慢性肾脏病患者心血管钙化的影响因素分析

慢性肾脏病(chronic kidney disease,CKD)患者因高龄、高血压、高血脂、糖尿病、吸烟、男性等传统心血管钙化危险因素,加上CKD特有因素:矿物质代谢紊乱、含钙磷结合剂及活性维生素D的不合理使用、微炎症状态、氧化应激等常引起严重的心血管钙化,病情进一步发展会加速心血管事件的发生,影响CKD患者的预后。使用磷结合剂、活性维生素D及其类似物、西那卡塞等药物控制高钙、高磷、高PTH对预防心血管钙化至关重要。药物治疗无效或在治疗过程中出现不能控制的矿物质代谢异常,则要考虑手术切除甲状旁腺。甲状旁腺切除术(parathyroidectomy,PTX)作为难治性继发性甲状旁腺功能亢进患者的有效治疗之一,可迅速降低甲状旁腺素(parathyroid hormone,PTH)和血清钙磷水平,减少活性维生素D等药物的使用,缓解骨痛、瘙痒、肌无力等症状,但PTX后是否可以减轻心血管钙化?术后长期的低PTH状态与心血管钙化的关系如何?目前还没有明确的结论,本文就CKD患者心血管钙化的影响因素,尤其是PTX对CKD患者心血管钙化的影响作一综述。     

Prognosis and risk factors for cardiac valve calcification in Chinese end-stage kidney disease patients on combination therapy with hemodialysis and hemodiafiltration

BackgroundCardiac valve calcification (CVC) is an important risk factor for cardiovascular complications. However, limited data are available concerning the prevalence, clinical features and risk factors for CVC in end-stage kidney disease (ESKD) patients. In this study, we aimed to assess these parameters in Chinese ESKD patients receiving combination therapy with hemodialysis and hemodiafiltration.MethodsWe conducted a cross-sectional study on 293 ESKD patients undergoing combination therapy of hemodialysis and hemodiafiltration at the First Affiliated Hospital of Chongqing Medical University from October 2014 to December 2015. CVC was evaluated via echocardiography.ResultsESKD patients with CVC had a higher prevalence of diabetes mellitus, aortic and/or coronary artery calcification, arrhythmia, heart failure and coronary heart disease; increased systolic, diastolic and pulse pressure; longer duration of hemodialysis and hypertension; reduced hemoglobin, albumin and high-density lipoprotein cholesterol levels; and increased serum calcium and calcium-phosphorus product levels compared with those without CVC. Logistic regression analysis showed that increased dialysis duration (p = 0.006, OR = 2.25), serum calcium levels (p = 0.046, OR = 2.04) and pulse pressure (p < 0.001, OR = 3.22), the presence of diabetes (p = 0.037, OR = 1.81) and decreased serum albumin levels (p = 0.047, OR = 0.54) were risk factors for CVC. The correlation analysis indicated a significantly increased CVCs prevalence with an increase prevalence of heart failure, aortic and coronary artery calcification.ConclusionsCVC represents a common complication and a danger signal for cardiovascular events in ESKD patients undergoing combination therapy of hemodialysis and hemodiafiltration. The presence of diabetes, increased pulse pressure, long dialysis duration, hypoalbuminemia and high serum calcium levels were independent risk factors for CVC.     

Using vertebral bone densitometry to determine aortic calcification in patients with chronic kidney disease

Background: Vascular calcification (VC) is a major contributor to increased cardiovascular (CV) disease in chronic kidney disease (CKD) and an independent predictor of mortality. VC is inversely correlated with bone mineral density (BMD). Screening for VC may be useful to determine those at greater CV risk and dual‐energy X‐ray absorptiometry (DXA) may have a dual role in providing VC measurement as well as BMD. Methods: We report cross‐sectional data on 44 patients with CKD stages 3–4 and aim to determine and validate measurement of VC using DXA. Patients had computed tomography (CT) of abdominal aorta and DXA of lateral lumbar spine, to determine both aortic VC and BMD. Semi‐quantitative measurement of VC from DXA was determined (blinded) using previously validated 8‐ and 24‐point scales, and compared with VC from CT. BMD determination from L2 to L4 vertebrae on CT was compared with DXA‐reported BMD. Results: Patients 66% male, 57% diabetic, had mean age 63.4 years and mean estimated glomerular filtration rate 31.4 ± 12 mL/min. Aortic VC was present in 95% on CT, mean 564.9 ± 304 Hounsfield units (HU). Aortic VC was seen in 68% on lateral DXA, mean scores 5.1 ± 5.9 and 1.9 ± 1.9 using 24‐ and 8‐point scales, respectively. Strong correlation of VC measurement was present between CT and DXA (r 0.52, P < 0.001). For DXA VC 24‐point score, intraclass correlations for intra‐rater and inter‐rater agreement were 0.91 and 0.64, respectively (8‐point scale, intraclass correlations 0.90 and 0.69). Vertebral BMD measured by CT (mean 469.3 HU L2–4) also significantly correlated with lateral DXA‐reported BMD (mean spine T‐score –0.67 ± 1.6) (r 0.56, P < 0.001). Conclusion: Despite limitations in CKD, DXA may be useful as lateral DXA images provide concurrent assessment of aortic calcification as well as lumbar spine BMD, both correlating significantly with CT measurements. Lateral DXA may provide VC screening to determine patients at greater CV risk although more studies are needed to evaluate their potential role.     

Detection of coronary and peripheral artery calcification in patients with chronic kidney disease stages 3 and 4, with and without diabetes.

BACKGROUND: The purpose of this study was to describe the prevalence and extent of coronary artery calcification (CAC) in subjects with chronic kidney disease (CKD) stages 3 and 4 comparing those with and without diabetes. We also wished to determine if the presence of peripheral artery calcification (PAC) would assist in identifying patients positive for CAC. METHODS: CAC was detected by multi-slice computed tomography and PAC was detected by plain foot radiography. Study population was 112 patients, 54 with diabetes and 58 without, all asymptomatic for heart disease. Demographic and laboratory data were collected and analysed. RESULTS: The prevalence of CAC in CKD patients was 76 and 46.5% with and without diabetes, respectively. Patients with diabetes had higher CAC scores with more vessels affected, and in the presence of diabetes men and women had the same risk for CAC. In patients with diabetes, age was the unique explanatory variable for detecting the presence of CAC, while age and smoking history predicted severity. In patients without diabetes, age, male gender, body mass index, estimated glomerular filtration rate and serum phosphate levels predicted the presence of CAC, while parathyroid hormone predicted severity. Prevalence of PAC was 63 and 12% in subjects with and without diabetes. PAC detected by foot radiography was not an adequate alternative-screening marker for identifying patients with CAC. CONCLUSIONS: CAC is common in CKD stages 3 and 4 patients, especially in men and women with diabetes.     

Vascular calcification and arterial stiffness in chronic kidney disease: implications and management

Cardiovascular (CV) disease is the commonest cause of mortality in patients with chronic kidney disease (CKD). Vascular calcification (VC), induced by calcium and phosphate excess and uraemia, is a major risk factor and is independently associated with CV events and death. Local and systemic calcium-regulatory proteins as well as inhibitory extracellular factors are involved in the pathogenesis of VC. In CKD the balance becomes dysregulated leading to differentiation of vascular smooth muscle cells into phenotypically distinct osteoblast-like cells with subsequent ossification of the arterial wall. Associated with imbalances in mineral metabolism, VC has intimate interactions with bone mineralization and enhanced bone resorption. Arterial stiffness represents the functional disturbance of VC, with reduced compliance of large arteries, and predominantly results from greater medial calcification. As with VC, arterial stiffness is an independent predictor of CV mortality and patients with CKD have greater arterial stiffness than the general population resulting in the principal consequences of left ventricular hypertrophy and altered coronary perfusion. Both VC and arterial stiffness can be measured through non-invasive techniques involving computed tomography, ultrasound, echocardiography, and pulse wave velocity. Management in CKD is difficult but detection, prevention and treatment is crucial to reduce CV mortality. The optimal control of mineral metabolism, especially hyperphosphatemia with non-calcium based phosphate binders, has been shown to be effective to reduce VC, and attenuation of arterial stiffness, especially with good blood pressure control, can have a favourable effect with regression of left ventricular hypertrophy. The use of bisphosphonates, calcimimetics, vitamin D therapy and newer experimental treatments, as well as nocturnal dialysis, may have potential benefit.     

桡动脉中膜内膜厚度比值在监测慢性肾脏病5期患者血管钙化中的意义

目的本研究探讨桡动脉内膜中膜厚度（IMT）、内膜厚度（IT）、中膜厚度（MT）以及中膜内膜厚度比值（MITR）与慢性肾脏病5期（CKD5期）患者桡动脉钙化的关系。方法40例CKD5期患者为试验组,于行首次动静脉内瘘术时取桡动脉的修剪为试验组标本;38例单纯性外伤性脾破裂患者为对照组,取其脾小梁动脉为对照组标本。用钙盐特异性染色法（von Kossa法）对动脉进行钙化染色;应用计算机病理图像分析系统（IPP6．0）对组织切片进行半定量化图像分析;采用SPSS19．0统计分析软件进行数据处理。结果试验组40例患者有12例（30％）有明显钙盐染色阳性,位于中膜的平滑肌细胞层,而对照组无明显钙盐染色。试验组MITR与钙盐染色程度呈正相关,试验组IT与钙盐染色程度呈负相关。试验组MT、IMT与钙盐染色程度无统计学相关性。结论MITR可以作为慢性肾脏病患者中型动脉钙化的早期标志,而IMT不能准确反应动脉的钙化程度。     

Progression of coronary calcification in pediatric chronic kidney disease stage 5

Coronary artery calcification (CAC) is common in adults with chronic kidney disease (CKD) and progresses with time. However, data are limited for younger patients. We have previously reported CAC in eight of 53 children with CKD. After 2 years, CAC evaluation was repeated in 48 patients. The median CAC score (CACS) increased from 101.3 (1473.6 ± 1978.6, range 8.5–4332) to 1759.2 (2236.4 ± 2463.3, range 0–5858) Agatston units (AU). When the individual changes in CACS were evaluated one by one, we showed a mild decrease in two patients on hemodialysis (HD) and in one transplant (Tx) recipient, a moderate increase in one patient on HD, one on peritoneal dialysis (PD) and one Tx recipient, and a large increase in one HD patient. Also, CAC disappeared in one HD patient. All patients with no calcification at baseline remained calcification-free at follow-up. To obtain the individual cumulative exposure, we calculated time-averaged mean values, using the laboratory values from the beginning of dialysis to the first and second multidetector spiral computed tomography (MDCT) scans (baseline and final values, respectively). Final CACS was positively related to final calcium–phosphorus (Ca×P) product, while CAC progression was inversely associated with final serum albumin level. This report is the first study with the largest number and the youngest cohort to document the natural history of coronary calcification.     

Association of a low ankle brachial index with progression to end-stage kidney disease in patients with advanced-stage diabetic kidney disease

IntroductionsThe effect of a low ankle-brachial index (ABI) in patients with advanced-stage diabetic kidney disease is not fully understood. This study investigates the prevalence of a low ABI in patients with advanced-stage diabetic kidney disease, which was defined as a urinary albumin-to-creatinine ratio (UACR) ≥300 mg/g and an estimated glomerular filtration rate (eGFR) between 15–60 mL/min/1.73 m². Furthermore, the association between a low ABI and end-stage kidney disease (ESKD) was determined.MethodsThis single-center, retrospective, cohort study included 529 patients with advanced-stage diabetic kidney disease who were stratified into groups according to the ABI: high (>1.3), normal (0.9–1.3), and low (<0.9). The Kaplan-Meier method and Cox proportional analysis were used to examine the association between the ABI and ESKD.ResultsA total of 42.5% of patients with a low ABI progressed to ESKD. A low ABI was associated with a greater risk of ESKD (hazard ratio (HR): 1.073). After adjusting for traditional chronic kidney disease risk factors, a low ABI remained associated with a greater risk of ESKD (HR: 1.758; 95% confidence interval: 1.243–2.487; p = 0.001).ConclusionsThese results indicate that patients with a low ABI should be monitored carefully. Furthermore, preventive therapy should be considered to improve the long-term kidney survival of patients with residual kidney function.     

Lateral lumbar X-ray assessment of abdominal aortic calcification in Australian haemodialysis patients

Aim: Vascular calcification is prevalent in patients with chronic kidney disease. Abdominal aortic calcification (AAC) can be detected by X‐ray, although AAC is less well documented in anatomical distribution and severity compared with coronary calcification. Using simple radiological imaging we aimed to assess AAC and determine associations in prevalent Australian haemodialysis (HD) patients. Methods: Lateral lumbar X‐ray of the abdominal aorta was used to determine AAC, which is related to the severity of calcific deposits at lumbar vertebral segments L1 to L4. Two radiologists determined AAC scores, by semi‐quantitative measurement using a validated 24‐point scale, on HD patients from seven satellite dialysis centres. Regression analysis was used to determine associations between AAC and patient characteristics. Results: Lateral lumbar X‐ray was obtained in 132 patients. Median age of patients was 69 years (range 29–90), 60% were male, 36% diabetic, median duration of HD 38 months (range 6–230). Calcification (AAC score ≥ 1) was present in 94.4% with mean AAC score 11.0 ± 6.4 (median 12). Independent predictors for the presence and severity of calcification were age (P = 0.03), duration of dialysis (P = 0.04) and a history of cardiovascular disease (P = 0.009). There was no significant association between AAC and the presence of diabetes or time‐averaged serum markers of mineral metabolism, lipid status and C‐reactive protein. Conclusions: AAC detected by lateral lumbar X‐ray is highly prevalent in our cohort of Australian HD patients and is associated with cardiovascular disease, increasing age and duration of HD. This semi‐quantitative method of determining vascular calcification is widely available and inexpensive and may assist cardiovascular risk stratification.     

Radial artery calcification in end-stage renal disease patients is associated with deposition of osteopontin and diminished expression of alpha-smooth muscle actin

Aim:   Vascular access is the lifeline of haemodialysis patients and radial-cephalic fistula is the preferred type of access. We investigated vascular calcification in uraemia radial arteries and compared it with clinical parameters.
Methods:   Artery specimens from 30 end-stage renal disease patients were collected, examined calcification by von Kossa and Alizarin red staining. Expression of α-smooth muscle actin (α-SMA) and the main component of bone matrix, osteopontin (OP) were detected by immunohistochemistry.
Results:   In uraemia vessels, calcification was mainly located in the medial layer. Nineteen (63.33%) patients had no evidence of calcification, six (20%) had mild/moderate calcification and five (16.66%) had severe calcification. Upregulation of OP and diminished expression of α-SMA occurred in the medial layer, especially in the area of severe calcification. The calcification score, decreased expression of α-SMA and upregulation of OP were positively correlated with older age, serum calcium, serum phosphorus and calcium × phosphorus product ( P  < 0.01).
Conclusion:   Vascular calcification in uraemia radial arteries is mainly located in the media layer. The risk factors appear to be older age, an elevated serum level of phosphorus, calcium and calcium × phosphorus product.     

Associations between vascular calcification, arterial stiffness and bone mineral density in chronic kidney disease.

BACKGROUND: Vascular calcification (VC) and arterial stiffness are major contributors to cardiovascular (CV) disease in chronic kidney disease (CKD). Both are independent predictors of CV mortality and are inversely correlated with bone mineral density (BMD). Few studies have addressed the extent of VC in the pre-dialysis CKD population, with associated measurements of BMD and arterial compliance. METHODS: We report cross-sectional data on 48 patients with CKD (GFR 17-55 ml/min) assessing the prevalence of VC and its associations. All patients had computed tomography (CT) scans through abdominal aorta and superficial femoral arteries (SFAs) to determine VC, pulse wave velocity (PWV) using SphygmoCor device (AtCor PWV Inc., Westmead, Australia) measuring arterial stiffness, and dual-energy X-ray absorptiometry (DEXA) scans to determine BMD, as well as serum markers of renal function and mineral metabolism. RESULTS: Patients, 71% male, 54% diabetic, had a median age 64.5 years. Mean estimated GFR was 35.1 +/- 10 ml/min. Mean PWV was 10.0 +/- 4.5 m/s and mean aortic VC score was 421.5 +/- 244 Hounsfield units, with 90% of subjects having some aortic VC present. In univariate linear regression analysis, aortic VC correlated positively with age (r 0.50, P < 0.001), triglycerides (r 0.47, P = 0.002) and PWV (r 0.33, P = 0.03). There was also greater VC with declining renal function (r -0.28, P = 0.05). There was no significant association between VC and serum markers of mineral metabolism, however phosphate and Ca x P correlated positively with PWV (r 0.35, P = 0.02, r 0.36, P = 0.02, respectively). There was also a positive association between PWV and triglycerides (P = 0.008), and a trend towards greater PWV with increasing age (P = 0.09). In multivariate regression analysis only increasing age and triglyceride levels were significantly associated with aortic VC and PWV. Mean spine and femoral T-scores on DEXA were 0.48 and -1.31 respectively, with 13% of subjects having femoral T-score <-2.5 (osteoporotic range). SFA VC inversely correlated with femoral T-scores (r -0.43, P = 0.004); however, there was a positive (likely false) association between spine T-scores and aortic VC (r 0.37, P = 0.01), related to the limitation of vertebral DEXA in CKD. CONCLUSION: There is a high prevalence of VC in pre-dialysis CKD patients, worse with increasing age, triglycerides and reducing renal function. Correlation exists between VC and PWV and determination of one or both may be useful for CKD patient CV risk assessment. Femoral BMD is inversely associated with SFA VC, but measurement of vertebral BMD by DEXA is unreliable in CKD patients with aortic VC.     

Mitral annular calcification and the serum osteocalcin level in patients with chronic kidney disease

Objective: To determine the relationships between inflammatory mediators, mitral annular calcification (MAC), and osteocalcin in patients with chronic kidney disease (CKD). Materials and methods: Echocardiographic data for 60 patients diagnosed as CKD were retrospectively evaluated. The patients were divided into 2 groups; patients with MAC (MAC+ group) and patients without MAC (MAC? group). The relationships between biochemical markers—including osteocalcin—and MAC were evaluated. Results: The study included 19 female and 41 male patients. In all, 29 patients were MAC+ and 31 were MAC?. High-sensitive C-reactive protein (hsCRP) and osteocalcin levels were significantly higher in the MAC+ group (p?0.05). The eGFR was lower, serum calcitonin (we could not obtain calcitonin data for 15 patients), Ca, PO4, CaxPO4, the erythrocyte sedimentation rate, red cell distribution width, the neutrophil/Lymphocyte rate, and PTH were higher in the MAC+ group; however, the differences between the groups were not significant (p?>?0.05). The mitral E/A ratio, mitral peak Ea velocity, tricuspid E/A ratio, hsCRP, and the osteocalcin level were strongly correlated with MAC. Multivariate logistic regression analysis showed that only the osteocalcin level and mitral E/A ratio were independent variables, each with an independent effect on MAC. Conclusion: CKD patients in the MAC+ group had higher osteocalcin levels than those in the MAC? group, and left ventricular diastolic dysfunction was more common in the MAC+ group.     

Cardiovascular calcification in end-stage renal disease.

Cardiovascular diseases are common in patients with end-stage renal disease (ESRD) and cardiovascular morbidity and mortality among dialysis patients are substantially higher than in the general population. The reasons for this high incidence are multiple. They include traditional factors such as hypertension, diabetes, dyslipidaemia, sodium overload, and elevated homocysteine levels as well as disturbances of mineral metabolism, specifically abnormalities in phosphorus and calcium homeostasis. This review will describe the specific cardiovascular complications related to calcifications in ESRD, the implications of the abnormalities of mineral metabolism in its pathogenesis and the current imaging techniques available for the detection of cardiovascular calcifications. Excess of calcium load contributes to the development of cardiac calcifications; therefore, alternative strategies to diminish exogenous calcium load should be considered in patients with ESRD.     

The impact of traditional and non-traditional risk factors on coronary calcification in pre-dialysis patients.

BACKGROUND: Coronary heart disease (CHD) is the leading cause of death among end-stage renal disease patients. There is evidence that coronary calcification is a marker of atherosclerotic vascular disease and is predictive of cardiovascular events, especially in patients on renal replacement therapy. It has recently been suggested that CHD begins in the pre-dialysis period. However, data regarding coronary calcification in this population is scarce. This study was aimed at evaluating such coronary calcification and identifying related factors. METHODS: A total of 96 chronic kidney disease out-patients who were not on dialysis were included. Patients presenting neoplastic, infectious or inflammatory diseases were excluded. Demographic characteristics, clinical profiles, laboratory test results and multislice computed tomography scans were evaluated. RESULTS: The median age was 55 years (range 20-69 years), 67% were men and the median creatinine clearance was 37 ml/min/1.73 m(2). Coronary calcification, defined as a coronary artery calcification score (CACS) >0 Agatston units (AU), was seen in 61 patients (median 89.1 AU, range 0.37-2299.3 AU). On average, these patients were older, more often had diabetes, higher body mass indices and higher Framingham risk indices, as well as presenting higher proteinuria, intact parathyroid hormone (iPTH), blood glucose and triglyceride levels compared with those without calcification. Multiple logistic regression analysis, adjusted for age and diabetes, identified iPTH and triglyceride levels as independent determinants of calcification. Severe calcification (CACS >400 AU) was seen in 22 patients, who were also older and more frequently had a history of cardiovascular disease (CVD), as well as having higher levels of phosphorus, blood glucose and soluble Fas (sFas). Multiple logistic regression analysis, adjusted for age and diabetes, identified phosphorus and sFas levels as independent determinants of severe coronary calcification. CONCLUSION: Coronary calcification is highly prevalent in pre-dialysis patients and correlates with traditional and non-traditional risk factors for CVD.     

The relationship between calcification inhibitor levels in chronic kidney disease and the development of atherosclerosis

AimWe aimed to investigate the factors affecting the development of atherosclerosis and the role of calcification inhibitors fetuin-A, matrix-Gla protein (MGP), osteoprotegerin (OPG) in atherosclerosis progress.Material and methodsThe study was planned to investigate the relationship of serum OPG, MGP and fetuin-A levels with the development of atherosclerosis in the stage 2–3–4–5 chronic kidney disease (CKD) patients who did not require dialysis treatment.Results32 (17 female, 15 male) healthy individuals and 92 (49 females, 43 males) CKD patients were included. The mean carotid intima-media thickness (CIMT), C-reactive protein (CRP), fetuin-A, OPG and MGP of the two groups were compared statistically. In CKD patients, age, body mass index (BMI), CRP, triglyceride, urea, systolic blood pressure (SBP), fasting blood sugar have a positive linear relationship, fetuin-A, OPG, GFR have a negative linear relationship with CIMT. The mean CIMT, right CIMT, left CIMT, blood urea, CRP, urinary albumin excretion creatinine and age show a negative linear relationship with fetuin-A.ConclusionFetuin-A levels begin to decline from the early stages of CKD and are significantly lower in patients with atherosclerosis as expressed with CIMT. This suggests that fetuin-A may be used as an early marker in CKD for increased cardiovascular risk. Early recognition of these risk factors is important and large-scale studies on vascular calcification inhibitors are needed.