys. The Wilcoxon test showed a significant difference between the two methods (P < 0.0001). AIA‐Pack showed a delta value of +38% in comparison with Elecsys and a median bias of 27.4%. For PTH values <150 pg/dL, nine patients were detected with AIA‐Pack (47.4%) versus nine patients detected with Elecsys (47.4%). For PTH values between 150 and 300 pg/dL, six patients were detected with AIA‐Pack (31.6%) versus four patients with Elecsys (21.0%). For PTH values >300 pg/dL four patients were detected with AIA‐Pack (21.0%) versus six patients with Elecsys (31.6%). The two assays showed no differences for each of the three PTH ranges considered. The two PTH assays tested are different and the attending physician should be aware of the differences when patients change their dialysis facility.     

CKD与非CKD患者冠状动脉钙化发生情况的比较研究

目的:比较CKD患者与非CKD患者的冠状动脉钙化情况。方法:选取473例曾在我院行冠脉CT检查的CKD及非CKD患者,通过收集其生化指标及冠脉CT检查结果,分析并比较两组患者冠状动脉钙化的发生情况。结果:CKD患者冠状动脉钙化的发生率为76.5%,且钙化累及分支更多,LAD、RCA多发。钙化组的尿素氮、血磷水平及钙磷乘积显著高于非钙化组,而GFR则显著低于非钙化组(P<0.01)。结论:CKD患者冠状动脉钙化发生率高,累及范围广,程度更重,且LAD、RCA钙化多发。钙化组的尿素氮、血磷水平及钙磷乘积显著高于非钙化组,而GFR则显著低于非钙化组。     

Early Subclinical Coronary Artery Calcification in Young Adults Who Were Pediatric Kidney Transplant Recipients

Coronary artery disease (CAD) is the leading cause of death in adults after successful kidney transplantation. Children who have undergone successful kidney transplantation are entering young adulthood; however, the prevalence and extent of CAD in this population is unknown. We conducted a pilot study in young adults with stable allograft function, who received kidney transplants as children to measure coronary artery calcification (CAC), a marker of coronary artery atherosclerosis and CAD. We evaluated 19 young adults after successful pediatric kidney transplantation for known CAD risk factors; these patients underwent noninvasive imaging with electron-beam computed tomography (EBCT) for measurement of CAC. Prevalence and quantity of CAC were then compared to asymptomatic individuals from the community. All patients had multiple risk factors for CAD. Mean age at evaluation was 32 years (range: 21-48 years). CAC is uncommon in individuals in the community in this age range; however, nearly half of our patients had CAC detected with the quantity of CAC comparable to asymptomatic individuals from the community 10-40 years older. These data suggest young adults who received pediatric kidney transplants are at increased risk for developing early CAC and need close monitoring to detect early CAD so as to prevent premature cardiac morbidity and mortality.